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Meta-Analysis of the Prognostic Role of Late Gadolinium Enhancement and Global Systolic Impairment in Left Ventricular Noncompaction

Grigoratos, Chrysanthos; Barison, Andrea; Ivanov, Alexander; Andreini, Daniele; Amzulescu, Mihaela-Silvia; Mazurkiewicz, Lukasz; De Luca, Antonio; Grzybowski, Jacek; Masci, Pier Giorgio; Marczak, Magdalena; Heitner, John F; Schwitter, Juerg; Gerber, Bernhard L; Emdin, Michele; Aquaro, Giovanni Donato
OBJECTIVES:The objective of this meta-analysis was to assess the predictive value of late gadolinium enhancement (LGE) and global systolic impairment for future major adverse cardiovascular events in left ventricular noncompaction (LVNC). BACKGROUND:The prognosis of patients with LVNC, with and without left ventricular dysfunction and LGE, is still unclear. METHODS:A systematic review of published research and a meta-analysis reporting a combined endpoint of hard (cardiac death, sudden cardiac death, appropriate defibrillator firing, resuscitated cardiac arrest, cardiac transplantation, assist device implantation) and minor (heart failure hospitalization and thromboembolic events) events was performed. RESULTS:Four studies with 574 patients with LVNC and 677 with no LVNC and an average follow-up duration of 5.2 years were analyzed. In patients with LVNC, LGE was associated with the combined endpoint (pooled odds ratio: 4.9; 95% confidence interval: 1.63 to 14.6; p = 0.005) and cardiac death (pooled odds ratio: 9.8; 95% confidence interval: 2.44 to 39.5; p < 0.001). Preserved left ventricular systolic function was found in 183 patients with LVNC: 25 with positive LGE and 158 with negative LGE. In LVNC with preserved ejection fraction, positive LGE was associated with hard cardiac events (odds ratio: 6.1; 95% confidence interval: 2.1 to 17.5; p < 0.001). No hard cardiac events were recorded in patients with LVNC, preserved ejection fraction, and negative LGE. CONCLUSIONS:Patients with LVNC but without LGE have a better prognosis than those with LGE. When LGE is negative and global systolic function is preserved, no hard cardiac events are to be expected. Currently available criteria allow diagnosis of LVNC, but to further define the presence and prognostic significance of the disease, LGE and/or global systolic impairment must be considered for better risk stratification.
PMID: 30878415
ISSN: 1876-7591
CID: 4777802

Cardiac Magnetic Resonance Stress Perfusion Imaging for Evaluation of Patients With Chest Pain

