Impaired Myocardial Perfusion Research Articles

Abstract 11377: Takotsubo Syndrome Among Patients With Spontaneous Coronary Artery Dissection: A Report of the ISCAD Registry

Introduction: Association of takotsubo syndrome (TTS) with spontaneous coronary artery dissection (SCAD) has been described previously. Characteristics and in-hospital prognosis of SCAD patients with concomitant TTS remain unclear. Methods: Patients with angiography-confirmed SCAD were selected from the iSCAD Registry and underwent core lab adjudication of left ventriculography (LVG) and coronary angiography including assessment of SCAD lesion characteristics, TIMI Flow Grade (TFG), and TIMI Myocardial Perfusion Grade (TMPG). Classic TTS was defined as wall motion abnormality (WMA) presenting as apical ballooning. TTS variants were defined as non-apical WMA discordant to dissected coronary territory with apical sparing. In-hospital event was defined as composite of recurrent myocardial infarction (MI), cerebrovascular accident, heart failure requiring diuretics, or new arrhythmia. Results: On blinded review of LVG from 216 patients, TTS was identified in 38 (17.6%) patients (classic, midventricular, and focal pattern: 86.8%, 2.6%, and 10.5%, respectively). There was no significant difference in age, cardiovascular risk factors, history of anxiety or depression, recreational substance use, emotional or physical stressors, extracoronary vascular abnormalities, peak troponin levels, or TFG of dissected arteries between TTS and non-TTS groups. TTS patients were more likely to present with ST-segment elevation MI (47.4% vs 27.5%; p=0.02), left anterior descending artery (LAD) involvement (89.5% vs 59.0%; p=0.0004), and TMPG < 3 (68.4% vs 48.3%; p=0.02) compared to non-TTS patients. TTS patients had a greater risk of in-hospital events (32.4% vs 15.1%; p=0.01), mainly attributed to new arrhythmia (27.0% vs 6.5%; p=0.0009) and heart failure (11.4% vs 3.0%; p=0.03). Conclusion: Coexistence of TTS and SCAD was associated with ST-elevation MI, LAD involvement, impaired microvascular myocardial perfusion, and adverse in-hospital outcomes.

Abstract 11488: Comparative Effectiveness of PET and SPECT Myocardial Perfusion Imaging for Identification of Low-Risk Patients With Cardiometabolic Disease

Introduction: The epidemiology of coronary artery disease (CAD) has shifted, with increasing cardiometabolic (CM) disease and decreasing obstructive CAD in patients referred for myocardial perfusion imaging (MPI). Coronary microvascular dysfunction, defined as impaired coronary flow reserve (CFR) by positron emission tomography (PET), has emerged as a key mediator of risk. Our objective was to assess whether CFR provides additive value to identify low-risk CM disease patients compared with single-photon emission computed tomography (SPECT) MPI. Methods: We retrospectively studied patients with CM disease (obesity, diabetes, or chronic kidney disease (CKD) stage ≥3) and without known CAD referred for PET or SPECT MPI at our center from 2006 to 2020. Annualized all-cause and cardiac mortality was determined from death certificates, and propensity-matched low-risk PET and SPECT patients were compared using Poisson and Cox regression. Results: CM disease was prevalent in consecutive MPI referrals without CAD including obesity (N=8869), diabetes (N=4896) and CKD (N=3555), and higher among PET MPI (p <0.001). Prevalence of summed stress score (SSS) >3 reflecting obstructive CAD was low (12%, 15% and 16%). Conversely, prevalence of CFR <2 was high (52%, 61% and 69%), reflecting impaired myocardial perfusion. In adjusted hazard analysis, normal MPI was associated with lower risk of all-cause and cardiac death (p <0.001). Normal PET (SSS ≤3 and CFR >2) was associated with lower all-cause death compared to normal SPECT (Figure, A). Normal PET and SPECT identified low-risk (<1%/year cardiac death) patients with obesity and diabetes, however those with CKD remained moderate-risk (1-3%/year) (Figure, B). Conclusion: CM disease is common among patients without CAD referred for MPI. Normal PET and SPECT MPI identify a low-risk group for obesity and diabetes, but not CKD. PET with CFR has additive prognostic utility to identify low-risk individuals compared to SPECT.

Quantitative myocardial blood flow as a prognostic marker for cardiovascular outcomes in patients with Type 2 Diabetes Mellitus: a multicentre study

