Person: Jerosch-Herold, Michael
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Jerosch-Herold
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Jerosch-Herold, Michael
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Publication Risk Stratification by Regadenoson Stress Magnetic Resonance Imaging in Patients With Known or Suspected Coronary Artery Disease(Elsevier BV, 2014) Abbasi, Siddique Akbar; Heydari, Bobak; Shah, Ravi; Murthy, Venkatesh; Zhang, Ying-Yi; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, RaymondThe aim of this study was to investigate the association between major adverse cardiovascular events (MACEs) and inducible ischemia on regadenoson cardiac magnetic resonance (CMR) myocardial perfusion imaging (MPI) performed at 3.0 T. Regadenoson stress CMR MPI is increasingly used to assess patients with suspected ischemia; however, its value in patient prognostication and risk reclassification is only emerging. A total of 346 patients with suspected ischemia who were referred for regadenoson CMR were studied. The prognostic association of presence of inducible ischemia by CMR with MACEs was determined. In addition, we assessed the extent of net reclassification improvement by CMR beyond a clinical risk model. There were 52 MACEs during a median follow-up period of 1.9 years. Patients with inducible ischemia were fourfold more likely to experience MACEs (hazard ratio, 4.14, 95% confidence interval 2.37 to 7.24, p <0.0001). In the best overall model, presence of inducible ischemia conferred a 2.6-fold increased hazard for MACEs adjusted to known clinical risk markers (adjusted hazard ratio 2.59, 95% confidence interval 1.30 to 5.18, p = 0.0069). Patients with no inducible ischemia experienced a low rate of cardiac death and myocardial infarction (0.6% per patient-year), whereas those with inducible ischemia had an annual event rate of 3.2%. Net reclassification improvement across risk categories (low <5%, intermediate 5% to 10%, and high >10%) by CMR was 0.29 (95% confidence interval 0.15 to 0.44), and continuous net reclassification improvement was 0.58. In conclusion, in patients with clinical suspicion of myocardial ischemia, regadenoson stress CMR MPI provides robust risk stratification. CMR MPI negative for ischemia was associated with a very low annual rate of hard cardiac events. In addition, CMR MPI provides effective risk reclassification in a substantial proportion of patients.Publication Left Atrial Passive Emptying Function Determined by Cardiac Magnetic Resonance Predicts Atrial Fibrillation Recurrence After Pulmonary Vein Isolation(Ovid Technologies (Wolters Kluwer Health), 2014) Dodson, John; Neilan, Tomas; Shah, Ravi; Farhad, H.; Blankstein, Ron; Steigner, Michael; Michaud, Gregory F.; John, Roy M.; Abbasi, Siddique Akbar; Jerosch-Herold, Michael; Kwong, RaymondBackground While pulmonary vein isolation (PVI) has become a mainstream therapy for selected patients with atrial fibrillation (AF), late recurrent AF is common and its risk factors remain poorly defined. The purpose of our study was to test the hypothesis that reduced left atrial passive emptying function (LAPEF) as determined by cardiac magnetic resonance (CMR) has a strong association with late recurrent AF following PVI. Methods and Results 346 AF patients referred for CMR PV mapping prior to PVI were included. Maximum LA volumes (VOLmax) and volumes before atrial contraction (VOLbac) were measured; LAPEF was calculated as (VOLmax − VOLbac)/VOLmax × 100. Kaplan-Meier curves were constructed to determine late recurrent AF stratified by LAPEF quintile. Cox proportional hazards regression was used to adjust for known markers of recurrence. Over a median follow-up of 27 months, 124 patients (35.8%) experienced late recurrent AF. Patients with recurrence were more likely to have non-paroxysmal AF (75.8% vs. 51.4%, P<0.01), higher mean VOLmax (60.2 ml/m2 vs. 52.8 ml/m2, P<0.01), and lower mean LAPEF (19.1% vs. 26.0%, P<0.01). Patients in the lowest LAPEF quintile were at highest risk of developing recurrent AF (two-year recurrence lowest vs. highest: 60.5% vs. 17.3%, P<0.01). After adjusting for known predictors of recurrence, patients with low LAPEF remained significantly more likely to recur (HR lowest vs. highest quintile = 3.92, 95% CI 2.01–7.65). Conclusion We found a strong association between LAPEF and recurrent AF after PVI that persisted after multivariable adjustment.Publication Vasodilator Stress Perfusion CMR Imaging Is Feasible and Prognostic in Obese Patients(Elsevier BV, 2014) Shah, Ravi; Heydari, Bobak; Coelho-Filho, Otavio; Abbasi, Siddique Akbar; Feng, Jiazhuo H.; Neilan, Tomas; Francis, Sanjeev A.; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, RaymondObjectives This study sought to determine feasibility and prognostic performance of stress cardiac magnetic resonance (CMR) in obese patients (body mass index [BMI] ≥30 kg/m2). Background Current stress imaging methods remain limited in obese