Kwong, Raymond Y; Ge, Yin; Steel, Kevin; Bingham, Scott; Abdullah, Shuaib; Fujikura, Kana; Wang, Wei; Pandya, Ankur; Chen, Yi-Yun; Mikolich, J Ronald; Boland, Sebastian; Arai, Andrew E; Bandettini, W Patricia; Shanbhag, Sujata M; Patel, Amit R; Narang, Akhil; Farzaneh-Far, Afshin; Romer, Benjamin; Heitner, John F; Ho, Jean Y; Singh, Jaspal; Shenoy, Chetan; Hughes, Andrew; Leung, Steve W; Marji, Meera; Gonzalez, Jorge A; Mehta, Sandeep; Shah, Dipan J; Debs, Dany; Raman, Subha V; Guha, Avirup; Ferrari, Victor A; Schulz-Menger, Jeanette; Hachamovitch, Rory; Stuber, Matthias; Simonetti, Orlando P
BACKGROUND:Stress cardiac magnetic resonance imaging (CMR) has demonstrated excellent diagnostic and prognostic value in single-center studies. OBJECTIVES:This study sought to investigate the prognostic value of stress CMR and downstream costs from subsequent cardiac testing in a retrospective multicenter study in the United States. METHODS:In this retrospective study, consecutive patients from 13 centers across 11 states who presented with a chest pain syndrome and were referred for stress CMR were followed for a target period of 4 years. The authors associated CMR findings with a primary outcome of cardiovascular death or nonfatal myocardial infarction using competing risk-adjusted regression models and downstream costs of ischemia testing using published Medicare national payment rates. RESULTS:In this study, 2,349 patients (63 ± 11 years of age, 47% female) were followed for a median of 5.4 years. Patients with no ischemia or late gadolinium enhancement (LGE) by CMR, observed in 1,583 patients (67%), experienced low annualized rates of primary outcome (<1%) and coronary revascularization (1% to 3%), across all years of study follow-up. In contrast, patients with ischemia+/LGE+ experienced a >4-fold higher annual primary outcome rate and a >10-fold higher rate of coronary revascularization during the first year after CMR. Patients with ischemia and LGE both negative had low average annual cost spent on ischemia testing across all years of follow-up, and this pattern was similar across the 4 practice environments of the participating centers. CONCLUSIONS:In a multicenter U.S. cohort with stable chest pain syndromes, stress CMR performed at experienced centers offers effective cardiac prognostication. Patients without CMR ischemia or LGE experienced a low incidence of cardiac events, little need for coronary revascularization, and low spending on subsequent ischemia testing. (Stress CMR Perfusion Imaging in the United States [SPINS]: A Society for Cardiovascular Resonance Registry Study; NCT03192891).
PMID: 31582133
ISSN: 1558-3597
CID: 4777842

Response to Comment on Elliott et al. Prevalence and Prognosis of Unrecognized Myocardial Infarction in Asymptomatic Patients With Diabetes: A Two-Center Study With Up to 5 Years of Follow-up. Diabetes Care 2019;42:1290-1296 [Comment]

Elliott, Michael D; Heitner, John F; Kim, Han; Wu, Edwin; Parker, Michelle A; Lee, Daniel C; Kaufman, Dixon B; Bonow, Robert O; Judd, Robert; Kim, Raymond J
PMID: 31431498
ISSN: 1935-5548
CID: 4777832

Prognostic Implications of Mitral Annular Plane Systolic Excursion in Patients with Hypertension and a Clinical Indication for Cardiac Magnetic Resonance Imaging: A Multicenter Study

Romano, Simone; Judd, Robert M; Kim, Raymond J; Kim, Han W; Heitner, John F; Shah, Dipan J; Devereux, Richard B; Salazar, Pablo; Trybula, Michael; Chia, Richard C; Evans, Kaleigh; Farzaneh-Far, Afshin
OBJECTIVES:This study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived mitral annular plane systolic excursion (MAPSE) in a large multicenter population of patients with hypertension. BACKGROUND:In patients with hypertension, cardiac abnormalities are powerful predictors of adverse outcomes. Long-axis mitral annular movement plays a fundamental role in cardiac mechanics and is an early marker for a number of pathological processes. Given the adverse consequences of cardiac involvement in hypertension, the authors hypothesized that lateral MAPSE may provide incremental prognostic information in these patients. METHODS:Consecutive patients with hypertension and a clinical indication for CMR at 4 U.S. medical centers were included in this study (n = 1,735). Lateral MAPSE was measured in the 4-chamber cine view. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the association between lateral MAPSE and death. The incremental prognostic value of lateral MAPSE was assessed in nested models. RESULTS:Over a median follow-up period of 5.1 years, 235 patients died. By Kaplan-Meier analysis, risk of death was significantly higher in patients with a lateral MAPSE < median (10 mm) (log-rank; p < 0.0001). Lateral MAPSE was associated with risk of death after adjustment for clinical and imaging risk factors (hazard ratio [HR]: 1.402-per-millimeter decrease; p < 0.001). Addition of lateral MAPSE in this model resulted in significant improvement in the C-statistic (0.735 to 0.815; p < 0.0001). Continuous net reclassification improvement was 0.739 (95% confidence interval: 0.601 to 0.902). Lateral MAPSE remained significantly associated with death even after adjustment for feature tracking global longitudinal strain (HR: 1.192-per-millimeter decrease; p < 0.001). Lateral MAPSE was independently associated with death among the subgroups of patients with preserved ejection fraction (HR = 1.339; p < 0.001) and in those without history of myocardial infarction (HR: 1.390; p < 0.001). CONCLUSIONS:CMR-derived lateral MAPSE is a powerful, independent predictor of mortality in patients with hypertension and a clinical indication for CMR, incremental to common clinical and CMR risk factors. These findings may suggest a role for CMR-derived lateral MAPSE in identifying hypertensive patients at highest risk of death.
PMID: 30409557
ISSN: 1876-7591
CID: 4777752

