Impact of renin-angiotensin-aldosterone system polymorphisms on myocardial perfusion: Correlations with myocardial single photon emission computed tomography-derived parameters.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) has an important role in atherosclerosis. We investigated the effects of six RAAS gene polymorphisms on myocardial perfusion. METHODS AND RESULTS: We examined 810 patients with known or suspected coronary artery disease (CAD) using stress-rest myocardial single-photon emission computed tomography. Summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), transient ischemic dilation (TID), and lung/heart ratio (LHR) were recorded. The following gene polymorphisms were investigated: angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T and T174M, angiotensin II type 1 receptor (AT1R) A1166C, renin (REN) C5312T, and angiotensin II type 2 receptor (AT2R) C3123A. The heterozygotes or homozygotes on ACE D allele were 7.54 times more likely to have abnormal SSS, while the AGT (T174M) heterozygotes were 5.19 times more likely to have abnormal SSS. The homozygotes of ACE D had significantly higher values on TID and LHR, while the AGT (T174M) heterozygotes had higher values on TID. The AT1R heterozygotes had greater odds for having SSS ≥ 3. The patients carried AT1R homozygosity of C allele had significantly higher values on TID, while heterozygotes of AT1R had significantly higher values on LHR. CONCLUSIONS: Among the polymorphisms investigated, ACE D allele had the strongest association with abnormal myocardial perfusion.

Performance and safety profile of regadenoson myocardial perfusion imaging: first experience in Greece.

OBJECTIVE: MPI can provide valuable information in the investigation of patients with known or suspected coronary artery disease. The stress component of the studies can be conducted with regadenoson, which was approved for clinical use in Greece in 2016. We investigated the performance and safety profile of regadenoson MPI based on our 7 months institutional experience. PATIENTS AND METHODS: We studied 96 consecutive patients (59 males, 37 females, mean age 70.35y.o, range: 46-87y.o.) referred to our department for a clinically indicated MPI study with pharmacological stress. Eleven patients suffered from chronic obstructive pulmonary disease. Patients underwent regadenoson stress test, combined with both stress and rest imaging. Data on the symptoms and electrocardiographic changes due to regadenoson administration were recorded. Symptoms were graded as 1-mild: a symptom that did not distress the patient, 2-moderate: a symptom that distressed the patient but it was self-limiting, or 3-severe: a symptom that distressed the patient requiring medical intervention. RESULTS: Regadenoson-related symptoms were reported in 56 patients and were: dyspnea, discomfort, dizziness, chest pain, epigastric pain, neck pain, headache, flushing, nausea, heartburn, weakness, and upper limbs numbness. The severity of symptoms was recorded as grade 1 in 30 patients, grade 2 in 25 patients, and grade 3 in 1 patient. Two or more different symptoms were reported in 28 patients. Ischemic electrocardiographic changes and arrhythmias were observed in 8 patients. CONCLUSION: Our findings support previously published data indicating the optimal safety profile of regadenoson MPI, even in the group of patients suffering from chronic obstructive pulmonary disease.

Incremental prognostic value of 99mTc-tetrofosmin early poststress pulmonary uptake. Determination of the optimal cut-off value.

OBJECTIVES: To evaluate the incremental prognostic value of (99m)Tc-tetrofosmin early poststress lung/heart ratio (eLHR) and to assess the optimal cut-off value. MATERIALS AND METHODS: We studied 503 patients (aged 61.3 years/SD = 8.6 years, 302 men) with stress/rest (99m)Tc-tetrofosmin myocardial gated-single photon emission computed tomography and coronary angiography. To evaluate myocardial ischemia, the summed stress score, summed rest score, and summed difference score indices were calculated. For the eLHR calculation, an anterior image was acquired 4-6 min after radiotracer injection at stress; eLHR was defined as the mean counts/pixel in the lung region of interest divided by the mean counts/pixel in the myocardial region of interest. The incremental prognostic value of eLHR was evaluated by a significant increase in the global χ(2) of the Cox proportional hazard model that included clinical, exercise, angiographic, and scintigraphic variables. Using the receiver operating characteristic analysis, the optimal cut-off of eLHR for the prediction of cardiac events was determined. RESULTS: During the follow-up period, hard cardiac events occurred in 50 (9.9%) and soft cardiac events in 61 (12.1%) patients. Receiver operating characteristic curve analysis showed that the optimal cut-off of eLHR for the prediction of cardiac events was 0.51, with a sensitivity of 78.4% and specificity of 72.2%. The area under the curve was 0.82 (95% confidence interval: 0.77-0.87). Multiple Cox regression analysis revealed that eLHR more than 0.51 (hazard ratio = 7.78; 95% confidence interval: 5.00-12.11) provided incremental prognostic value over clinical exercise testing and scintigraphic data for cardiac events. CONCLUSION: A (99m)Tc-tetrofosmin eLHR value larger than 0.51 added incremental value to other variables for the prediction of cardiac events.

