Objectives This study sought to relate imaging findings on positron emission tomography (PET) to adverse cardiac events in patients referred for evaluation of known or suspected cardiac sarcoidosis. ...Background Although cardiac PET is commonly used to evaluate patients with suspected cardiac sarcoidosis, the relationship between PET findings and clinical outcomes has not been reported. Methods We studied 118 consecutive patients with no history of coronary artery disease, who were referred for PET, using 18 Ffluorodeoxyglucose (FDG) to assess for inflammation and rubidium-82 to evaluate for perfusion defects (PD), following a high-fat/low-carbohydrate diet to suppress normal myocardial glucose uptake. Blind readings of PET data categorized cardiac findings as normal, positive PD or FDG, positive PD and FDG. Images were also used to identify whether findings of extra-cardiac sarcoidosis were present. Adverse events (AE)—death or sustained ventricular tachycardia (VT)—were ascertained by electronic medical records, defibrillator interrogation, patient questionnaires, and telephone interviews. Results Among the 118 patients (age 52 ± 11 years; 57% males; mean ejection fraction: 47 ± 16%), 47 (40%) had normal and 71 (60%) had abnormal cardiac PET findings. Over a median follow-up of 1.5 years, there were 31 (26%) adverse events (27 VT and 8 deaths). Cardiac PET findings were predictive of AE, and the presence of both a PD and abnormal FDG (29% of patients) was associated with hazard ratio of 3.9 (p < 0.01) and remained significant after adjusting for left ventricular ejection fraction (LVEF) and clinical criteria. Extra-cardiac FDG uptake (26% of patients) was not associated with AE. Conclusions The presence of focal PD and FDG uptake on cardiac PET identifies patients at higher risk of death or VT. These findings offer prognostic value beyond Japanese Ministry of Health and Welfare clinical criteria, the presence of extra-cardiac sarcoidosis and LVEF.
We aimed to determine whether the myocardial extracellular volume (ECV), measured using T1 measurements obtained during cardiac magnetic resonance imaging were increased in patients treated with ...anthracyclines. We performed cardiac magnetic resonance imaging and echocardiography and measured the ECV in 42 patients treated with anthracyclines. The data from the cardiac magnetic resonance study were compared to those from healthy volunteers. The anthracycline-treated cohort consisted of 21 men and 21 women with a mean age of 55 ± 17 years, who presented a median of 84 months after chemotherapy with a cumulative anthracycline exposure of 282 ± 65 mg/m2 and a mean left ventricular ejection fraction of 52 ± 12%. The ECV was elevated in the anthracycline-treated patients compared to the age- and gender-matched controls (0.36 ± 0.03 vs 0.28 ± 0.02, p <0.001). A positive association was found between the ECV and left atrial volume (ECV vs indexed left atrial volume, r = 0.65, p <0.001), and negative association was found between the ECV and diastolic function (E′ lateral, r = −0.64, p <0.001). In conclusion, the myocardial ECV is elevated in patients with previous anthracycline treatment and is associated with the diastolic function and increased atrial volumes.
We aimed to describe the cardiac magnetic resonance (CMR) findings and determine the prognostic variables in patients with a cardiomyopathy after treatment with anthracyclines. CMR imaging was ...performed in 91 patients (58% men, mean age 43 ± 18 years, and mean anthracycline dose of 276 ± 82 mg/m2 ) with a reduced ejection fraction after anthracycline-based chemotherapy. Major adverse cardiovascular events were defined as cardiovascular death, appropriate implantable cardioverter-defibrillator therapy, and admission for decompensated heart failure. Patients presented a median of 88 months (interquartile range 37 to 138) after chemotherapy and were followed for 27 months (interquartile range 22 to 38). Late gadolinium enhancement was an uncommon finding (5 patients, 6%) despite a reduced ejection fraction (36 ± 8%). An inverse association was found between the anthracycline dose and the indexed left ventricular (LV) mass by CMR (r = −0.67, p <0.001). A total of 52 adverse cardiac events occurred (event rate of 22%/year). When the patients were grouped according to the presence or absence of a major adverse cardiovascular event, the indexed LV mass and glomerular filtration rate were lower and the anthracycline dose was greater among the patients who experienced an adverse event. In a multivariate model, the indexed LV mass demonstrated the strongest association with major adverse cardiovascular events (hazard ratio 0.89, chi-square 26, p <0.001). In conclusion, myocardial scar by late gadolinium enhancement-CMR is infrequent in patients with anthracycline-cardiomyopathy despite a reduced ejection fraction, the event rate in patients with established anthracycline-cardiotoxicity is high, and indexed LV mass by CMR imaging is a predictor of adverse cardiovascular events.
