Changes In Myocardial Blood Flow Research Articles

Links Between Obstructive Sleep Apnea and Myocardial Blood Flow Changes Impacting Adverse Cardiovascular Disease-related Outcomes.

Recent studies have demonstrated an association between obstructive sleep apnea (OSA) and abnormal myocardial blood flow (MBF), myocardial flow reserve (MFR), and coronary microvascular dysfunction (CMD). Here, we review the evidence and describe the potential underlying mechanisms linking OSA to abnormal MBF. Examining relevant studies, we assess the impact of OSA-specific therapy, such as continuous positive airway pressure (CPAP), on MBF. Recent studies suggest an association between moderate to severe OSA and abnormal MBF/MFR. OSA promotes functional and structural abnormalities of the coronary microcirculation. OSA also promotes the uncoupling of MBF to cardiac work. In a handful of studies with small sample sizes, CPAP therapy improved MBF/MFR. Moderate to severe OSA is associated with abnormal MFR, suggesting an association with CMD. Evidence suggests that CPAP therapy improves MBF. Future studies must determine the clinical impact of improved MBF with CPAP.

Natural History of Myocardial αvβ3 Integrin Expression After Acute Myocardial Infarction: Correlation with Changes in Myocardial Blood Flow.

Angiogenesis is an essential part of the cardiac repair process after myocardial infarction, but its spatiotemporal dynamics remain to be fully deciphered.68Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting αvβ3 integrin expression, which is a marker of angiogenesis. Methods: In this prospective single-center trial, we aimed to monitor angiogenesis through myocardial integrin αvβ3 expression in 20 patients with ST-segment elevation myocardial infarction (STEMI). In addition, the correlations between the expression levels of myocardial αvβ3 integrin and the subsequent changes in 82Rb PET/CT parameters, including rest and stress myocardial blood flow (MBF), myocardial flow reserve (MFR), and wall motion abnormalities, were assessed. The patients underwent 68Ga-NODAGA-RGD PET/CT and rest and stress 82Rb-PET/CT at 1 wk, 1 mo, and 3 mo after STEMI. To assess 68Ga-NODAGA-RGD uptake, the summed rest 82Rb and 68Ga-NODAGA-RGD images were coregistered, and segmental SUVs were calculated (RGD SUV). Results: At 1 wk after STEMI, 19 participants (95%) presented increased 68Ga-NODAGA-RGD uptake in the infarcted myocardium. Seventeen participants completed the full imaging series. The values of the RGD SUV in the infarcted myocardium were stable 1 mo after STEMI (1 wk vs. 1 mo, 1.47 g/mL [interquartile range (IQR), 1.37-1.64 g/mL] vs. 1.47 g/mL [IQR, 1.30-1.66 g/mL]; P = 0.9), followed by a significant partial decrease at 3 mo (1.32 g/mL [IQR, 1.12-1.71 g/mL]; P = 0.011 vs. 1 wk and 0.018 vs. 1 mo). In segment-based analysis, positive correlations were found between RGD SUV at 1 wk and the subsequent changes in stress MBF (Spearman ρ: r = 0.17, P = 0.0033) and MFR (Spearman ρ: r = 0.31, P < 0.0001) at 1 mo. A negative correlation was found between RGD SUV at 1 wk and the subsequent changes in wall motion abnormalities at 3 mo (Spearman ρ: r = -0.12, P = 0.035). Conclusion: The present study found that αvβ3 integrin expression is significantly increased in the infarcted myocardium 1 wk after STEMI. This expression remains stable after 1 mo and partially decreases after 3 mo. Initial αvβ3 integrin expression at 1 wk is significantly weakly correlated with subsequent improvements in stress MBF, MFR, and wall motion analysis.