Abstract Introduction: Patients with Type 2 Diabetes Mellitus (T2DM) are at increased risk of cardiovascular disease, including epicardial coronary heart disease, silent myocardial infarction (MI), and coronary microvascular dysfunction (CMD) [1]. All of these can be assessed and quantified using cardiac magnetic resonance (CMR), including most recently quantitative myocardial blood flow (MBF). We aimed to determine the prognostic relevance of MBF in patients with T2DM and test the hypothesis that impaired stress MBF and myocardial perfusion reserve (MPR) have independent prognostic value over standard clinical and imaging parameters. Methods A 4-centre study of patients with T2DM who underwent quantitative perfusion assessment using CMR. Diagnosis of T2DM was based on Hba1c >48mmol/l or a known diagnosis of T2DM. Image analysis was performed automatically using an artificial intelligence approach deriving global MBF and MPR [2]. Cox proportional hazard models adjusting for comorbidities and CMR parameters sought associations between stress MBF and MPR with death and major adverse cardiovascular events (MACE), including MI, non-fatal stroke, heart failure hospitalisation and death. Results A total of 630 patients with T2DM were included with a median follow-up of 722 days (interquartile range 493) days. There were 27 (4.3%) deaths and 76 MACE events in 62 (12.1%) patients. Patient data was represented into groups depending on threshold stress MBF values of 1.94ml/g/min and MPR thresholds of 1.96 using validated data from invasive coronary physiology [3]. Patient demographics and CMR data are seen in table 1. Kaplan-Meier curves are seen in figure 1. Stress MBF was associated with mortality and MACE after adjusting for age, LV ejection fraction and HbA1c. The stress MBF adjusted hazard ratios for all cause death and death and MACE were 0.35 (95% CI, 0.13–0.95, P=0.04) and 0.54 (95% CI, 0.30–0.96, P=0.04), respectively. MPR was not significantly associated with death and MACE after adjusting for age, LV ejection fraction and HbA1c; hazard ratio for all cause death and death and MACE was 0.83 (95% CI, 0.41–1.69, P=0.60) and 0.81 (95% CI, 0.53–1.23, p=0.32) respectively. Conclusion In patients with T2DM, reduced stress MBF measured automatically inline using artificial intelligence quantification of cardiovascular magnetic resonance perfusion mapping provides a strong, independent predictor of adverse cardiovascular outcome. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): 1. REC ID 14/EE/0007 (Barts Heart Centre funding). 2. For PREDICT (Leicester data) ethical approval was provided by the UK Health Research Authority Research Ethics Committee (reference 17/WM/0192). 3. MATCH Study, Leeds - British Heart Foundation - 17/YH/0300. 4. LEAN-DM, Leeds - British Heart Foundation - 18/YH/01685. CEED, Leeds: British Heart Foundation - REC reference - 18/YH/0190

Radiomics-based analysis by machine learning techniques improves characterization of functionally significant coronary lesions

Abstract Background Computed Tomography Coronary Angiography (CTCA) is an effective non-invasive imaging modality for anatomo-functional assessment of coronary artery disease (CAD). Radiomics features have been used for diagnosis or outcome prediction, however, their potential value for characterizing flow limiting coronary lesions has not been explored. Purpose To assess whether application of novel radiomics and machine learning (ML) techniques on CTCA derived datasets improves characterization of functionally significant coronary lesions. Methods Consecutive patients with stable chest pain and intermediate pre-test likelihood for CAD, who underwent CTCA and PET-or SPECT-Myocardial Perfusion Imaging (MPI) respectively, were prospectively evaluated and included in the analysis. PET-MPI was considered abnormal when >1 contiguous segments showed both stress Myocardial Blood Flow ≤2.3mL/g/min and Myocardial Flow Reserve (MFR) ≤2.5 for 15O-water or <1.79 mL/g/min and ≤2.0 for 13N-ammonia respectively. Defect reversibility (DR) was defined as a summed difference score (SDS) between stress and rest images ≥2. CTCA and functional images were fused to assign each myocardial segment to the pertinent coronary territory. Stenosis severity, plaque characteristics and radiomic plaque features were assessed in the total length of the 3 main coronary vessels. In total, 1765 features were extracted from each vessel and a feature reduction and model creation pipeline was constructed [Figure 1]. Two separate datasets: a) coronary stenosis (≥50%) + plaque characteristics and b) coronary stenosis (≥50%) + plaque characteristics + radiomics were formulated and compared in terms of AUCs accordingly. Results A total of 292 coronary vessels (140 with corresponding PET-MPI data and 152 with SPECT MPI data) were analysed. Plaque burden and stenosis severity were the only independent predictors of impaired myocardial perfusion on PET-MPI, with an AUC = 0.749, (95% CI: 0.658–0.826). Stenosis severity, kurtosis, contrast, interquartile range and entropy were predictors of an abnormal PET-MPI result and their combination resulted in an AUC = 0.854, (95% CI: 0.775–0.914). The difference between the 2 models was statistically significant (p-diff: 0.02, 95% CI: 0.0165–0.194). Stenosis severity was the only predictor of a DR on SPECT-MPI, AUC = 0.624 (95% CI: 0.542–0.702). Small Dependence High Gray Level Emphasis, Cluster Prominence, Region Length, wavelet Median and square Median were predictors of a positive SPECT result, with AUC = 0.816, (95% CI: 0.745–0.875). The difference between the two models was statistically significant (p-diff: 0.006, 95% CI: 0.152–0.329) Conclusion Radiomic futures can be combined with anatomical and morphological characteristics of coronary lesions in CTCA imaging and provide valuable complementary information for characterizing functionally significant coronary lesions. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2022 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR)

Intracoronary pharmacological therapy versus aspiration thrombectomy in STEMI (IPAT-STEMI): A systematic review and meta-analysis of randomized trials.