Myocardial Perfusion SPECT Imaging in Patients after Percutaneous Coronary Intervention.

Coronary artery disease (CAD) is the most prevalent form of cardiovascular disease affecting about 13 million Americans, while more than one million percutaneous transluminal intervention (PCI) procedures are performed annually in the USA. The relative high occurrence of restenosis, despite stent implementation, seems to be the primary limitation of PCI. Over the last decades, single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), has proven an invaluable tool for the diagnosis of CAD and patients' risk stratification, providing useful information regarding the decision about revascularization and is well suited to assess patients after intervention. Information gained from post-intervention MPI is crucial to differentiate patients with angina from those with exo-cardiac chest pain syndromes, to assess peri-intervention myocardial damage, to predict-detect restenosis after PCI, to detect CAD progression in non-revascularized vessels, to evaluate the effects of intervention if required for occupational reasons and to evaluate patients' long-term prognosis. On the other hand, chest pain and exercise electrocardiography are largely unhelpful in identifying patients at risk after PCI.Although there are enough published data demonstrating the value of myocardial perfusion SPECT imaging in patients after PCI, there is still debate on whether or not these tests should be performed routinely.

Long-term prognostic value of early poststress (99m)Tc-tetrofosmin lung uptake during exercise (SPECT) myocardial perfusion imaging.

PURPOSE: The aim of this study was to determine the long-term prognostic value of early poststress lung/heart ratio (LHR) of (99m)Tc-tetrofosmin radioactivity. METHODS: We studied 276 patients (aged 62.2 + or - 8.9 years, 168 men) with stress/rest (99m)Tc-tetrofosmin myocardial gated-SPECT and coronary angiography. To evaluate myocardial ischaemia, we calculated the summed stress score, summed rest score and summed difference score indices. For the eLHR calculation, an anterior image was acquired, 4-6 min after radiotracer injection at stress (eLHR was defined as mean counts per pixel in the lung region of interest divided by the mean counts per pixel in the myocardial region of interest). Cardiovascular death and nonfatal myocardial infarction were considered as hard cardiac events, and late revascularization procedures as soft cardiac events. The Cox proportional hazards model in a stepwise method was used to determine the independent predictors for hard and soft cardiac events. RESULTS: During the follow-up period hard cardiac events occurred in 28 patients (10.1%) and soft cardiac events in 32 patients (11.6%). Implying multiple Cox regression analysis, eLHR was found to be a significant independent predictor for both soft and hard cardiac events. The hazard ratio (for a 0.1 unit increase) was 4.41 (95% CI 1.52-12.73, p=0.006) for soft cardiac events and 4.22 (95% CI 2.07-8.62, p<0.001) for hard cardiac events. The other significant prognostic factors were use of beta-blockers, the summed stress score and the use of nitrates for soft events, and exercise duration and the summed stress score for hard cardiac events. CONCLUSION: Early poststress (99m)Tc-tetrofosmin LHR has an independent and powerful value in predicting hard and soft cardiac events.

Long-term prognostic value of heart-rate recovery after treadmill testing in patients with diabetes mellitus.

