Myocardial Perfusion Scintigraphy for the Evaluation of Atypical Chest Pain - Likely Non-Cardiac - in Type 2 Diabetic Individuals with Systemic Hypertension

Myocardial Perfusion Scintigraphy for the Evaluation of Atypical Chest Pain - Likely Non-Cardiac - in Type 2 Diabetic Individuals with Systemic Hypertension | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Myocardial Perfusion Scintigraphy for the Evaluation of Atypical Chest Pain - Likely Non-Cardiac - in Type 2 Diabetic Individuals with Systemic Hypertension Luis Jesuino de Oliveira Andrade, Gabriela Correia Matos de Oliveira, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6027018/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Myocardial perfusion scintigraphy (MPS) is an essential diagnostic tool for evaluating coronary artery disease, particularly in high-risk populations such as hypertensive type 2 diabetic patients (T2DM). Despite its clinical relevance, there remains a significant gap in understanding its optimal application and diagnostic accuracy in this subgroup, warranting further research to refine risk stratification and improve patient outcomes. Objective: This study aimed to assess the prevalence of myocardial ischemic abnormalities in hypertensive T2DM, patients presenting with atypical chest pain and either normal resting electrocardiogram (ECG) or ventricular repolarization disturbances, through MPS. Methods: A total of 165 participants, comprising 50 men (30.3%) and 115 women (69.7%), with a mean age of 65.6 ± 6 years, underwent MPS using a 2-day protocol. Results : The results revealed that 63.0% of patients exhibited normal perfusion scans, while 37% demonstrated findings consistent with myocardial ischemia. Additionally, a subset of the cohort underwent exercise stress testing (90.9%), which yielded positive results for ischemia in 33.3% of cases. The agreement between MPS and exercise ECG was analyzed, revealing a moderate correlation (Kappa = 0.52; P < 0.001). Conclusion : These findings reinforce the clinical utility of MPS as a reliable diagnostic tool for detecting coronary artery disease in patients with T2DM and systemic hypertension who present with atypical chest pain, particularly in those with inconclusive findings on resting ECG. Endocrinology & Metabolism Myocardial perfusion scintigraphy type 2 diabetes mellitus hypertension myocardial ischemia atypical angina INTRODUCTION Atypical chest pain is a common yet diagnostically complex presentation, particularly in high-risk populations such as hypertensive type 2 diabetic (T2DM) patients. Unlike typical angina, which follows predictable patterns, atypical chest pain often lacks clear characteristics, making it challenging to differentiate between cardiac and non-cardiac causes. 1 This diagnostic ambiguity is exacerbated in diabetic patients, who frequently experience silent ischemia due to autonomic neuropathy, leading to delayed diagnosis and increased cardiovascular morbidity and mortality. 2 The presence of hypertension further complicates the clinical scenario, as it accelerates atherosclerosis and increases myocardial oxygen demand, predisposing these patients to ischemic events. 3 Coronary artery disease (CAD) is a leading cause of death in T2DM patients, with hypertension serving as a significant comorbid factor that amplifies cardiovascular risk. 4 Studies have shown that the prevalence of CAD in diabetic patients is two to four times higher than in the general population, highlighting the need for accurate diagnostic tools to detect ischemia early. 5 Myocardial perfusion scintigraphy (MPS) has emerged as a powerful non-invasive imaging technique, offering high sensitivity and specificity for identifying myocardial ischemia, even in patients with atypical symptoms or inconclusive electrocardiographic findings. 6 The pathophysiology of CAD in diabetic patients is distinct, characterized by diffuse atherosclerosis, endothelial dysfunction, and microvascular disease, which often result in atypical presentations of ischemia. 7 Hypertensive diabetic patients are particularly vulnerable to these changes, as chronic hypertension promotes vascular remodeling and increases myocardial workload, further complicating the clinical picture. Traditional diagnostic methods, such as stress electrocardiography (ECG), may fail to detect ischemia in this population due to the high prevalence of silent ischemia and baseline ECG abnormalities, such as repolarization disturbances. 8 Despite its clinical utility, the application of MPS in hypertensive T2DM patients with atypical chest pain remains underutilized. This gap is partly due to limited awareness of its diagnostic benefits, concerns about radiation exposure, and the lack of standardized protocols for this specific patient population. 9 Furthermore, there is a paucity of large-scale studies evaluating the prevalence of ischemic abnormalities in hypertensive T2DM patients with atypical chest pain and normal resting ECG or repolarization disturbances. This represents a critical knowledge gap, as early detection of ischemia in this high-risk group could significantly improve outcomes through timely intervention. 10 Recent advancements in imaging technology, such as hybrid single-photon emission computed tomography (SPECT/CT) systems, have enhanced the diagnostic accuracy of MPS by integrating anatomical and functional data, providing a more comprehensive assessment of myocardial perfusion. 11 Additionally, the prognostic value of MPS in diabetic patients has been well-documented, with studies demonstrating its ability to identify high-risk individuals who may benefit from revascularization or intensified medical therapy. 12 This study aimed to assess the prevalence of myocardial ischemic abnormalities in hypertensive T2DM, patients presenting with atypical chest pain and either normal resting ECG or ventricular repolarization disturbances, through MPS. METHODS The study included 165 patients with T2DM who underwent MPS at rest and under stress, induced either by treadmill exercise testing or pharmacological stress for those unable to perform physical exercise. To be eligible, patients had to present with atypical chest pain, a normal resting ECG, or ventricular repolarization abnormalities, along with systemic hypertension and age over 40 years. Myocardial perfusion imaging was performed using SPECT/CT with technetium-99m sestamibi (99mTc-MIBI) as the radiotracer. The tracer was administered intravenously at a dose adjusted to the patient’s body weight, both at rest and during stress. Stress was induced either by treadmill exercise testing or pharmacological agents (dipyridamole) for patients with physical limitations or contraindications to exercise. Imaging was conducted using a VARICAM gamma camera (Elscint ® ) equipped with two detectors in an L-mode configuration (90 degrees). Images were acquired 45 minutes after radiotracer administration, using standardized parameters: 140 keV photopeak, 20% energy window, 64 x 64 matrix, low-energy high-resolution parallel collimators, and a 