BackgroundThrombus load in STEMI patients remains a challenge in practice. It aggravates coronary obstruction leading to impaired myocardial perfusion, worsened cardiac function, and adverse clinical outcomes. Various strategies have been advocated to reduce thrombus burden.ObjectivesThis meta-analysis aimed to evaluate the effectiveness of intracoronary-administered thrombolytics or glycoprotein IIb/IIIa inhibitors (GPI) in comparison with aspiration thrombectomy (AT) as an adjunct to percutaneous coronary intervention (PCI) among patients presenting with ST-segment elevation myocardial infarction (STEMI).MethodsA comprehensive literature search for randomized trials that compared intracoronary-administered thrombolytics or GPI with AT in STEMI patients who underwent PCI, was conducted using various databases (e.g., MEDLINE, EMBASE, CENTRALE). Primary outcome was procedural measures (e.g., TIMI flow grade 3, TIMI myocardial perfusion grade (TMPG) 3, Myocardial blush grade (MBG) 2/3, ST-segment resolution (STR)).ResultsTwelve randomized trials enrolled 1,466 patients: 696 were randomized to intracoronary-administered pharmacological interventions and 553 to AT. Patients randomized to PCI alone were excluded. Thrombolytics significantly improved TIMI flow grade 3 (odds ratio = 3.71, 95% CI: 1.85–7.45), complete STR (odds ratio = 3.64, 95% CI: 1.60–8.26), and TMPG 3 (odds ratio = 5.31, 95% CI: 2.48–11.36). Thrombolytics significantly reduced major adverse cardiovascular events (MACE) (odds ratio = 0.29, 95% CI: 0.13–0.65) without increasing bleeding risk. Trial sequential analysis assessment confirmed the superiority of thrombolytics for the primary outcome. Intracoronary GPI, either alone or combined with AT, did not improve procedural or clinical outcomes.ConclusionsCompared with AT, intracoronary-administered thrombolytics significantly improved myocardial perfusion and MACE in STEMI patients.

Additive Effects of Obesity on Myocardial Microcirculation and Left Ventricular Deformation in Essential Hypertension: A Contrast-Enhanced Cardiac Magnetic Resonance Imaging Study.

ObjectiveThe combination of hypertension and obesity is a major cause of cardiovascular risk, and microvascular changes and subclinical dysfunction should be considered to illustrate the underlying mechanisms and early identification, thereby developing targeted therapies. This study aims to explore the effect of obesity on myocardial microcirculation and left ventricular (LV) deformation in hypertensive patients by cardiac magnetic resonance (CMR).MethodsThis study comprised 101 hypertensive patients, including 54 subjects with a body mass index (BMI) of 18.5–24.9 kg/m2 and 47 subjects with a BMI ≥25 kg/m2, as well as 55 age- and sex-matched controls with a BMI of 18.5–24.9 kg/m2. Myocardial perfusion indicators [upslope, time to maximum signal intensity (TTM), maximum signal intensity (Max SI)] and LV strains [radial, circumferential, and longitudinal global peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR)] were measured.ResultsUpslope was numerically increased in obese patients but statistically decreased in non-obese patients compared with controls. Longitudinal PS deteriorated significantly and gradually from controls to non-obese and obese hypertensive patients. Longitudinal PSSR and PDSR were significantly decreased in obese hypertensive patients compared with the other two groups. BMI was associated with upslope (β = −0.136, P < 0.001), Max SI (β = −0.922, P < 0.001), longitudinal PSSR (β = 0.018, P < 0.001), and PDSR (β = −0.024, P = 0.001). Myocardial perfusion was independently associated with longitudinal PSSR (TTM: β = 0.003, P = 0.017) and longitudinal PDSR (upslope: β = 0.067, P = 0.020) in hypertension.ConclusionObesity had adverse effects on microvascular changes and subclinical LV dysfunction in hypertension, and BMI was independently associated with both myocardial perfusion and LV deformation. Impaired myocardial perfusion was independently associated with subclinical LV dysfunction in hypertension.

The Relationship Between ST-Segment Depression in Lead aVR and Coronary Microvascular Function in Acute Inferior Myocardial Infarction

Aim: The aim of this study was to investigate the relationship between ST-segment depression in the aVR lead and coronary microvascular function in acute inferior myocardial infarction undergoing primary percutaneous intervention.&#x0D; Methods: 287 patients with inferior myocardial infarction confirmed by coronary angiography were divided into two groups with and without ST-segment depression in lead aVR ≥ 0.1 mV on the 12 lead ECG. Electrocardiographic recordings were made for the evaluation of ST-segment resolution before and after primary PCI. Angiographic assessment in the infarct-related artery was performed by using the myocardial blush grade and thrombolysis in myocardial infarction flow. &#x0D; Results: Overall, 51 of 287 patients had ST-segment depression in lead aVR. The number of patients with RCA-induced infarction was higher in the group with ST-segment depression in lead aVR. RCA involvement was present in 44 patients. Peak troponin was higher in the group with ST-segment depression in lead aVR compare to the other group (P &lt;0.001). The MBG was more impaired, and the STR was less regressed in patients with ST depression in lead aVR (p&lt;0,001). The ejection fraction of patients with ST-segment depression in lead aVR was lower.&#x0D; Conclusion: We found that ST-segment depression in lead aVR was associated with impaired myocardial perfusion in patients with inferior myocardial infarction.

