Aukelien C. Dimitriu-Leen

123I-MIBG SPECT for Evaluation of Patients with Heart Failure

Heart failure (HF) is characterized by activation of the sympathetic cardiac nerves. The condition of cardiac sympathetic nerves can be evaluated by 123I-metaiodobenzylguanidine (123I-MIBG) imaging. Most cardiac 123I-MIBG studies have relied on measurements from anterior planar images of the chest. However, it has become progressively more common to include SPECT imaging in clinical and research protocols. This review examines recent trends in 123I-MIBG SPECT imaging and evidence that provides the basis for the increased use of the procedure in the clinical management of patients with HF. 123I-MIBG SPECT has been shown to be complementary to planar imaging in patients with HF in studies of coronary artery disease after an acute myocardial infarction. Moreover, 123I-MIBG SPECT has been used in numerous studies to document regional denervation for arrhythmic event risk assessment. For better quantification of the size and severity of innervation abnormalities in 123I-MIBG SPECT, programs and protocols specifically for 123I have been developed. Also, the introduction of new solid-state cameras has created the potential for more rapid SPECT acquisitions or a reduction in radiopharmaceutical activity. Although PET imaging has superior quantitative capabilities, 123I-MIBG SPECT is, for the foreseeable future, the only widely available nuclear imaging method for assessing regional myocardial sympathetic innervation.

Cardiac sympathetic nervous system imaging with (123)I-meta-iodobenzylguanidine: Perspectives from Japan and Europe

Cardiac sympathetic nervous system dysfunction is closely associated with risk of serious cardiac events in patients with heart failure (HF), including HF progression, pump-failure death, and sudden cardiac death by lethal ventricular arrhythmia. For cardiac sympathetic nervous system imaging, 123I-meta-iodobenzylguanidine (123I-MIBG) was approved by the Japanese Ministry of Health, Labour and Welfare in 1992 and has therefore been widely used since in clinical settings. 123I-MIBG was also later approved by the Food and Drug Administration (FDA) in the United States of America (USA) and it was expected to achieve broad acceptance. In Europe, 123I-MIBG is currently used only for clinical research. This review article is based on a joint symposium of the Japanese Society of Nuclear Cardiology (JSNC) and the American Society of Nuclear Cardiology (ASNC), which was held in the annual meeting of JSNC in July 2016. JSNC members and a member of ASNC discussed the standardization of 123I-MIBG parameters, and clinical aspects of 123I-MIBG with a view to further promoting 123I-MIBG imaging in Asia, the USA, Europe, and the rest of the world.

Association Between Posterior Left Atrial Adipose Tissue Mass and Atrial Fibrillation

Background— Epicardial adipose tissue located close to the atrial wall can change the electric conduction of the left atrium, potentially leading to atrial fibrillation (AF). The aim of this study was to assess whether an increased atrial adipose tissue mass posterior to the left atrium is related to AF independent of demographical and cardiovascular risk factors. Methods and Results— Two hundred patients with AF and 200 patients without AF who underwent computed tomographic angiography were included. The posterior left atrial adipose tissue mass was quantified on computed tomographic angiography images as tissue with Hounsfield Units between −195 and −45. The adipose tissue mass was significantly larger in patients with AF compared with patients with sinus rhythm: 10.6±5.5 versus 4.7±3.5 g, P<0.001. In a multiple variable model (including age, body mass index, sex, coronary artery calcium score, diabetes mellitus, hypertension, hypercholesterolemia, family history of coronary artery disease, and known coronary artery disease), each gram increase of posterior left atrial adipose tissue was associated with 1.32 odds ratio of having AF (95% confidence interval, 1.22–1.43; P<0.001). Furthermore, the addition of the adipose tissue mass to the multiple variable analysis significantly increased the discriminatory ability to predict AF: increase in the area under the receiver operating characteristic, 0.88 (95% confidence interval, 0.84–0.91) versus 0.81 (0.76–0.85), P<0.001. Conclusions— Posterior left atrial adipose tissue mass is significantly larger in patients with AF versus without AF. An increase in adipose tissue was independently associated with AF and provided incremental value over well-known predictors of AF. These findings add to the hypothesis that the posterior left atrial adipose tissue mass contributes to structural and electric remodeling leading to AF.