BACKGROUND: Heart-rate recovery (HRR) is considered to be an independent predictor of cardiac and all-cause mortality. We examined the long-term prognostic value of HRR in patients suffering from diabetes mellitus. METHODS: In this study, we included 258 consecutive patients. Patients whose HRR value or myocardial perfusion imaging could have been influenced by factors other than myocardial ischaemia, were excluded. The value of HRR was defined as the decrease in the heart-rate from peak exercise to 1 min after the termination of the exercise. All patients underwent SPECT myocardial perfusion imaging combined with exercise testing. Cardiovascular death and non-fatal myocardial infarction were considered as hard cardiac events, while late revascularization procedures as soft events. Cox proportional-hazard models were applied to evaluate the association between HRR and the investigated outcome. RESULTS: During the follow-up period (30.8+/-6.9 months), hard cardiac events occurred in 21 (8%) patients (15 with abnormal HRR value, p<0.001), while 35 (14%) patients underwent revascularization (31 with abnormal HRR value, p<0.001). Considering it as a continuous variable, HRR was a strong predictor for both hard cardiac (coefficient=-0.41, SE=0.052, p<0.001) and soft cardiac events (coefficient=-0.63, SE=0.058, p<0.001). After adjustments were made for potential confounders, including scintigraphic variables, abnormal HRR remained an independent predictor for hard and soft cardiac events (p<0.001). CONCLUSION: Our results suggest that among patients with diabetes, a decreased HRR is a significant independent predictor of hard and soft cardiac events.

Long-term prognostic value of Tc-99m tetrofosmin myocardial gated-SPECT imaging in asymptomatic patients after percutaneous coronary intervention.

PURPOSE: To evaluate the long-term prognostic value of Tc-99m tetrofosmin myocardial gated-SPECT in asymptomatic patients after coronary artery stenting. MATERIALS AND METHODS: We included 246 consecutive patients in the study. All patients underwent exercise gated-single photon emission computed tomography (SPECT) myocardial imaging 5 to 7 months after percutaneous coronary intervention (PCI) and were followed for a mean period of 8.3 years (SD = 2.9). Myocardial scintigrams were evaluated calculating the summed stress score (SSS), summed rest score, and summed difference score (SDS) indexes. Cardiovascular death and nonfatal myocardial infarction were considered hard cardiac events, whereas late revascularization (>3 months after myocardial SPECT) procedures were considered to be soft events. Cox proportional hazard models were applied to evaluate the association between several variables and the investigated outcome. RESULTS: During the follow-up period, hard cardiac events occurred in 32 (13%) patients (cardiac death occurred in 12 patients and nonfatal myocardial infarction in 20 patients). In addition, 60 (24.4%) patients underwent a late revascularization procedure. When multiple Cox regression analysis was implied, the factors that remained significant in the final model for soft events were SSS, SDS, and angina during exercise testing. In addition, SSS, SDS, and left ventricular dilatation were independently associated with hard cardiac events as defined from the results of multiple analysis. However, SSS and SDS were the only independent predictors for both hard and soft events. CONCLUSIONS: Tc-99m tetrofosmin myocardial perfusion imaging (MPI), performed 6 months post-percutaneous coronary intervention, has an independent and powerful clinical value to predict hard and soft cardiac events in asymptomatic patients after PCI.

Radiopharmaceuticals in neurological and psychiatric disorders.

The development of functional brain nuclear medicine techniques and their application in the investigation of neuropsychiatric disorders, have contributed significantly in the illumination of the underlying pathophysiological processes of these disorders. Furthermore, Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) brain studies provide information in early diagnosis, differential diagnosis, development of new drugs, and monitoring the response to therapeutic management. SPECT and PET brain imaging require the use of radiopharmaceuticals that cross the intact Blood Brain Barrier (BBB). Such radiotracers have been used in regional Cerebral Blood Flow (rCBF) SPECT and PET imaging and brain metabolism imaging with PET; these are well established methods in the diagnosis and management of various cerebral vascular diseases (e.g. stroke, dementia, epilepsy). Advances in radiotracer chemistry have resulted in the development of molecular imaging which represents the molecular and cellular processes of neuropsychiatric diseases. SPECT and PET molecular imaging has become available for the study of acetylcholinergic, dopaminergic and serotonergic systems, as well as for benzodiazepine and opioid receptors, with promising results. More studies are needed to validate the role of molecular imaging in the clinical practice of neuropsychiatric disorders.

Incremental prognostic value of (99m)Tc-tetrofosmin myocardial SPECT after percutaneous coronary intervention.