Aortic diastolic pressure decay explains sex-related differences in the subendocardial viability ratio: the Wakuya study.

Coronary heart disease is the leading cause of mortality in women. Despite a higher risk of heart failure after the first myocardial infarction in women compared with men, the sex-specific mechanisms are unknown. We hypothesized that myocardial ischemia is attributable to sex-related diastolic alterations in the central hemodynamics. We investigated the subendocardial viability ratio (myocardial oxygen supply/demand) and aortic diastolic pressure decay index in 962 apparently healthy adults (mean age, 56 ± 10 years). Using noninvasive applanation tonometry, the subendocardial viability ratio, aortic diastolic pressure decay index, and aortic augmentation index were estimated in all participants. The aortic diastolic pressure decay index was quantified by fitting an exponential curve: P(t) = P0e-λt (λ, decay index; P0, end-systolic pressure; t, time from end-systole). Women showed a significantly higher aortic diastolic pressure decay index, even after adjusting for age, hypercholesterolemia, and diabetes, and a significantly lower subendocardial viability ratio than men (P < 0.001). Analysis demonstrated a mediating effect of the aortic decay index on the sex-related differences in the subendocardial viability ratio (71%), despite different effects of the augmentation index (5%). These results suggest that the predisposition of women to coronary heart disease is more likely attributable to impaired myocardial perfusion caused by accelerated aortic diastolic pressure decay, rather than increased myocardial load due to augmented aortic systolic pressure.

Impaired subendocardial perfusion in patients with metabolic syndrome.

BackgroundMetabolic Syndrome (MS) is associated to vascular damage, increased arterial stiffness, and impaired myocardial perfusion. Subendocardial viability ratio (SEVR) is a noninvasive estimation of myocardial workload, oxygen supply, and perfusion. The aim of the study was to describe the relation between arterial stiffness, SEVR, and cardio-metabolic risk factors.MethodsA cohort of 55 patients, aged 59.9 ± 10.8 years, was studied; 28 subjects (50.9%) had metabolic syndrome. All patients underwent a clinical evaluation and blood venous sampling, to assess glico-lipid profile. Applanation tonometry was performed, to obtain pulse wave analysis and SEVR values.ResultsIn the overall study population, SEVR showed negative associations with mean (r = −0.301; p = 0.026) and systolic (borderline relation, r = −0.257; p = 0.058) arterial pressure. Metabolic syndrome patients presented lower level of SEVR (p = 0.012), even after adjusting for age, sex, and mean arterial pressure (p = 0.040). Subdividing the study population by the number of metabolic syndrome components, SEVR significantly decreased as the number of Metabolic Syndrome components increased (p for trend 0.005). In a logistic backward regression analysis, both metabolic syndrome and mean arterial pressure resulted significant predictors of SEVR, accounting for 18% of variance.ConclusionThe reduced SEVR in metabolic syndrome patients could be an important pathophysiological determinant of the increased cardiovascular risk.

Intracoronary pharmacological therapy versus aspiration thrombectomy in patients presenting with ST-segment elevation myocardial infarction (IPAT-STEMI): a systematic review and meta-analysis