Mental stress-induced myocardial ischemia detected by global longitudinal strain and quantitative myocardial contrast echocardiography in women with nonobstructive coronary artery disease

BackgroundThe utility of radionuclide myocardial perfusion imaging including positron emission tomography (PET) for diagnosing mental stress-induced myocardial ischemia (MSIMI) is clinically restricted. This study aims to assess the diagnostic performance of novel echocardiographic techniques, including automated strain and quantitative myocardial contrast echocardiography (MCE) with dedicated software and deep neural network (DNN) model, for MSIMI detection. The secondary objective was to explore the correlation between changes in myocardial blood flow (MBF) and MSIMI. Methods72 female patients aged 18 to 75 with angina and nonobstructive coronary artery disease (ANOCA), and 23 healthy controls were prospectively recruited. Both echocardiography with contrast agent and PET imaging were performed during structured mental stress testing. MSIMI was defined as a summed difference score ≥3 on PET. Echocardiographic parameters including left ventricular global longitudinal strain (LVGLS), β and A×β were obtained, and their trends during mental stress testing were observed. ΔGLS, β reserve and A×β reserve were respectively calculated. Results32 ANOCA patients (44%) and 1 control (4%) were diagnosed with MSIMI (P<0.01). For ANOCA patients with MSIMI, LVGLS, β and A×β declined to varied extent during mental stress testing compared to those without MSIMI and the controls (P<0.05). Bland-Altman plots demonstrated good consistency between β reserve and A×β reserve output by the DNN model and iMCE software. Receiver operating characteristic (ROC) curve analyses showed that ΔGLS, β reserve and A×β reserve demonstrated favorable ability to predict MSIMI, especially the combination of A×β reserve using iMCE analysis and ΔGLS (area under the curve [AUC] 0.94, sensitivity 83%, specificity 97%). ConclusionsNovel technologies in echocardiography exhibit the potential to be a clinical alternative to cardiac PET for effectively detecting MSIMI. Attenuated MBF response during structured mental stress testing was correlated with MSIMI, providing a reasonable explanation for the chest discomfort persisting in ANOCA women.

Quantitative analysis of myocardial blood flow in surgically revascularized and not revascularized myocardial segments. A pilot PET study.

To prospectively compare changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) in multivessel coronary artery disease (MVCAD) patients undergoing incomplete revascularization (IR) versus complete revascularization (CR) by coronary artery bypass grafting (CABG). Seven male patients (age 68 ± 9years) with MVCAD underwent myocardial perfusion PET/CT with [13N]ammonia before and at least 4months after CABG. Segmental resting and stress MBF as well as MFR were measured. Resting and during stress left ventricle ejection fraction (LVEF) were also calculated. Three patients (43%) underwent CR and four (57%) IR. Among 119 myocardial segments, 101 (85%) were revascularized, and 18 (15%) were not. After CABG, stress MBF (mL/min/gr) and MFR are significantly increased in all myocardial segments, with a greater increase in the revascularized segments (p = 0.013). In both groups, LVEF significantly decreased during stress at baseline PET (p = 0.04), but not after CABG. Stress MBF and MFR significantly improve after CABG in both revascularized and not directly revascularized myocardial segments. IR strategy may be considered in patients with high surgical risk for CR.

Abstract 13787: Restricted Coronary Flow Reserve of Mental Stress Induced Myocardial Ischemia in Angina and No Obstructive Coronary Artery Disease

Background: The myocardial blood flow (MBF) mechanism in mental stress-induced myocardial ischemia (MSIMI) in angina with no obstructive coronary artery disease (ANOCA) population is unknown. Methods: 13-NH 3 cardiac PET-CT was utilized to assess MBF and perfusion changes under mental stress (ms) and adenosine stress (as) in ANOCA subjects and gender- and age-matched healthy controls. MSIMI was defined as an increase in perfusion defect score of ≥3 points. Results: Among the 126 participants enrolled, ANOCA women showed a significantly higher prevalence of MSIMI compared to the healthy controls (36/84 vs. 1/42, p &lt;0.001). Perfusion defects under ms occurred synchronously however more pronounced in the left anterior descending and right coronary artery territories, consistent with a significantly higher MBF hyperemia in the left circumflex territory. MBF ms shows a close correlation with rate-pressure product (RPP ms ) ( p &lt;0.05 in ANOCA&amp;MSIMI+, ANOCA&amp;MSIMI-, and control groups with r pearson ranging from 0.39-0.65). Although no differences existed in absolute MBF ms values between groups, there were notable increasing trends among the three groups in corrected MBF, which reflected blood flow supply-demand balance (ANOCA&amp;MSIMI+: 0.96±0.23 vs. control group: 1.10±0.29, p =0.020), and in coronary flow reserve (CFR) (ANOCA&amp;MSIMI+: 2.41±0.75 vs. control group: 2.89±0.77, p =0.016). Furthermore, after adjusting for confounding factors, only subjects in ANOCA&amp;MSIMI+ group did not exhibit a corresponding increase in MBF ms matching MBF as . Conclusion: Restricted CFR, indicating impaired coronary microvascular function, and mismatch between myocardial blood supply and demand together constitute the pathogenic mechanism of MSIMI in ANOCA population. More researches are still needed in exploring the brain-heart interaction in MSIMI.