180° rotation with 64 steps. Gated SPECT, synchronized with ECG, was employed during stress imaging for select patients, with an R-R acceptance window of 20%. For image processing, an XPERT workstation (APEX 5.0 software, Elscint ® ) was utilized, complemented by the Quantitative Gated SPECT (QGS) software for gated studies. Images were analyzed in paired stress-rest views across short-axis, vertical long-axis, and horizontal long-axis orientations. Additional three-dimensional end-systolic and end-diastolic images, along with polar maps (Bull’s Eye), were generated to enhance diagnostic accuracy. A two-day protocol was followed, with rest imaging performed first, followed by stress imaging, maintaining consistent acquisition parameters throughout. Qualitative and quantitative criteria were applied to interpret the scintigraphic findings. Normal myocardium exhibited uniform radiotracer uptake in both stress and rest/redistribution phases, while ischemic myocardium demonstrated reduced uptake during stress with normalization at rest. Fibrotic tissue showed persistently reduced uptake in both phases, whereas viable ischemic tissue displayed partial improvement during redistribution. Quantitative analysis utilized polar maps to quantify perfusion defects based on pixel counts and standard deviations from normal perfusion areas, providing supplementary data to support visual interpretation. Exercise treadmill testing (ETT) was conducted using the ramp protocol, 13 with modifications for patients unable to achieve maximal effort due to physical or clinical limitations. Test positivity was defined by specific ECG criteria, including ST-segment depression ≥ 2.0 mm, ST depression > 1.0 mm in the first stage, multi-lead ST changes, persistent ST abnormalities for over 5 minutes during recovery, maximal workload < 4 METs, abnormal blood pressure response, or ventricular arrhythmias. Pharmacological stress with dipyridamole (0.5 mg/kg intravenously over 4 minutes) was employed for patients with orthopedic, neurological, or vascular limitations. Statistical analyses were performed using PSPP software, with results expressed as mean ± standard deviation and relative frequency. The Chi-square test was used for proportion comparisons, and the Mann-Whitney test for mean comparisons. The Kappa index assessed agreement between MPS and exercise ECG results. A 95% confidence interval was applied, with statistical significance set at p < 0.05. The study protocol was approved by the Ethics Committee of Santa Casa de Itabuna, Ba. RESULTS The study included 165 patients, comprising 50 men (30.3%) and 115 women (69.7%), with ages ranging from 40 to 75 years and a mean age of 65.6 ± 6.0 years. Men were significantly older than women (67.6 ± 10.0 years vs. 63.2 ± 8.1 years, P = 0.031) (Table 1 ). Table 1 Demographic date Characteristics Women Men Total Gender 115 (69.7%) 50 (30.3%) 165 Average age (years) 63.2 ± 8.1 67.6 ± 10.0 65.6 ± 6.0 Of the total cohort, 150 patients (90.9%) underwent exercise stress testing, while pharmacological stress with dipyridamole was used in 15 patients (9.1%). Among those who performed ETT, 55 patients (33.3%) had negative results, whereas 55 (33.3%) tested positive for myocardial ischemia. MPS was performed in all patients, revealing normal perfusion in 104 cases (63.0%) and ischemia in 61 (37.0%). Among the 15 patients who underwent pharmacological stress testing, 4.8% showed evidence of ischemia (Table 2 ). Table 2 Association among MPS, ETT and Pharmacological stress MPS ETT Pharmacological stress Normal 104 (63.0%) 55 (33.3%) 7 (4.2%) Ischemia 61 (37.0%) 55 (33.3%) 8 (4.8%) Total 165 110 15 Notably, 15.7% of patients with normal exercise ECG results demonstrated ischemia on MPS, highlighting the superior sensitivity of scintigraphy in detecting myocardial ischemia. Of the 50 patients with positive exercise tests, 32 had concordant positive MPS findings, while 18 showed normal perfusion on scintigraphy. The agreement between MPS and ETT was assessed using the Kappa index, which revealed a moderate correlation between the two tests (Kappa = 0.52, P = 0.0001). No statistically significant differences were observed in the proportion of abnormal MPS findings between men and women (43.5% vs. 35.2%, P = 0.53). Similarly, the prevalence of abnormal ETT results did not differ significantly by gender (37.7% in men vs. 29.2% in women, P = 0.52). DISCUSSION In this study, we evaluated the role of MPS in hypertensive diabetic patients with atypical chest pain, normal ECG, or ventricular repolarization disturbances, and demonstrated that MPS is a reliable diagnostic tool for detecting coronary artery disease in T2DM patients presenting with atypical angina, particularly in those with inconclusive resting ECG findings. Individuals with T2DM experience higher rates of mortality and complications linked to myocardial infarction when compared to those without diabetes. 14 The occurrence of silent myocardial ischemia is notably more common among diabetic patients than in the broader population. Consequently, diabetic individuals with myocardial ischemia often lack the hallmark symptom of typical chest pain, resulting in delays in diagnosis and treatment. 15 This atypical clinical manifestation plays a significant role in the increased morbidity and mortality rates seen in this patient group. CAD continues to be a leading contributor to morbidity and death among individuals with DM. Beyond the elevated risk of mortality inherently associated with diabetes, the presence of cardiovascular disease manifestations exacerbates this risk, doubling the mortality rate. This combination results in an estimated decline in life expectancy of roughly 12 years. Genetic factors also play a significant role as a risk indicator in the link between T2DM and CAD. 16 Comprehensive global epidemiological research, particularly the landmark Framingham study, has demonstrated that the prevalence of CAD is significantly elevated in individuals with diabetes. Specifically, diabetic men exhibit a twofold increase in CAD incidence, while diabetic women experience a threefold rise compared to their non-diabetic counterparts in the general population. 17 These results underscore the heightened cardiovascular risk associated with diabetes across genders. Chest pain poses a considerable diagnostic challenge within emergency care settings, necessitating a thorough and meticulous clinical evaluation. The distinctions between "atypical" and "typical" chest pain are often inadequate, as they may fail to account for clinical scenarios unrelated to ischemic events. An innovative framework, which classifies underlying causes into cardiac, potentially cardiac, and likely non-cardiac origins, provides a more holistic and collaborative approach to developing a symptom-driven diagnostic algorithm. 