Abstract Background Large thrombus load remains a challenge in the interventional cardiology practice. It precludes direct stent implementation and aggravates coronary obstruction leading to impaired myocardial perfusion, worsened cardiac function, and adverse clinical outcomes. Thus, various strategies have been advocated such as aspiration thrombectomy (AT), and/or localized or intracoronary (IC) treatment with thrombolytic agents and/or glycoprotein IIb/IIIa inhibitors (GPI). Purpose To evaluate the effectiveness of IC-administered pharmacological agents alone or combined with AT compared with AT alone as an adjunct to percutaneous coronary intervention (PCI) in STEMI patients with large thrombus burden. Methods The method was conducted according to the Cochrane Handbook for Systematic Reviews and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A systematic search strategy using MEDLINE, EMBASE, CENTRALE, Scopus, ProQuest Public Health, Web of Science databases was performed on February 22, 2020 and updated on February 13, 2021. Eligible trials were randomized controlled trials (RCT) comparing IC-administered thrombolytic agents and/or GPI with or without AT to AT alone in patients presenting with STEMI who underwent PCI. The primary outcomes included coronary reperfusion indices e.g., thrombolysis in myocardial infarction (TIMI) flow grade 3 (G3), TIMI myocardial perfusion grade (TMPG) 3, Myocardial blush grade (MBG) 2/3, ST-segment resolution (STR). Others included clinical outcomes e.g., major adverse cardiovascular events (MACE). Results Twelve RCT enrolled 1,466 patients were included in the final analysis. The trials were categorized into 3 groups: (1) Thrombolytics [4 RCT], (2) GPI [3 RCT], and (3) GPI+AT [7 RCT]. Groups 2 and 3 included two mutual studies with multiple arms. In comparison with AT alone, thrombolytic therapy, as presented in four RCT, significantly improved TIMI flow G3 (OR = 3.71, 95% CI: 1.85–7.45; P overall effect = 0.0002; heterogeneity = 0%), complete STR (OR = 3.64, 95% CI: 1.60–8.26; P overall effect = 0.002; heterogeneity = 34%) and MACE (OR = 0.47, 95% CI: 0.22–0.99; P overall effect = 0.05; heterogeneity = 46%), but not TMPG 3. Pooling the data of the two studies with similar intervention i.e., thrombolytics + AT further refined the results with statistical improvement of TMPG 3 as well (OR = 5.44, 95% CI: 2.61- 11.34; P overall effect &amp;lt;0.ehab724.211201; heterogeneity = 0%) (Fig. 1). Pooled results for GPI and GPI+AT groups did not show statistical improvement in TIMI flow G3, MBG 2/3, nor complete STR (Fig. 2). Conclusion The findings of this meta-analysis showed that IC-administered thrombolytic agents improved myocardial reperfusion and MACE compared with AT alone in STEMI patients undergoing PCI. Funding Acknowledgement Type of funding sources: None.

Coronary artery spasm and impaired myocardial perfusion in patients with ANOCA: Predictors from a multimodality study using stress CMR and acetylcholine testing

BackgroundFunctional coronary disorders such as coronary spasm and microvascular dysfunction (including microvascular spasm and impaired microvascular dilatation) are frequent findings among patients with angina and non-obstructed coronary arteries (ANOCA). In this study, we investigated a potential association of coronary spasm and myocardial perfusion abnormalities as well as predictors of such functional coronary disorders in ANOCA patients using a multimodality diagnostic strategy including adenosine stress CMR and intracoronary acetylcholine testing. MethodsWe enrolled 129 patients with ANOCA who underwent acetylcholine testing and adenosine stress perfusion CMR. Patients were allocated to 3 groups according to their spasm testing result with regard to standardized COVADIS criteria: 1) epicardial spasm, 2) microvascular spasm, and 3) no spasm. The myocardial perfusion reserve index (MPRI) was semiquantitatively determined from adenosine stress perfusion CMR. Multivariate regression analyses were performed to identify predictors of coronary functional disorders. ResultsPatients with epicardial spasm had lower MPRI than patients without, whereas MPRI was preserved in patients with microvascular spasm. Multivariate analyses revealed age, previous myocardial infarction, LVEF and epicardial spasm as independent predictors of diminished MPRI, whereas previous PCI was associated with epicardial spasm, and female sex was a strong predictor of microvascular spasm. ConclusionsOur results demonstrate coexistence of different functional coronary disorder endotypes involving the macro- and microvascular level of the coronary circulation in patients with ANOCA. We demonstrate that epicardial spasm is associated with diminished myocardial perfusion reserve and report further predictors of coronary functional disorders.

Reduced nitric oxide bioavailability impairs myocardial oxygen balance during exercise in swine with multiple risk factors

In the present study, we tested the hypothesis that multiple risk factors, including diabetes mellitus (DM), dyslipidaemia and chronic kidney disease (CKD) result in a loss of nitric oxide (NO) signalling, thereby contributing to coronary microvascular dysfunction. Risk factors were induced in 12 female swine by intravenous streptozotocin injections (DM), a high fat diet (HFD) and renal artery embolization (CKD). Female healthy swine (n = 13) on normal diet served as controls (Normal). After 5 months, swine were chronically instrumented and studied at rest and during exercise. DM + HFD + CKD swine demonstrated significant hyperglycaemia, dyslipidaemia and impaired kidney function compared to Normal swine. These risk factors were accompanied by coronary microvascular endothelial dysfunction both in vivo and in isolated small arteries, due to a reduced NO bioavailability, associated with perturbations in myocardial oxygen balance at rest and during exercise. NO synthase inhibition caused coronary microvascular constriction in exercising Normal swine, but had no effect in DM + HFD + CKD animals, while inhibition of phosphodiesterase 5 produced similar vasodilator responses in both groups, indicating that loss of NO bioavailability was principally responsible for the observed coronary microvascular dysfunction. This was associated with an increase in myocardial 8-isoprostane levels and a decrease in antioxidant capacity, while antioxidants restored the vasodilation to bradykinin in isolated coronary small arteries, suggesting that oxidative stress was principally responsible for the reduced NO bioavailability. In conclusion, five months of combined exposure to DM + HFD + CKD produces coronary endothelial dysfunction due to impaired NO bioavailability, resulting in impaired myocardial perfusion at rest and during exercise.