Prognosis of complete versus incomplete revascularisation of patients with STEMI with multivessel coronary artery disease: an observational study

Objective The best strategy in patients with acute ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease (CAD) regarding completeness of revascularisation of the non-culprit lesion(s) is still unclear. To establish which strategy should be followed, survival rates over a longer period should be evaluated. The aim of this study was to investigate whether complete revascularisation, compared with incomplete revascularisation, is associated with reduced short-term and long-term all-cause mortality in patients with first STEMI and multivessel CAD. Methods This retrospective study consisted of 518 patients with first STEMI with multivessel CAD. Complete revascularisation (45%) was defined as the treatment of any significant coronary artery stenosis (≥70% luminal narrowing) during primary or staged percutaneous coronary intervention prior to discharge. The primary end point was all-cause mortality. Results Incomplete revascularisation was not independently associated with 30-day all-cause mortality in patients with acute first STEMI and multivessel CAD (OR 1.98; 95% CI 0.62to6.37; p=0.25). During a median long-term follow-up of 6.7 years, patients with STEMI with multivessel CAD and incomplete revascularisation showed higher mortality rates compared with patients who received complete revascularisation (24% vs 12%, p<0.001), and these differences remained after excluding the first 30 days. However, in multivariate analysis, incomplete revascularisation was not independently associated with increased all-cause mortality during long-term follow-up in the group of patients with STEMI who survived the first 30 days post-STEMI (HR 1.53 95% CI 0.89-2.61, p=0.12). Conclusion In patients with acute first STEMI and multivessel CAD, incomplete revascularisation compared with complete revascularisation was not independently associated with increased short-term and long-term all-cause mortality.

Prevalence by Computed Tomographic Angiography of Coronary Plaques in South Asian and White Patients With Type 2 Diabetes Mellitus at Low and High Risk Using Four Cardiovascular Risk Scores (UKPDS, FRS, ASCVD, and JBS3)

The aim of this study was to explore the association between various cardiovascular (CV) risk scores and coronary atherosclerotic burden on coronary computed tomography angiography (CTA) in South Asians with type 2 diabetes mellitus and matched whites. Asymptomatic type 2 diabetic South Asians and whites were matched for age, gender, body mass index, hypertension, and hypercholesterolemia. Ten-year CV risk was estimated using different risk scores (United Kingdom Prospective Diabetes Study [UKPDS], Framingham Risk Score [FRS], AtheroSclerotic CardioVascular Disease [ASCVD], and Joint British Societies for the prevention of CVD [JBS3]) and categorized into low- and high-risk groups. The presence of coronary artery calcium (CAC) and obstructive coronary artery disease (CAD; ≥50% stenosis) was assessed using coronary CTA. Finally, the relation between coronary atherosclerosis on CTA and the low- and high-risk groups was compared. UKPDS, FRS, and ASCVD showed no differences in estimated CV risk between 159 South Asians and 159 matched whites. JBS3 showed a significant greater absolute CV risk in South Asians (18.4% vs 14.2%, p <0.01). Higher presence of CAC score >0 (69% vs 55%, p <0.05) and obstructive CAD (39% vs 27%, p <0.05) was observed in South Asians. South Asians categorized as high risk, using UKPDS, FRS, and ASCVD, showed more CAC and CAD compared than whites. JBS3 showed no differences. In conclusion, asymptomatic South Asians with type 2 diabetes mellitus more frequently showed CAC and obstructive CAD than matched whites in the population categorized as high-risk patients using UKPDS, FRS, and ASCVD as risk estimators. However, JBS3 seems to correlate best to CAC and CAD in both ethnicity groups compared with the other risk scores.

The influence of clinical and acquisition parameters on the interpretability of adenosine stress myocardial computed tomography perfusion.