patients. Given the impact of the obesity epidemic on cardiovascular disease, alternative methods to effectively risk stratify obese patients are needed. Methods Consecutive patients with a BMI ≥30 kg/m2 referred for vasodilating stress CMR were followed for major adverse cardiovascular events (MACE), defined as cardiac death or nonfatal myocardial infarction. Univariable and multivariable Cox regressions for MACE were performed to determine the prognostic association of inducible ischemia or late gadolinium enhancement (LGE) by CMR beyond traditional clinical risk indexes. Results Of 285 obese patients, 272 (95%) completed the CMR protocol, and among these, 255 (94%) achieved diagnostic imaging quality. Mean BMI was 35.4 ± 4.8 kg/m2, with a maximum weight of 200 kg. Reasons for failure to complete CMR included claustrophobia (n = 4), intolerance to stress agent (n = 4), poor gating (n = 4), and declining participation (n = 1). Sedation was required in 19 patients (7%; 2 patients with intravenous sedation). Sixteen patients required scanning by a 70-cm-bore system (6%). Patients without inducible ischemia or LGE experienced a substantially lower annual rate of MACE (0.3% vs. 6.3% for those with ischemia and 6.7% for those with ischemia and LGE). Median follow-up of the cohort was 2.1 years. In a multivariable stepwise Cox regression including clinical characteristics and CMR indexes, inducible ischemia (hazard ratio 7.5; 95% confidence interval: 2.0 to 28.0; p = 0.002) remained independently associated with MACE. When patients with early coronary revascularization (within 90 days of CMR) were censored on the day of revascularization, both presence of inducible ischemia and ischemia extent per segment maintained a strong association with MACE. Conclusions Stress CMR is feasible and effective in prognosticating obese patients, with a very low negative event rate in patients without ischemia or infarction.Publication The Incidence, Pattern, and Prognostic Value of Left Ventricular Myocardial Scar by Late Gadolinium Enhancement in Patients With Atrial Fibrillation(Elsevier BV, 2013) Neilan, Tomas; Shah, Ravi; Abbasi, Siddique Akbar; Farhad, Hoshang; Groarke, John; Dodson, John; Coelho-Filho, Otavio; McMullan, Ciaran Joseph; Heydari, Bobak; Michaud, Gregory F.; John, Roy M.; van der Geest, Rob; Steigner, Michael; Blankstein, Ron; Jerosch-Herold, Michael; Kwong, RaymondObjectives We aimed to identify the frequency, pattern, and prognostic significance of left ventricular (LV) late gadolinium enhancement (LGE) in patients with atrial fibrillation (AF). Background There are limited data on the presence, pattern, and prognostic significance of LV myocardial fibrosis in patients with AF. Late gadolinium enhancement during cardiac magnetic resonance (CMR) is a marker for myocardial fibrosis. Methods We studied a consecutive group of 664 patients without known prior myocardial infarction being referred for radiofrequency ablation of AF. CMR was requested to assess pulmonary venous anatomy. Results Overall, 73% were male, with an average age of 56 years, and an ejection fraction of 55±10%. Left ventricular LGE was found in 88 patients (13%). The endpoint was all-cause mortality, and in this cohort we observed 68 deaths over a median follow-up period of 42 months. On univariable analysis, age (HR 1.05, CI 1.03–1.08, LRχ2 15.2, p=0.0001), diabetes (HR 2.39, CI 1.41–4.09, LRχ210.3, p=0.001), a history of heart failure (HR 1.78, CI 1.09–2.91, LRχ2 5.37, p=0.02), left atrial dimension (HR 1.04, CI 1.01–1.08, LRχ2 6.47, p=0.01), presence of LGE (HR 5.08, CI 3.08–8.36, LRχ2 28.8, p<0.0001), and LGE extent (HR 1.15, CI 1.10–1.21, LRχ2 35.6, p<0.0001) provided the strongest association with mortality. The mortality rate was 8.1% per patient-years in patients with LGE vs. 2.3% patients without LGE. In the best overall multivariable model for mortality, age and the extent of LGE were independent predictors of mortality. Indeed, each 1% increase in LGE associated with a 15% increased risk of death. Conclusions In patients with AF, LV LGE is a frequent finding and is a powerful predictor of mortality.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 Left Atrial structure and function in hypertrophic cardiomyopathy sarcomere mutation carriers with and without left ventricular hypertrophy(BioMed Central, 2017) Farhad, Hoshang; Seidelmann, Sara; Vigneault, Davis; Abbasi, Siddique A.; Yang, Eunice; Day, Sharlene M.; Colan, Steven D.; Russell, Mark W.; Towbin, Jeffrey; Sherrid, Mark V.; Canter, Charles E.; Shi, Ling; Jerosch-Herold, Michael; Bluemke, David A.; Ho, Carolyn; Neilan, TomasBackground: Impaired left atrial (LA) function is an early marker of cardiac dysfunction and predictor of adverse cardiac events. Herein, we assess LA structure and function in hypertrophy in hypertrophic cardiomyopathy (HCM) sarcomere mutation carriers with and without left ventricular hypertrophy (LVH). Method Seventy-three participants of the HCMNet study who underwent