Ischemic Test Research Articles

Coronary artery disease screening in renal transplant candidates: insights from a large prospective cohort

Abstract Background There is currently no specific consensus regarding the screening strategy for CAD in renal transplant candidates. Purposes To describe in renal transplant candidates 1/ Strategies and results of CAD screening and 2/ renal and cardiovascular outcomes in this population Methods All patients registered on kidney transplant waiting list in our tertiary centre were classified into no screening for CAD (unscreened), screened, or with prior CAD. Unscreened was defined as no ischemia or anatomic testing while on waiting list or within the year prior to listing. Screening was considered as "positive" when it led to diagnostic of obstructive CAD (stenosis > 50%). Primary outcome was a composite outcome defined as [death or unplanned revascularization]. Primary outcome and renal transplant were analysed using multivariable Cox model. Results From 2005 to 2023, 3248 patients were registered as candidates for kidney transplantation, 228 (7.0%) patients had a history of CAD, 1987 (61.2%) patients were screened for CAD and 1033 (31.8%) were unscreened. Initial screening investigation were mainly stress cardiovascular MRI (33.7%), stress TTE (27.7%) or myocardial perfusion imaging (26.4%). Among screened patients, 133 (6.7%) patients had a positive screening for obstructive CAD. Within 4.7 [1.2 – 7.2] years, using patients with a negative screening as a reference, patients with positive screening and known CAD were less likely to receive renal transplant (aHR 0.70 [0.53 ; 0.93] and 0.64 [0.49 ; 0.84] respectively), while patients without screening were similarly transplanted (aHR 1.01 [0.89 ; 1.15]). Patients without screening or with a prior history of CAD were at higher risk of primary outcome compared with patients with negative screening (aHR 1.49 [1.16; 1.91]) and aHR 1.97 [1.48; 2.62] respectively), along with patients on dialysis at registration (1.37 [1.13; 1.66]), diabetic patients (1.79 [1.47; 2.18]) and smokers (1.25 [1.03; 1.53]). Age was an interaction factor between unscreening and primary outcome, as there was no association in younger patients (aHR 1.21 [0.81; 1.81]). Conclusion Among candidates for kidney transplantation, 2 out of 3 patients underwent non-invasive testing for obstructive CAD resulting in less than 10 % of positive cases. Positive testing and history of CAD were associated with a lower opportunity for kidney transplantation compared with negative testing or absence of screening. Nonetheless, absence of screening was associated with a higher risk of [death + unplanned revascularization], especially in older patients.Central illustration

Time to target heart rate in dobutamine stress echocardiography is shortened by using dynamic, but not isometric handgrip

Abstract Background Dobutamine stress echocardiography (DSE) is widely used for the detection of obstructive ischaemic heart disease. In our previous study we demonstrated that the magnitude of myocardial injury measured by hsTnT is associated with DSE duration. Shortening of DSE time is therefore desirable. Use of hangrip (HG) during DSE is generally recommended. However, there are no published studies comparing the efect of dynamic and isometric HG on the length of DSE. Purpose To compare the effect of dynamic and static HG on DSE duration. Methods 211 patients undergoing DSE for ischaemia assessment were randomised into no HG (noHG, n=74), isometric HG (isoHG, n=68) and gynamic HG (dynHG, n=69) groups. All patients taking rate limiting medication were instructed to stop it 48 hours prior the test. DSE was performed according to the standard protocol (dobutamine infusion 5, 10, 20, 30, 40 ug/kg/min., increased in 3 min. intervals). HG was applied at the level of 40% maximum isometric muscular effort from the dobutamine dose of 20ug/kg/min. and atropine was administered in 1 min. intervals in 100 ug increments from the dose of 30 ug/kg/min. Patients who did not achieve their target heart rate (HR) or suffered from dobutamine side effects were excluded from the study. Results There were no differences in the groups characteristics (gender p=0.187, known ischaemic heart disease p=0.361, age p=0.128, basal HR p=0.367, target HR p=0.107, achieved HR p=0.257, positive test for ischaemia p=0.583). There was a significant difference in the time to target HR between dynHG and noHG groups (9.97±2.34 vs 11.96±3.02 min., p< 0.001) but not between isoHG and noHG groups (10.76±3.12 vs 11.96±3.02 min., p=0.058). Also, the was a similar difference in the length of dobutamine infusion between dynHG and noHG, but not between isoHG and noHG groups (11.76±2.37 vs 13.78±3.09 min., p< 0.001 and 13.34±4.90 vs 13.78±3.09 min., p=0.308, respectively). No significant correlation was found between the time to target HR and basal (r=0.43) or target HR (r=0.38). Conclusion Dynamic, but not isometric handgrip shortens the length of dobutamine stress echocardiography.