18 Our investigation encompassed hypertensive diabetic patients presenting with atypical chest pain, likely attributable to non-cardiac etiologies. In diabetic patients, CAD frequently presents without noticeable symptoms, largely due to the presence of autonomic neuropathy. Additionally, a standard twelve-lead resting ECG may appear normal even when CAD has progressed to advanced stages. Consequently, a normal ECG reading, particularly in individuals with T2DM, does not eliminate the possibility of significant CAD. However, it may still reveal subtle indicators of the condition, such as evidence of a prior myocardial infarction or abnormalities in ventricular repolarization. 19 , 20 In our investigation, the patient cohort not only included individuals with diabetes and hypertension but also those reporting atypical chest pain. This group encompassed patients with both normal ECG and those displaying ventricular repolarization abnormalities, all of whom showed no signs of myocardial ischemia. These findings highlight the complexity of diagnosing CAD in T2DM populations, even in the absence of clear ischemic indicators. A highly reliable and well-established method for evaluating CAD is the exercise stress test, which boasts high specificity and is endorsed by international clinical guidelines. 21 This diagnostic tool is particularly valuable for diabetic patients experiencing atypical chest pain, as well as for those with non-cardiac pain but presenting coronary risk factors. 22 However, it is important to note that a positive result on an exercise stress test may carry a higher likelihood of being a false positive, especially in women, due to the increased prevalence of vasospastic effects in this demographic compared to men. 23 , 24 Additionally, a normal exercise stress test result in diabetic individuals does not entirely rule out the possibility of underlying myocardial ischemia, emphasizing the need for a comprehensive diagnostic approach in this high-risk population. 25 In our study, ETT was performed on 90.8% of the participants, with 33.3% of these individuals yielding positive results indicative of myocardial ischemia. This highlights the utility of stress testing as a diagnostic tool in identifying ischemic conditions within the studied population. MPS is a well-established and frequently used non-invasive imaging examination modality for evaluating CAD, providing both diagnostic and prognostic information. The technique involves the administration of radiopharmaceuticals to assess myocardial blood flow under both stress and rest conditions. This allows for the identification of myocardial ischemia and infarction with high sensitivity and specificity. 26 Contemporary clinical practice often incorporates hybrid imaging, combining SPECT with coronary computed tomography angiography. This integrated approach, merging functional perfusion data with anatomical coronary vessel information, leads to improved diagnostic performance. 27 Beyond qualitative assessment, quantitative perfusion analysis, including the calculation of myocardial flow reserve, offers additional prognostic value, particularly in complex CAD presentations such as multivessel disease. 28 While other imaging modalities, are available, MPS remains a clinically relevant tool, supported by substantial evidence from large-scale clinical trials. 29 It continues to be an important component in the diagnostic and in the risk stratification of patients with suspected or known CAD. Our research investigated hypertensive patients with T2DM presenting with atypical chest pain. We employed SPECT/CT with 99mTc-MIBI as the radiotracer to evaluate myocardial ischemia, given its established high sensitivity and specificity in diagnosing CAD. The integration of ETT with MPS represents a highly effective approach for diagnosing myocardial ischemia. Conducting ETT immediately prior to MPS ensures the preservation of physiological stress parameters, such as heart rate, blood pressure, and symptom manifestation, in addition to diagnosing myocardial ischemia thereby optimizing the alignment between functional and imaging data. 30 ETT delivers essential insights into exercise capacity and hemodynamic performance, whereas MPS detects perfusion abnormalities with greater diagnostic accuracy, especially in individuals with intermediate clinical risk or indeterminate ETT outcomes. 31 In our study, the agreement between MPS and ETT was assessed using the Kappa index, which demonstrated a moderate correlation between the two methods. Pharmacological stress MPS identifies alterations in coronary flow resulting from arterial obstruction without the necessity of inducing ischemia through physical exertion. 32 This approach employs pharmacological agents such as vasodilators (e.g., dipyridamole or adenosine) or inotropic agents like dobutamine. The diagnostic rationale for vasodilator use lies in the disparity in blood flow between regions supplied by healthy coronary arteries and those affected by stenosis, making it highly compatible with scintigraphy, which relies on the visualization of flow distribution patterns. 33 To ensure test efficacy, it is critical to achieve at least a 10% increase in baseline heart rate during pharmacological stress, as this enhances the detection of flow discrepancies. 34 In our investigation, MPS was conducted using pharmacological stress with dipyridamole as the inducing agent. This approach was selected because certain physical limitations, such as joint-related issues or exercise intolerance, rendered traditional exercise stress testing impractical or unreliable. Among the fifteen patients who underwent pharmacological stress, eight exhibited positive findings, indicating detectable perfusion abnormalities consistent with ischemic pathology. In patients with T2DM and systemic hypertension presenting with atypical chest pain of likely non-cardiac origin, the strategic incorporation of MPS significantly enhances diagnostic accuracy compared to relying solely on clinical evaluation. MPS, with its ability to identify subtle alterations in myocardial blood flow, uncovers occult ischemic processes, enabling timely interventions and potentially improving long-term cardiovascular outcomes in this high-risk population. This study underscores the value of MPS in refining risk stratification to guide therapeutic strategies, highlighting its role as an essential adjunct in the comprehensive management of these patients. By integrating MPS with clinical assessment, we can obtain a more precise diagnosis and optimize care for individuals with complex comorbidities. CONCLUSION The MPS demonstrates significant diagnostic value in patients with T2DM and systemic hypertension presenting with atypical chest pain, particularly in those with normal ECG results. Our findings support the utility of MPS as a reliable diagnostic tool for detecting CAD, even in the absence of ETT changes. MPS may aid in identifying high-risk patients who would benefit from further diagnostic investigation and early therapeutic interventions. Declarations CONFLICTS OF INTEREST: None declared. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6027018","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":415609570,"identity":"5aa502d8-da0f-4f05-9853-7bfd46f7ced7","order_by":0,"name":"Luis Jesuino de Oliveira Andrade","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYBACPgbGBgYGHiCLGYg/MDAkwGQScOhgYEPWwjiDOC1IgJmHKC0Syc0fGGRs7A2O8x58bNtml8fP3sD44WMOQ555Ay4tiW0SDDxpiRsO8yUb57YlF0v2HGCWnLmNoVjmAG4tQL8cTjA4zGMmndvGnLjhRgIbM+82hsQZOB2WCHQYz397sBbLtnqitDQAHXaAcQNIC2PbYSK08DwE+SU5ceZhHmPDnnPHE2f2HGwG+kWiWAKHFn729McfGHvs7PnOnzF88KOsOrGfvfngh4/bbPJwaQEB5r89UBYjOJpAkcuATwMI/IAx/hBQOApGwSgYBSMSAAAthFHtBhERUQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-7714-0330","institution":"Departamento de Saúde Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brazil.","correspondingAuthor":true,"prefix":"","firstName":"Luis","middleName":"Jesuino de Oliveira","lastName":"Andrade","suffix":""},{"id":415609571,"identity":"8a3a3d7a-2433-4c07-95e7-eeb86c6cc97d","order_by":1,"name":"Gabriela Correia Matos de Oliveira","email":"","orcid":"https://orcid.org/0000-0002-3447-3143","institution":"Programa Saúde da Família, Bahia, Brazil.","correspondingAuthor":false,"prefix":"","firstName":"Gabriela","middleName":"Correia Matos","lastName":"de Oliveira","suffix":""},{"id":415609572,"identity":"f5efd956-5092-4a7e-880b-2fef51f4918b","order_by":2,"name":"João Cláudio Nunes Carneiro Andrade","email":"","orcid":"https://orcid.org/0009-0000-6004-4054","institution":"Faculdade de Medicina Universidade Federal da Bahia, Salvador, Bahia, Brazil.","correspondingAuthor":false,"prefix":"","firstName":"João","middleName":"Cláudio Nunes Carneiro","lastName":"Andrade","suffix":""},{"id":415609573,"identity":"25b37921-5f30-44c9-afb2-df469241d42b","order_by":3,"name":"Daniela Oda","email":"","orcid":"https://orcid.org/0009-0006-1065-4923","institution":"Instituto de Medicina Nuclear, Itabuna, Bahia, Brasil.","correspondingAuthor":false,"prefix":"","firstName":"Daniela","middleName":"","lastName":"Oda","suffix":""},{"id":415609574,"identity":"d643e8af-d649-4d1c-bd05-d6c3faee0671","order_by":4,"name":"Isabela Pimenta Xavier","email":"","orcid":"https://orcid.org/0009-0001-4742-6637","institution":"Sociedade Cardiológica Jairo Xavier, Itabuna, Bahia, Brasil","correspondingAuthor":false,"prefix":"","firstName":"Isabela","middleName":"Pimenta","lastName":"Xavier","suffix":""},{"id":415609575,"identity":"d6fb8838-f4b1-43d1-b532-a1bd2006b5c1","order_by":5,"name":"Luís Matos de Oliveira","email":"","orcid":"https://orcid.org/0000-0003-4854-6910","institution":"Departamento de Saúde Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brazil.","correspondingAuthor":false,"prefix":"","firstName":"Luís","middleName":"Matos","lastName":"de Oliveira","suffix":""}],"badges":[],"createdAt":"2025-02-14 03:41:01","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6027018/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6027018/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":76427422,"identity":"6b3cf646-cb1d-4509-ae5f-57d3397fae14","added_by":"auto","created_at":"2025-02-17 06:00:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":430775,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6027018/v1/4c01e737-a755-4f7d-8b1e-df9e9db8a911.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eMyocardial Perfusion Scintigraphy for the Evaluation of Atypical Chest Pain - Likely Non-Cardiac - in Type 2 Diabetic Individuals with Systemic Hypertension\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAtypical chest pain is a common yet diagnostically complex presentation, particularly in high-risk populations such as hypertensive type 2 diabetic (T2DM) patients. Unlike typical angina, which follows predictable patterns, atypical chest pain often lacks clear characteristics, making it challenging to differentiate between cardiac and non-cardiac causes.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e This diagnostic ambiguity is exacerbated in diabetic patients, who frequently experience silent ischemia due to autonomic neuropathy, leading to delayed diagnosis and increased cardiovascular morbidity and mortality.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e The presence of hypertension further complicates the clinical scenario, as it accelerates atherosclerosis and increases myocardial oxygen demand, predisposing these patients to ischemic events.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCoronary artery disease (CAD) is a leading cause of death in T2DM patients, with hypertension serving as a significant comorbid factor that amplifies cardiovascular risk.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Studies have shown that the prevalence of CAD in diabetic patients is two to four times higher than in the general population, highlighting the need for accurate diagnostic tools to detect ischemia early.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Myocardial perfusion scintigraphy (MPS) has emerged as a powerful non-invasive imaging technique, offering high sensitivity and specificity for identifying myocardial ischemia, even in patients with atypical symptoms or inconclusive electrocardiographic findings.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe pathophysiology of CAD in diabetic patients is distinct, characterized by diffuse atherosclerosis, endothelial dysfunction, and microvascular disease, which often result in atypical presentations of ischemia.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Hypertensive diabetic patients are particularly vulnerable to these changes, as chronic hypertension promotes vascular remodeling and increases myocardial workload, further complicating the clinical picture. Traditional diagnostic methods, such as stress electrocardiography (ECG), may fail to detect ischemia in this population due to the high prevalence of silent ischemia and baseline ECG abnormalities, such as repolarization disturbances.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eDespite its clinical utility, the application of MPS in hypertensive T2DM patients with atypical chest pain remains underutilized. This gap is partly due to limited awareness of its diagnostic benefits, concerns about radiation exposure, and the lack of standardized protocols for this specific patient population.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Furthermore, there is a paucity of large-scale studies evaluating the prevalence of ischemic abnormalities in hypertensive T2DM patients with atypical chest pain and normal resting ECG or repolarization disturbances. This represents a critical knowledge gap, as early detection of ischemia in this high-risk group could significantly improve outcomes through timely intervention.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eRecent advancements in imaging technology, such as hybrid single-photon emission computed tomography (SPECT/CT) systems, have enhanced the diagnostic accuracy of MPS by integrating anatomical and functional data, providing a more comprehensive assessment of myocardial perfusion.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Additionally, the prognostic value of MPS in diabetic patients has been well-documented, with studies demonstrating its ability to identify high-risk individuals who may benefit from revascularization or intensified medical therapy.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThis study aimed to assess the prevalence of myocardial ischemic abnormalities in hypertensive T2DM, patients presenting with atypical chest pain and either normal resting ECG or ventricular repolarization disturbances, through MPS.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cul\u003e\n \u003cli\u003e\n \u003cp\u003eThe study included 165 patients with T2DM who underwent MPS at rest and under stress, induced either by treadmill exercise testing or pharmacological stress for those unable to perform physical exercise. To be eligible, patients had to present with atypical chest pain, a normal resting ECG, or ventricular repolarization abnormalities, along with systemic hypertension and age over 40 years.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eMyocardial perfusion imaging was performed using SPECT/CT with technetium-99m sestamibi (99mTc-MIBI) as the radiotracer. The tracer was administered intravenously at a dose adjusted to the patient’s body weight, both at rest and during stress. Stress was induced either by treadmill exercise testing or pharmacological agents (dipyridamole) for patients with physical limitations or contraindications to exercise. Imaging was conducted using a VARICAM gamma camera (Elscint\u003csup\u003e®\u003c/sup\u003e) equipped with two detectors in an L-mode configuration (90 degrees). Images were acquired 45 minutes after radiotracer administration, using standardized parameters: 140 keV photopeak, 20% energy window, 64 x 64 matrix, low-energy high-resolution parallel collimators, and a 180° rotation with 64 steps. Gated SPECT, synchronized with ECG, was employed during stress imaging for select patients, with an R-R acceptance window of 20%.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eFor image processing, an XPERT workstation (APEX 5.0 software, Elscint\u003csup\u003e®\u003c/sup\u003e) was utilized, complemented by the Quantitative Gated SPECT (QGS) software for gated studies. Images were analyzed in paired stress-rest views across short-axis, vertical long-axis, and horizontal long-axis orientations. Additional three-dimensional end-systolic and end-diastolic images, along with polar maps (Bull’s Eye), were generated to enhance diagnostic accuracy. A two-day protocol was followed, with rest imaging performed first, followed by stress imaging, maintaining consistent acquisition parameters throughout.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eQualitative and quantitative criteria were applied to interpret the scintigraphic findings. Normal myocardium exhibited uniform radiotracer uptake in both stress and rest/redistribution phases, while ischemic myocardium demonstrated reduced uptake during stress with normalization at rest. Fibrotic tissue showed persistently reduced uptake in both phases, whereas viable ischemic tissue displayed partial improvement during redistribution. Quantitative analysis utilized polar maps to quantify perfusion defects based on pixel counts and standard deviations from normal perfusion areas, providing supplementary data to support visual interpretation.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eExercise treadmill testing (ETT) was conducted using the ramp protocol,\u003csup\u003e13\u003c/sup\u003e with modifications for patients unable to achieve maximal effort due to physical or clinical limitations. Test positivity was defined by specific ECG criteria, including ST-segment depression ≥ 2.0 mm, ST depression \u0026gt; 1.0 mm in the first stage, multi-lead ST changes, persistent ST abnormalities for over 5 minutes during recovery, maximal workload \u0026lt; 4 METs, abnormal blood pressure response, or ventricular arrhythmias. Pharmacological stress with dipyridamole (0.5 mg/kg intravenously over 4 minutes) was employed for patients with orthopedic, neurological, or vascular limitations.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eStatistical analyses were performed using PSPP software, with results expressed as mean ± standard deviation and relative frequency. The Chi-square test was used for proportion comparisons, and the Mann-Whitney test for mean comparisons. The Kappa index assessed agreement between MPS and exercise ECG results. A 95% confidence interval was applied, with statistical significance set at p \u0026lt; 0.05.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003e The study protocol was approved by the Ethics Committee of Santa Casa de Itabuna, Ba.\u003c/p\u003e\n \u003c/li\u003e\n\u003c/ul\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe study included 165 patients, comprising 50 men (30.3%) and 115 women (69.7%), with ages ranging from 40 to 75 years and a mean age of 65.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0 years. Men were significantly older than women (67.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0 years vs. 63.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1 years, P\u0026thinsp;=\u0026thinsp;0.031) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic date\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWomen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e115 (69.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50 (30.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage age (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOf the total cohort, 150 patients (90.9%) underwent exercise stress testing, while pharmacological stress with dipyridamole was used in 15 patients (9.1%). Among those who performed ETT, 55 patients (33.3%) had negative results, whereas 55 (33.3%) tested positive for myocardial ischemia.\u003c/p\u003e \u003cp\u003eMPS was performed in all patients, revealing normal perfusion in 104 cases (63.0%) and ischemia in 61 (37.0%). Among the 15 patients who underwent pharmacological stress testing, 4.8% showed evidence of ischemia (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation among MPS, ETT and Pharmacological stress\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMPS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eETT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePharmacological stress\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 (63.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (37.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (4.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNotably, 15.7% of patients with normal exercise ECG results demonstrated ischemia on MPS, highlighting the superior sensitivity of scintigraphy in detecting myocardial ischemia. Of the 50 patients with positive exercise tests, 32 had concordant positive MPS findings, while 18 showed normal perfusion on scintigraphy.\u003c/p\u003e \u003cp\u003eThe agreement between MPS and ETT was assessed using the Kappa index, which revealed a moderate correlation between the two tests (Kappa\u0026thinsp;=\u0026thinsp;0.52, P\u0026thinsp;=\u0026thinsp;0.0001). No statistically significant differences were observed in the proportion of abnormal MPS findings between men and women (43.5% vs. 35.2%, P\u0026thinsp;=\u0026thinsp;0.53). Similarly, the prevalence of abnormal ETT results did not differ significantly by gender (37.7% in men vs. 29.2% in women, P\u0026thinsp;=\u0026thinsp;0.52).