Changes in myocardial blood flow in a canine model of left sided breast cancer radiotherapy.

Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured. In five canines, Ammonia PET (13NH3) derived MBF was measured at baseline, 1-week, 1, 3, 6 and 12-months after cardiac external beam irradiation. MBF measurements were correlated with concurrent 18FDG uptake. Simultaneously MBF was measured using the dual bolus MRI method. MBF was significantly increased at all time points, in comparison to baseline, except at 3-months. This was seen globally throughout the entire myocardium independent of the coronary artery territories. MBF showed a modest significant correlation with 18FDG activity for the entire myocardium (r = 0.51, p = 0.005) including the LAD (r = 0.49, p = 0.008) and LCX (r = 0.47, p = 0.013) coronary artery territories. In this canine model of radiotherapy for left-sided breast cancer, resting MBF increases as early as 1-week and persists for up to one year except at 3-months. This pattern is similar to that of 18FDG uptake. A possible interpretation is that the increase in resting MBF is a response to myocardial inflammation.

Coronary artery bypass grafting transiently improves myocardial flow reserve in patients with impaired left ventricular function

BackgroundMyocardial flow reserve (MFR) derived from 13N-ammonia positron emission tomography is an index used to evaluate ischemic cardiomyopathy and predict the prognosis of patients with coronary artery disease (CAD). This study aimed to evaluate the short-term changes in MFR in patients who underwent coronary artery bypass grafting (CABG). In addition, as a reference, we showed the changes in MFR in the percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) patient groups. MethodsTo determine the short-term effects of CABG in CAD with left ventricular dysfunction, myocardial blood flow (MBF) and MFR were measured before and after CABG. Additionally, we showed changes in MBF and MFR of the PCI and OMT patient groups during treatment. ResultsWe observed that resting MBF did not significantly increase from baseline to post-CABG (0.84 ± 0.32 vs. 0.83 ± 0.23, P = 0.958); however, stress MBF increased significantly from baseline to post-CABG (1.23 ± 0.64 vs. 1.49 ± 0.42, P < 0.001). The global MFR increased significantly from baseline to post-CABG (1.49 ± 0.42 mL/g/min vs. 1.91 ± 0.51 mL/g/min, P < 0.001). Additionally, stress and resting ejection fraction (EF) significantly increased (stress EF: 42 ± 18.7% vs. 50.9 ± 18%, P = 0.005; resting EF: 45.8 ± 19.5% vs. 52.1 ± 19.4%, P = 0.031). ConclusionsThis study demonstrated that CABG significantly improved MFR in a short period of time with left ventricular dysfunction. These findings suggest that epicardial coronary artery patency restores myocardial microcirculatory dysfunction in the short term.

Dynamic myocardial perfusion computed tomography with mental stress test to detect changes in myocardial microcirculation in patients with anxiety and no obstructive coronary artery disease.