AI derived myocardial left ventricular volumes outperforms clinician segmentation for prediction of all-cause mortality

Abstract Background Measuring heart structure and function drives much cardiac decision making and therapy. Precise quantification is therefore of high importance, but manual (clinician) segmentation introduces measurement variability. Purpose Automated segmentation of cardiac MRI (CMR) left ventricular (LV) volumes provides improved precision but how this translates into clinical outcomes has yet to be defined. In order to test predictive accuracy in a wide range of adverse LV morphologies, we applied AI LV segmentation to patients with coronary disease or cardiomyopathy. Methods Scans were analysed from a retrospective clinical CMR database and mortality data was obtained from a national database. Clinician measurement of indexed LV end-diastolic volume (LVEDVi), LV mass (LVMi), myocardial contraction fraction (MCF: ratio of stroke volume to myocardial volume; a measure of myocardial efficiency) and EF were recorded from clinical reports (all senior clinicians with >5 years level 3 experience) and compared to AI measurement using a segmentation algorithm. This has previously been shown to exceed human precision and required no manual correction (1,2). Random survival forests were built to identify overall predictive value of AI vs clinician derived LV volumes. These are machine-learning algorithms for predicting time-to-event outcomes and can capture complex relationships between predictors and outcome. Random survival forests were built from AI and clinician models with EF, EDVi, LVMi and MCF as predictors for all-cause mortality. A train:test (80:20) split, stratified for outcome was employed. Concordance (C)-indices (measuring predictive accuracy) and permutation importances (measuring significance of each predictor within the model) (Table) with 1000 bootstrapped 95% confidence intervals and p-values were derived. Results 8,299 patients were analysed. Patients were 60(51-70) years old and 37% female. 49% had coronary disease, 25% had DCM and 19% had HCM. At a median follow-up of 5.3 years (IQR 4.2-6.6 years) there were 1,384 deaths (17%). AI derived LV-parameter models had higher predictive accuracy than clinician derived models (C-Indices: 0.66±0.002 vs 0.65±0.005, p<0.001). A subgroup analysis of patients undergoing ischaemia testing for coronary disease was performed (n=3,560) and markers of ischaemia (positive vs negative) and infarction (non-viable vs viable) were included in the models. AI had a higher predictive accuracy compared to clinicians when including these additional predictors (C-Indices: 0.68±0.03 vs 0.63±0.01, p<0.001). Conclusion AI derived LV volumes outperforms clinicians in prediction of all-cause mortality reflecting improved precision. Improvements in predictive accuracy are likely to be clinically important when applied to populations and high-risk groups. Manual clinician segmentation should be superseded by clinician-supervised AI.

Invasive testing leads to significantly altered (surgical) management strategy in coronary anomalies with interarterial course: 3 year interim analysis of MuSCAT

Abstract Introduction Diagnostic work-up of patients with an anomalous aortic origin of a coronary artery (AAOCA) includes an anatomical and functional assessment. The approach to functional evaluation currently varies widely and mainly includes noninvasive assessment. Intracoronary hemodynamic assessment can potentially enhance risk assessment for myocardial ischemia and sudden cardiac death and guide management of AAOCA patients. Hence, this study aims to evaluate invasive detection of ischemia on top of the standard of care diagnostic work-up for interarterial or intraseptal AAOCA and the impact on patient management. We report the first clinical outcomes. Methods In this multicenter prospective cohort study on AAOCA, all consecutive patients of 16 years and older with AAOCA with a newly diagnosed interarterial or intraseptal course in whom diagnostic work-up according to the protocol of the MuSCAT trial was performed between January 2021 and January 2024, were included for analysis. Exclusion comprised incomplete diagnostic evaluation, hemodynamically significant concomitant congenital heart disease or obstructive coronary artery disease in the AAOCA effluence. The work-up included invasive ischemia testing using fractional flow reserve (FFR) and or instantaneous wave-free ratio (iFR)/resting full-cycle ratio (RFR) at baseline and during pharmacological stress using adenosine, adrenaline and dobutamine. Results Fifty-eight patients (50% female, median age at AAOCA diagnosis 51.5 years (IQR 44.0-59.0)) were included, Table 1. The right coronary artery was anomalous in 88%, 93% patients had an interarterial and 69% an intramural course. Non-invasive ischemia detection was positive in 12%, negative in 84% and inconclusive in 4%. Invasive hemodynamic assessment was positive for ischemia in 22%, negative in 74% and inconclusive in 3%. Class of recommendation for surgery based on ESC guidelines was I or IIa in 28% patients and IIb, III or unclassified in 72%. Invasive hemodynamic assessment changed the treatment decision in 24% of the patients; 50% with initially recommended surgical treatment and 14% with initially a conservative treatment adjudication, Figure 1. Median follow-up after initial diagnosis was 20 [IQR 10-28] months and in 56% of all patients who completed 6 months follow-up the initial symptoms alleviated. One (2%) patient underwent a percutaneous re-intervention of the operated AAOCA. Conclusions This national prospective study of invasive hemodynamic assessment in patients with AAOCA showed clinically significant impact on the adjustment of initial management strategy in 24% of the patients. No cardiac death of myocardial infarction in the AAOCA supply area occurred during follow-up. Analysis of the complete follow-up of the MuSCAT trial can further substantiate the role of additional invasive functional imaging in AAOCA.

Prospective evaluation of treatment strategies in patients presenting with chronic total occlusion at coronary angiogram: rationale, design and baseline data of the PETS-CTO Registry.

