The aim of this study was to describe the role of contrast-enhanced cardiac magnetic resonance (CMR) in the workup of patients with aborted sudden cardiac arrest (SCA) and in the prediction of long-term outcomes.
Myocardial fibrosis is a key substrate for SCA, and late gadolinium enhancement (LGE) on a CMR study is a robust technique for imaging of myocardial fibrosis.
We performed a retrospective review of all survivors of SCA who were referred for CMR studies and performed follow-up for the subsequent occurrence of an adverse event (death and appropriate defibrillator therapy).
After a workup that included a clinical history, electrocardiogram, echocardiography, and coronary angiogram, 137 patients underwent CMR for workup of aborted SCA (66% male; mean age 56 ± 11 years; left ventricular ejection fraction 43 ± 12%). The presenting arrhythmias were ventricular fibrillation (n = 105 [77%]) and ventricular tachycardia (n = 32 [23%]). Overall, LGE was found in 98 patients (71%), with an average extent of 9.9 ± 5% of the left ventricular myocardium. CMR imaging provided a diagnosis or an arrhythmic substrate in 104 patients (76%), including the presence of an infarct-pattern LGE in 60 patients (44%), noninfarct LGE in 21 (15%), active myocarditis in 14 (10%), hypertrophic cardiomyopathy in 3 (2%), sarcoidosis in 3, and arrhythmogenic cardiomyopathy in 3. In a median follow-up of 29 months (range 18 to 43 months), there were 63 events. In a multivariable analysis, the strongest predictors of recurrent events were the presence of LGE (adjusted hazard ratio: 6.7; 95% CI: 2.38 to 18.85; p < 0.001) and the extent of LGE (hazard ratio: 1.15; 95% CI: 1.11 to 1.19; p < 0.001).
Among patients with SCA, CMR with contrast identified LGE in 71% and provided a potential arrhythmic substrate in 76%. In follow-up, both the presence and extent of LGE identified a group at markedly increased risk of future adverse events.
cardiac magnetic resonance; implantable cardioverter-defibrillator; late gadolinium enhancement
Impact of weight loss on cardiac structure has not been extensively investigated in large, multi-ethnic, community-based populations. We investigated the longitudinal impact of weight loss on cardiac structure by cardiac magnetic resonance (CMR).
Methods and results
2351 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent CMR at Exam 1 (2002) and Exam 5 (2011) were included. Primary outcomes were percentage change in LV mass (indexed to height) and LV mass-to-volume ratio (concentric LV remodelling). Multivariable linear regression was used to measure the association between outcomes and weight change. At median 9.4 years' follow-up, 639 individuals (27%) experienced >5% weight loss (median 6.9 kg) and 511 (22%) had >5% weight gain (median 6.4 kg). A >5% weight gain was associated with the greatest increase in LV mass (+5.4% median) and LV mass-to-volume ratio (+12.2% median). Adjusting for medications, hypertension/diabetes (and change in these risk factors), age, race and other risk factors, every 5% weight loss was associated with a 1.3% decrease in height-indexed LV mass and 1.3% decrease in LV mass-to-volume ratio (p <0.0001). There was no effect modification/confounding by age, race, gender or baseline BMI. Change in LV mass-to-volume ratio was roughly linear, specifically for modest degrees of weight loss (−10% to +10%). Change in LV mass was linear with weight loss, suggesting no threshold of weight loss is needed for LV mass regression.
In a large multi-ethnic population, weight loss is associated with beneficial effects on cardiac structure, independent of age, race, gender, BMI and obesity-related cardiometabolic risk. There is no threshold of weight loss required to produce these effects.
Obesity; cardiac magnetic resonance; weight loss
We aimed to assess whether chronic obstructive pulmonary disease (COPD) is associated with expansion of the myocardial extracellular volume (ECV) using T1 measurements.
Adult COPD patients (GOLD stage 2 or higher) and free of known cardiovascular disease were recruited. All study patients underwent measures of pulmonary function, 6-minute walk test, serum measures of inflammation, overnight polysomnography, and a contrast CMR study.
Eight patients with COPD were compared to 8 healthy control subjects. The mean predicted FEV1% of COPD subjects was 68%. Compared to controls, patients had normal left ventricular (LV) and right ventricular size, mass, and function. However, as compared to controls, the LV remodeling index (median 0.87 IQR 0.43 vs. median 0.62 IQR 0.17, p=0.03) and active left atrial emptying fraction was increased (median 46 IQR 8 vs. median 38 IQR 10, p=0.005), and passive left atrial emptying fraction was reduced (median 24 IQR 10 vs. median 44 IQR 20, p=0.007). The ECV was increased in patients with COPD (median 0.32 IQR 0.05 vs. median 0.27 IQR 0.05, p=0.001). The ECV showed a strong positive association with LV remodeling (r = 0.72, p = 0.04) and an inverse association with the 6-minute walk duration (r = −0.79, p = 0.02) and passive left atrial emptying fraction (r = −0.68, p = 0.003).