Mental stress can induce myocardial ischemia in patients with anxiety and other psychological disorders. Computed tomography myocardial perfusion imaging (CT-MPI) has the potential to quantitatively diagnose myocardial ischemia. The aim of this study was to measure changes in myocardial microcirculation perfusion (MMP) in patients with anxiety who have angina symptoms/ischemia but no obstructive coronary artery disease (INOCA) using dynamic CT-MPI in combination with a mental stress test. Patients with INOCA were divided into five subgroups (none, minimal, mild, moderate, and severe) according to the generalized anxiety disorder scale. Patients underwent dynamic CT-MPI with mental stress testing using a series of the standardized color word/arithmetic stressors. Myocardial blood flow (MBF) during resting and stress phases of CT-MPI was recorded. Fifty-eight patients with 986 segments were included for final analysis. Compared to patients with none, minimal, mild, and moderate anxiety, those with severe anxiety had the largest rate of MBF decrease and the largest MBF decrease value. At the same time, those with no anxiety had the largest rate of MBF increase, the largest MBF increase value (all p< 0.05). As anxiety intensified, the rate of MBF increased and the MBF value increased (r= -0.24, r= -0.27, p< 0.05). Concomitantly, the rate of MBF decreased and the MBF value decreased (r= 0.63, r= 0.43, p< 0.05). Dynamic CT-MPI with a mental stress test can be used to evaluate MMP in patients with anxiety and INOCA. Mental stress resulted in significant differences in changes in the rate and value of MBF among patients with different anxiety degrees. • Dynamic CT-MPI with mental stress test worked well to quantitatively evaluate myocardial microcirculation perfusion in patients with anxiety and INOCA. • The rates of MBF decrease and MBF decrease value were positively correlated with anxiety degree of anxiety patients with INOCA. • MBF change derived from CT-MPI with mental stress test had a good performance to predicting anxiety degree of patients with anxiety and INOCA.

Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report

ObjectiveCardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and < 80%), with or without previous percutaneous coronary intervention (> 6 months) but no HF.MethodsThis was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by 13N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT 03313752).Results16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 μmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 μmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; pint = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; pint = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054).ConclusionsSGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction.Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752

INOCA: Non-Invasive Assessment of the Pathophysological Mechanisms Using CZT-SPECT

Background: One of the causes of INOCA (Ischemia with Non- Obstructive Coronary Arteries) is microvascular dysfunction (MVD), which can be noninvasively assessed through the quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Dynamic myocardial perfusion imaging (MPI) by CZT-SPECT at rest, with dipyridamole stress test and cold pressor test (CPT) can establish the presence of two different pathophysiological mechanisms of MVD: endothelium-independent or endothelium-dependent, respectively. Objectives: The aim of this study was to evaluate the usefulness of CZT-SPECT for the diagnosis of MVD and the different mechanisms involved in patients with INOCA. Materials and Methods: A total of 93 consecutive INOCA patients were prospectively included and underwent dynamic MPI with CZT-SPECT at rest and with dipyridamole stress test and CPT. THe MBF was quantified using 4DM® software. A MFR response to dipyridamole &lt;2, and changes in MBF (ΔMBF) &lt;1.5 with CPT were considered abnormal responses. MVD was defined in the presence of one abnormal response or both. Results: CZT-SPECT detected MVD in 85% (n = 79) of the patients with INOCA. Forty-two percent had an abnormal response to both stressors while 43% presented an abnormal response of MBF only with CPT. Conclusion: The use of CZT-SPECT with both stress tests allowed the evaluation of different possible pathophysiological mechanisms of MVD present in most patients with INOCA

Effects of passive heat exposure on myocardial blood flow in healthy young and older adults

