Coronary microvascular dysfunction and atrial reservoir function.

BACKGROUND: Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the coronary microcirculation, which may be diagnosed using invasive coronary physiology. CMD is responsible for impaired diastolic cardiac function. It has recently been suggested that left atrial strain (LASr) represents a highly sensitive tool for detecting cardiac diastolic function abnormalities. Accordingly, the aim of this study was to investigate the relationship between CMD and LASr. METHODS: Consecutively enrolled patients with non-obstructed coronary arteries (NOCA) underwent CMD and LASr evaluation by invasive thermodilution and noninvasive echocardiography, respectively. RESULTS: Forty-two (42) patients were included, out of which 26 presented with CMD. There were no significant differences between CMD-positive and negative patients in terms of clinical and echocardiographic characteristics. LASr was significantly reduced in patients with CMD (24.6% ± 6.1 vs. 30.3 ± 7.8%, p = 0.01). A moderate correlation was observed between coronary flow reserve and LAsr (r = 0.47, p = 0.002). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LASr (OR = 0.88, 95%CI 0.78-0.99.135, p = 0.04). A LASr cut-off of 25.5% enabled an optimal classification of patients with or without CMD. CONCLUSION: Patients with NOCA and CMD had a significantly reduced LASr compared with patients without CMD, suggesting the early impairment of diastolic function in these patients.

Coronary microvascular dysfunction as assessed by multimodal diagnostic imaging in patients with hypertrophic cardiomyopathy is related to the severity of cardiac dysfunction.

INTRODUCTION: Coronary microvascular dysfunction (CMD) plays a major role in hypertrophic cardiomyopathy (HCM) physiopathology but its assessment in clinical practice remains a challenge. Nowadays, innovations in invasive and noninvasive coronary evaluation using multimodal imaging provide options for the diagnosis of CMD. The objective of the present study was to investigate if new multimodal imaging diagnosis of CMD could detect HCM patients with more impaired cardiac function by left atrioventricular coupling index (LACI). METHODS AND RESULTS: A total of 32 consecutive patients with a confirmed diagnosis of HCM (62 ± 13 years, 62% men) were prospectively screened for CMD using a multimodal imaging method. LACI was assessed by cardiovascular magnetic resonance imaging. Fifteen (47%) patients had CMD by multimodal imaging method. Patients with CMD presented a significantly higher LACI (48.5 ± 25.4 vs. 32.5 ± 10.6, p = .03). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LACI (OR = 1.069, 95% CI 1.00-1.135, p = .03). CONCLUSION: Multimodal imaging diagnosis of CMD is applicable to HCM patients and is associated with more impaired cardiac function.

Assessment of the Objective Effect of Virtual Reality for Preoperative Anxiety in Interventional Cardiology.

The management of anxiety because of upcoming invasive coronary angiography (ICA) remains suboptimal. Previously published studies investigating the potential of virtual reality (VR) for the reduction of anxiety in ICA procedures used a subjective evaluation method. The purpose of this study was to determine whether the use of a VR program before ICA objectively decreases anxiety as assessed by the SD of normal to normal (SDNN). Lower SDNN is associated with worse anxiety. A total of 156 patients referred for ICA after a positive noninvasive test for coronary disease were included in the present randomized study. The interventional group benefited from the use of a VR mask in the transfer room before ICA, whereas the control group underwent the procedure as usual. In both groups, SDNN was measured before ICA. No statistical difference in SDNN was observed between the VR and control groups (45.5 ± 17.8 vs 50.6 ± 19.5, p = 0.12). The preoperative use of a VR mask for anxiolytic purposes in the setting of ICA did not result in a decrease in anxiety.

Coronary Angiography Upgraded by Imaging Post-Processing: Present and Future Directions.