Myocardial Perfusion Defects in Hypertrophic Cardiomyopathy Mutation Carriers.

BackgroundImpaired myocardial blood flow (MBF) in the absence of epicardial coronary disease is a feature of hypertrophic cardiomyopathy (HCM). Although most evident in hypertrophied or scarred segments, reduced MBF can occur in apparently normal segments. We hypothesized that impaired MBF and myocardial perfusion reserve, quantified using perfusion mapping cardiac magnetic resonance, might occur in the absence of overt left ventricular hypertrophy (LVH) and late gadolinium enhancement, in mutation carriers without LVH criteria for HCM (genotype‐positive, left ventricular hypertrophy‐negative).Methods and ResultsA single center, case‐control study investigated MBF and myocardial perfusion reserve (the ratio of MBF at stress:rest), along with other pre‐phenotypic features of HCM. Individuals with genotype‐positive, left ventricular hypertrophy‐negative (n=50) with likely pathogenic/pathogenic variants and no evidence of LVH, and matched controls (n=28) underwent cardiac magnetic resonance. Cardiac magnetic resonance identified LVH‐fulfilling criteria for HCM in 5 patients who were excluded. Individuals with genotype‐positive, left ventricular hypertrophy‐negative had longer indexed anterior mitral valve leaflet length (12.52±2.1 versus 11.55±1.6 mm/m2, P=0.03), lower left ventricular end‐systolic volume (21.0±6.9 versus 26.7±6.2 mm/m2, P≤0.005) and higher left ventricular ejection fraction (71.9±5.5 versus 65.8±4.4%, P≤0.005). Maximum wall thickness was not significantly different (9.03±1.95 versus 8.37±1.2 mm, P=0.075), and no subject had significant late gadolinium enhancement (minor right ventricle‒insertion point late gadolinium enhancement only). Perfusion mapping demonstrated visual perfusion defects in 9 (20%) carriers versus 0 controls (P=0.011). These were almost all septal or near right ventricle insertion points. Globally, myocardial perfusion reserve was lower in carriers (2.77±0.83 versus 3.24±0.63, P=0.009), with a subendocardial:subepicardial myocardial perfusion reserve gradient (2.55±0.75 versus 3.2±0.65, P=<0.005; 3.01±0.96 versus 3.47±0.75, P=0.026) but equivalent MBF (2.75±0.82 versus 2.65±0.69 mL/g per min, P=0.826).ConclusionsRegional and global impaired myocardial perfusion can occur in HCM mutation carriers, in the absence of significant hypertrophy or scarring.

The feasibility of SPECT CZT measurement of myocardial blood flow and reserve in patients with acute coronary syndrome: comparison with cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is currently of interest in terms of diagnostic and treatment strategy. The diagnosis of MINOCA has been included in the STEMI guidelines of the European Society of Cardiology. However, there is lack of data regarding the relationship between myocardial damage according to cardiac magnetic resonance (CMR) and myocardial blood flow (MBF), myocardial flow reserve (MFR) obtained by dynamic SPECT. Purpose. To elucidate impairment of myocardial perfusion, MBF and MFR in patients with MINOCA. Methods. The study included 31 patients (21 men, age 62(56;70) years) with ASC. According to electrocardiography, cardiac biomarkers, invasive coronary angiography two groups were identified: with non-obstructive coronary arteries MINOCA (n = 10); MICAD (n = 21). Within 7-14 days after admission to the hospital all patients underwent dynamic SPECT on CZT gamma-camera with the assessment of standard indices of myocardial perfusion (SSS, SRS, SDS) and quantitative parameters (stress/rest myocardial blood flow (s/r MBF), myocardial flow reserve (MFR)). All patients underwent CMR with late gadolinium enhancement as well. Infarct size (IS), microvascular obstruction (MVO) and myocardial edema size (ME) were evaluated. Results. SSS and SRS differed significantly (p &amp;lt; 0.05) in MINOCA and MICAD patients: MINOCA: SSS 5.0(3.0;5.0), SRS 2.0(1.0;3.0); MICAD: SSS 9.0(5.0;13.0), SRS 6.0(3.0;11.0). However, SDS did not differ significantly in these two groups 2.5(1.0;4.0) vs 4.0(2.0;5.0). Moreover MINOCA patients in comparison with those with MIACD had higher values of quantitative parameters (p &amp;lt; 0.05): sMBF 2.02 (1.71;2.37) vs 0.86 (0.72;1.02) ml/min/g, rMBF 0.68 (0.66;0.86) vs 0.49 (0.4;0.57) ml/min/g, MFR 2.61 (2.23;3.14) vs 1.67 (1.1;1.9), respectively. Based on CMR, a total of 93 left ventricular vessel territories were analyzed. A total of 36(39%) vessel territories were considered as having acute myocardial injury (5 in MICAD, 31 in MINOCA). In patients with MICAD the values of IS, ME were significantly higher as compared to those with MINOCA (IS: 19.4(10.4;29.7)% vs1.8(0.0;6.9)%, ME: 19.5(12.0;30.0)% vs 3.0(0.0;12.0)% - p &amp;lt; 0.01). Based on regional analysis sMBF and MFR were significantly lower in vessel territories considering as CMR positive compared to those without MR signs of myocardial injury: regional sMBF 0.98(0.73;1.79) vs 1.33(0.94;2.08); regional MFR 0.58(0.43;0.9) vs 0.71(0.57;0.88), respectively. Conclusion. SPECT CZT is feasible in identifying both global and regional disturbances of myocardial blood flow and reserve in patients with acute coronary syndrome. MINOCA patients are characterized by mild reduction of myocardial blood flow and perfusion assessed visually and quantitatively. Therefore despite the absence of obstructive coronary artery lesion this group of patients has more pronounced risk of cardiac events and need more aggressive observation and treatment.