Prevalence and Prognosis of Unrecognized Myocardial Infarction in Asymptomatic Patients With Diabetes: A Two-Center Study With Up to 5 Years of Follow-up

Elliott, Michael D; Heitner, John F; Kim, Han; Wu, Edwin; Parker, Michele A; Lee, Daniel C; Kaufman, Dixon B; Bonow, Robert O; Judd, Robert; Kim, Raymond J
OBJECTIVE:To determine the prevalence and prognostic significance of unrecognized myocardial infarction (MI) by delayed-enhancement MRI (DE-MRI) in asymptomatic patients with diabetes. RESEARCH DESIGN AND METHODS:= 70). The primary end point was a composite of all-cause mortality and clinical MI. RESULTS:= 0.001). CONCLUSIONS:Unrecognized MI is prevalent in asymptomatic patients with diabetes without a history of cardiac disease and confers a markedly increased risk of death and clinical MI.
PMID: 31010876
ISSN: 1935-5548
CID: 4777812

Utilizing mobile technologies to improve physical activity and medication adherence in patients with heart failure and diabetes mellitus: Rationale and design of the TARGET-HF-DM Trial

Sharma, Abhinav; Mentz, Robert J; Granger, Bradi B; Heitner, John F; Cooper, Lauren B; Banerjee, Dipanjan; Green, Cynthia L; Majumdar, Maulik D; Eapen, Zubin; Hudson, Lori; Felker, G Michael
Heart failure (HF) and diabetes mellitus (DM) are major public health issues that place significant burden on patients and health care systems. Patients with both HF and DM are at higher risk of adverse cardiovascular and HF outcomes than those with either disease in isolation. Different antihyperglycemic medications (even within the same medication class) have conflicting results of benefit or harm in patients with established and incident HF. Recent data highlight the importance of a renewed focus on optimal pharmacotherapy for this population with DM and HF (or at risk for HF). Both HF and DM require major lifestyle modification for optimal management, in terms of both optimizing health behaviors (eg, physical activity, diet) and adherence to complex medical and self-care regimens. Mobile health (mHealth) technologies (eg, apps, wearables) are widely available in the community and may play a role in optimizing the health status of patients; however, there is limited and conflicting information on whether such technologies are actually beneficial in at-risk populations. In this article, we summarize current strategies, including mobile health interventions, to improve physical activity levels, drug adherence, and outcomes in patients with DM, HF, or both and describe the design and rationale for the Technologies to improve drug Adherence and Reinforce Guideline based Exercise Targets in patients with heart Failure and Diabetes Mellitus trial, which is designed to test the efficacy of using mHealth technology to improve health behaviors and outcomes in this high-risk population.
PMID: 30831331
ISSN: 1097-6744
CID: 4777792

Identifying the Infarct-Related Artery in Patients With Non-ST-Segment-Elevation Myocardial Infarction