Advances in computer technology and image processing now allow us to obtain from angiographic images a large variety of information on coronary physiology without the use of a guide-wire as a diagnostic information equivalent to FFR and iFR but also information allowing for the performance of a real virtual percutaneous coronary intervention (PCI) and finally the ability to obtain information to optimize the results of PCI. With specific software, it is now possible to have a real upgrading of invasive coronary angiography. In this review, we present the different advances in this field and discuss the future perspectives offered by this technology.

Regional CZT myocardial perfusion reserve for the detection of territories with simultaneously impaired CFR and IMR in patients without obstructive coronary artery disease: a pilot study.

OBJECTIVES: To assess the diagnostic performances of CZT myocardial perfusion reserve (MPR) for the detection of territories with simultaneous impaired coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients without obstructive coronary artery disease. METHODS: Patients were prospectively included before being referred for coronary angiography. All patients underwent CZT MPR before invasive coronary angiography (ICA) and coronary physiology assessment. Rest and dipyridamole-induced stress myocardial blood flow (MBF) and MPR were quantified using 99mTc-SestaMIBI and a CZT camera. Fractional flow reserve (FFR), Thermodilution CFR, and IMR were assessed during ICA. RESULTS: Between December 2016 and July 2019, 36 patients were included. 25/36 patients presented no obstructive coronary artery disease. A complete functional assessment was performed in 32 arteries. No territory presented a significant ischemia on CZT myocardial perfusion imaging. A moderate yet significant correlation was observed between regional CZT MPR and CFR (r = 0.4, P = .03). Sensitivity, specificity, positive and negative predictive value, and accuracy of regional CZT MPR versus the composite invasive criterion (impaired CFR and IMR) were 87 [47% to 99%], 92% [73% to 99%], 78% [47% to 93%], 96% [78% to 99%], and 91% [75% to 98%], respectively. All territories with a regional CZT MPR ≤ 1.8 showed a CFR < 2. Regional CZT MPR values were significantly higher in arteries with CFR ≥ 2 and IMR < 25 (negative composite criterion, n = 14) than in those with CFR < 2 and IMR ≥ 25 (2.6 [2.1 to 3.6] versus 1.6 [1.2 to 1.8]), P < .01). CONCLUSION: Regional CZT MPR presented excellent diagnostic performances for the detection of territories with simultaneously impaired CFR and IMR reflecting a very high cardiovascular risk in patients without obstructive coronary artery disease.

Prognostic significance of severe coronary microvascular dysfunction post-PCI in patients with STEMI: A systematic review and meta-analysis.

Coronary microvascular dysfunction (CMVD) is common and associated with poorer outcomes in patients with ST Segment Elevation Myocardial Infarction (STEMI). The index of microcirculatory resistance (IMR) and the index of hyperemic microvascular resistance (HMR) are both invasive indexes of microvascular resistance proposed for the diagnosis of severe CMVD after primary percutaneous coronary intervention (pPCI). However, these indexes are not routinely assessed in STEMI patients. Our main objective was to clarify the association between IMR or HMR and long-term major adverse cardiovascular events (MACE), through a systematic review and meta-analysis of observational studies. We searched Medline, PubMed, and Google Scholar for studies published in English until December 2020. The primary outcome was a composite of cardiovascular death, non-cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and rehospitalization for heart failure occurring after at least 6 months following CMVD assessment. We identified 6 studies, reporting outcomes in 1094 patients (mean age 59.7 ± 11.4 years; 18.2% of patients were women) followed-up from 6 months to 7 years. Severe CMVD, defined as IMR > 40 mmHg or HMR > 3mmHg/cm/sec was associated with MACE with a pooled HR of 3.42 [2.45; 4.79]. Severe CMVD is associated with an increased risk of long-term adverse cardiovascular events in patients with STEMI. Our results suggest that IMR and HMR are useful for the early identification of severe CMVD in patients with STEMI after PCI, and represent powerful prognostic assessments as well as new therapeutic targets for clinical intervention.

Non-invasive Multimodality Imaging of Coronary Vulnerable Patient.