INTRODUCTIONExtreme heat is associated with a greater risk of cardiovascular mortality in older adults (≥60 years). However, the pathophysiology that links extreme heat and cardiovascular mortality remains unknown. One possibility is that myocardial oxygen requirements during heat exposure cannot be met by sufficient increased in myocardial blood flow (MBF) thereby predisposing to ischemia. However, the extent to which MBF increases during heat exposure, and whether age alters this increase, is unknown. The objective of this study was to test the hypothesis that passive heat exposure increases MBF and that this increase is attenuated in healthy older adults.METHODSMBF was measured during passive heat exposure (water‐perfused suit) in 15 young (27 years, range: 24‐30) and 14 older (68 years, range: 64‐72) healthy adults with 82‐Rubidium positron emission tomography. Four MBF measurements were performed: prior to heat exposure (baseline) and at an increase in rectal temperature of 0.5°C, 1.0°C, and 1.5°C. Heart rate (ECG) and blood pressure (automated auscultation) were also measured to calculate rate pressure product (RPP; heart rate x systolic blood pressure). MBF reserve (MFR) was calculated by dividing the MBF at 1.5°C by baseline MBF.RESULTSBaseline MBF was 0.76 ± 0.19 mL/min/g in young adults and 0.88 ± 0.21 mL/min/g in older adults (p=0.14). MBF increased similarly in both groups during heat exposure (interaction, p=0.31). Nonetheless, older adults displayed a lower MFR at an increase in rectal temperature of 1.5°C (young: 2.3 ± 0.7 vs. older: 1.8 ± 0.4, p=0.03). The lower MFR in older adults was paralleled by an attenuated increase in RPP during passive heating (at + 1.5°C, young: 6.8 ± 1.7vs. older: 3.6 ± 2.2 bpm·mmHg·103, p&lt;0.01), due to a blunted increase in heart rate (young: 50 ± 12vs. older: 34 ± 14 bpm, p&lt;0.01). When the change in MBF was plotted against the change in RPP, the slope of the regression lines did not differ between young (0.11 [95% CI; 0.07, 0.15]) and older (0.08 [95% CI; 0.04, 0.11] mL/g/min/ bpm·mmHg·103,p=0.24) adults.CONCLUSIONThese results show that passive heat exposure roughly doubles MBF in healthy young and older adults. Furthermore, the results demonstrate that the increase in MBF during passive heat exposure is not altered by age and is proportional to the increase in RPP.

Microcirculatory Function in Nonhypertrophic and Hypertrophic Myocardium in Patients With Aortic Valve Stenosis.

BackgroundLeft ventricular hypertrophy (LVH) has often been supposed to be associated with abnormal myocardial blood flow and resistance. The aim of this study was to evaluate and quantify the physiological and pathological changes in myocardial blood flow and microcirculatory resistance in patients with and without LVH attributable to severe aortic stenosis.Methods and ResultsAbsolute coronary blood flow and microvascular resistance were measured using a novel technique with continuous thermodilution and infusion of saline. In addition, myocardial mass was assessed with cardiac magnetic resonance imaging. Fifty‐three patients with aortic valve stenosis were enrolled in the study. In 32 patients with LVH, hyperemic blood flow per gram of tissue was significantly decreased compared with 21 patients without LVH (1.26±0.48 versus 1.66±0.65 mL·min−1·g−1; P=0.018), whereas minimal resistance indexed for left ventricular mass was significantly increased in patients with LVH (63 [47–82] versus 43 [35–63] Wood Units·kg; P=0.014).ConclusionsPatients with LVH attributable to severe aortic stenosis had lower hyperemic blood flow per gram of myocardium and higher minimal myocardial resistance compared with patients without LVH.

Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2.

Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO2 ). Cardiac T2 is sensitive to these changes and therefore is a promising non-contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14-0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2= 37.6-41.8 ms; MBF = 0.48-1.32 mL/min/g; RPP = 6507-4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant β-values >7). Myocardial oxygen consumption had almost no effect on T2 (β-values <0.002); since PvO2 is influenced by both oxygen consumption and MBF, PvO2 changes detected by T2 during adenosine stress can be attributed to MBF. Simulations varying PvO2 and MBV confirmed that PvO2 had the strongest influence on T2, but MBV became important at high PvO2 . Together, these data suggest a model where, during adenosine stress, myocardial T2 responds predominantly to changes in MBF, but at high hyperemia MBV is also influential. Thus, changes in adenosine stress T2 can now be interpreted in terms of the physiological changes that led to it, enabling T2 mapping to become a viable non-contrast option to detect ischemic myocardial tissue.