High residual platelet aggregation in patients with coronary artery disease: a new methodological approach to detection

Aim. To develop a new methodological approach to assessment of collagen-induced platelet aggregation in patients with coronary artery disease (CAD) and to determine the quality of various methods for detecting high residual platelet reactivity (HRPR) to predict the risk of myocardial perfusion disturbance. Materials and methods. 36 patients (10 men and 26 women) aged 41–83 years and having stable CAD were examined. All patients had been undergoing continuous antiaggregation therapy for 6 months. We evaluated platelet aggregation using a laser analyzer with collagen as an aggregation inducer by the standard method 1 and our own patented method 2. The degree of platelet aggregation (%) and the size of aggregates in relative units (r.u.) in platelet-rich plasma were estimated. Myocardial perfusion scintigraphy with 99mTc-methoxy-isobutylisonitrile was performed according to a two-day stress-rest protocol. The summed stress score (SSS) values were used for analysis. SSS &lt; 4 was regarded as normal myocardial perfusion. Results . The degree of platelet aggregation according to method 1 was 12 (5; 64)%, the aggregate size was 3 (2; 7) r.u. The degree of platelet aggregation according to method 2 was 44 (13; 78)%, and the aggregate size was 5 (4; 8) r.u. Method 2 allowed to diagnose the presence of myocardial ischemia with an aggregation degree ≥ 44.9% with sensitivity of 84% and specificity of 92% (area under the curve (AUC) = 0.89; p &lt; 0.0001; odds ratio (OR) 2.18; 95% confidence interval (CI) 0.57–0.98) and an increase in aggregate size ≥ 4.80 r.u. with sensitivity of 84% and specificity of 84% (AUC = 0.95; p &lt; 0.00001; OR 5.83; 95% CI 0.72–0.99). Conclusion. In patients with CAD, detection of high rates of collagen- induced platelet aggregation using the patented technique is associated with the risk of impaired myocardial perfusion. The developed new methodological approach to detection of HRPR allowed to determine high risk of atherothrombotic complications in additional 22% of the examined patients.

Clinical and imaging predictors of impaired myocardial perfusion in symptomatic patients after percutaneous coronary intervention: insights from dynamic CT myocardial perfusion imaging.

We aimed to investigate the relationship between baseline clinical characteristics and postprocedural myocardial perfusion as determined by dynamic computed tomography myocardial perfusion imaging (CT-MPI). We retrospectively included consecutive symptomatic post percutaneous coronary intervention (PCI) patients, who underwent dynamic CT-MPI + coronary CT angiography (CCTA) and who were revealed to have patent stents on previously revascularized lesions. Myocardial blood flow (MBF) was measured for stented territories and reference territories. Various baseline clinical and angiographic parameters were tested for the association with reduced MBF of stented territories. A total of 81 patients with 96 stented vessels were included in the analysis. The mean effective doses of radiation for the whole integrated CT protocol (calcium score + dynamic CT-MPI + CCTA) was 4.89±1.14 (2.58-6.93) mSv. Overall, 49 stented vessels had reduced MBF (75.3±17.2 mL/100 mL/min) within related territories, whereas 47 stented vessels had normal MBF (138.6±20.5 mL/100 mL/min). Peak levels of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), high-sensitivity C-reactive protein (hs-CRP), and glucose were significantly higher, while preprocedural thrombolysis in myocardial infarction (TIMI) flow grade was lower in participants with reduced MBF of stented territories. Acute myocardial infarction (AMI) also predominantly presented in participants with decreased MBF after revascularization. According to multivariate analysis, peak hs-cTnI level was the strongest predictor [adjusted hazard ratio (HR): 4.548, P=0.003] for decreased myocardial perfusion, followed by TIMI flow grade, AMI, stenotic extent, and NT-pro-BNP. The baseline hs-cTnI peak level was the strongest predictor for decreased myocardial perfusion after revascularization, followed by AMI, stenotic extent, and NT-pro-BNP.