Atherosclerotic plaque rupture or erosion remain the primary mechanism responsible for myocardial infarction and the major challenge of cardiovascular researchers is to develop non-invasive methods of accurate risk prediction to identify vulnerable plaques before the event occurs. Multimodal imaging, by CT-TEP or CT-SPECT, provides both morphological and activity information about the plaque and cumulates the advantages of anatomic and molecular imaging to identify vulnerability features among coronary plaques. However, the rate of acute coronary syndromes remains low and the mechanisms leading to adverse events are clearly more complex than initially assumed. Indeed, recent studies suggest that the detection of a state of vulnerability in a patient is more important than the detection of individual sites of vulnerability as a target of focal treatment. Despite this evolution of concepts, multimodal imaging offers a strong potential to assess patient's vulnerability. Here we review the current state of multimodal imaging to identify vulnerable patients, and then focus on emerging imaging techniques and precision medicine.

Noninvasive assessment of coronary microvascular dysfunction using SPECT myocardial perfusion imaging and myocardial perfusion entropy quantification in a rodent model of type 2 diabetes.

PURPOSE: Coronary microvascular dysfunction (CMVD) plays a major role in the occurrence of cardiovascular events (CVE). We recently suggested the clinical potential of myocardial perfusion entropy (MPE) quantification from SPECT myocardial perfusion images (MPI) for the prognosis of CVE occurrence. We hypothesized that the quantification of MPE from SPECT MPI would allow the assessment of CMVD-related MPE variations in a preclinical model of type 2 diabetes (T2D) including treatment with the anti-diabetic incretin liraglutide (LIR). METHODS: Optimal conditions for the preclinical quantification of MPE using 201Tl SPECT MPI were determined in rats with a T2D-like condition induced by a high-fat diet and streptozotocin injection (feasibility study, n = 43). Using such conditions, echocardiography and post-mortem LV capillary density evaluation were then used in order to assess the effect of LIR and the ability of MPE to assess CMVD (therapeutic study, n = 39). RESULTS: The feasibility study identified dobutamine stress and acute NO synthase and cyclooxygenase inhibition as optimal conditions for the quantification of MPE, with significant increases in MPE being observed in T2D animals (P < 0.01 vs controls). In the therapeutic study, T2D rats were hyperglycemic (5.5 ± 0.5 vs 1.1 ± 0.3 g/L for controls, P < 0.001) and had a significantly lower left ventricular ejection fraction (LVEF) (65 ± 4% vs 74 ± 9%, P < 0.01) and LV capillary density (2400 ± 300 vs 2800 ± 600 mm-3, P < 0.05). LIR partially restored glycemia (3.9 ± 0.6 g/L, P < 0.05 vs controls and T2D), totally prevented LVEF impairment (72 ± 7%, P = NS vs CTL), with no significant effect on capillary density. MPE was significantly increased in T2D rats (7.6 ± 0.5 vs 7.1 ± 0.5, P < 0.05), with no significant improvement in T2D-LIR rats (7.4 ± 0.4, P = NS vs controls and T2D). CONCLUSION: MPE quantification allowed the preclinical noninvasive assessment of CMVD. Both MPE and capillary density quantification suggested that LIR did not improve T2D-induced CMVD. The relevance of MPE for CMVD assessment warrants further clinical investigation.

Preclinical and clinical evaluation of a new method to assess cardiac insulin resistance using nuclear imaging.