Mechanistic insights from a multiparametric magnetic resonance imaging study regarding the role of sodium glucose co-transporter 2 inhibitors

Abstract Background Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF) and cardiovascular (CV) mortality. Sodium–glucose-co transporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalisation for HF in T2D patients with high cardiovascular risk, despite only a modest improvement in glycemic control. Restoring cellular energy homeostasis and reversing adverse cardiac remodelling in diabetes have been speculated as a potential metabolic modulatory effect of SGLT2 inhibitors leading to their beneficial CV outcomes. Myocardial energy deficient states can be detected non-invasively by 31-phosphorus magnetic resonance spectroscopy (31P-MRS). Objectives Utilising cardiovascular magnetic resonance imaging (CMR) and 31P-MRS in a single centre longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics, function, perfusion, and myocardial cellular volume in patients with T2D. Methods Eighteen consecutive T2D patients who were commenced on empagliflozin in cardiometabolic optimisation clinics underwent CMR and 31P-MRS scans before and after twelve-week empagliflozin treatment, and plasma N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten controls with no diabetes underwent an identical 31P-MRS and CMR protocol on a single visit. Results When compared to controls, patients with T2D showed: lower myocardial energetics (1.52±0.40 vs 2.20±0.5, p=0.0005), lower stress myocardial blood flow (1.60±0.50 vs 2.10±0.50, p=0.02) and lower left ventricular ejection fraction (52±13% vs 63±4%, p=0.01). Treatment with empagliflozin led to significant improvements in myocardial energetics (PCr/ATP: 1.52 to 1.76, p=0.009). This was accompanied by a relative 13% improvement in left ventricular ejection fraction (p=0.001), 3% improvement in global longitudinal strain (p=0.01), 61% reduction in NTproBNP (p=0.05), and 9% reduction in myocardial cell volume (p=0.04). No significant change in myocardial blood flow or diastolic strain was detected. Conclusions For the first time, we demonstrate that empagliflizon improves myocardial energetics and function, reduces myocardial cellular volume, and reduces NT-proBNP levels in patients with T2D. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation PCr/ATPLVEF

Empagliflozin Treatment Is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes.

Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization for heart failure (HF) in patients with type 2 diabetes (T2D). Using CV MRI (CMR) and 31P-MRS in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics and cellular volume, function, and perfusion. Eighteen patients with T2D underwent CMR and 31P-MRS scans before and after 12 weeks’ empagliflozin treatment. Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten volunteers with normal glycemic control underwent an identical scan protocol at a single visit. Empagliflozin treatment was associated with significant improvements in phosphocreatine-to-ATP ratio (1.52 to 1.76, P = 0.009). This was accompanied by a 7% absolute increase in the mean left ventricular ejection fraction (P = 0.001), 3% absolute increase in the mean global longitudinal strain (P = 0.01), 8 mL/m2 absolute reduction in the mean myocardial cell volume (P = 0.04), and 61% relative reduction in the mean NT-proBNP (P = 0.05) from baseline measurements. No significant change in myocardial blood flow or diastolic strain was detected. Empagliflozin thus ameliorates the “cardiac energy-deficient” state, regresses adverse myocardial cellular remodeling, and improves cardiac function, offering therapeutic opportunities to prevent or modulate HF in T2D.

No changes in myocardial perfusion following radiation therapy of left-sided breast cancer: A positron emission tomography study

BackgroundAdjuvant radiation therapy (RT) for breast cancer has improved overall survival. However, incidental exposure of the heart has been linked to development of radiation-induced heart disease. The aim of this study was, in a cohort of asymptomatic post-irradiation breast cancer patients, to investigate changes in myocardial blood flow (MBF) and presence of perfusion defects in myocardial perfusion positron-emission-tomography (PET) in the irradiated myocardium. Methods and ResultsTwenty patients treated with RT for left-sided breast cancer underwent 13N-ammonia myocardial perfusion PET 7(± 2) years after breath adapted RT to a total dose of 48 Gy given in 24 fractions. No differences in rest or stress MBF were noted between the irradiated and non-irradiated myocardium (1.29 (± 0.29) vs 1.33 (± 0.29) mL/g/min, ns; 2.74 (± 0.59) vs 2.78 (± 0.66) mL/g/min, ns, respectively). One patient demonstrated a myocardial perfusion defect localized in the irradiated anterior wall myocardium. ConclusionAlthough limited by a small sample size, early signs of cardiac injury detected by NH3 myocardial perfusion PET was at least not frequent in our cohort of patients treated with a modern RT technique for left-sided breast cancer, even 7 years after treatment. The findings however, may not rule out subsequent development of myocardial injury.