Expansion of the ECV, suggestive of diffuse myocardial fibrosis, is present in COPD and is associated with LV remodeling, reduced left atrial function and exercise capacity.
This study sought to evaluate differential effects of visceral fat (VF) and subcutaneous fat and their effects on metabolic syndrome (MetS) risk across body mass index (BMI) categories.
The regional distribution of adipose tissue is an emerging risk factor for cardiometabolic disease, although serial changes in fat distribution have not been extensively investigated. VF and its alterations over time may be a better marker for risk than BMI in normal weight and overweight or obese individuals.
We studied 1,511 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) with adiposity assessment by computed tomography (CT). A total of 253 participants without MetS at initial scan underwent repeat CT (median interval 3.3 years). We used discrete Cox regression with net reclassification to investigate whether baseline and changes in VF area are associated with MetS.
Higher VF was associated with cardiometabolic risk and coronary artery calcification, regardless of BMI. After adjustment, VF was more strongly associated with incident MetS than subcutaneous fat regardless of weight, with a 28% greater MetS hazard per 100 cm2/m VF area and significant net reclassification (net reclassification index: 0.44, 95% confidence interval [CI]: 0.29 to 0.60) over clinical risk. In individuals with serial imaging, initial VF (hazard ratio: 1.24 per 100 cm2/m, 95% CI: 1.08 to 1.44 per 100 cm2/m, p = 0.003) and change in VF (hazard ratio: 1.05 per 5% change, 95% CI: 1.01 to 1.08 per 5% change, p = 0.02) were associated with MetS after adjustment. Changes in subcutaneous fat were not associated with incident MetS after adjustment for clinical risk and VF area.
VF is modestly associated with BMI. However, across BMI, a single measure of and longitudinal change in VF predict MetS, even accounting for weight changes. Visceral adiposity is essential to assessing cardiometabolic risk, regardless of age, race, or BMI, and may serve as a marker and target of therapy in cardiometabolic disease.
cardiometabolic risk; metabolic syndrome; obesity
Studies have shown the feasibility of imaging plaques with 2-Deoxy-2-[18F]fluoroglucose positron emission tomography (FDG-PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with inconsistent results. We sought to investigate the relationship between markers of inflammatory activation, plaque microvascularization and vessel wall permeability in subjects with carotid plaques using a multi-modality approach combining FDG-PET, DCE-MRI and histopathology.
Methods and Results
Thirty-two subjects with carotid stenoses underwent noninvasive imaging with FDG PET and DCE-MRI, 46.9% (n=15) prior to carotid endarterectomy (CEA). We measured FDG uptake (target to background ratio, TBR) by PET and Ktrans (reflecting microvascular permeability and perfusion) by MRI, and correlated imaging with immunohistochemical markers of macrophage content (CD68), activated inflammatory cells (MHC-II), and microvessels (CD31) in plaque and control regions. TBR and Ktrans correlated significantly with tertiles of CD68+ (P=0.009 and P=0.008, respectively), MHC-II+ (P=0.003 and P<0.001, respectively), and CD31+ (P=0.004 and P=0.008, respectively). Regions of plaques were associated with increased CD68+ (P=0.002), MHCII+ (P=0.002), CD31+ (P=0.02), TBR (P<0.0001), and Ktrans (P<0.0001), as compared to those without plaques. Microvascularization correlated with macrophage content (rs=0.52, P=0.007) and inflammatory activity (rs=0.68, P=0.0001), and TBR correlated with Ktrans(rs=0.53, P<0.0001). In multivariable mixed linear regression modeling, TBR remained independently associated with Ktrans [β(standard error) 2.68(0.47), P<0.0001].
Plaque regions with active inflammation, as determined by macrophage content and MHC-II expression, showed increased FDG uptake, which correlated with increased Ktrans and microvascularization. The correlation between Ktrans and TBR was moderate, direct, highly significant, and independent of clinical symptoms and plaque luminal severity.
plaque; inflammation; neovascularization; FDG-PET; DCE-MRI; histopathology
To measure association between hepatic fat and albuminuria (an early marker of renal injury) in individuals without diabetes or hypertension.
2,281 individuals in the Multi-Ethnic Study of Atherosclerosis without diabetes or hypertension, renal disease, or excess alcohol consumption underwent computed tomography (CT) for assessment of liver attenuation (marker of hepatic lipid content) and urinalysis (for albuminuria) at initial study visit, with assessment of incident and prevalent albuminuria by logistic regression in follow-up.