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, we evaluated the role of MPS in hypertensive diabetic patients with atypical chest pain, normal ECG, or ventricular repolarization disturbances, and demonstrated that MPS is a reliable diagnostic tool for detecting coronary artery disease in T2DM patients presenting with atypical angina, particularly in those with inconclusive resting ECG findings.\u003c/p\u003e \u003cp\u003eIndividuals with T2DM experience higher rates of mortality and complications linked to myocardial infarction when compared to those without diabetes.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e The occurrence of silent myocardial ischemia is notably more common among diabetic patients than in the broader population. Consequently, diabetic individuals with myocardial ischemia often lack the hallmark symptom of typical chest pain, resulting in delays in diagnosis and treatment.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e This atypical clinical manifestation plays a significant role in the increased morbidity and mortality rates seen in this patient group.\u003c/p\u003e \u003cp\u003eCAD continues to be a leading contributor to morbidity and death among individuals with DM. Beyond the elevated risk of mortality inherently associated with diabetes, the presence of cardiovascular disease manifestations exacerbates this risk, doubling the mortality rate. This combination results in an estimated decline in life expectancy of roughly 12 years. Genetic factors also play a significant role as a risk indicator in the link between T2DM and CAD.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Comprehensive global epidemiological research, particularly the landmark Framingham study, has demonstrated that the prevalence of CAD is significantly elevated in individuals with diabetes. Specifically, diabetic men exhibit a twofold increase in CAD incidence, while diabetic women experience a threefold rise compared to their non-diabetic counterparts in the general population.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e These results underscore the heightened cardiovascular risk associated with diabetes across genders.\u003c/p\u003e \u003cp\u003eChest pain poses a considerable diagnostic challenge within emergency care settings, necessitating a thorough and meticulous clinical evaluation. The distinctions between \"atypical\" and \"typical\" chest pain are often inadequate, as they may fail to account for clinical scenarios unrelated to ischemic events. An innovative framework, which classifies underlying causes into cardiac, potentially cardiac, and likely non-cardiac origins, provides a more holistic and collaborative approach to developing a symptom-driven diagnostic algorithm.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Our investigation encompassed hypertensive diabetic patients presenting with atypical chest pain, likely attributable to non-cardiac etiologies.\u003c/p\u003e \u003cp\u003eIn diabetic patients, CAD frequently presents without noticeable symptoms, largely due to the presence of autonomic neuropathy. Additionally, a standard twelve-lead resting ECG may appear normal even when CAD has progressed to advanced stages. Consequently, a normal ECG reading, particularly in individuals with T2DM, does not eliminate the possibility of significant CAD. However, it may still reveal subtle indicators of the condition, such as evidence of a prior myocardial infarction or abnormalities in ventricular repolarization.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e In our investigation, the patient cohort not only included individuals with diabetes and hypertension but also those reporting atypical chest pain. This group encompassed patients with both normal ECG and those displaying ventricular repolarization abnormalities, all of whom showed no signs of myocardial ischemia. These findings highlight the complexity of diagnosing CAD in T2DM populations, even in the absence of clear ischemic indicators.\u003c/p\u003e \u003cp\u003eA highly reliable and well-established method for evaluating CAD is the exercise stress test, which boasts high specificity and is endorsed by international clinical guidelines.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e This diagnostic tool is particularly valuable for diabetic patients experiencing atypical chest pain, as well as for those with non-cardiac pain but presenting coronary risk factors.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e However, it is important to note that a positive result on an exercise stress test may carry a higher likelihood of being a false positive, especially in women, due to the increased prevalence of vasospastic effects in this demographic compared to men.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Additionally, a normal exercise stress test result in diabetic individuals does not entirely rule out the possibility of underlying myocardial ischemia, emphasizing the need for a comprehensive diagnostic approach in this high-risk population.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e In our study, ETT was performed on 90.8% of the participants, with 33.3% of these individuals yielding positive results indicative of myocardial ischemia. This highlights the utility of stress testing as a diagnostic tool in identifying ischemic conditions within the studied population.\u003c/p\u003e \u003cp\u003eMPS is a well-established and frequently used non-invasive imaging examination modality for evaluating CAD, providing both diagnostic and prognostic information. The technique involves the administration of radiopharmaceuticals to assess myocardial blood flow under both stress and rest conditions. This allows for the identification of myocardial ischemia and infarction with high sensitivity and specificity.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Contemporary clinical practice often incorporates hybrid imaging, combining SPECT with coronary computed tomography angiography. This integrated approach, merging functional perfusion data with anatomical coronary vessel information, leads to improved diagnostic performance.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Beyond qualitative assessment, quantitative perfusion analysis, including the calculation of myocardial flow reserve, offers additional prognostic value, particularly in complex CAD presentations such as multivessel disease.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e While other imaging modalities, are available, MPS remains a clinically relevant tool, supported by substantial evidence from large-scale clinical trials.