BACKGROUND: Myocardial insulin resistance (IR) could be a predictive factor of cardiovascular events. This study aimed to introduce a new method using 123I-6-deoxy-6-iodo-D-glucose (6DIG), a pure tracer of glucose transport, for the assessment of IR using cardiac dynamic nuclear imaging. METHODS: The protocol evaluated first in rat-models consisted in two 6DIG injections and one of insulin associated with planar imaging and blood sampling. Compartmental modeling was used to analyze 6DIG kinetics in basal and insulin conditions and to obtain an index of IR. As a part of a translational approach, a clinical study was then performed in 5 healthy and 6 diabetic volunteers. RESULTS: In rodent models, the method revealed reproducible when performed twice at 7 days apart in the same animal. Rosiglitazone, an insulin-sensitizing drug, induced a significant increase of myocardial IR index in obese Zucker rats from 0.96 ± 0.18 to 2.26 ± 0.44 (P<.05) after 7 days of an oral treatment, and 6DIG IR indexes correlated with the gold standard IR index obtained through the hyperinsulinemic-euglycemic clamp (r=.68, P<.02). In human, a factorial analysis was applied on images to obtain vascular and myocardial kinetics before compartmental modeling. 1.5-fold to 2.2-fold decreases in mean cardiac IR indexes from healthy to diabetic volunteers were observed without reaching statistical significance. CONCLUSIONS: These preclinical results demonstrate the reproducibility and sensibility of this novel imaging methodology. Although this first in-human study showed that this new method could be rapidly performed, larger studies need to be planned in order to confirm its performance.

Comparison of Cadmium Zinc Telluride ECG-gated SPECT equilibrium radionuclide angiocardiography to magnetic resonance imaging to measure right ventricular volumes and ejection fraction in patients with cardiomyopathy.

AIMS: The objective of this study was to determine the accuracy of right ventricular function (RVF) assessed by Cadmium Zinc Telluride ECG-gated SPECT equilibrium radionuclide angiocardiography (CZT-ERNA). METHODS AND RESULTS: Twenty-one consecutive patients with cardiomyopathy (aged 54 ± 19 years; 62% male) were included. RV ejection fraction (EF) and volumes were analyzed by CZT-ERNA and compared with values obtained by cardiac magnetic resonance imaging (CMR). Mean values were not different between CZT-ERNA and MRI for RVEF (48.1 ± 10.4% vs 50.8 ± 10.0%; P = .23). Significant correlations (P < .0001) were observed between CZT-ERNA and MRI for RVEF, RV end-diastolic volume, and end-systolic volume (r = 0.81, r = 0.93, and r = 0.96, respectively). Bland-Altman analysis showed a mean difference (bias) between CZT-ERNA and MRI for RVEF of -2.69% (95% CI - 5.35 to - 0.42) with good agreement between the 2 techniques (limits of agreement, -14.3 to 8.99). Intraobserver and interobserver reproducibility of RVF measured by CZT-ERNA was high. CONCLUSION: CZT-ERNA provides accurate, reproducible assessment of RVF and appears as a good alternative to cardiac magnetic resonance for the evaluation of the magnitude of RVF in patients with cardiomyopathy.

Impact of a micro-net mesh technology covering stent on coronary microvascular dysfunction in patients with high thrombus burden.

BACKGROUND: Highly thrombotic coronary lesions continue to be a serious and clinically significant problem that is not effectively and completely addressed by current technology. OBJECTIVES: We aimed to investigate whether a micro-net mesh (MNM) technology covering stent could preserve the index of microcirculatory resistance (IMR) after percutaneous coronary intervention (PCI) in patients with high thrombus burden. METHODS AND RESULTS: Fifty-two patients with non-ST elevation myocardial infarction or ST Elevation Myocardial Infarction and high thrombus burden (TIMI thrombus grade ≥ 3) were randomized into two groups, PCI with a MNM covering stent (MNM group, n = 25) and PCI with any commercially available stent (DES group, n = 27). As the primary endpoint, IMR was measured immediately after PCI using a pressure-temperature sensor-tipped coronary wire. The secondary endpoint was left ventricular ejection fraction (LVEF) at 6 months of follow-up. The IMR in the MNM group was significantly lower in comparison to the DES group (33.2 [21.3, 48.9] vs. 57.2 [39.9, 98.0], p = 0.005). No significant differences were observed in baseline LVEF (54.5 ± 10.2% vs. 53.1 ± 6.87%, p = .57), while LVEF was significantly improved at follow-up in the MNM group (61.1 ± 7.1% vs. 53.9 ± 6.35%, p = .0001). CONCLUSION: MNM technology significantly improved coronary microvascular dysfunction after PCI in patient with acute coronary syndrome and appears as a useful technological option for thrombus management.