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction

Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied. To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF. A total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index. The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis. Of 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%]). In this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.

Assessment of Myocardial Dysfunction by Three-Dimensional Echocardiography Combined With Myocardial Contrast Echocardiography in Type 2 Diabetes Mellitus.

Background: We aimed to explore the value of combining real-time three-dimensional echocardiography (RT-3DE) and myocardial contrast echocardiography (MCE) in the left ventricle (LV) evaluating myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients.Patients and Methods: A total of 58 T2DM patients and 32 healthy individuals were selected for this study. T2DM patients were further divided into T2DM without microvascular complications (n = 29) and T2DM with microvascular complications (n = 29) subgroups. All participants underwent RT-3DE and MCE. The standard deviation (SD) and the maximum time difference (Dif) of the time to the minimum systolic volume (Tmsv) of the left ventricle were measured by RT-3DE. MCE was performed to obtain the perfusion measurement of each segment of the ventricular wall, including acoustic intensity (A), flow velocity (β), and A·β.Results: There were significant differences in all Tmsv indices except for Tmsv6-Dif among the three groups (all P < 0.05). After heart rate correction, all Tmsv indices of the T2DM with microvascular complications group were prolonged compared with the control group (all P < 0.05). The parameters of A, β, and A·β for overall segments showed a gradually decreasing trend in three groups, while the differences between the three groups were statistically significant (all P < 0.01). For segmental evaluation of MCE, the value of A, β, and A·β in all segments showed a decreasing trend and significantly differed among the three groups (all P < 0.05).Conclusions: The RT-3DE and MCE can detect subclinical myocardial dysfunction and impaired myocardial microvascular perfusion. Left ventricular dyssynchrony occurred in T2DM patients with or without microvascular complications and was related to left ventricular dysfunction. Myocardial perfusion was reduced in T2DM patients, presenting as diffuse damage, which was aggravated by microvascular complications in other organs.

Comparison between cardiac magnetic resonance stress T1 mapping and [15O]H2O positron emission tomography in patients with suspected obstructive coronary artery disease.

To compare cardiac magnetic resonance (CMR) measurement of T1 reactivity (ΔT1) with [15O]H2O positron emission tomography (PET) measurements of quantitative myocardial perfusion. Forty-three patients with suspected obstructed coronary artery disease underwent [15O]H2O PET and CMR at 1.5-T, including rest and adenosine stress T1 mapping (ShMOLLI) and late gadolinium enhancement to rule out presence of scar tissue. ΔT1 was determined for the three main vascular territories and compared with [15O]H2O PET-derived regional stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). ΔT1 showed a significant but poor correlation with stress MBF (R2 = 0.04, P = 0.03) and MFR (R2 = 0.07, P = 0.004). Vascular territories with impaired stress MBF (i.e. ≤2.30 mL/min/g) demonstrated attenuated ΔT1 compared with vascular territories with preserved stress MBF (2.9 ± 2.2% vs. 4.1 ± 2.2%, P = 0.008). In contrast, ΔT1 did not differ between vascular territories with impaired (i.e. <2.50) and preserved MFR (3.2 ± 2.6% vs. 4.0 ± 2.1%, P = 0.25). Receiver operating curve analysis of ΔT1 resulted in an area under the curve of 0.66 [95% confidence interval (CI): 0.57-0.75, P = 0.009] for diagnosing impaired stress MBF and 0.62 (95% CI: 0.53-0.71, P = 0.07) for diagnosing impaired MFR. CMR stress T1 mapping has poor agreement with [15O]H2O PET measurements of absolute myocardial perfusion. Stress T1 and ΔT1 are lower in vascular territories with reduced stress MBF but have poor accuracy for detecting impaired myocardial perfusion.

Author Response: First-Ever Ischemic Stroke and Increased Risk of Incident Heart Disease in Older Adults.

We thank Dr. Sioka et al. for their positive comments about our article1 showing a high risk of major adverse cardiovascular events after acute ischemic stroke. They also summarized the results of their study on myocardial perfusion tests among patients with a recent (<30 days) ischemic stroke.2 Dr. Sioka et al. found changes suggestive of myocardial ischemia in 62% of the cases.2 Notably, this was a wittingly selected population of patients with atherosclerotic strokes and a high prevalence of smokers (63%) and hyperlipidemia (58%). Thus, the high prevalence of asymptomatic coronary artery disease (CAD) in this study is somehow expected. Indeed, consistent with their interpretation, asymptomatic CAD is the most likely explanation for the impaired myocardial perfusion tests. However, in less selected populations, cardiovascular complications may not be due to asymptomatic CAD, since the reported prevalence of severe coronary artery atherosclerosis in patients with acute ischemic stroke and no history of CAD undergoing systematic coronary angiography is only 16%.3 Interestingly, the meaning of impaired myocardial perfusion scanning in stroke patients is not well understood. Takotsubo myocardiopathy can occur after stroke and is associated with transiently impaired myocardial perfusion tests in the absence of atherosclerotic CAD.4