OBJECTIVE: Percutaneous transluminal coronary angioplasty is a well-established therapeutic method in selected patients with coronary artery disease. The aim of this study was to assess the incremental prognostic value of technetium-99m ((99m)Tc)-tetrofosmin myocardial gated-single- photon emission computed tomography (SPECT) in asymptomatic patients after coronary artery stenting. METHODS: A total of 246 consecutive patients (aged 55.5 +/- 8.2 years, 182 men) participated in the study with a median follow-up of 9.5 years (interquartile ra 5.8-10.5 years). All patients underwent exercise gated-SPECT myocardial imaging within 5-7 months. Myocardial scintigrams were performed using 99mTc-tetrofosmin, and were evaluated calculating the summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) indexes. Cardiovascular death and non-fatal myocardial infarction were considered as hard cardiac events, and late revascularization (>3 months after myocardial SPECT) procedures as soft events. Receiver-operating characteristic (ROC) analysis was used to test the prognostic ability of SSS and SDS for cardiac events. Cox proportional hazards models were used to evaluate the incremental value of SPECT variables. RESULTS: Cardiac death occurred in 12 (4.9%) patients and non-fatal myocardial infarction in 20 (8.1%) patients. In addition, 60 (24.4%) patients underwent a late revascularization procedure. Using ROC analysis the optimal cut-offs of SSS (AUC = 0.94; 95% CI 0.92-0.97) and SDS (AUC = 0. 76; 95% CI 0.70-0.82) for the prediction of cardiac events were 10 and 1.7, respectively. Multiple Cox regression analyses revealed that SSS > 10 (HR = 24.2; 95% CI 7.44-78.79) and SDS > 1.7 (HR = 2.72; 95% CI 1.23-6.00) provided incremental prognostic value over clinical and exercise test data for the composite end points of any cardiac event. CONCLUSIONS: (99m)Tc-tetrofosmin myocardial gated- SPECT, performed 6 months post-percutaneous coronary intervention (PCI), provides incremental prognostic information for the prediction of cardiac events in asymptomatic patients after PCI.

Evaluation of abnormal heart-rate recovery after exercise testing in patients with diabetes mellitus: correlation with myocardial SPECT and chronotropic parameters.

OBJECTIVE: Diabetes is associated with abnormal function of the autonomic nervous system, while autonomic dysfunction is related to attenuated heart-rate recovery (HRR) after exercise testing. The purpose of this study was to test whether HRR could be a useful index of myocardial ischaemia in patients suffering from diabetes mellitus. METHODS: We included 206 consecutive patients in this study and excluded patients whose HRR value or the myocardial perfusion imaging could have been influenced by factors other than myocardial ischaemia. The value of HRR was defined as the decrease in the heart rate from peak exercise to 1 min after the termination of the exercise. All patients underwent SPECT myocardial perfusion imaging, combined with exercise testing and we calculated the summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS) indexes. RESULTS: Sixty patients had abnormal HRR value. A significant correlation was found between HRR 1 min after exercise and SSS (r=-0.64, P<0.001), SDS (r=0.56, P<0.001) and chronotropic variables. Patients with abnormal HRR value, had a higher frequency of other risk factors (besides diabetes) for CAD, were mostly taking cardioactive medications, had lower efficiency during treadmill testing, and presented more pathologic findings on the scintigram. CONCLUSIONS: Our results suggest that myocardial ischaemia, as it is mainly assessed by myocardial perfusion imaging, has an important correlation with HRR in diabetic patients. HRR value 1 min after exercise may be considered as a useful index of the severity of myocardial ischaemia, in this cohort of patients.

Early post-stress pulmonary uptake of 99mTc tetrofosmin during exercise (SPECT) myocardial perfusion imaging: correlation with haemodynamic, perfusion and function parameters.

OBJECTIVE: To test the association of early post-stress lung/heart ratio (LHR) of 99mTc tetrofosmin radioactivity with gated-SPECT findings and angiographic results. METHODS: We studied 158 consecutive patients, with stress/rest 99mTc tetrofosmin myocardial SPECT and coronary angiography. Rest scans were obtained as gated SPECT and the left ventricular ejection fraction and end diastolic volume were calculated. To evaluate myocardial ischaemia, we calculated the summed stress score, summed rest score and summed difference score indices. For the LHR calculation, we acquired an anterior image, 4-6 min after radiotracer injection at stress; LHR was defined as mean counts/pixel in the lung region of interest divided by the mean counts/pixel in the myocardial region of interest. RESULTS: An early post-stress LHR value of 0.500 was defined as the upper normal limit. The most significant correlation (P<0.001) was observed among early post-stress LHR, summed stress score and the number of stenosed vessels. The incidence of multi-vessel coronary artery disease in the subgroup of patients with increased values of early post-stress LHR, was significantly higher than in the normal group (81% vs. 42%, P<0.001). There was a significant difference (P<0.001) of the early post-stress LHR value between patients with normal coronary arteries or one-vessel disease and patients with multi-vessel disease. Early post-stress LHR was an independent predictor of multi-vessel coronary artery disease (coefficient 1.85, SD 0.16, P<0.001), with an incremental value for its identification. CONCLUSIONS: Our results suggest that early post-stress 99mTc tetrofosmin LHR appears to be a useful index of extensive myocardial ischaemia dysfunction and multi-vessel coronary artery disease.