cardiovascular magnetic resonance (CMR) imaging were studied, including mutation carriers with overt HCM (n = 34), preclinical mutation carriers without HCM (n = 24) and healthy, familial controls (n = 15). Results: LA volumes were similar between preclinical, control and overt HCM cohorts after covariate adjustment. However, there was evidence of impaired LA function with decreased LA total emptying function in both preclinical (64 ± 8%) and overt HCM (59 ± 10%), compared with controls (70 ± 7%; p = 0.002 and p = 0.005, respectively). LA passive emptying function was also decreased in overt HCM (35 ± 11%) compared with controls (47 ± 10%; p = 0.006). Both LAtotal emptying function and LA passive emptying function were inversely correlated with the extent of late gadolinium enhancement (LGE; p = 0.005 and p < 0.05, respectively), LV mass (p = 0.02 and p < 0.001) and interventricular septal thickness (p < 0.001 for both) and serum NT-proBNP levels (p < 0.001 for both). Conclusion: LA dysfunction is detectable by CMR in preclinical HCM mutation carriers despite non-distinguishable LV wall thickness and LA volume. LA function appears most impaired in subjects with overt HCM and a greater extent of LV fibrosis. Electronic supplementary material The online version of this article (10.1186/s12968-017-0420-0) contains supplementary material, which is available to authorized users.Publication Plasma Circulating Extracellular RNAs in Left Ventricular Remodeling Post-Myocardial Infarction(Elsevier, 2018) Danielson, Kirsty M.; Shah, Ravi; Yeri, Ashish; Liu, Xiaojun; Camacho Garcia, Fernando; Silverman, Michael; Tanriverdi, Kahraman; Das, Avash; Xiao, Chunyang; Jerosch-Herold, Michael; Heydari, Bobak; Abbasi, Siddique; Van Keuren-Jensen, Kendall; Freedman, Jane E.; Wang, Yaoyu E.; Rosenzweig, Anthony; Kwong, Raymond; Das, SaumyaDespite substantial declines in mortality following myocardial infarction (MI), subsequent left ventricular remodeling (LVRm) remains a significant long-term complication. Extracellular small non-coding RNAs (exRNAs) have been associated with cardiac inflammation and fibrosis and we hypothesized that they are associated with post-MI LVRm phenotypes. RNA sequencing of exRNAs was performed on plasma samples from patients with “beneficial” (decrease LVESVI ≥ 20%, n = 11) and “adverse” (increase LVESVI ≥ 15%, n = 11) LVRm. Selected differentially expressed exRNAs were validated by RT-qPCR (n = 331) and analyzed for their association with LVRm determined by cardiac MRI. Principal components of exRNAs were associated with LVRm phenotypes post-MI; specifically, LV mass, LV ejection fraction, LV end systolic volume index, and fibrosis. We then investigated the temporal regulation and cellular origin of exRNAs in murine and cell models and found that: 1) plasma and tissue miRNA expression was temporally regulated; 2) the majority of the miRNAs were increased acutely in tissue and at sub-acute or chronic time-points in plasma; 3) miRNA expression was cell-specific; and 4) cardiomyocytes release a subset of the identified miRNAs packaged in exosomes into culture media in response to hypoxia/reoxygenation. In conclusion, we find that plasma exRNAs are temporally regulated and are associated with measures of post-MI LVRm.Publication Myocardial T1 mapping and extracellular volume quantification: an overview of technical and biological confounders(Springer Netherlands, 2017) Piechnik, Stefan K.; Jerosch-Herold, MichaelNovel tissue biomarkers based on the spin–lattice relaxation time T1, a fundamental property in the theory of magnetic resonance physics, have emerged as a new approach for myocardial tissue characterization with many validated clinical applications. This article is intended as an overview of the physical and physiological mechanisms underlying the interpretation and the accuracy of any practical measurement of T1, or derived biomarkers such as extravascular volume fraction, and also includes a discussion of potential pitfalls. Numerous caveats und knowledge gaps related to the precise interpretation of T1-based biomarkers remain, which are being addressed incrementally through ongoing research. Equally important, further careful standardization will pave the way for a wider clinical translation of these novel T1-based biomarkers of tissue remodeling, which have been well validated for their sensitivity to pathophysiological changes, though for the most part in single-center studies.Publication Left atrial passive function after aortic valve replacement in aortic stenosis(BioMed Central, 2014) Farhad, Hoshang; Neilan, Tomas; Abbasi, Siddique; Shah, Ravi; Feng, Jiazuo; Kwong, Raymond Y; Jerosch-Herold, MichaelPublication Myocardial strain imaging with radial acquisitions (SIRA) reduces tag fading compared to Cartesian sampling(BioMed Central, 2014) Hulten, Edward; Shah, Ravi; Abbasi, Siddique; Neilan, Tomas; Feng, Jiazuo; Groarke, John; Waller, Alfonso H; Blankstein, Ron; Kwong, Raymond; Jerosch-Herold, Michael