Effect of Dapagliflozin on Myocardial Insulin Sensitivity and Perfusion: Rationale and Design of The DAPAHEART Trial.

IntroductionSodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to have beneficial effects on various cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) in primary prevention and in those with a high CV risk profile. However, the mechanism(s) responsible for these CV benefits remain elusive and unexplained. The aim of the DAPAHEART study will be to demonstrate that treatment with SGLT-2 inhibitors is associated with greater myocardial insulin sensitivity in patients with T2D, and to determine whether this improvement can be attributed to a decrease in whole-body (and tissue-specific) insulin resistance and to increased myocardial perfusion and/or glucose uptake. We will also determine whether there is an appreciable degree of improvement in myocardial-wall conditions subtended by affected and non-affected coronary vessels, and if this relates to changes in left ventricular function.MethodsThe DAPAHEART trial will be a phase III, single-center, randomized, two-arm, parallel-group, double-blind, placebo-controlled study. A cohort of 52 T2D patients with stable coronary artery disease (without any previous history of myocardial infarction, with or without previous percutaneous coronary intervention), with suboptimal glycemic control (glycated hemoglobin [HbA1c] 7–8.5%) on their current standard of care anti-hyperglycemic regimen, will be randomized in a 1:1 ratio to dapagliflozin or placebo. The primary outcome is to detect changes in myocardial glucose uptake from baseline to 4 weeks after treatment initiation. The main secondary outcome will be changes in myocardial blood flow, as measured by 13N-ammonia positron emission tomography/computed tomography (PET/CT). Other outcomes include cardiac function, glucose uptake in skeletal muscle, adipose tissue, liver, brain and kidney, as assessed by fluorodeoxyglucose (FDG) PET-CT imaging during hyperinsulinemic-euglycemic clamp; pericardial, subcutaneous and visceral fat, and browning as observed on CT images during FDG PET-CT studies; systemic insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamp, glycemic control, urinary glucose output; and microbiota modification.DiscussionSGLT-2 inhibitors, in addition to their insulin-independent plasma glucose-lowering effect, are able to directly (substrate availability, fuel utilization, insulin sensitivity) as well as indirectly (cardiac after-load reduction, decreased risk factors for heart failure) affect myocardial functions. Our study will provide novel insights into how these drugs exert CV protection in a diabetic population.Trial registrationEudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01083-1.

Myocardial blood flow during passive heat exposure in healthy young adults

INTRODUCTION Extreme heat events, such as heatwaves, are associated with a greater risk of cardiovascular mortality. However, the pathophysiology that links extreme heat and cardiovascular mortality remains unknown. Upon exposure to a hot environment, cardiac contractility and heart rate increase thereby presumably increasing myocardial metabolism. Although greater oxygen extraction contributes, an increase in myocardial metabolism is primarily met by greater myocardial blood flow. It is therefore conceivable that the required myocardial blood flow during heat exposure exceeds the capacity for myocardial blood flow to increase in vulnerable individuals. However, the extent to which myocardial blood flow increases during heat exposure is unknown. The purpose of this study is to test the hypothesis that passive heat exposure increases myocardial blood flow. METHODS Five healthy adults (31 ± 3 years, 2 women/3 men) participated in 1 experimental visit during which myocardial blood flow was measured by positron emission computed/tomography. Measurements were performed at baseline and during passive heat stress (water-perfused suit with water at 50°C) at an increase in core (rectal) temperature of 0.5°C, 1.0°C, and 1.5°C. Heart rate and rhythm (ECG) and blood pressure (automated auscultation) were also measured. RESULTS Relative to baseline, rate pressure product was greater at an increase in rectal temperature of 0.5°C (+4165 ± 623 bpm × mmHg, p=0.01), 1.0°C (+5015 ± 519 bpm × mm Hg, p<0.01) and 1.5°C (+7516 ± 261 bpm × mm Hg, p<0.01). The increase in rate pressure product was primarily due to an increase in heart rate (p<0.01), as systolic blood pressure was not affected by heat exposure (p=0.12). Relative to baseline values, myocardial blood flow increased at an increase in rectal temperature of 0.5°C (+0.45 ± 0.09 mL/min/g, p=0.03), 1.0°C (+0.61 ± 0.06 mL/min/g, p<0.01) and 1.5°C (+1.10 ± 0.22 mL/min/g, p=0.02). Overall, myocardial blood flow increased 2.7 ± 1.0-fold relative to baseline at an increase in rectal temperature of 1.5°C. The change in myocardial blood flow during heat exposure correlated with the change in rate pressure product (r=0.78, p<0.01). CONCLUSION These results suggest that passive heat exposure increases myocardial blood flow in proportion with the increase in rate pressure product in young healthy adults.