Coronary chronic total occlusions (CTO) are associated with an increased chance of untreatable symptoms and worse prognosis. However, limited data are available about the interaction between treatment strategy, potential ischemia burden reduction and quality of life (QoL) improvement. Our prospective registry aims to assess the potentially different impacts of treatment strategies (coronary artery bypass grafting vs.. percutaneous coronary intervention vs. optimal medical therapy) on clinical outcomes and QoL domains. This article specifically focuses on describing the registry's rationale, design, and baseline characteristics of the enrolled patients. A total of 157 patients were enrolled. Every patient was evaluated for baseline symptoms, ischemic burden and QoL and allocated to a treatment arm. In 112 patients (71.3%) ischemia baseline assessment was performed and for 116 (73.9%) Seattle Angina Questionnaire (SAQ) was available. At baseline, a significant functional limitation was evident, especially in terms of angina stability (mean score 69±31%) and disease perception (mean score 69±27%). In 49.1% of patients, ischemia testing was positive. Patients with documented ischemia were generally more symptomatic (CCS class 1 36.4% vs.. 57.9%, P=0.023) and a significant inverse correlation between CCS class and SAQ domains was found. No association between ischemia burden and self-reported QoL scores was found. The PETS-CTO registry is the first prospective registry investigating the impact of different treatment strategies on QoL and ischemia burden in patients with CTOs. At baseline, the severity of symptoms was directly associated with ischemia burden and inversely associated with self-reported QoL evaluation.

Diagnostic utility of coronary artery calcium score percentiles and categories to exclude abnormal scans and relevant ischemia in rubidium positron emission tomography.

Despite clinical suspicion, most non-invasive ischemia tests for coronary artery disease (CAD) reveal unremarkable results. Patients with a coronary artery calcium score (CACS) of zero rarely have an abnormal positron emission tomography (PET) and could be deferred from further testing. However, most patients have some extent of coronary calcification. CACS percentiles could be useful to exclude abnormal perfusion in patients with CACS >0, but data from patients with 82Rb PET are lacking. The aim of this study was to assess the diagnostic utility of CACS percentiles in comparison to zero calcium and absolute CACS classes. Consecutive patients with suspected CAD (n = 1,792) referred for 82Rb PET were included and analyzed for abnormal PET (SSS ≥4) and relevant ischemia (>10% myocardium). Test characteristics were calculated. The mean age was 65 ± 11 years, 43% were female, and typical angina was reported in 21%. Abnormal PET/relevant ischemia (>10%) were observed in 19.8%/9.3%. Overall, the sensitivity/negative predictive value (NPV) of a <25th percentile CACS to rule out abnormal PET and relevant ischemia were 93.0%/95.7% and 98.2%/99.5%, respectively. The sensitivity/NPV of CACS 1-9 to rule out abnormal PET and relevant ischemia were 96.0%/91.8% and 97.6%/97.6%, respectively. Except for patients <50 years old, sensitivity for abnormal PET was >90.9% in all age groups. In patients >50 years, the <25th percentile and CACS 1-9 had good test characteristics to rule out abnormal PET and relevant ischemia (>10%). They could be used to extend the scope of application of CACS 0 by 8%-10% to 32%-34% overall of patients who could be deferred from further testing.

Lipid-Lowering Medication and Outcomes After Anatomical and Functional Imaging in Suspected Coronary Artery Disease.

Anatomical and functional imaging identify different phenotypes of coronary artery disease (CAD) that may have implications for lipid-lowering medication (LLM). The aim of this study was to assess the associations between LLM and long-term outcomes after combined anatomical and functional imaging in patients with suspected obstructive CAD. Consecutive patients (n=1,973; 41% men; median age: 63 years) underwent coronary computed tomography angiography (CTA) because of suspected CAD. Patients in whom obstructive CAD was not ruled out by CTA underwent ischemia testing by positron emission tomography. Data on LLM purchases were collected until 2 years, and the combined endpoints of death, myocardial infarction, and unstable angina pectoris were assessed at a median of 6.7 years. After imaging, LLM was used by 24% of patients with no CAD, 51% of patients with nonobstructive CAD, 72% of patients with obstructive CAD on CTA without myocardial ischemia, and 91% of patients with myocardial ischemia. The use of LLM decreased during follow-up, with 77% of patients with myocardial ischemia using LLM for 2 years. The use ofLLM was associated with a lower annual rate of adverse events in patients with myocardial ischemia (6.1% vs 2.8%; P= 0.032) or obstructive CAD without myocardial ischemia (2.9% vs 1.4%; P = 0.004) but not in patients with nonobstructive CAD (1.5% vs 1.4%; P = 0.89) or no CAD (0.3% vs 0.3%; P = 0.68). The CAD phenotype defined by anatomical and functional imaging guides the use of LLM. The presence of myocardial ischemia and anatomical obstructive coronary lesions were associated with a long-term outcome benefit from LLM.

Objective Ischemia, Subjective Angina, and Psychological Distress in Angina With No Obstructive Coronary Disease.