After adjustment for age, gender, race, smoking, blood pressure, insulin resistance, and body mass index, individuals with less liver fat (higher liver CT attenuation) had a lower probability of having albuminuria at Exam 1 (OR per 10 unit increase in attenuation 0.77, 95 % CI 0.61–0.97, P = 0.02). At median 9.3 years follow-up, albuminuria was identified in 129 individuals were (5.8 %). In fully adjusted models (with age, smoking, body mass index, blood pressure, diabetes and hypertension as time-dependent covariates), lower liver attenuation (greater liver fat) was associated with higher risk of incident albuminuria (OR 0.79, 95 % CI 0.66–0.94, P = 0.008).
Hepatic attenuation is associated with prevalent and incident albuminuria, an early, potent risk factor for renal risk in a population not clearly at risk for future renal failure.
Albuminuria; Inflammation; Obesity; Hepatic steatosis
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).
We found a strong association between LAPEF and recurrent AF after PVI that persisted after multivariable adjustment.
Magnetic resonance imaging; fibrillation; ablation; atrium
Cardiac resynchronization therapy (CRT) is a novel therapy for patients with refractory heart failure (HF). Large clinical trials evaluating CRT have demonstrated significant improvements in cardiac survival, decreases in recurrent HF hospitalization, and improvements in indexes of quality of life. Although numerous mechanisms are involved in CRT’s therapeutic effects, correction of both interventricular and intraventricular mechanical dyssynchrony has been postulated as the key mechanism. To date, most large randomized controlled trials evaluating CRT have identified dyssynchronous patients on the basis of prolongation of the QRS complex from the baseline electrocardiogram. Concerns have been raised regarding the use of this measure for patient selection, stemming from a significant 30% to 40% nonresponse rate to CRT. Because of the cost and invasive nature of CRT, optimal patient selection for this therapy has become a priority for HF specialists and electrophysiologists. Cardiac imaging modalities have attempted to fulfill this need to improve patient selection by identifying mechanical dyssynchrony. Although early echocardiographic studies reported promising results, more recent larger scale studies have curtailed this enthusiasm, with a lack of established selection criteria for CRT in the current practice guidelines. This review summarizes the evidence to date and the potential role of imaging modalities in the selection and care of patients with HF referred for CRT.
cardiac computed tomography; cardiac magnetic resonance imaging; cardiac resynchronization therapy; noninvasive imaging; radionuclide imaging
Strategies for prevention of sudden cardiac death focus on severe left ventricular (LV) dysfunction, although most sudden cardiac death postmyocardial infarction occurs in patients with mild/moderate LV dysfunction. We tested the hypothesis that infarct heterogeneity by cardiac magnetic resonance is associated with mortality beyond LV ejection fraction (LVEF) in patients with coronary artery disease and LV dysfunction. In addition, we examined the association between infarct heterogeneity and mortality in those with LVEF >35%.
Methods and Results
We studied 301 patients with coronary artery disease and LV dysfunction referred for cardiac magnetic resonance. We quantified total infarct mass, infarct core mass, and peri-infarct zone (PIZ) normalized for total infarct mass (%PIZ) using signal-intensity criteria of >2 SDs, >3 SDs, and 2- to -3 SDs above remote myocardium, respectively. Mean LVEF was 41±14%. After 3.9 years median follow-up, 66 (22%) patients died (13 sudden cardiac death; 33 with LVEF >35%). In patients with LVEF >35%, below-median %PIZ carried an annual death rate of 2.8% versus 12% in patients with above-median %PIZ (P<0.001). In a multivariable model, %PIZ maintained strong association with mortality adjusted to patient age, LVEF, right ventricular ejection fraction , prolonged QT interval, and total infarct size and resulted in improve risk reclassification 0.492 (95% confidence interval, 0.183–0.817).
Cardiac magnetic resonance infarct heterogeneity has a strong association with mortality independent of LVEF in patients with coronary artery disease and LV dysfunction, particularly in patients with mild or moderate LV dysfunction. Further studies incorporating cardiac magnetic resonance in clinical decision making for defibrillator therapy are warranted.
cardiac magnetic resonance imaging; coronary artery disease; cardiac mortality
The 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.
Obesity is associated with the development of atrial fibrillation (AF), and both obesity and AF are independently associated with the development of heart failure with preserved ejection fraction. We tested the hypothesis that sleep apnea (SA) would have a body mass index (BMI) independent association with adverse left ventricular (LV) remodeling and clinical outcomes in patients with AF and preserved LV function.
