Adam Ali Ghotbi

Review: comparison of PET rubidium-82 with conventional SPECT myocardial perfusion imaging

Nuclear cardiology has for many years been focused on gamma camera technology. With ever improving cameras and software applications, this modality has developed into an important assessment tool for ischaemic heart disease. However, the development of new perfusion tracers has been scarce. While cardiac positron emission tomography (PET) so far largely has been limited to centres with on‐site cyclotron, recent developments with generator produced perfusion tracers such as rubidium‐82, as well as an increasing number of PET scanners installed, may enable a larger patient flow that may supersede that of gamma camera myocardial perfusion imaging.

Association of Hypoglycemic Treatment Regimens With Cardiovascular Outcomes in Overweight and Obese Subjects With Type 2 Diabetes A substudy of the SCOUT trial

OBJECTIVE To assess the association of hypoglycemic treatment regimens with cardiovascular adverse events and mortality in a large population of type 2 diabetic patients at increased cardiovascular risk. RESEARCH DESIGN AND METHODS This analysis included 8,192 overweight patients with type 2 diabetes from the Sibutramine Cardiovascular Outcomes (SCOUT) trial randomized to lifestyle intervention with or without sibutramine for up to 6 years. Patients were grouped according to hypoglycemic treatment at baseline. The primary end point was the time from randomization to the first occurrence of a primary outcome event (POE), nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death. Multivariable Cox proportional hazards regression models were used to assess the impact of antiglycemic treatment on POE and all-cause mortality. RESULTS Treatments for type 2 diabetes were as follows: diet alone (n = 1,394 subjects), metformin monotherapy (n = 1,631), insulin monotherapy (n = 1,116), sulfonylurea monotherapy (n = 1,083), metformin plus sulfonylurea (n = 1,565), and metformin plus insulin (n = 1,000); 905 subjects experienced a POE and 708 died. Metformin monotherapy was associated with lower risk of POE than insulin (hazard ratio [HR], 0.74; 95% CI, 0.57–0.95; P = 0.02). Diet alone also was associated with lower risk of POE (HR, 0.65; 95% CI, 0.48–0.87; P = 0.004). Metformin monotherapy also was associated with lower mortality (HR, 0.73; 95% CI, 0.54–0.99; P < 0.05), whereas no other monotherapies or combination therapies were significantly associated with POE or all-cause mortality compared with insulin as monotherapy. CONCLUSIONS In obese patients with type 2 diabetes and high risk of cardiovascular disease, monotherapy with metformin or diet-only treatment was associated with lower risk of cardiovascular events than treatment with insulin.

Quantification of myocardial perfusion using cardiac magnetic resonance imaging correlates significantly to rubidium-82 positron emission tomography in patients with severe coronary artery disease: A preliminary study

INTRODUCTION Aim was to compare absolute myocardial perfusion using cardiac magnetic resonance imaging (CMRI) based on Tikhonovs procedure of deconvolution and rubidium-82 positron emission tomography (Rb-82 PET). MATERIALS AND METHODS Fourteen patients with coronary artery stenosis underwent rest and adenosine stress imaging by 1.5-Tesla MR Scanner and a mCT/PET 64-slice Scanner. CMRI were analyzed based on Tikhonovs procedure of deconvolution without specifying an explicit compartment model using our own software. PET images were analyzed using standard clinical software. CMRI and PET data was compared with Spearmans rho and Bland-Altman analysis. RESULTS CMRI results were strongly and significantly correlated with PET results for the absolute global myocardial perfusion differences (r=0.805, p=0.001) and for global myocardial perfusion reserve (MPR) (r=0.886, p<0.001). At vessel territorial level, CMRI results were also significantly correlated with absolute PET myocardial perfusion differences (r=0.737, p<0.001) and MPR (r=0.818, p<0.001). Each vessel territory had similar strong correlation for absolute myocardial perfusion differences (right coronary artery (RCA): r=0.787, p=0.001; left anterior descending artery (LAD): r=0.796, p=0.001; left circumflex artery (LCX): r=0.880, p<0.001) and for MPR (RCA: r=0.895, p<0.001; LAD: r=0.886, p<0.001; LCX: r=0.886, p<0.001). CONCLUSION On a global and vessel territorial basis, CMRI-measured absolute myocardial perfusion differences and MPR were strongly and significantly correlated with the Rb-82 PET findings.

Transthoracic Doppler echocardiography compared with positron emission tomography for assessment of coronary microvascular dysfunction: The iPOWER study