Prognosis of Coronary Atherosclerotic Burden in Non-Ischemic Dilated Cardiomyopathies.

BACKGROUND: Atherosclerosis is associated with a worse prognosis in many diseases such as ischemic cardiomyopathy, but its impact in non-ischemic dilated cardiomyopathy (dCMP) is lesser known. Our aim was to study the prognostic impact of coronary atherosclerotic burden (CAB) in patients with dCMP. METHODS: Consecutive patients with dCMP and left ventricular (LV) dysfunction diagnosed by concomitant analysis of invasive coronary angiography (ICA) and CMR imaging were identified from registry-database. CAB was measured by Gensini score. The primary composite endpoint was the occurrence of major adverse cardiovascular events (MACE) defined as cardiovascular (CV) mortality, non-fatal MI and unplanned myocardial revascularization. The results of 139 patients constituting the prospective study population (mean age 59.4 ± 14.7 years old, 74% male), average LV ejection fraction was 31.1 ± 11.02%, median Gensini score was 0 (0-3), and mid-wall late gadolinium enhancement (LGE) was the most frequent LGE pattern (42%). Over a median follow-up of 2.8 years, 9% of patients presented MACE. Patients with MACE had significantly higher CAB compared to those who were free of events (0 (0-3) vs. 3.75 (2-15), p < 0.0001). CAB remained the significant predictor of MACE on multivariate logistic analysis (OR: 1.12, CI: 1.01-1.23, p = 0.02). CONCLUSION: High CAB may be a new prognostic factor in dCMP patients.

Prognostic value of SPECT myocardial perfusion entropy in high-risk type 2 diabetic patients.

PURPOSE: Risk stratification of patients with type 2 diabetes mellitus (T2D) remains suboptimal. We hypothesized that myocardial perfusion entropy (MPE) quantified from SPECT myocardial perfusion images may provide incremental prognostic value in T2D patients independently from myocardial ischemia. METHODS: T2D patients with very high and high cardiovascular risk were prospectively included (n = 166, 65 ± 12 years). Stress perfusion defect was quantified by visual evaluation of SPECT MPI. SPECT MPI was also used for the quantification of rest and stress MPE. The primary end point was major adverse cardiac events (MACEs) defined as cardiac death, myocardial infarction (MI), and myocardial revascularization > 3 months after SPECT. RESULTS: Forty-four MACEs were observed during a 4.6-year median follow-up. Significant differences in stress MPE were observed between patients with and without MACEs (4.19 ± 0.46 vs. 3.93 ± 0.40; P ≤ .01). By Kaplan-Meier analysis, the risk of MACEs was significantly higher in patients with higher stress MPE (log-rank P ≤ 01). Stress MPE and stress perfusion defect (SSS ≥ 4) were significantly associated with the risk of MACEs (hazard ratio 2.77 and 2.06, respectively, P < .05 for both) after adjustment for clinical and imaging risk predictors as identified from preliminary univariate analysis. MPE demonstrated incremental prognostic value over clinical risk factors, stress test EKG and SSS as evidenced by nested models showing improved Akaike information criterion (AIC), reclassification (global continuous net reclassification improvement [NRI]: 63), global integrated discrimination improvement (IDI: 6%), and discrimination (change in c-statistic: 0.66 vs 0.74). CONCLUSIONS: Stress MPE provided independent and incremental prognostic information for the prediction of MACEs in diabetic patients. TRIAL REGISTRATION NUMBER: NCT02316054 (12/12/2014).

Aggressive Bone Metastatic Prostate Cancer With Periosteal Reaction in 18F-Choline PET/CT.