Stress fracture of the ulnar styloid protuberance.

Stress fractures of the upper extremities are uncommon but can be a serious source of morbidity if not correctly diagnosed. We present a rare case of a 49-year-old female typist, who reported a 4-month history of a pain located in the region of the left lower ulnar epiphysis and extended to the left portion of the wrist. The patient did not mention any injury. The pain was exacerbated during typing and the clinical diagnosis of tendonitis was made initially. Because of the patient's persistent symptoms, she underwent a plain radiograph investigation in the region of the left lower forearm and wrist, which did not reveal any bone lesion. Consequently, we performed a 3-phase bone scan that showed findings consistent with a fracture of the left ulnar styloid protuberance. The fracture was thought to have a stress origin attributed to the patient's tough working.

Abnormal heart rate recovery immediately after treadmill testing: correlation with clinical, exercise testing, and myocardial perfusion parameters.

BACKGROUND: The increase in heart rate during exercise is considered to be attributed to sympathetic system activation combined with parasympathetic withdrawal. The prognostic importance of the chronotropic response to exercise and heart rate recovery 1 minute after exercise has already been established. The purpose of this study was to evaluate heart rate recovery as an index of myocardial ischemia, by correlating heart rate recovery with known parameters of myocardial ischemia. METHODS AND RESULTS: Included in the study were 304 consecutive patients (73% men), aged 34 to 82 years. Patients whose heart rate recovery value or myocardial perfusion imaging could have been influenced by factors other than ischemic disease were excluded from the study. The patients underwent single photon emission computed tomography myocardial perfusion imaging combined with symptom-limited exercise testing with thallium 201 or technetium 99m tetrofosmin. The value for heart rate recovery was defined as the decrease in heart rate from peak exercise to 1 minute after termination of exercise. For semiquantitation of the scintigram, the uptake of the radiotracer was graded on a scale from 0 to 4. Twenty-one beats per minute was defined as the lowest normal value for heart rate recovery. We found 74 patients (24%) with an abnormal value. We also found a significant correlation between heart rate recovery 1 minute after exercise and stress myocardial perfusion score. In addition, there was a statistically significant relationship between heart rate recovery and chronotropic variables. Patients with an abnormal value of heart rate recovery were generally of an older age, were more likely men, had a higher frequency of risk factors for coronary artery disease, were mostly taking cardioactive medications, had lower efficiency during treadmill testing, and had more pathologic findings on the scintigram. CONCLUSIONS: Myocardial ischemia, as assessed by myocardial perfusion imaging, is an important correlate of heart rate recovery. There is a significant correlation between chronotropic variables during exercise testing and heart rate recovery 1 minute after exercise. It seems that the heart rate recovery value 1 minute after peak exercise may be considered a reliable index of the severity of myocardial ischemia.

Tc-99m tetrofosmin myocardial SPECT combined with a modified exercise protocol in an unusual case of steal phenomenon.

A 61-year-old diabetic woman was referred for myocardial perfusion single photon emission computed tomographic (SPECT) imaging 4 years after coronary artery bypass grafting to the left anterior descending (LAD) artery using a left internal mammary artery (LIMA) graft. She had 3 months' angina associated with fatigue of her left upper extremity (the patient is left-handed). Stress myocardial imaging using a Bruce protocol did not exhibit significant myocardial ischemia, but because of her typical angina symptoms, she underwent repeat stress myocardial imaging in combination with exercise of her left arm. During the aforementioned modified stress protocol, the patient reported angina, and radionuclide perfusion imaging showed extensive myocardial ischemia. The patient underwent coronary angiography and arteriography of the left subclavian artery, which revealed severe stenosis before the origin of the LIMA, resulting in reversed blood flow from the LAD artery through the LIMA graft to the left subclavian artery.