BACKGROUND Coronary microvascular function can be assessed by transthoracic Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET MBFR is regarded the noninvasive reference standard for measuring coronary microvascular function but has limited availability. We compared TTDE CFVR with PET MBFR in women with angina pectoris and no obstructive coronary artery disease and assessed repeatability of TTDE CFVR. METHODS From a cohort of women with angina and no obstructive coronary artery stenosis at invasive coronary angiography, TTDE CFVR by dipyridamole induced stress and MBFR by rubidium-82 PET with adenosine was successfully measured in 107 subjects. Repeatability of TTDE CFVR was assessed in 10 symptomatic women and in 10 healthy individuals. RESULTS MBFR was systematically higher than CFVR. Median MBFR (interquartile range, IQR) was 2.68 (2.29-3.10) and CFVR (IQR) was 2.31 (1.89-2.72). Pearsons correlation coefficient was 0.36 (p<0.01). Limits of agreement (2·standard deviation) assessed by the Bland-Altman (confidence interval, CI) method was 1.49 (1.29;1.69) and unaffected by time-interval between examinations. Results were similar when adjusting for rate pressure product or focusing on perfusion of the left anterior descending artery region. Limits of agreement (CI) for repeated CFVR in 10 healthy individuals and in 10 women with angina was 0.44 (0.21;0.68) and 0.48 (0.22; 0.74), respectively. CONCLUSION CFVR had a good repeatability, but the agreement between CFVR and MBFR was modest. Divergence could be due to methodology differences; TTDE estimates flow velocities whereas PET estimates myocardial blood flow.

Basal hyperaemia is the primary abnormality of perfusion in Takotsubo cardiomyopathy: a quantitative cardiac perfusion positron emission tomography study

AIMS Takotsubo cardiomyopathy (TTC) is characterized by acute completely reversible regional left ventricle (LV) akinesia and decreased tracer uptake in the akinetic region on semi-quantitative perfusion imaging. The latter may be due to normoperfusion of the akinetic mid/apical area and basal hyperperfusion. Our aim was to examine abnormalities of perfusion in TTC, and we hypothesized that basal hyperperfusion is the primary perfusion abnormality in the acute state. METHOD AND RESULTS Twenty-five patients were diagnosed with TTC due to (i) acute onset of symptoms, (ii) typical apical ballooning, (iii) absence of significant coronary disease, and (iv) complete remission on 4-month follow-up. The patients underwent coronary angiography (CAG), echocardiography, cardiac magnetic resonance imaging (CMR), and (13)NH3/(82)Rb positron emission tomography (PET) in the acute state and-except CAG-on follow-up. Patients initially had severe heart failure, mid/apical oedema but no infarction, and a rise in cardiac biomarkers. On initial perfusion PET imaging, eight patients appeared to have normal, whereas 17 patients had impaired LV perfusion. In the latter, flow in the basal region was increased in the acute state (1.5 ± 0.1 vs. 1.2 ± 0.1 mL/g/minRPP-corrected, P < 0.01), whereas midventricular (1.7 ± 0.1 vs. 1.6 ± 0.1 mL/g/minRPP-corrected, P = 0.21) and apical (1.4 ± 0.1 vs. 1.5 ± 0.1 mL/g/minRPP-corrected, P = 0.36) flow was unchanged between acute and follow-up, and within normal range. CONCLUSION Our results suggest an abnormal LV perfusion distribution in the acute state of TTC with basal hyperperfusion and a normoperfused akinetic region. The proportion of patients without visualized perfusion abnormalities in the acute state may represent a subgroup with fast remission.

Normal Myocardial Flow Reserve in HIV-Infected Patients on Stable Antiretroviral Therapy: A Cross-Sectional Study Using Rubidium-82 PET/CT.

AbstractStudies have found HIV-infected patients to be at increased risk of myocardial infarction, which may be caused by coronary microvascular dysfunction. For the first time among HIV-infected patients, we assessed the myocardial flow reserve (MFR) by Rubidium-82 (82Rb) positron emission tomography (PET), which can quantify the coronary microvascular function. MFR has proved highly predictive of future coronary artery disease and cardiovascular events in the general population.In a prospective cross-sectional study, HIV-infected patients all receiving antiretroviral therapy (ART) with full viral suppression and HIV-uninfected controls were scanned using 82Rb PET/computed tomography at rest and adenosine-induced stress, thereby obtaining the MFR (stress flow/rest flow), stratified into low ⩽1.5, borderline >1.5 to 2.0, or normal >2.0.Fifty-six HIV-infected patients and 25 controls were included. The HIV-infected patients had a mean age of 53 years (range 37–68 years) with 23% active smokers. The controls had a mean age of 52 years (range 36–68 years) and 26% active smokers. In the HIV-infected group 73% had a normal MFR, 17% borderline, and 10% low values of MFR. Among controls these values were 71%, 19%, and 10%, respectively (P = 0.99). However, the HIV-infected group had lower values of stress myocardial blood flow (MBF) (2.63 ± 0.09 mL/g/min vs 2.99 ± 0.14 mL/g/min; P = 0.03). We found no evidence of decreased MFR as assessed by 82Rb PET among HIV-infected patients on stable ART with full viral suppression compared with HIV-uninfected controls. We did notice a decreased MBF during stress.