Heitner, John F; Senthilkumar, Annamalai; Harrison, J Kevin; Klem, Igor; Sketch, Michael H; Ivanov, Alexandr; Hamo, Carine; Van Assche, Lowie; White, James; Washam, Jeffrey; Patel, Manesh R; Bekkers, Sebastiaan C A M; Smulders, Martijn W; Sacchi, Terrence J; Kim, Raymond J
BACKGROUND:Determining the infarct-related artery (IRA) in non-ST-segment-elevation myocardial infarction (MI) can be challenging. Delayed-enhancement cardiac magnetic resonance (DE-CMR) can accurately identify small MIs. The purpose of this study was to determine whether DE-CMR improves the ability to identify the IRA in patients with non-ST-segment-elevation MI. METHODS AND RESULTS:In this 3-center, prospective study, we enrolled 114 patients presenting with their first MI. Patients underwent DE-CMR followed by coronary angiography. The interventional cardiologist was blinded to the DE-CMR results. Later, coronary angiography and DE-CMR images were reviewed independently and blindly for identification of the IRA. The pattern of DE-CMR hyperenhancement was also used to determine whether there was a nonischemic pathogenesis for myocardial necrosis. The IRA was not identifiable by coronary angiography in 37% of patients (n=42). In these, the IRA or a new noncoronary artery disease diagnosis was identified by DE-CMR in 60% and 19% of patients, respectively. Even in patients with an IRA determined by coronary angiography, a different IRA or a noncoronary artery disease diagnosis was identified by DE-CMR in 14% and 13%, respectively. Overall, DE-CMR led to a new IRA diagnosis in 31%, a diagnosis of nonischemic pathogenesis in 15%, or either in 46% (95% CI, 37%-55%) of patients. Of 55 patients undergoing revascularization, 27% had revascularization solely to nonculprit coronary artery territories as determined by DE-CMR. CONCLUSIONS:Identification of the IRA by coronary angiography can be challenging in patients with non-ST-segment-elevation MI. In nearly half, DE-CMR may lead to a new IRA diagnosis or elucidate a nonischemic pathogenesis. Revascularization solely of coronary arteries that are believed to be nonculprit arteries by DE-CMR is not uncommon.
PMID: 31035776
ISSN: 1941-7632
CID: 4777822

Prognostic Value of Vasodilator Stress Cardiac Magnetic Resonance Imaging: A Multicenter Study With 48 000 Patient-Years of Follow-up

Heitner, John F; Kim, Raymond J; Kim, Han W; Klem, Igor; Shah, Dipan J; Debs, Dany; Farzaneh-Far, Afshin; Polsani, Venkateshwar; Kim, Jiwon; Weinsaft, Jonathan; Shenoy, Chetan; Hughes, Andrew; Cargile, Preston; Ho, Jean; Bonow, Robert O; Jenista, Elizabeth; Parker, Michele; Judd, Robert M
Importance:Stress cardiac magnetic resonance imaging (CMR) is not widely used in current clinical practice, and its ability to predict patient mortality is unknown. Objective:To determine whether stress CMR is associated with patient mortality. Design, Setting, and Participants:Real-world evidence from consecutive clinically ordered CMR examinations. Multicenter study of patients undergoing clinical evaluation of myocardial ischemia. Patients with known or suspected coronary artery disease (CAD) underwent clinical vasodilator stress CMR at 7 different hospitals. An automated process collected data from the finalized clinical reports, deidentified and aggregated the data, and assessed mortality using the US Social Security Death Index. Main Outcomes and Measures:All-cause patient mortality. Results:Of the 9151 patients, the median (interquartile range) patient age was 63 (51-70) years, 55% were men, and the median (interquartile range) body mass index was 29 (25-33) (calculated as weight in kilograms divided by height in meters squared). The multicenter automated process yielded 9151 consecutive patients undergoing stress CMR, with 48 615 patient-years of follow-up. Of these patients, 4408 had a normal stress CMR examination, 4743 had an abnormal examination, and 1517 died during a median follow-up time of 5.0 years. Using multivariable analysis, addition of stress CMR improved prediction of mortality in 2 different risk models (model 1 hazard ratio [HR], 1.83; 95% CI, 1.63-2.06; P < .001; model 2: HR, 1.80; 95% CI, 1.60-2.03; P < .001) and also improved risk reclassification (net improvement: 11.4%; 95% CI, 7.3-13.6; P < .001). After adjustment for patient age, sex, and cardiac risk factors, Kaplan-Meier survival analysis showed a strong association between an abnormal stress CMR and mortality in all patients (HR, 1.883; 95% CI, 1.680-2.112; P < .001), patients with (HR, 1.955; 95% CI, 1.712-2.233; P < .001) and without (HR, 1.578; 95% CI, 1.235-2.2018; P < .001) a history of CAD, and patients with normal (HR, 1.385; 95% CI, 1.194-1.606; P < .001) and abnormal left ventricular ejection fraction (HR, 1.836; 95% CI, 1.299-2.594; P < .001). Conclusions and Relevance:Clinical vasodilator stress CMR is associated with patient mortality in a large, diverse population of patients with known or suspected CAD as well as in multiple subpopulations defined by history of CAD and left ventricular ejection fraction. These findings provide a foundational motivation to study the comparative effectiveness of stress CMR against other modalities.
PMID: 30735566
ISSN: 2380-6591
CID: 4777782