Assessing mental stress on myocardial perfusion and myocardial blood flow in women without obstructive coronary disease: protocol for a mechanistic clinical trial

IntroductionTwo-thirds of women with symptoms of angina have ‘angina with no obstructive coronary artery disease’ (ANOCA). Growing evidence supports the use of coronary artery function testing for the diagnosis of...

Impact of rapid versus gradual changes in arterial partial pressure of carbon dioxide on blood flow and myocardial oxygenation in an experimental anaesthetized model

Introduction Hyper- and hypocapnia have known vaso-modulatory effects in the coronary circulation. Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) detects changes in tissue oxygenation and can provide a comprehensive assessment of the impact of systemic blood gas changes on the myocardium. The purpose of this study was to compare the physiological responses to rapid blood gas changes induced by hyperventilation followed by apnea in comparison to steady-state levels of hypocapnia and hypercapnia in an experimental animal model. Methods Eighteen anaesthetized female swine were used in this study. A blood flow probe was attached to the left descending coronary artery (LAD) after a left-sided thoracotomy. In ten animals a hemodynamically significant LAD stenosis was induced, while eight animals served as controls. In a 3 Tesla MRI, paCO2 was modulated from a pre-set baseline (paO2=100mmHg/paCO2=40mmHg) to 30mmHg and subsequently 50mmHg by minor changes in ventilation rate. Rapid changes in paCO2 were achieved by 60s of hyperventilating (30/min) from baseline followed by an apnea of up to 90 seconds. OS-CMR images, coronary blood flow (CBF) of the LAD and arterial blood gases were recorded at each state. Results Targeting stable hypocapnia of 30mmHg from baseline did not alter CBF or myocardial oxygenation. Subsequent stable hypercapnia (paCO2=50mmHg) increased CBF significantly in control (5±5%, p=0.007) and stenosed (4±6%, p=0.036) animals, and myocardial oxygenation rose in both post-stenotic territories (4.2±6.2%, p=0.036) and in control subjects (6.2±6.2%, p=0.011). Rapid hyperventilation induced a similar degree of hypocapnia (control: paCO2=25±7mmHg, stenosed: 27±3mmHg) and showed a significant decrease of CBF by -34±23% (p=0.012) in healthy animals, and a significant decrease of -10±6% (p=0.010) in stenosed animals. This had no effect on tissue oxygenation. Apnea resulted in a similar paCO2 (control: paCO2=52±9mmHg, stenosed: 47±7mmHg) compared to steady-state blood gas levels, which increased CBF significantly in controls 346±327% (p=0.008) and stenosed 82±110 (p=0.039) animals markedly. By the end of apnea, a rise in tissue oxygenation of 2.9±2.2% was observed in controls (p=0.008), -2.7±5.1 (0.125) was observed in the stenosed group (Figure). Significant difference in myocardial oxygenation responses observed between control and stenosed subject was exclusively observed with apnea (p=0.011). Discussion Rapid hyperventilation followed by apnea results in more pronounced changes in myocardial blood flow than similar steady state deflections in paCO2. Only apnea after hyperventilation induced deoxygenation in the stenotic myocardium, which is in agreement with the concept of hypercapnia induced intercoronary steal, while steady state deviation did not compromise myocardial oxygenation. Similar breathing maneuvers may be seen in the induction phase of anaesthesia, which could potentially be a harbinger of perioperative ischemic myocardial events.