Identification of Myocardial Damage in Systemic Sclerosis: A Nuclear Cardiology Approach

Myocardial involvement is an important prognostic factor in patients with systemic sclerosis, and early diagnosis and staging of the disease have been sought after. Since myocardial damage is characterized by connective tissue disease, including fibrosis and diffuse vascular lesions or microcirculation, nuclear myocardial perfusion imaging has been a promising option for evaluating myocardial damages in early stages. In addition to the conventional stress-rest perfusion imaging, the current use of quantitative electrocardiographic gated imaging has contributed to more precise evaluation of cardiac perfusion, ventricular wall motion, and diastolic function, all of which have enhanced diagnostic ability of evaluating myocardial dysfunction. Abnormal sympathetic imaging with Iodine-123 metaiodobenzylguanidine might be another option for identifying myocardial damage. This paper deals with approaches from nuclear cardiology to detect perfusion and functional abnormality as an early sign of myocardial involvement as well as possible prognostic values in patients with abnormal imaging results. The role of nuclear cardiology in the era of multiple imaging modalities is discussed

The additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress cardiac MRI for the detection of myocardial ischemia

Purpose of this study was to assess the additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress Cardiac-MR (CMR). Dobutamine Stress CMR was performed in 115 patients with an inconclusive diagnosis of myocardial ischemia on a 1.5 T system (Magnetom Avanto, Siemens Medical Systems). Three short-axis cine and grid series were acquired during rest and at increasing doses of dobutamine (maximum 40 μg/kg/min). On peak dose dobutamine followed immediately by a first pass myocardial perfusion imaging sequence. Images were graded according to the sixteen-segment model, on a four point scale. Ninety-seven patients showed no New (Induced) Wall Motion Abnormalities (NWMA). Perfusion imaging showed absence of perfusion deficits in 67 of these patients (69%). Perfusion deficits attributable to known previous myocardial infarction were found in 30 patients (31%). Eighteen patients had NWMA, indicative for myocardial ischemia, of which 14 (78%) could be confirmed by a corresponding perfusion deficit. Four patients (22%) with NWMA did not have perfusion deficits. In these four patients NWMA were caused by a Left Bundle Branch Block (LBBB). They were free from cardiac events during the follow-up period (median 13.5 months; range 6–20). Addition of first-pass myocardial perfusion imaging during peak-dose dobutamine stress CMR can help to decide whether a NWMA is caused by myocardial ischemia or is due to an (inducible) LBBB, hereby preventing a false positive wall motion interpretation

A multimodality cross-validation study of cardiac perfusion using MR and CT.

Modern advances in magnetic resonance (MR) and computed tomography (CT) perfusion imaging techniques have developed methods for myocardial perfusion assessment. However, individual imaging techniques present limitations that are possible to be surpassed by a multimodality cross-validation of perfusion imaging and analysis. We calculated the absolute myocardial blood flow (MBF) in MR using a Fermi function and the transmural perfusion ratio (TPR) in CT perfusion data in a patient with coronary artery disease (CAD). Comparison of MBF and TPR results showed good correlation emphasizing a promising potential to continue our multimodality perfusion assessment in a cohort of patients with CAD

Prevalence of myocardial viability assessed by single photon emission computed tomography in patients with chronic ischaemic left ventricular dysfunction

OBJECTIVE: To assess the prevalence of myocardial viability by technetium-99m (Tc-99m)-tetrofosmin/fluorine-18-fluorodeoxyglucose (FDG) single photon emission computed tomography (SPECT) in patients with ischaemic cardiomyopathy. DESIGN: A retrospective observational study. SETTING: Thoraxcenter Rotterdam (a tertiary referral centre). PATIENTS: 104 patients with chronic coronary artery disease and severely depressed left ventricular function presenting with heart failure symptoms. MAIN OUTCOME MEASURES: Prevalence of myocardial viability as evaluated by Tc-99m-tetrofosmin/FDG SPECT imaging. Two strategies for assessing viability in dysfunctional myocardium were used: perfusion imaging alone, and the combination of perfusion and metabolic imaging. RESULTS: On perfusion imaging alone, 56 patients (54%) had a significant amount of viable myocardium, whereas 48 patients (46%) did not. Among the 48 patients with no significant viability by perfusion imaging alone, seven additional patients (15%) had significantly viable myocardium on combined perfusion and metabolic imaging. Thus with a combination of perfusion and metabolic imaging, 63 patients (61%) had viable myocardium and 41 (39%) did not. CONCLUSIONS: On the basis of the presence of viable dysfunctional myocardium, 61% of patients with chronic coronary artery disease and depressed left ventricular ejection fraction presenting with heart failure symptoms may be considered for coronary revascularisation. The combination of perfusion and metabolic imaging identified more patients with significant viability than myocardial perfusion imaging alone

Current status of myocardial perfusion imaging after percutaneous transluminal coronary angioplasty

AbstractControversy exists with regard to the diagnostic accuracy and optimal technique of myocardial perfusion imaging after coronary angioplasty. Exercise treadmill testing is inexpensive, with adequate predictive value for restenosis and clinical events in patients with single vessel coronary angioplasty with a normal rest electrocardiogram (ECG). Myocardial tomography has advantages for assessing patients with multivessel coronary angioplasty. Exercise stress imaging is generally preferable to pharmacologic stress in patients without physical limitations after angioplasty. Delayed thallium-201 imaging and reinjection protocols may be useful to reconcile whether residual ischemia exists in “fixed” perfusion defects. Appropriately timed stress myocardial perfusion imaging 2 to 4 weeks after procedurally successful coronary angioplasty can document improved cardiac functional capacity and reduced ECG and imaging evidence of myocardial ischemia. Although routine serial postangioplasty evaluations cannot be recommended, stess myocardial imaging may be valuable in subjects with defective anginal nocioception or extensive myocardium at risk in the area subtended by the angioplasty vessel