Angina with no obstructive coronary disease (ANOCA) and ischemia with no obstructive coronary disease, prevalent yet underrecognized conditions, mostly affect women. Previous studies rarely distinguished between them. We aimed to compare the prevalence of objective ischemia through various examinations in women with ANOCA and assess the impact of objective and subjective ischemia on their mental health. A total of 84 eligible women with ANOCA and 42 controls underwent mental stress, pharmacological stress, exercise stress, and Holter testing. Objective evidence of myocardial ischemia was assessed by positron emission tomography-computed tomography and ECG, and subjective symptoms were graded using the Canadian Cardiovascular Society scale (CCS). Psychological assessments were conducted using 6 scales. Among 84 women with ANOCA, 37 (44%) received a diagnosis of ischemia with no obstructive coronary disease following mental stress testing, 20 (28.6%) through pharmacological stress testing, 14 (21.2%) via exercise stress testing, and 24 (32.9%) from Holter. Mental stress-induced myocardial ischemia was more prevalent (P<0.05). Among 54 patients with ANOCA who completed all tests, 30% showed no ischemia, and only 1 (1.9%) showed ischemia in all tests. In addition, patients with ANOCA had higher psychological scores than controls (P<0.01). No significant differences was observed in psychological scores between ANOCA with positive and negative ischemia test results (P>0.05). However, ANOCA with milder angina (CCS I) exhibited higher scores across the Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, Perceived Stress Scale, and Posttraumatic Stress Disorder Checklist-Civilian Version and a higher prevalence of Type D personality traits (P<0.05). In patients with ANOCA, the positive rate of myocardial ischemia exhibits variability among several noninvasive tests. A worsened psychological state is more closely linked to milder angina symptoms than to ischemia performance, highlighting the importance of focusing on symptom management in their psychological care. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03982901.

The role of coronary artery reimplantation for anomalous right coronary artery originating from the opposite sinus of Valsalva: preliminary outcomes and insights from a Latin American country.

Despite promising results, reimplantation appears to have fallen into oblivion among the multiple possible approaches for repairing anomalous coronary arteries. We describe the outcomes of 12 patients with an anomalous right coronary artery originating from the opposite sinus of Valsalva with an interarterial course who were surgically treated with this technique between 2018 and 2023 in 2 institutions in Bogota, Colombia. We provide preliminary evidence of the value reimplantation as a more than suitable technique, particularly in resource-constrained settings. It offers high rates of control of symptoms and functional class recovery while assessing all potential high-risk features, with a low risk of complications, even in middle-aged patients. We also advocate using noninvasive anatomical descriptions and patient symptoms over inducible ischaemia tests in decision making.

Three years' registry on myocardial perfusion imaging patients in Ain shams university nuclear cardiology unit

Abstract Background The development in nuclear myocardial perfusion imaging (MPI) has provided diagnostic and prognostic implications in CAD patients, leading to an explosive increase in the performanceofthesestudies. Thisexpansionofimagingspectrumisassociatedwithwidespread concern regarding imaging utilization and increased healthcare costs. There is no comparative data that guide the use of these modalities with respect to appropriateness and patients’ benefit. Targeted data collection, through registry studies, enable analysis of both quality and outcomes with big advantages of reflecting real world daily practice and identifying the gaps in care which may not otherwise be feasible in high-quality randomized control trials. Objective To explore the extent to which stress myocardial perfusion imaging (MPI) studies met published appropriate use criteria (AUC), and the real world practice in the nuclear cardiology unit of Ain shams University. Patients and Methods It was a retrospective cohort study that included 2598 patients who underwent myocardial perfusion imaging in Ain Shams university nuclear cardiology unit throughout the period from January 2017 to December2019. All patients were subjected to thorough demographic data, history of cardiovascular risk factors (arterial hypertension, diabetes mellitus, smoking, family history of premature cardiovascular diseases), indication of the test, preprocedural ECG, ejection fraction by echocardiography, previous coronary angiography and PCI or CABG, calculation of pretest probability and Framingham risk score, determination of appropriateness use criteria and stress-rest Tc 99m imaging to detect the presence of ischemia and one day Tc 99m imaging to detect viability. Results The study included 2598 patients with mean age of 57.76 years, with male predominance (68.1%), 38.2% were diabetics and 53% had hypertension. The most common indications to undergo MPI was the exclusion of CAD as a cause of chest pain in 38.8% of patients followed by the evaluation of symptomatic post PCI patients in 21.9%. Moreover 63.8% of patients showed appropriate tests, while 18.6% of patients showed uncertain tests. Whereas 17.6% of patients had inappropriate studies. 81% of appropriate tests showed positive results of SPECT. Whereas in the inappropriate and the uncertain category, the negative test for ischemia predominated. Conclusion We have established that appropriateness criteria are effective in identifying appropriateness of SPECT in a university center located in Cairo. Also, we concluded that in our unit the appropriate tests were more prominent than inappropriate and unclassified tests. Most of the appropriate studies were positive for ischemia. While, most of the inappropriate and uncertain tests were normal and the commonest cause of referral for MPI was exclusion of CAD as a cause of chest pain.

Refining Cardiovascular Calcification in the Appraisal of Ischemic Heart.

Even in asymptomatic patients, there is a high association of ischemia on myocardial perfusion scans in those with coronary artery calcification or valvular calcifications. Patients without coronary artery calcifications have exceeding-low rates of cardiovascular events. The absence of cardiovascular calcification, including coronary artery, valvular, and thoracic aorta is a strong negative predictor of myocardial ischemia. In individuals with suspected ischemia who had chest computed tomography imaging, evaluation for cardiovascular calcification (coronary artery, valves, and thoracic aorta) is an invaluable tool to guide management for further diagnostic imaging. We hypothesize that the complete absence of cardiovascular calcification has a high negative predictive value for defects in myocardial perfusion imaging such as single-photon emission computed tomography(SPECT) or positron emission tomography(PET). Non-contrast computed tomography performed for SPECT/PET CT attenuation correction from March 1, 2017, to September 30, 2017, were retrospectively reviewed for the absence of cardiovascular calcification by a cardiologist andradiologist who were blinded to patients' medical history. Medical records were reviewed to include patient demographics and medical history. A total of 132 patients were analyzed. Of the 132 patients without calcifications, seven patients had small myocardial perfusion defects suggestive of ischemia or infarct, but none were considered significant defects. Of these seven patients, six were managed medically and one was from an outside institution with no follow-up data. Two of the seven patients had follow-up invasive angiography or coronary CTA that did not show significant atherosclerotic coronary artery disease. A complete absence of cardiovascular calcification indicates a 100% negative predictive value for a significant perfusion defect on same-day confirmatory nuclear stress testing. Patients with suspected ischemia but absent cardiovascular calcifications can be safely managed medically without further testing for ischemia.

A CASE REPORT OF AN ASYMPTOMATIC PATIENT WITH TYPE 2 WELLENS’ SYNDROME AND RENAL CARCINOMA

Abstract A 65–year–old male with renal cell carcinoma, previously treated with nephrectomy and recently diagnosed with lung metastases, presented to the cardiology clinic for investigations before starting chemotherapy. He reported a history of ischemic heart disease, a non–ST–elevation myocardial infarction for which he refused coronary angiography in 2005, and a negative maximal stress test for ischemia in 2017. Additionally, the patient reported insulin–dependent type 2 diabetes mellitus and well–controlled arterial hypertension. The patient was referred for a cardiological evaluation due to a reported short–term rhythmic heartbeat without other cardiological symptoms. Cardiological parameters were stable (blood pressure: 140/95 mmHg; heart rate: 42 bpm, and oxygen saturation without oxygen supplementation: 98%). Physical examination was normal. Laboratory investigations did not show elevated levels of high–sensitivity troponin I, and only signs of mild chronic kidney disease were observed. The initial ECG showed sinus bradycardia with deeply inverted T–waves in the extended anterior area (Fig. 1), which were not present in an ECG performed one month earlier. There was no reported chest pain. An echocardiogram examination demonstrated hypertensive heart disease with marked hypokinesia of the mid–apical portion of the anterior wall and anterior interventricular septum, together with a moderate reduction in global systolic function (LV ejection fraction: 40%). The patient was hospitalized, and underwent coronary angiography the following day. He had a low–risk score (GRACE: 95 pts) As shown in Fig. 2, there was evidence of long sub–occlusive stenosis of the proximal part of the anterior descending coronary artery that was treated with angioplasty and a single drug–eluted stent placement, resulting in a good angiographic result. After the procedure, there was a rapid recovery of regional kinetics but a slower normalization of the electrocardiographic morphology (Fig. 3). Comment Wellens‘ syndrome identifies a particular subtype of unstable angina characterized by the appearance of ischemic changes on the ECG,. The clinical risk assessment of this subgroup of patients with ACS, apparently having a more benign prognosis due to their definition as unstable angina with a low GRACE risk score, potentially has an evolution toward a large myocardial infarction if not promptly diagnosed.

A Narrative Review of Revascularization in Chronic Coronary Syndrome/Disease: Concepts and Misconceptions.

Ischemic heart disease represents a significant global burden of morbidity and mortality. While revascularization strategies are well defined in acute settings, there are uncertainties regarding chronic coronary artery disease treatment. Recent trials have raised doubts about the necessity of revascularization for "stable", chronic coronary syndromes or disease, leading to a shift towards a more conservative approach. However, the issue remains far from settled. In this narrative review, we offer a summary of the most pertinent evidence regarding revascularization for chronic coronary disease, while reflecting on less-often-discussed details of major clinical trials. The cumulative evidence available indicates that there can be a prognostic benefit from revascularization in chronic coronary syndrome patients, provided there is significant ischemia, as demonstrated by either imaging or coronary physiology. Trials that have effectively met this criterion consistently demonstrate a reduction in rates of spontaneous myocardial infarction, which holds both prognostic and clinical significance. The prognostic benefit of revascularization in patients with heart failure with reduced ejection fraction remains especially problematic, with a single contemporary trial favouring surgical revascularization. The very recent publication of a trial focused on revascularizing non-flow-limiting "vulnerable" plaques adds further complexity to the field. The ongoing debates surrounding revascularization in chronic coronary syndromes emphasize the importance of personalized strategies. Revascularization, added to the foundational pillar of medical therapy, should be considered, taking into account symptoms, patient preferences, coronary anatomy and physiology, ischemia tests and intra-coronary imaging.

Usability of myocardial work parameters in demonstrating myocardial involvement in INOCA patients.

Myocardial work (MW) is a novel echocardiographic modality, which has been shown to have diagnostic and prognostic values in patients with cardiovascular diseases, patients with obstructive coronary artery disease, in particular. However, only a handful of studies have examined the MW analysis in ischemia with nonobstructive coronary artery (INOCA) disease. This study, therefore, aimed to detect the early left ventricular involvement in INOCA patients diagnosed by an invasive coronary angiography performing the MW analysis. This study included a total of 119 patients with nonobstructive coronary artery disease diagnosed by invasive coronary angiography, who were checked for prior ischemia tests performing myocardial perfusion scintigraphy. Out of these 119 patients, 49 patients developed ischemia (i.e., ischemic group) diagnosed using cardiac single-photon emission computed tomography, whereas 70 patients did not (i.e., nonischemic group). The subjects were divided into three groups based on the global MW tertiles. The groups were compared in terms of the conventional, longitudinal strain, and MW findings by conducting echocardiographic examinations. The study subjects were divided into three groups based on the global constrictive work (GCW) value. The three groups were not statistically different in terms of the mean age of the patients (53.0 ± 12 vs. 52.4 ± 13.3 vs. 52.1 ± 12.3; p = 0.96). Furthermore, the three groups were not statistically different regarding the gender, height, weight, and laboratory parameters of the patients except albumin. There was no statistically difference among the tertiles of GCW groups in the measurements of cardiac chambers, LA diameter, interventricular septum, E wave, and A wave. Also, there was no statistical difference in tissue Doppler recordings. The parameters associated with MW were examined, three groups were not statistically different in terms of the global waste work (GWW) (116 ± 92, 122 ± 73, 135 ± 62, p = 0.52, respectively). In contrast, the three groups were different regarding the Global work index (GWI) (1716 ± 300, 1999 ± 130, 2253 ± 195, p < 0.001, respectively), GCW(1888 ± 206, 2298 ± 75, 2614 ± 155, p < 0.001, respectively), and Global work efficiency parameters (92.8 ± 3.6, 94.4 ± 3.2, 95.1 ± 1.8 p = 0.004, respectively). It was concluded that the MW parameters GCW and GWI may have been used for predicting INOCA in patients.

From chest pain to coronary functional testing: Clinical and economic impact of coronary microvascular dysfunction

BackgroundCoronary functional testing to formally diagnose coronary microvascular dysfunction (CMD) reduces cardiovascular events and alleviates angina. This study aims to investigate the extensive and complex journey that patients with CMD undergo, from the onset of chest pain to eventual diagnosis. MethodsData from the Coronary Microvascular Disease Registry (CMDR) were analyzed, including information on the date of first documentation of chest pain, number of non-invasive and invasive tests the patient underwent, emergency department visits, and hospitalizations. In addition, we estimated the total cost per patient. A total of 61 patients with CMD diagnosis were included in this analysis. ResultsMost patients in our cohort were older than 50 years of age. The median time from initial chest pain symptoms to diagnosis was 0.62 (interquartile range [IQR]: 0.06–2.96) years. During this period, patients visited the emergency department a median of 1.0 (IQR: 0.0–2.0) times. Diagnostic tests included 3.0 (IQR: 2.0–6.0) electrocardiograms, 3.0 (IQR: 0.0–6.0) high-sensitivity troponin tests, and 1.0 (IQR: 1.0–2.0) echocardiograms. Prior to diagnosis of CMD, 13 (21.3 %) patients had left heart catheterization without coronary functional testing. Non-invasive testing for ischemia was conducted in 43 (70.5 %) patients. Alternative non-cardiac diagnoses were given to 11 (18.0 %) patients during the diagnostic process, with referrals made to gastroenterology for 16 (26.2 %) and pulmonology for 10 (16.4 %) patients. The cost was almost $2000/patient. ConclusionTimely identification of CMD offers promising opportunities for prompt symptom alleviation, accompanied by reduced visits to the emergency department, cardiovascular testing, invasive medical procedures, and consequently reduced healthcare expenses.

Recovery Rates of Diagnostic Cardiac Procedural Volume in Oceania 1 Year Into COVID-19: The IAEA Non-Invasive Cardiology Protocol Survey on COVID-19 (INCAPS COVID 2)

The aim of this study was to assess the recovery rates of diagnostic cardiac procedure volumes in the Oceania Region, midway through the coronavirus disease 2019 (COVID-19) pandemic. A survey was performed comparing procedure volumes between March 2019 (pre-pandemic), April 2020 (during first wave of COVID-19 pandemic), and April 2021 (1 year into the COVID-19 pandemic). A total of 31 health care facilities within Oceania that perform cardiac diagnostic procedures were surveyed, including a mixture of metropolitan and regional, hospital and outpatient, public and private sites, as well as teaching and non-teaching hospitals. A comparison was made with 549 centres in 96 countries in the rest of the world (RoW) outside of Oceania. The total number and median percentage change in procedure volume were measured between the three timepoints, compared by test type and by facility. A total of 11,902 cardiac diagnostic procedures were performed in Oceania in April 2021 as compared with 11,835 pre-pandemic in March 2019 and 5,986 in April 2020; whereas, in the RoW, 499,079 procedures were performed in April 2021 compared with 497,615 pre-pandemic in March 2019 and 179,014 in April 2020. There was no significant difference in the median recovery rates for total procedure volumes between Oceania (-6%) and the RoW (-3%) (p=0.81). While there was no statistically significant difference in percentage recovery been functional ischaemia testing and anatomical coronary testing in Oceania as compared with the RoW, there was, however, a suggestion of poorer recovery in anatomical coronary testing in Oceania as compared with the RoW (CT coronary angiography -16% in Oceania vs-1% in RoW, and invasive coronary angiography-20% in Oceania vs-9% in RoW). There was no statistically significant difference in recovery rates in procedure volume between metropolitan vs regional (p=0.44), public vs private (p=0.92), hospital vs outpatient (p=0.79), or teaching vs non-teaching centres (p=0.73). Total cardiology procedure volumes in Oceania normalised 1 year post-pandemic compared to pre-pandemic levels, with no significant difference compared with the RoW and between the different types of health care facilities.

“The INOCA-IT: Rationale and design of a multicenter registry investigating ischemia in patients with non-obstructive coronary artery (INOCA) disease in Italy”

BackgroundIschemia with non-obstructive coronary artery (INOCA) disease is being progressively acknowledged as one of the pathophysiological mechanisms of chronic coronary syndrome (CCS) in an increasingly wide range of clinical pictures. Although the research has already begun to move towards a defined diagnostic pathway and a specific medical therapy for this disease, at present it remains a clinical challenge, especially if not thoroughly investigated. Methods and resultsThe INOCA IT Multicenter Registry RF-2019-12369486 is a prospective, multicentric, non-randomized, single-arm, open label clinical study which aims to evaluate the efficacy of a stratified diagnostic and therapeutic approach on adverse events prevention and symptom relief in Italian patients with INOCA disease. The study population includes patients with a clinical presentation of CCS for angina and/or positive stress test for myocardial ischemia and evidence of non-obstructive coronary artery disease (CAD) at coronary angiography. In these patients a complete invasive coronary physiology assessment is performed with the guidewire-based measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), followed by acetylcholine (ACh) spasm provocation test. On the basis of the results of coronary function testing, patients are stratified into different INOCA endotypes (coronary microvascular disease, vasospastic angina, microvascular spasm, non-cardiac chest pain) and given a tailored medical therapy in accordance with the latest scientific evidence. At one year follow-up the impact of such a target therapy on angina class and quality of life, as well as on cardiovascular adverse events (hospitalization and coronary revascularization) is evaluated. ConclusionsThe INOCA-IT Multicenter Registry will inform clinicians on sex-specific prevalence of INOCA in Italy and will show the impact of a stratified diagnostic and therapeutic approach on symptoms burden and prognosis of INOCA patients.

Predictors of non-obstructive coronary slow flow in poorly controlled type 2 diabetes mellitus: a cross-sectional study

BackgroundCoronary slow flow (CSF) can occur due to various factors, such as inflammation, small vessel disease, endothelial dysfunction, and inadequate glucose control. However, the exact pathological mechanisms behind CSF remain incompletely understood.The objective of this study was to identify the risk factors associated with slow coronary flow in individuals with Type 2 Diabetes Mellitus (T2DM) who have non-obstructive coronary artery disease (CAD) and experience CSF.MethodsWe conducted a prospective cohort study involving 120 patients with T2DM who were referred for invasive coronary angiography due to typical chest pain or inconclusive results from non-invasive tests for myocardial ischemia. Using a 2 × 2 design, we categorized patients into groups based on their glycemic control (adequate or poor) and the presence of CSF (yes or no), defined by a TIMI frame count > 27. All patients had non-obstructive CAD, characterized by diameter stenosis of less than 40%. We identified many variables associated with CSF.ResultsOur investigation revealed no significant differences in age, sex, family history of coronary artery disease, ECG ischemia abnormalities, or echocardiographic (ECHO) data between the groups. In patients with adequate glycemic control, hypertension increased the risk of CSF by 5.33 times, smoking by 3.2 times, while dyslipidemia decreased the risk by 0.142. Additionally, hematocrit increased the risk by 2.3, and the platelet-to-lymphocyte ratio (PLR) increased the risk by 1.053.Among patients with poor glycemic control, hematocrit increased the risk by 2.63, and the Neutrophil-to-Lymphocyte Ratio (NLR) by 24.6. Notably, NLR was positively correlated with glycemic control parameters in T2DM patients with CSF.ConclusionsIn T2DM patients with CSF, various factors strongly correlate with glycemic control parameters and can be employed to predict the likelihood of CSF. These factors encompass hypertension, smoking, increased body mass index (BMI), elevated platelet count, hematocrit, NLR, PLR, and C-reactive protein (CRP).Trial registrationRegistry: ZU-IRB (ZU-IRB#9419–3-4-2022), Registered on: 3 April 2022, Email: IRB_123@medicine.zu.edu.eg.