Aims The interpretation of adenosine stress myocardial computed tomography perfusion (CTP) is often hampered by image artefacts caused by cardiac motion, beam hardening, and cone beam. The aim of the present analysis was to assess the influence of the heart-rate response during adenosine infusion, patient characteristics, and medication use on the interpretability of stress myocardial CTP examinations. Methods and results Interpretability of stress myocardial CTP examinations was evaluated in 120 patients who underwent sequentially coronary CTA and adenosine stress myocardial CTP (320-row CT scanner, temporal resolution 175 ms) and scored as follows: excellent = absence of any artefact (n = 27, 22%); good = presence of artefacts that do not interfere with the study interpretability (n = 56, 47%); fair = artefacts that do interfere with interpretability (n = 35, 29%); poor = uninterpretable study due to artefacts (n = 2, 2%). ‘Fair’ and ‘poor’ were merged into ‘reduced’ for comparisons. Increasing heart rate during stress myocardial CTP acquisition was related to worse interpretability (excellent: 61.7 ± 13.4 bpm vs. good: 69.8 ± 13.5 bpm vs. reduced: 78.1 ± 17.0 bpm, P < 0.001). Thirteen (11%) of all examinations were considered non-diagnostic. In patients with a heart rate exceeding 85 bpm, 76% of the studies were ‘reduced’ interpretable. In multivariate analysis, no use of beta blocker (baseline or additional use prior to coronary CTA) (OR: 0.2, P = 0.012), increasing heart rate during coronary CTA (OR: 1.09, P = 0.032), younger age (OR: 0.92, P = 0.021), and the use of calcium antagonist (OR: 6.48, P = 0.017) were independently associated with a heart rate ≥85 bpm during stress myocardial CTP. Conclusion Higher heart rate during the acquisition of stress myocardial CTP was related to worse interpretability. Furthermore, increasing heart rate during and no beta blocker use prior to the previously performed coronary CTA, younger age, and the use of calcium antagonist were independently associated with a heart rate ≥85 bpm during stress myocardial CTP acquisition.

Cardiac 123 I-MIBG Imaging beyond Heart Failure: Potential Clinical Indications

Iodine-meta-iodobenzylguanidine ( 123 I-MIBG) imaging can visualize cardiac sympathetic innervation by providing (semi-) quantitative information on the myocardial sympathetic activity. Although there are lots of prognostic studies in patients with heart failure, clinical application of cardiac 123 IMIBG outside Japan is still limited. However, the number of potential clinical indications for 123 I-MIBG imaging is growing as autonomic dysfunction is also present in other cardiac diseases. The present review gives an overview of the potential clinical cardiac indications beyond heart failure of 123 I

Accuracy and reproducibility of fast fractional flow reserve computation from invasive coronary angiography

Fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) is associated with favourable outcome compared with revascularization based on angiographic stenosis severity alone. The feasibility of the new image-based quantitative flow ratio (QFR) assessed from 3D quantitative coronary angiography (QCA) and thrombolysis in myocardial infarction (TIMI) frame count using three different flow models has been reported recently. The aim of the current study was to assess the accuracy, and in particular, the reproducibility of these three QFR techniques when compared with invasive FFR. QFR was derived (1) from adenosine induced hyperaemic coronary angiography images (adenosine-flow QFR [aQFR]), (2) from non-hyperemic images (contrast-flow QFR [cQFR]) and (3) using a fixed empiric hyperaemic flow [fixed-flow QFR (fQFR)]. The three QFR values were calculated in 17 patients who prospectively underwent invasive FFR measurement in 20 vessels. Two independent observers performed the QFR analyses. Mean difference, standard deviation and 95% limits of agreement (LOA) between invasive FFR and aQFR, cQFR and fQFR for observer 1 were: 0.01 ± 0.04 (95% LOA: −0.07; 0.10), 0.01 ± 0.05 (95% LOA: −0.08; 0.10), 0.01 ± 0.04 (95% LOA: −0.06; 0.08) and for observer 2: 0.00 ± 0.03 (95% LOA: −0.06; 0.07), −0.01 ± 0.03 (95% LOA: −0.07; 0.05), 0.00 ± 0.03 (95% LOA: −0.06; 0.05). Values between the 2 observers were (to assess reproducibility) for aQFR: 0.01 ± 0.04 (95% LOA: −0.07; 0.09), for cQFR: 0.02 ± 0.04 (95% LOA: −0.06; 0.09) and for fQFR: 0.01 ± 0.05 (95% LOA: −0.07; 0.10). In a small number of patients we showed good accuracy of three QFR techniques (aQFR, cQFR and fQFR) to predict invasive FFR. Furthermore, good inter-observer agreement of the QFR values was observed between two independent observers.