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e It continues to be an important component in the diagnostic and in the risk stratification of patients with suspected or known CAD. Our research investigated hypertensive patients with T2DM presenting with atypical chest pain. We employed SPECT/CT with 99mTc-MIBI as the radiotracer to evaluate myocardial ischemia, given its established high sensitivity and specificity in diagnosing CAD.\u003c/p\u003e \u003cp\u003eThe integration of ETT with MPS represents a highly effective approach for diagnosing myocardial ischemia. Conducting ETT immediately prior to MPS ensures the preservation of physiological stress parameters, such as heart rate, blood pressure, and symptom manifestation, in addition to diagnosing myocardial ischemia thereby optimizing the alignment between functional and imaging data.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e ETT delivers essential insights into exercise capacity and hemodynamic performance, whereas MPS detects perfusion abnormalities with greater diagnostic accuracy, especially in individuals with intermediate clinical risk or indeterminate ETT outcomes.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e In our study, the agreement between MPS and ETT was assessed using the Kappa index, which demonstrated a moderate correlation between the two methods.\u003c/p\u003e \u003cp\u003ePharmacological stress MPS identifies alterations in coronary flow resulting from arterial obstruction without the necessity of inducing ischemia through physical exertion.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e This approach employs pharmacological agents such as vasodilators (e.g., dipyridamole or adenosine) or inotropic agents like dobutamine. The diagnostic rationale for vasodilator use lies in the disparity in blood flow between regions supplied by healthy coronary arteries and those affected by stenosis, making it highly compatible with scintigraphy, which relies on the visualization of flow distribution patterns.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e To ensure test efficacy, it is critical to achieve at least a 10% increase in baseline heart rate during pharmacological stress, as this enhances the detection of flow discrepancies.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e In our investigation, MPS was conducted using pharmacological stress with dipyridamole as the inducing agent. This approach was selected because certain physical limitations, such as joint-related issues or exercise intolerance, rendered traditional exercise stress testing impractical or unreliable. Among the fifteen patients who underwent pharmacological stress, eight exhibited positive findings, indicating detectable perfusion abnormalities consistent with ischemic pathology.\u003c/p\u003e \u003cp\u003eIn patients with T2DM and systemic hypertension presenting with atypical chest pain of likely non-cardiac origin, the strategic incorporation of MPS significantly enhances diagnostic accuracy compared to relying solely on clinical evaluation. MPS, with its ability to identify subtle alterations in myocardial blood flow, uncovers occult ischemic processes, enabling timely interventions and potentially improving long-term cardiovascular outcomes in this high-risk population. This study underscores the value of MPS in refining risk stratification to guide therapeutic strategies, highlighting its role as an essential adjunct in the comprehensive management of these patients. By integrating MPS with clinical assessment, we can obtain a more precise diagnosis and optimize care for individuals with complex comorbidities.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe MPS demonstrates significant diagnostic value in patients with T2DM and systemic hypertension presenting with atypical chest pain, particularly in those with normal ECG results. Our findings support the utility of MPS as a reliable diagnostic tool for detecting CAD, even in the absence of ETT changes. MPS may aid in identifying high-risk patients who would benefit from further diagnostic investigation and early therapeutic interventions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCONFLICTS OF INTEREST:\u0026nbsp;\u003c/strong\u003eNone declared.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eVirani SS, Newby LK, Arnold SV, Bittner V, Brewer LC, Demeter SH, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023(9):e9-e119.\u003c/li\u003e\n \u003cli\u003eKaze AD, Fonarow GC, Echouffo-Tcheugui JB. Cardiac Autonomic Dysfunction and Risk of Silent Myocardial Infarction Among Adults With Type 2 Diabetes. J Am Heart Assoc. 2023;12(20):e029814.\u003c/li\u003e\n \u003cli\u003eBosone D, Fogari R, Ramusino MC, Ghiotto N, Guaschino E, Zoppi A, et al. Ambulatory 24-h ECG monitoring and cardiovascular autonomic assessment for the screening of silent myocardial ischemia in elderly type 2 diabetic hypertensive patients. Heart Vessels. 2017;32(5):507-513.\u003c/li\u003e\n \u003cli\u003eYen FS, Wei JC, Chiu LT, Hsu CC, Hwu CM. Diabetes, hypertension, and cardiovascular disease development. J Transl Med. 2022;20(1):9.\u003c/li\u003e\n \u003cli\u003eAkın S, B\u0026ouml;l\u0026uuml;k C. Prevalence of comorbidities in patients with type-2 diabetes mellitus. Prim Care Diabetes. 2020;14(5):431-434.\u003c/li\u003e\n \u003cli\u003eValenta I, Schindler TH. PET-determined myocardial perfusion and flow in coronary artery disease characterization. J Med Imaging Radiat Sci. 2024;55(2S):S44-S50.\u003c/li\u003e\n \u003cli\u003eYahagi K, Kolodgie FD, Lutter C, Mori H, Romero ME, Finn AV, et al. Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus. Arterioscler Thromb Vasc Biol. 2017;37(2):191-204.\u003c/li\u003e\n \u003cli\u003eHarms PP, Elders PPJM, Rutters F, Lissenberg-Witte BI, Tan HL, Beulens JWJ, et al. Longitudinal association of electrocardiogram abnormalities with major adverse cardiac events in people with Type 2 diabetes: the Hoorn Diabetes Care System cohort. Eur J Prev Cardiol. 2023;30(8):624-633.\u003c/li\u003e\n \u003cli\u003eBaur LH. What is the best myocardial perfusion protocol in diabetic patients? Int J Cardiovasc Imaging. 2008;24(2):183-4.\u003c/li\u003e\n \u003cli\u003eLiga R, Gimelli A. Detection of ischemia with early myocardial perfusion imaging: You see more if you watch before. J Nucl Cardiol. 2017;24(4):1157-1160.\u003c/li\u003e\n \u003cli\u003e\u0026Ouml;zdemir E, Bur\u0026ccedil;ak Polat Ş, Yıldırım N, T\u0026uuml;rk\u0026ouml;lmez Ş, Ersoy R, Durmaz T, et al. Evaluation of Silent Myocardial Ischemia with Single-Photon Emission Computed Tomography/Computed Tomography in Asymptomatic Subjects with Diabetes and Pre-Diabetes. Mol Imaging Radionucl Ther. 2016;25(2):70-8.\u003c/li\u003e\n \u003cli\u003eHan D, Rozanski A, Gransar H, Sharir T, Einstein AJ, Fish MB, et al. Myocardial Ischemic Burden and Differences in Prognosis Among Patients With and Without Diabetes: Results From the Multicenter International REFINE SPECT Registry. Diabetes Care. 2020;43(2):453-459.\u003c/li\u003e\n \u003cli\u003eFroelicher VF, Myers J. Exercise and the Heart. 5\u003csup\u003eth\u003c/sup\u003e ed. Philadelphia: Elsevier; 2006.\u003c/li\u003e\n \u003cli\u003eHaffner SM, Lehto S, R\u0026ouml;nnemaa T, Py\u0026ouml;r\u0026auml;l\u0026auml; K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339(4):229-34.