Association of left atrial volume index and all-cause mortality in patients referred for routine cardiovascular magnetic resonance: a multicenter study

Khan, Mohammad A; Yang, Eric Y; Zhan, Yang; Judd, Robert M; Chan, Wenyaw; Nabi, Faisal; Heitner, John F; Kim, Raymond J; Klem, Igor; Nagueh, Sherif F; Shah, Dipan J
BACKGROUND:Routine cine cardiovascular magnetic resonance (CMR) allows for the measurement of left atrial (LA) volumes. Normal reference values for LA volumes have been published based on a group of European individuals without known cardiovascular disease (CVD) but not on one of similar United States (US) based volunteers. Furthermore, the association between grades of LA dilatation by CMR and outcomes has not been established. We aimed to assess the relationship between grades of LA dilatation measured on CMR based on US volunteers without known CVD and all-cause mortality in a large, multicenter cohort of patients referred for a clinically indicated CMR scan. METHOD:). Mortality data were ascertained for the patient group using electronic health records and social security death index. Cox proportional hazard risk models were used to derive hazard ratios for measuring association of LA enlargement and all-cause mortality. RESULTS:. In clinical patients, enlarged LA was associated with older age, atrial fibrillation, hypertension, heart failure, inpatient status and biventricular dilatation. The median follow-up duration was 48.9 (IQR 32.1-71.2) months. On univariate analyses, mild [Hazard Ratio (HR) 1.35 (95% Confidence Interval [CI] 1.11 to 1.65], moderate [HR 1.51 (95% CI 1.22 to 1.88)] and severe LA enlargement [HR 2.14 (95% CI 1.81 to 2.53)] were significant predictors of death. After adjustment for significant covariates, moderate [HR 1.45 (95% CI 1.1 to 1.89)] and severe LA enlargement [HR 1.64 (95% CI 1.29 to 2.08)] remained independent predictors of death. CONCLUSION:LAVi determined on routine cine-CMR is independently associated with all-cause mortality in patients undergoing a clinically indicated CMR.
PMCID:6322235
PMID: 30612579
ISSN: 1532-429x
CID: 4777772

STRESS CMR IN ABNORMAL LVEF: CLINICAL IMPACT AND COST EFFECTIVENESS [Meeting Abstract]

Ge, Yin; Steel, Kevin; Abdullah, Shuaib; Bingham, Scott; Mikolich, J. Ronald; Heitner, John; Arai, Andrew; Bandettini, W. Patricia; Patel, Amit; Farzaneh-Far, Afshin; Raman, Subha; Shenoy, Chetan; Gonzalez, Jorge; Leung, Steve; Shah, Dipan; Ferrari, Victor; Schulz-Menger, Jeanette; Hachamovitch, Rory; Stuber, Matthias; Simonetti, Orlando; Kwong, Raymond
ISI:000460565901443
ISSN: 0735-1097
CID: 4778132