Left Ventricular Hypertrophy Is Associated With Increased Infarct Size and Decreased Myocardial Salvage in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Background Approximately one third of patients with ST‐segment elevation myocardial infarction (STEMI) have left ventricular hypertrophy (LVH), which is associated with impaired outcome. However, the causal association between LVH and outcome in STEMI is unknown. We evaluated the association between LVH and: myocardial infarct size, area at risk, myocardial salvage, microvascular obstruction, left ventricular (LV) function (all determined by cardiac magnetic resonance [CMR]), and all‐cause mortality and readmission for heart failure in STEMI patients treated with primary percutaneous coronary intervention. Methods and Results In this substudy of the DANAMI‐3 trial, 764 patients underwent CMR. LVH was defined by CMR and considered present if LV mass exceeded 77 (men) and 67 g/m2 (women). One hundred seventy‐eight patients (24%) had LVH. LVH was associated with a larger final infarct size (15% [interquartile range {IQR}, 10–21] vs 9% [IQR, 3–17]; P<0.001) and smaller final myocardial salvage index (0.6 [IQR, 0.5–0.7] vs 0.7 [IQR, 0.5–0.9]; P<0.001). The LVH group had a higher incidence of microvascular obstruction (66% vs 45%; P<0.001) and lower final LV ejection fraction (LVEF; 53% [IQR, 47–60] vs 61% [IQR, 55–65]; P<0.001). In a Cox regression analysis, LVH was associated with a higher risk of all‐cause mortality and readmission for heart failure (hazard ratio 2.59 [95% CI, 1.38–4.90], P=0.003). The results remained statistically significant in multivariable models. Conclusions LVH is independently associated with larger infarct size, less myocardial salvage, higher incidence of microvascular obstruction, lower LVEF, and a higher risk of all‐cause mortality and incidence of heart failure in STEMI patients treated with primary percutaneous coronary intervention. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01435408.

Perfusion imaging using rubidium-82 (82Rb) PET in rats with myocardial infarction: First small animal cardiac 82Rb-PET

Assessing myocardial perfusion using Rb-PET is emerging as a valuable clinical tool. The rapid decay (T = 76 s) allows for absolute quantification of both rest and stress perfusion within 30 minutes. In addition to evaluation of epicardial disease with perfusion defects, also evaluation of balanced coronary and small vessel disease is possible. For further evaluation of how Rb-PET can be used clinically, pre-clinical application of the method would be valuable. However, so far no data on the use of Rb-PET in small animals have been published nor has the use of Rb-PET, to the best of our knowledge, been successfully tried. Therefore, we wanted to develop and test the applicability of the method in rats, despite the high positron range of Rb. To do so, we adapted the clinical method and tested it in rats with experimentally induced myocardial infarction. CASE SUMMARY

Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients: A Randomized Crossover Pilot Trial.

Background The optimal pacing rate during cardiac resynchronization therapy (CRT) is unknown. Therefore, we investigated the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL). Methods Twelve CRT patients with non-ischemic heart failure (NYHA class II–III) were enrolled in a randomized, double-blind, crossover trial, in which the basal pacing rate was set at DDD-60 and DDD-80 for 3 months (DDD-R for 2 patients). At baseline, 3 months and 6 months, we assessed sympathetic nerve activity by microneurography (MSNA), peak oxygen consumption (pVO2), N-terminal pro-brain natriuretic peptide (p-NT-proBNP), echocardiography and QoL. Results DDD-80 pacing for 3 months increased the mean heart rate from 77.3 to 86.1 (p = 0.001) and reduced sympathetic activity compared to DDD-60 (51±14 bursts/100 cardiac cycles vs. 64±14 bursts/100 cardiac cycles, p<0.05). The mean pVO2 increased non-significantly from 15.6±6 mL/min/kg during DDD-60 to 16.7±6 mL/min/kg during DDD-80, and p-NT-proBNP remained unchanged. The QoL score indicated that DDD-60 was better tolerated. Conclusion In CRT patients with non-ischemic heart failure, 3 months of DDD-80 pacing decreased sympathetic outflow (burst incidence only) compared to DDD-60 pacing. However, Qol scores were better during the lower pacing rate. Further and larger scale investigations are indicated. Trial Registration ClinicalTrials.gov NCT02258061

Retention and Functional Effect of Adipose-Derived Stromal Cells Administered in Alginate Hydrogel in a Rat Model of Acute Myocardial Infarction

Background Cell therapy for heart disease has been proven safe and efficacious, despite poor cell retention in the injected area. Improving cell retention is hypothesized to increase the treatment effect. In the present study, human adipose-derived stromal cells (ASCs) were delivered in an in situ forming alginate hydrogel following acute myocardial infarction (AMI) in rats. Methods ASCs were transduced with luciferase and tested for ASC phenotype. AMI was inducted in nude rats, with subsequent injection of saline (controls), 1 × 106 ASCs in saline or 1 × 106 ASCs in 1% (w/v) alginate hydrogel. ASCs were tracked by bioluminescence and functional measurements were assessed by magnetic resonance imaging (MRI) and 82rubidium positron emission tomography (PET). Results ASCs in both saline and alginate hydrogel significantly increased the ejection fraction (7.2% and 7.8% at 14 days and 7.2% and 8.0% at 28 days, resp.). After 28 days, there was a tendency for decreased infarct area and increased perfusion, compared to controls. No significant differences were observed between ASCs in saline or alginate hydrogel, in terms of retention and functional salvage. Conclusion ASCs improved the myocardial function after AMI, but administration in the alginate hydrogel did not further improve retention of the cells or myocardial function.