\u003c/li\u003e\n \u003cli\u003eLee JW, Moon JS, Kang DR, Lee SJ, Son JW, Youn YJ, et al. Clinical Impact of Atypical Chest Pain and Diabetes Mellitus in Patients with Acute Myocardial Infarction from Prospective KAMIR-NIH Registry. J Clin Med. 2020;9(2):505.\u003c/li\u003e\n \u003cli\u003eSchmidt AM. Diabetes Mellitus and Cardiovascular Disease. Arterioscler Thromb Vasc Biol. 2019;39(4):558-568.\u003c/li\u003e\n \u003cli\u003eKengne AP, Turnbull F, MacMahon S. The Framingham Study, diabetes mellitus and cardiovascular disease: turning back the clock. Prog Cardiovasc Dis. 2010;53(1):45-51.\u003c/li\u003e\n \u003cli\u003eSettelmeier S, Steven S, Post F, Ahrens I, Giannitsis E, Breuckmann F, et al. New categorization of chest pain: noncardiac is in, atypical is out! Herz. 2024;49(3):181-184.\u003c/li\u003e\n \u003cli\u003eGregers MCT, Schou M, Jensen MT, Jensen J, Petrie MC, Vilsb\u0026oslash;ll T, et al. Diagnostic and prognostic value of the electrocardiogram in stable outpatients with type 2 diabetes. Scand Cardiovasc J. 2022;56(1):256-263.\u003c/li\u003e\n \u003cli\u003eKittnar O. Electrocardiographic changes in diabetes mellitus. Physiol Res. 2015;64(Suppl 5):S559-66.\u003c/li\u003e\n \u003cli\u003eGibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, et al. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Circulation. 2002;106(14):1883-92.\u003c/li\u003e\n \u003cli\u003eSuyama A, Sunagawa K, Hayashida K, Sugimachi M, Todaka K, Nose Y, et al. Random exercise stress test in diagnosing effort angina. Circulation. 1988;78(4):825-30.\u003c/li\u003e\n \u003cli\u003eTowashiraporn K, Krittayaphong R, Yindeengam A. Predicting factors for a false positive treadmill exercise stress test. J Med Assoc Thai. 2013;96 Suppl 2:S133-8.\u003c/li\u003e\n \u003cli\u003eAdekunle AE, Akintomide AO. Gender differences in the variables of exercise treadmill test in type 2 diabetes mellitus. Ann Afr Med. 2012;11(2):96-102.\u003c/li\u003e\n \u003cli\u003eSekiya M, Suzuki M, Fujiwara Y, Sumimoto T, Hamada M, Hiwada K. Hemodynamic characteristics of patients with coronary artery disease presenting false-negative exercise stress test. Angiology. 1992;43(6):506-11.\u003c/li\u003e\n \u003cli\u003eNotghi A, Low CS. Myocardial perfusion scintigraphy: past, present and future. Br J Radiol. 2011;84 Spec No 3(Spec Iss 3):S229-36.\u003c/li\u003e\n \u003cli\u003eKelion AD. Advances in SPECT in evaluating coronary disease. Br J Hosp Med (Lond). 2014;75(7):372-7.\u003c/li\u003e\n \u003cli\u003eBailly M, Ribeiro MJ, Angoulvant D. Combining flow and reserve measurement during myocardial perfusion imaging: A new era for myocardial perfusion scintigraphy? Arch Cardiovasc Dis. 2021;114(12):818-827.\u003c/li\u003e\n \u003cli\u003eHueb W. Single Photon Computed Tomography-Myocardial Perfusion Scintigraphy. Diagnostic Tool Anticipating the Disease. Arq Bras Cardiol. 2019;112(2):129.\u003c/li\u003e\n \u003cli\u003eVacanti LJ, Sposito AC, S\u0026eacute;spedes L, Sarpi M, Ramires JA, Bortnick AE. In comparison to the myocardial perfusion scintigraphy, a treadmill stress test is a viable, efficient and cost effective option to predict cardiovascular events in elderly patients. Arq Bras Cardiol. 2007;88(5):531-6.\u003c/li\u003e\n \u003cli\u003eTurner DA, Battle WE, Deshmukh H, Colandrea MA, Snyder GJ, Fordham EW, et al. The predictive value of myocardial perfusion scintigraphy after stress in patients without previous myocardial infarction. J Nucl Med. 1978;19(3):249-55.\u003c/li\u003e\n \u003cli\u003eSharedalal P, Gerard P, Jain D. Pharmacological stress myocardial perfusion imaging after an inadequate exercise stress test. J Nucl Cardiol. 2022;29(4):1796-1798.\u003c/li\u003e\n \u003cli\u003eConti A, Mariannini Y, Canuti E, Petrova T, Innocenti F, Zanobetti M, et al. Nuclear scan strategy and outcomes in chest pain patients value of stress testing with dipyridamole or adenosine. World J Nucl Med. 2014;13(2):94-101.\u003c/li\u003e\n \u003cli\u003eSchumann CL, Bourque JM. Heart rate response to vasodilator stress: A potential new application for a proven prognostic parameter. J Nucl Cardiol. 2021;28(6):2684-2686.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Myocardial perfusion scintigraphy, type 2 diabetes mellitus, hypertension, myocardial ischemia, atypical angina","lastPublishedDoi":"10.21203/rs.3.rs-6027018/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6027018/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Myocardial perfusion scintigraphy (MPS) is an essential diagnostic tool for evaluating coronary artery disease, particularly in high-risk populations such as hypertensive type 2 diabetic patients (T2DM). Despite its clinical relevance, there remains a significant gap in understanding its optimal application and diagnostic accuracy in this subgroup, warranting further research to refine risk stratification and improve patient outcomes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e This study aimed to assess the prevalence of myocardial ischemic abnormalities in hypertensive T2DM, patients presenting with atypical chest pain and either normal resting electrocardiogram (ECG) or ventricular repolarization disturbances, through MPS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A total of 165 participants, comprising 50 men (30.3%) and 115 women (69.7%), with a mean age of 65.6 ± 6 years, underwent MPS using a 2-day protocol.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The results revealed that 63.0% of patients exhibited normal perfusion scans, while 37% demonstrated findings consistent with myocardial ischemia. Additionally, a subset of the cohort underwent exercise stress testing (90.9%), which yielded positive results for ischemia in 33.3% of cases. The agreement between MPS and exercise ECG was analyzed, revealing a moderate correlation (Kappa = 0.52; P \u0026lt; 0.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: These findings reinforce the clinical utility of MPS as a reliable diagnostic tool for detecting coronary artery disease in patients with T2DM and systemic hypertension who present with atypical chest pain, particularly in those with inconclusive findings on resting ECG.\u003c/p\u003e","manuscriptTitle":"Myocardial Perfusion Scintigraphy for the Evaluation of Atypical Chest Pain - Likely Non-Cardiac - in Type 2 Diabetic Individuals with Systemic Hypertension","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-17 05:28:19","doi":"10.21203/rs.3.rs-6027018/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ab6e42e9-7d0a-4b1a-b6b5-00f76d505028","owner":[],"postedDate":"February 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":44318858,"name":"Endocrinology \u0026 Metabolism"}],"tags":[],"updatedAt":"2025-02-17T05:28:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-17 05:28:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6027018","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6027018","identity":"rs-6027018","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}