Although exercise treadmill testing (ETT) is a useful initial test for patients with suspected cardiovascular (CV) disease, there is concern regarding the use of downstream imaging tests especially ...in the setting of equivocal or positive ETTs. Patients with no history of coronary artery disease who underwent ETT between 2009 and 2010 were prospectively included. Referring physicians were categorized as cardiologists and noncardiologists. Downstream tests included nuclear perfusion imaging, coronary computed tomography angiography, stress echocardiography, stress magnetic resonance, and invasive coronary angiography performed up to 6 months after the ETT. Patients were followed for CV death, myocardial infarction, and coronary revascularization for a median of 2.7 years. Among 3,656 patients, the ETT were negative in 2,876 (79%), positive in 132 (3.6%), and inconclusive in 643 (18%). Cardiologists ordered less downstream tests than noncardiologists (9.5% vs 12.2%, p = 0.02), with less noninvasive tests (5.9% vs 10.4%, p <0.0001) and more invasive angiography (3.6% vs 1.8%, p <0.0001). After adjustment for confounding, patients evaluated by cardiologists were less likely to undergo additional testing after equivocal (odds ratio: 0.65, p = 0.02) or positive ETT results (odds ratio: 0.39, p = 0.02), whereas after negative ETT, the odds ratio was 1.7 (p = 0.06). There was no difference in the rate of adverse CV events between patients referred by cardiologists versus noncardiologists. In conclusion, patients referred for ETT by cardiologists are less likely to undergo additional testing, particularly noninvasive tests, than those referred by noncardiologists. The lower rate of tests is driven by a lower rate of tests after positive or inconclusive ETT.
The diagnosis of cardiac amyloidosis (CA) often necessitates invasive myocardial biopsy. We sought to evaluate whether late gadolinium enhancement (LGE) of the atrial myocardium by cardiac magnetic ...resonance imaging was associated with impaired left atrial (LA) function and whether the extent of LA LGE may enhance diagnostic differentiation of CA from other cardiomyopathies. Twenty-two patients with biopsy-proven CA, 37 with systemic hypertension (SH), and 22 with nonischemic dilated cardiomyopathy (NIDC) underwent cardiac magnetic resonance imaging and echocardiographic evaluation. Patients with CA had greater minimal LA volume (57 ± 53 vs 24 ± 18 in SH and 19 ± 25% in NIDC, p = 0.003), and significantly lower total LA emptying function (19 ± 14 vs 40 ± 14 in SH and 33 ± 20% in NIDC, p = 0.0006). The mean proportion of atrial enhancement (LGELA %) was significantly greater in patients with CA than with SH and NIDC (59 ± 36% vs 7.4 ± 2.1 and 2.9 ± 9.0%, p <0.0001, respectively). There was also a strong inverse correlation between both active and total atrial emptying ( r = −0.69, p = 0.001; r = −0.67, p = 0.01, respectively) with LGELA % for patients with CA. In multivariate regression analysis, LGELA % was the strongest adjusted predictor for CA diagnosis. Using receiver operating characteristic analysis, LGELA % ≥33% produced the greatest diagnostic utility for CA (sensitivity 76%, specificity 94%). Patients with CA may have extensive LGE of the LA myocardium, which is associated with marked reduction in LA emptying function. The extent of LA LGE was highly predictive for the diagnosis of CA.
Objectives 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.
Abstract Objectives 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. Background 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. Methods 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). Results 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). Conclusions 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.
Objectives The aim of this study was to perform direct quantification of myocardial extracellular volume fraction (ECF) with T1-weighted cardiac magnetic resonance (CMR) imaging in patients suspected ...to have infiltrative heart disease. Background Infiltrative heart disease refers to accumulation of abnormal substances within the myocardium. Qualitative assessment of late gadolinium enhancement (LGE) remains the most commonly used method for CMR evaluation of patients suspected with myocardial infiltration. This technique is widely available and can be performed in a reproducible and standardized manner. However, the degree of extracellular matrix expansion due to myocardial infiltration in the intercellular space has, to date, not been amenable to noninvasive quantification with LGE. Methods We performed 3-T CMR in 38 patients (mean age 68 ± 15 years) who were referred for assessment of infiltrative heart disease and also in 9 healthy volunteers as control subjects. The T1 quantification by Look-Locker gradient-echo before and after contrast determined segmental myocardial partition coefficients. The ECF was obtained by referencing the tissue partition coefficient for gadolinium to the plasma volume fraction in blood, derived from serum hematocrit. Cine CMR and LGE imaging in matching locations were also performed. Results Seventeen patients (45%) had cardiac amyloidosis (CA) (biopsy-confirmed or clinically highly probable), 20 (53%) had a non-amyloid cardiomyopathy, and 1 had lysosomal storage disease. Median global ECF was substantially higher in CA patients (0.49) compared with non-amyloid cardiomyopathy patients (0.33, p < 0.0001) and volunteers (0.24, p = 0.0001). The ECF strongly correlated with visually assessed segmental LGE (r = 0.80, p < 0.0001) and LV mass index (r = 0.69, p < 0.0001), reflecting severity of myocardial infiltration. In patients with CA, ECF was highest in segments with LGE, although it remained elevated in segments without qualitative LGE. Conclusions The CMR ECF quantification identified substantial expansion of the interstitial space in patients with CA compared with volunteers. Further studies using this technique for diagnosis and assessment of the severity of myocardial infiltration are warranted.