Methods and results
From 720 consecutive patients with AF, 403 patients without myocardial disease (preserved LV function) were identified and followed up for 3.3 ± 1.5 years. The primary outcome was a combination of all-cause mortality/heart failure hospitalization. Left ventricular mass and LV mass-to-volume ratio were higher in patients with SA and obesity (P < .0001 for all). Body mass index (β per log = .47; P < .0001) and SA (β = .05; P = .045) were independently associated with LV mass index. Patients with treated SA had a lower LV mass index (but not LV mass-to-volume ratio) compared with untreated (P = .002). In a best overall multivariable model, SA therapy (β = −.129; P = .001) and BMI (β per log = .373; P = .0007) had opposing associations with LV mass index. Sleep apnea (hazard ratio [HR] = 2.94; P = .0004) and BMI (HR per 1 kg/m2 = 1.08; P = .004) were associated with clinical outcome in unadjusted analysis. Only SA was associated with clinical outcome in a best overall multivariable model (HR = 2.14; P = .02).
Sleep apnea and obesity are independently associated with adverse LV remodeling and clinical outcomes in patients with preserved LV function, whereas continuous positive airway pressure therapy is associated with a beneficial effect on LV remodeling. Research investigating SA therapies in patients at high risk for LV remodeling and heart failure is warranted.
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).
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.
Clinical Trial Registration Information
http://clinicaltrials.gov/. Identifier: NCT01821924.
chronic ischemia; cardiac magnetic resonance imaging
High-fidelity 12-lead Electrocardiogram (ECG) is important for physiological monitoring of patients during MR-guided intervention and cardiac MR imaging. Issues in obtaining non-corrupted ECGs inside MRI include a superimposed Magneto-Hydro-Dynamic (MHD) voltage, gradient-switching induced-voltages, and radiofrequency (RF) heating. These problems increase with magnetic field. We intended to develop and clinically validate a 1.5T MRI-conditional 12-lead ECG system.
The system was constructed, including transmission-lines to reduce radio-frequency induction, and switching-circuits to remove induced voltages. Adaptive filters, trained by 12-lead measurements outside MRI and in two orientations inside MRI, were used to remove MHD. The system was tested on ten (one exercising) volunteers and four arrhythmia patients.
Switching circuits removed most imaging-induced voltages (residual noise <3% of the R-wave). MHD removal provided intra-MRI ECGs that varied by <3.8% from those outside the MRI, preserving the true ST segment. In premature-ventricular-contraction (PVC) patients, clean ECGs separated PVC and sinus-rhythm beats. Measured heating was <1.5 C0. The system reliably acquired multiphase (SSFP) wall-motion-cine and phase-contrast-cine scans, including in subjects where 4-lead gating failed. The system required a minimum TR of 4ms to allow robust ECG processing.
High-fidelity intra-MRI 12-lead ECG is possible.
ECG; Magneto-Hydro-Dynamic effect; Cardiac MRI; MRI-guided interventions
We assessed in the Multi-Ethnic Study of Atherosclerosis (MESA) whether impaired fasting glucose, insulin resistance, and waist-to-hip ratio had effects on cardiac remodeling, independent of obesity.
Recent studies suggest that central obesity and insulin resistance may be primary mediators of obesity-related cardiac remodeling independent of body mass index (BMI).
We investigated 4,364 individuals without diabetes in MESA. Impaired fasting glucose (IFG: 100-125 mg/dl) or insulin resistance (by homeostatic model assessment of insulin resistance, HOMA-IR) and waist-to-hip ratio (WHR) were used for cardiometabolic phenotyping. Multivariate linear regression analysis was used to determine the effects of the cardiometabolic markers on LV remodeling, assessed primarily through the LV mass-to-volume ratio obtained by cine cardiac magnetic resonance imaging.
Individuals with IFG were more likely to be older, hypertensive, with increased prevalence of cardiometabolic risk factors regardless of BMI. In each quartile of BMI, individuals with above-median HOMA-IR, above-median WHR, or IFG had a higher LV mass-to-volume ratio (p<0.05 for all). HOMA-IR (p<0.0001), WHR (p<0.0001), and the presence of IFG (p=0.04), but not BMI (p=0.24), were independently associated with LV mass-to-volume ratio after adjustment for age, gender, hypertension, race, and dyslipidemia.
Insulin resistance and waist-to-hip ratio are associated with concentric LV remodeling independent of BMI. These results support the emerging hypothesis that the cardiometabolic phenotype, defined by insulin resistance and central obesity, may play a critical role in LV remodeling independently of BMI.
obesity; metabolic syndrome; LV remodeling; MESA