Intracoronary electrocardiogram detects coronary microvascular dysfunction and ischemia in patients with no obstructive coronary arteries disease

Coronary microvascular dysfunction (CMD) is the leading cause of ischemia with no obstructive coronary arteries disease (INOCA) disease. Diagnosis of CMD relies on surrogate physiological indices without objective proof of ischemia. Intracoronary electrocardiogram (icECG) derived hyperemic indices may accurately and objectively detect CMD and reversible ischemia in related territory. INOCA patients with proven ischemia by myocardial perfusion scan (MPS) and completely normal coronary arteries underwent simultaneous intracoronary electrophysiological (icECG) and physiological (intracoronary Doppler) assessment in all 3 coronary arteries during rest and under adenosine induced hyperemia. Sixty vessels in 21 patients were included in the final analysis. All patients had at least one vessel with abnormal CFR. 41 vessels had CMD (CFR < 2.5), of which 26 had increased microvascular resistance (structural CMD, HMR > 1.9 mmHg.cm-1.s) and 15 vessels had CMD (CFR < 2.5) with normal microvascular resistance (functional CMD, HMR <= 1.9 mmHg.cm-1.s). Only one-third of the patients (n = 7) had impaired CFR < 2.5 in all 3 epicardial arteries. Absolute ST shift between hyperemia and rest (∆ST) has shown the best diagnostic performance for ischemia (cut-off 0.10 mV, sensitivity: 95%, specificity: 72%, accuracy: 80%, AUC: 0.860) outperforming physiological indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002). In INOCA patients, CMD involves coronary artery territories heterogeneously. icECG can accurately detect CMD causing perfusion abnormalities in patients with INOCA outperforming physiological CMD markers, by demonstrating actual ischemia instead of predicting the likelihood of inducible ischemia based on violated surrogate thresholds of blunted flow reserve or increased minimum microvascular resistance. In 21 INOCA patients with coronary microvascular dysfunction (CMD) and myocardial perfusion scan proved ischemia, hyperemic indices of intracoronary electrocardiogram (icECG) have accurately detected vessel-specific CMD and resulting perfusion abnormalities & ischemia, outperforming invasive hemodynamic indices. Absolute ST shift between hyperemia and rest (∆ST) has shown the best classification performance for ischemia in no Obstructive Coronary Arteries (AUC: 0.860) outperforming Doppler derived CMD indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002).icECG can be used to diagnose CMD causing perfusion defects by demonstrating actual reversible ischemia at vessel-level during the initial CAG session, obviating the need for further costly ischemia tests. GOV: NCT05471739.

Artificial intelligence to improve ischemia prediction in Rubidium Positron Emission Tomography—a validation study

BackgroundPatients are referred to functional coronary artery disease (CAD) testing based on their pre-test probability (PTP) to search for myocardial ischemia. The recommended prediction tools incorporate three variables (symptoms, age, sex) and are easy to use, but have a limited diagnostic accuracy. Hence, a substantial proportion of non-invasive functional tests reveal no myocardial ischemia, leading to unnecessary radiation exposure and costs. Therefore, preselection of patients before ischemia testing needs to be improved using a more predictive and personalised approach.AimsUsing multiple variables (symptoms, vitals, ECG, biomarkers), artificial intelligence–based tools can provide a detailed and individualised profile of each patient. This could improve PTP assessment and provide a more personalised diagnostic approach in the framework of predictive, preventive and personalised medicine (PPPM).MethodsConsecutive patients (n = 2417) referred for Rubidium-82 positron emission tomography were evaluated. PTP was calculated using the ESC 2013/2019 and ACC 2012/2021 guidelines, and a memetic pattern–based algorithm (MPA) was applied incorporating symptoms, vitals, ECG and biomarkers. Five PTP categories from very low to very high PTP were defined (i.e., < 5%, 5–15%, 15–50%, 50–85%, > 85%). Ischemia was defined as summed difference score (SDS) ≥ 2.ResultsIschemia was present in 37.1%. The MPA model was most accurate to predict ischemia (AUC: 0.758, p < 0.001 compared to ESC 2013, 0.661; ESC 2019, 0.673; ACC 2012, 0.585; ACC 2021, 0.667). Using the < 5% threshold, the MPA’s sensitivity and negative predictive value to rule out ischemia were 99.1% and 96.4%, respectively. The model allocated patients more evenly across PTP categories, reduced the proportion of patients in the intermediate (15–85%) range by 29% (ACC 2012)–51% (ESC 2019), and was the only tool to correctly predict ischemia prevalence in the very low PTP category.ConclusionThe MPA model enhanced ischemia testing according to the PPPM framework:The MPA model improved individual prediction of ischemia significantly and could safely exclude ischemia based on readily available variables without advanced testing (“predictive”).It reduced the proportion of patients in the intermediate PTP range. Therefore, it could be used as a gatekeeper to prevent patients from further unnecessary downstream testing, radiation exposure and costs (“preventive”).Consequently, the MPA model could transform ischemia testing towards a more personalised diagnostic algorithm (“personalised”).