ABSTRACT: Prostate cancer bone metastases usually appear as osteosclerotic lesions. However, atypical lesions have also been described. We report herein the case of a 65-year-old man treated since 2013 for prostate cancer with early bone metastases. This asymptomatic patient was referred for 18F-choline PET/CT due to a major elevation of prostate-specific antigen to >1500 ng/mL. The results indicated multiple bone lesions, disseminated on the axial skeleton, girdles, and upper extremities of femurs. Interestingly, we described the development of an intensely hypermetabolic spiculated periosteal reaction, evidencing a rapidly progressive disease.

Does whole-body bone SPECT/CT provide additional diagnostic information over [18F]-FCH PET/CT for the detection of bone metastases in the setting of prostate cancer biochemical recurrence?

BACKGROUND: To assess whether whole-body (WB) bone SPECT/CT provides additional diagnostic information over [18F]-FCH PET/CT for the detection of bone metastases in the setting of prostate cancer biochemical recurrence (PC-BR). METHODS: Patients referred for a PC-BR and whom benefited from a WB bone SPECT/CT and FCH PET/CT were retrospectively included. Tests were classified as positive, equivocal, or negative for bone metastases. A best valuable comparator (BVC) strategy including imaging and follow-up data was used to determine the metastatic status in the absence of systematic histological evaluation. RESULTS: Between January 2011 and November 2017, 115 consecutive patients with a PC-BR were evaluated. According to the BVC, 30 patients had bone metastases and 85 patients did not present with bone lesions. The sensitivity, specificity, positive and negative predictive values were respectively 86.7% [69.3-96.2], 98.8% [93.6-100.0], 96.3% [78.7-99.5], and 95.5% [89.4-98.1] for WB bone SPECT/CT and 93.3% [77.9-99.2], 100.0% [95.8-100.0], 100.0 and 97.7% [91.8-99.4] for FCH PET/CT. There was no significant difference in diagnostic accuracy of bone metastases between WB Bone SPECT/CT (AUC 0.824 [0.74-0.90]) and FCH PET/CT (AUC 0.829 [0.75-0.90], p = 0.41). CONCLUSION: Despite good performances for the diagnosis of bone metastases in PC-BR, WB bone SPECT/CT does not provide additive diagnostic information over concomitant FCH PET/CT.

Prospective diagnostic performance of semiconductor SPECT myocardial perfusion imaging: wall thickening analysis reduces the need for an additional prone acquisition.

PURPOSE: To determine whether the assessment of regional wall thickening (WT) in addition to myocardial perfusion from stress supine acquisitions could compensate for the lack of prone acquisition and the corresponding decrease in the diagnostic performance of SPECT myocardial perfusion imaging (MPI) in patients with known or suspected coronary artery disease (CAD). METHODS: The study group comprised 41 patients (123 vessels) with known or suspected CAD prospectively recruited for systematic prone and supine 201Tl stress SPECT MPI. The diagnostic performance of SPECT MPI was determined for various image sets including nongated supine images (supine NG), nongated combined prone and supine images (prone and supine NG) and gated supine images, allowing WT evaluation from NG images in addition to perfusion (supine NG + WT) using invasive coronary angiography and fractional flow reserve as the gold standards. RESULTS: The rate of false positives was significantly higher among the supine NG images (20.8%) than among either the prone and supine NG or the supine NG + WT images (3.3% and 2.7%, respectively, P < 0.05 vs. supine NG). Consequently, specificity was higher for the prone and supine NG images than for the supine NG images (96.1% vs. 76.1%, P < 0.01) and was highest for the supine NG + WT images (96.8%, P not significant vs. prone and supine NG), without significant differences in sensitivity (80.0%, 86.6% and 73.3%, respectively, P not significant for all comparisons). CONCLUSION: The diagnostic performance of supine stress SPECT MPI is improved when WT assessment of ischaemic segments is used as an additional diagnostic criterion to values not significantly different from those with combined prone and supine acquisitions.