Cardiac 123 I-MIBG Parameters at 4 Hours Derived from Earlier Acquisition Times

Background: The clinical implementation of cardiac 123 Iodine-meta-iodobenzylguanidine ( 123 I-MIBG) scintigraphy for the evaluation of prognosis in patients with heart failure (HF) is still limited. This may partially be related to the long examination time with an almost 4 hour delay between the early and late acquisition. Additionally, outcome derived at different late acquisition times cannot be compared with each other. To assess whether earlier acquisition time of the late image is justified, the aim of present study was to evaluate in a HF patient cohort whether a developed direct comparison method for cardiac 123 I-MIBG imaging enables comparison of washout rates and late heart-to-mediastinum (H/M) ratios from 1 to 3 hours post injection (pi) with measurements at 4 hours pi. Methods: Forty-eight patients with HF were clinically referred for cardiac 123 I-MIBG scintigraphy. The washout rate and late H/M ratio at 4 hours pi were estimated with a previous published linear model from heart and mediastinal counts at 1, 2 and 3 hour pi and compared with the actual values at 4 hour pi. Results: The estimated washout rate and late H/M ratio at 4 hours pi from counts at 1 hour pi demonstrated large differences. However, the average estimated late H/M ratio at 4 hours pi derived from 2 and 3 hours pi did not differ with the actual late H/M ratio at 4 hours pi (P=0.84 and P=0.06). As well as, the actual washout rate at 4 hours pi and estimated washout rate at 4 hours pi derived from 3 hours pi did not differ significantly (P=0.22). Yet, the mean estimated washout rate at 4 hours pi derived from the acquisition at 2 hours pi showed a difference compared with the actual washout rate at 4 hours pi (25±19 vs. 34±17, P<0.001). Conclusions: The direct comparison method for cardiac 123 I-MIBG imaging enables accurate estimation of the actual late H/M ratio and washout rate at 4 hours pi derived from the acquisitions at 3 hours pi. The acquisition at 2 hours pi should only be performed in exceptional cases when clinically necessary because of the existing difference between the actual and estimated washout rate at 4 hours pi derived from 2 hours pi.

Different manifestation of irradiation induced coronary artery disease detected with coronary computed tomography compared with matched non-irradiated controls

BACKGROUND AND PURPOSE Patients who received chest irradiation for treatment of a malignancy are at increased risk for the development of coronary artery atherosclerosis. Little is known about the anatomical coronary artery plaque characteristics of irradiation induced coronary artery disease (CAD). This study aimed to evaluate potential differences in the presence, extent, severity, composition and location of CAD in patients treated with mediastinal irradiation compared with non-irradiated controls matched on age, gender and cardiovascular risk factors. MATERIAL AND METHODS Seventy-nine asymptomatic Hodgkin and non-Hodgkin lymphoma survivors, all treated with mediastinal irradiation with or without chemotherapy, who underwent coronary computed tomography angiography (CTA) to exclude or detect CAD were included. Patients were 1:3 matched with non-irradiated controls (n=237) for age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD and currently smoking. Mean age at cancer diagnosis was 26±9years and age at the time of coronary CTA was 45±11years. RESULTS More patients had an abnormal CTA (defined as any coronary artery atherosclerosis): 59% vs. 36% (P<0.001) and significantly more patients had two vessel CAD: 10% vs. 6% and three vessel/left main CAD: 24% vs. 9% compared with controls (overall P<0.001). The maximum stenosis severity among patients was less often <30% (53% vs. 68%) and more often >70% (7% vs. 0%) (overall P=0.001). Patients had more coronary artery plaques in proximal coronary artery segments: left main (17% vs. 6%, P=0.004), proximal left anterior descending artery (30% vs. 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001) and proximal left circumflex artery (14% vs 6%, P=0.022), whereas the number of plaques in non-proximal segments did not differ between groups. CONCLUSIONS Hodgkin and non-Hodgkin lymphoma survivors treated with mediastinal irradiation with or without chemotherapy showed a higher presence, greater severity, larger extent and more proximally located CAD compared with age, gender and risk factor matched non-irradiated controls. These findings represent features of higher risk CAD and may explain the worse cardiovascular outcome after chest irradiation.