Objectives This study sought 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. LGE during cardiac magnetic resonance imaging is a marker for myocardial fibrosis. Methods A group of 664 consecutive patients without known prior myocardial infarction who were referred for radiofrequency ablation of AF were studied. Cardiac magnetic resonance imaging was requested to assess pulmonary venous anatomy. Results Overall, 73% were men, with a mean age of 56 years and a mean LV ejection fraction of 56 ± 10%. LV LGE was found in 88 patients (13%). The endpoint was all-cause mortality, and in this cohort, 68 deaths were observed over a median follow-up period of 42 months. On univariate analysis, age (hazard ratio HR: 1.05; 95% confidence interval CI: 1.03 to 1.08; chi-square likelihood ratio LRχ2 : 15.2; p = 0.0001), diabetes (HR: 2.39; 95% CI: 1.41 to 4.09; LRχ2 : 10.3; p = 0.001), a history of heart failure (HR: 1.78; 95% CI: 1.09 to 2.91; LRχ2 : 5.37; p = 0.02), left atrial dimension (HR: 1.04; 95% CI: 1.01 to 1.08; LRχ2 : 6.47; p = 0.01), presence of LGE (HR: 5.08; 95% CI: 3.08 to 8.36; LRχ2 : 28.8; p < 0.0001), and LGE extent (HR: 1.15; 95% CI: 1.10 to 1.21; LRχ2 : 35.6; p < 0.0001) provided the strongest associations with mortality. The mortality rate was 8.1% per patient-year in patients with LGE compared with 2.3% patients without LGE. In the best overall multivariate model for mortality, age and the extent of LGE were independent predictors of mortality. Indeed, each 1% increase in the extent of LGE was associated with a 15% increased risk for death. Conclusions In patients with AF, LV LGE is a frequent finding and is a powerful predictor of mortality.
Objectives This study tested whether myocardial extracellular volume (ECV) is increased in patients with hypertension and atrial fibrillation (AF) undergoing pulmonary vein isolation and whether ...there is an association between ECV and post-procedural recurrence of AF. Background Hypertension is associated with myocardial fibrosis, an increase in ECV, and AF. Data linking these findings are limited. T1 measurements pre-contrast and post-contrast in a cardiac magnetic resonance (CMR) study provide a method for quantification of ECV. Methods Consecutive patients with hypertension and recurrent AF referred for pulmonary vein isolation underwent a contrast CMR study with measurement of ECV and were followed up prospectively for a median of 18 months. The endpoint of interest was late recurrence of AF. Results Patients had elevated left ventricular (LV) volumes, LV mass, left atrial volumes, and increased ECV (patients with AF, 0.34 ± 0.03; healthy control patients, 0.29 ± 0.03; p < 0.001). There were positive associations between ECV and left atrial volume (r = 0.46, p < 0.01) and LV mass and a negative association between ECV and diastolic function (early mitral annular relaxation E′, r = −0.55, p < 0.001). In the best overall multivariable model, ECV was the strongest predictor of the primary outcome of recurrent AF (hazard ratio: 1.29; 95% confidence interval: 1.15 to 1.44; p < 0.0001) and the secondary composite outcome of recurrent AF, heart failure admission, and death (hazard ratio: 1.35; 95% confidence interval: 1.21 to 1.51; p < 0.0001). Each 10% increase in ECV was associated with a 29% increased risk of recurrent AF. Conclusions In patients with AF and hypertension, expansion of ECV is associated with diastolic function and left atrial remodeling and is a strong independent predictor of recurrent AF post–pulmonary vein isolation.
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