New directions in myocardial stress imaging

Non-invasive stress imaging techniques such as echocardiography and myocardial perfusion imaging are widely used for the diagnosis and functional evaluation of coronary artery disease and for the assessment of myocardial viability.1·8 The aim of this thesis was to analyse methods that may expand the clinical utility of stress echocardiographic and perfusion imaging, for the diagnosis of myocardial ischemia and viability in patients with suspected or known coronary artery disease

Role of sex hormones in modulating myocardial perfusion and coronary flow reserve

BACKGROUND A growing body of evidence highlights sex differences in the diagnostic accuracy of cardiovascular imaging modalities. Nonetheless, the role of sex hormones in modulating myocardial perfusion and coronary flow reserve (CFR) is currently unclear. The aim of our study was to assess the impact of female and male sex hormones on myocardial perfusion and CFR. METHODS Rest and stress myocardial perfusion imaging (MPI) was conducted by small animal positron emission tomography (PET) with [$^{18}$F]flurpiridaz in a total of 56 mice (7-8 months old) including gonadectomized (Gx) and sham-operated males and females, respectively. Myocardial [$^{18}$F]flurpiridaz uptake (% injected dose per mL, % ID/mL) was used as a surrogate for myocardial perfusion at rest and following intravenous regadenoson injection, as previously reported. Apparent coronary flow reserve (CFR$_{App}$) was calculated as the ratio of stress and rest myocardial perfusion. Left ventricular (LV) morphology and function were assessed by cardiac magnetic resonance (CMR) imaging. RESULTS Orchiectomy resulted in a significant decrease of resting myocardial perfusion (Gx vs. sham, 19.4 ± 1.0 vs. 22.2 ± 0.7 % ID/mL, p = 0.034), while myocardial perfusion at stress remained unchanged (Gx vs. sham, 27.5 ± 1.2 vs. 27.3 ± 1.2 % ID/mL, p = 0.896). Accordingly, CFR$_{App}$ was substantially higher in orchiectomized males (Gx vs. sham, 1.43 ± 0.04 vs. 1.23 ± 0.05, p = 0.004), and low serum testosterone levels were linked to a blunted resting myocardial perfusion (r = 0.438, p = 0.020) as well as an enhanced CFR$_{App}$ (r = -0.500, p = 0.007). In contrast, oophorectomy did not affect myocardial perfusion in females. Of note, orchiectomized males showed a reduced LV mass, stroke volume, and left ventricular ejection fraction (LVEF) on CMR, while no such effects were observed in oophorectomized females. CONCLUSION Our experimental data in mice indicate that sex differences in myocardial perfusion are primarily driven by testosterone. Given the diagnostic importance of PET-MPI in clinical routine, further studies are warranted to determine whether testosterone levels affect the interpretation of myocardial perfusion findings in patients

Doctor of Philosophy

dissertationMedical imaging has evolved in leaps and bounds during the last century. Several medical imaging modalities such as X-rays, single photon emission computer tomography (SPECT), positron emission tomography (PET), computer tomography (CT), magnetic resonance imaging (MRI) have been developed. However, MRI has a distinct advantage over most of these imaging techniques. MRI does not use ionizing radiation, and hence, is considered a safer option for noninvasive imaging. However, every imaging modality comes with its set of limitations and challenges. Although quantitative myocardial perfusion MRI has been studied by researchers over a few decades, it has still not developed into a clinical tool. There is no consensus on the choice of imaging protocol to be used. The scientific community is still divided on the choice of pharmacokinetic model to be used for quantification of myocardial perfusion. In this dissertation, novel techniques were developed and implemented to address a few of the challenges faced by fully quantitative myocardial perfusion MRI. We strive to make it simpler and more accurate. It is with the development of such easy-to-use techniques that cardiac perfusion MRI will find increasing clinical use. These developments are a step in the transition of quantitative myocardial perfusion MRI from an "evolving tool" to an "evolved and matured tool.

Recovery of left ventricular function after primary angioplasty for acute myocardial infarction.

AIMS: To study recovery of segmental wall thickening (SWT), ejection fraction (EF), and end-systolic volume (ESV) after acute myocardial infarction (AMI) in patients who underwent primary stenting with drug-eluting stents. Additionally, to evaluate the predictive value of magnetic resonance imaging (MRI)-based myocardial perfusion and delayed enhancement (DE) imaging. METHODS AND RESULTS: Twenty-two patients underwent cine-MRI, first-pass perfusion, and DE imaging 5 days after successful placement of a drug-eluting stent in the infarct-related coronary artery. Regional myocardial perfusion and the transmural extent of DE were evaluated. A per patient perfusion score was calculated and consisted of a summation of all segmental scores. Myocardial infarct size was quantified by measuring the volume of DE. At 5 months after AMI, cine-MRI was performed and SWT, EF, and ESV were quantified. EF increased from 48+/-11 to 55+/-9% (P<0.01). SWT at 5 months was inversely related to baseline segmental DE scores (P<0.001) and segmental perfusion scores (P<0.001). EF and ESV at 5 months were related to acute infarct size (R(2)=0.65; P<0.001 and R(2)=0.78; P<0.001, respectively) and the calculated perfusion score (R(2)=0.23; P=0.02 and R(2)=0.14; P=0.09, respectively) at baseline. CONCLUSION: Marked recovery of left ventricular function was observed in patients receiving a drug-eluting stent for AMI. DE imaging appears to be a better prognosticator than perfusion imaging

Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

BACKGROUND: Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness. METHODS: CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments. RESULTS: Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003). CONCLUSIONS: Pixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia