Infrared thermography for normal endothelial function screening.

BACKGROUND: Endothelial dysfunction (ED) suspicion will allow to prevent accelerated atherosclerosis and premature death. OBJECTIVE: To establish the usefulness of thermography for endothelial function screening in adults with cardiovascular risk factors. MATERIAL AND METHODS: Cross-sectional, analytical diagnostic test. A brachial arterial diameter (BAD) increase < 11% at one-minute post-ischemia meant probable ED and was confirmed if BAD was ≥ 11% post-sublingual nitroglycerin. Thermographic photographs of the palmar region were obtained at one minute. Descriptive statistics, ROC curve, Mann-Whitney's U-test, chi-square test, or Fisher's exact test were used. RESULTS: Thirty-eight subjects with a median age of 50 years, and with 624 thermographic measurements were included. Nine had ED (flow-mediated vasodilation [FMV]: 2.5%). The best cutoff point for normal endothelial function in subjects with cardiovascular risk factors was ≥ 36 °C at one minute of ischemia, with 85% sensitivity, 70% specificity, positive and negative predictive values of 78 and 77%, area under the curve of 0.796, LR+ 2.82, LR- 0.22. CONCLUSION: An infrared thermography-measured temperature in the palmar region greater than or equal to 36 °C after one minute of ischemia is practical, non-invasive, and inexpensive for normal endothelial function screening in adults with cardiovascular risk factors.

ANTECEDENTES: La sospecha de disfunción endotelial (DE) permitirá prevenir la aterosclerosis acelerada y la muerte prematura. OBJETIVO: Establecer la utilidad de la termografía en el cribado de la función endotelial en adultos con factores de riesgo cardiovascular. MATERIAL Y MÉTODOS: Estudio transversal analítico de prueba diagnóstica. El incremento del diámetro de la arteria braquial < 11 % a un minuto posisquemia significó probable DE, confirmada si el diámetro fue ≥ 11 % posnitroglicerina sublingual. Se obtuvieron fotografías termográficas al minuto de la región palmar. Se aplicó estadística descriptiva, curva ROC, pruebas U de Mann-Whitney, chi cuadrada o exacta de Fisher. RESULTADOS: Se incluyeron 38 sujetos, mediana de edad de 50 años, con 624 mediciones termográficas; nueve presentaron DE (vasodilatación mediada por flujo de 2.5 %). El mejor punto de corte para la función endotelial normal en sujetos con factores de riesgo cardiovascular fue ≥ 36 °C al minuto de isquemia, con sensibilidad de 85%, especificidad de 70%, valores predictivos positivo y negativo de 78 y 77%, área bajo la curva de 0.796, razón de verisimilitud positiva de 2.82 y razón de verisimilitud negativa de 0.22. CONCLUSIÓN: La medición de la temperatura en la región palmar mediante termografía infrarroja ≥ 36 °C tras un minuto de isquemia es práctica, no invasiva y económica para el cribado de la función endotelial normal en adultos con factores de riesgo cardiovascular.

Noninvasive assessment of human microvascular function in health and disease using incident dark-field microscopy.

Reduced peripheral microvascular reactivity is associated with an increased risk for major adverse cardiac events (MACEs). Tools for noninvasive assessment of peripheral microvascular function are limited, and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we used a handheld incident dark-field imaging tool (CytoCam) to test the hypothesis that, compared with healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥2 risk factors for CAD (at risk) would exhibit impaired peripheral microvascular reactivity. A total of 17 participants (11 healthy, 6 at risk) were included in this pilot study. CytoCam was used to measure sublingual microvascular total vessel density (TVD), perfused vessel density (PVD), and microvascular flow index (MFI) in response to the topical application of acetylcholine (ACh) and sublingual administration of nitroglycerin (NTG). Baseline MFI and PVD were significantly reduced in the at-risk cohort compared with healthy individuals. Surprisingly, following the application of acetylcholine and nitroglycerin, both groups showed a significant improvement in all three microvascular perfusion parameters. These results suggest that, despite baseline reductions in both microvascular density and perfusion, human in vivo peripheral microvascular reactivity to both endothelial-dependent and -independent vasoactive agents remains intact in individuals with CAD or multiple risk factors for disease.NEW & NOTEWORTHY To our knowledge, this is the first study to comprehensively characterize in vivo sublingual microvascular structure and function (endothelium-dependent and -independent) in healthy patients and those with CVD. Importantly, we used an easy-to-use handheld device that can be easily translated to clinical settings. Our results indicate that baseline microvascular impairments in structure and function can be detected using the CytoCam technology, although reactivity to acetylcholine may be maintained even during disease in the peripheral microcirculation.

Optimization of cardiopulmonary bypass prime fluid to preserve microcirculatory perfusion during on-pump coronary artery bypass graft surgery: PRIME study protocol for a double-blind randomized trial.

BACKGROUND: Acute microcirculatory perfusion disturbances and organ edema are important factors leading to organ dysfunction during cardiac surgery with cardiopulmonary bypass (CPB). Priming of the CPB system with crystalloid or colloid fluids, which inevitably leads to hemodilution, could contribute to this effect. However, there is yet no optimal evidence-based strategy for this type of priming. Hence, we will investigate different priming strategies to reduce hemodilution and preserve microcirculatory perfusion. METHODS: The PRIME study is a single-center double-blind randomized trial. Patients undergoing elective coronary artery bypass graft surgery with CPB will be randomized into three groups of prime fluid strategy: (1) gelofusine with crystalloid, (2) albumin with crystalloid, or (3) crystalloid and retrograde autologous priming. We aim to include 30 patients, 10 patients in each arm. The primary outcome is the change in microcirculatory perfusion. Secondary outcomes include colloid oncotic pressure; albumin; hematocrit; electrolytes; fluid balance and requirements; transfusion rates; and endothelial-, glycocalyx-, inflammatory- and renal injury markers. Sublingual microcirculatory perfusion will be measured using non-invasive sidestream dark field video microscopy. Microcirculatory and blood measurements will be performed at five consecutive time points during surgery up to 24 h after admission to the intensive care unit. DISCUSSION: PRIME is the first study to assess the effect of different prime fluid strategies on microcirculatory perfusion in cardiac surgery with CPB. If the results suggest that a specific crystalloid or colloid prime fluid strategy better preserves microcirculatory perfusion during on-pump cardiac surgery, the current study may help to find the optimal pump priming in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05647057. Registered on 04/25/2023. CLINICALTRIALS: gov PRS: Record Summary NCT05647057, all items can be found in the protocol.

Preserved endothelium-independent vascular function with aging in men and women: evidence from the peripheral and cerebral vasculature.

In the peripheral and cerebral vasculature, the impact of aging and sex on the endothelial-independent functional capacity of vascular smooth muscle cells (VSMCs) is not well understood, nor is it known whether such VSMC functions in these vascular beds reflect one another. Therefore, endothelium-independent dilation, at both the conduit (Δ diameter) and microvascular (Δ vascular conductance, VC) level, elicited by sublingual nitroglycerin (NTG, 0.8 mg of Nitrostat), compared with sham-delivery (control), was assessed using Doppler ultrasound in the popliteal (PA) and middle cerebral (MCA) artery of 20 young [23 ± 4 yr, 10 males (YM)/10 females (YF)] and 21 old [69 ± 5 yr, 11 males (OM)/10 females (OF)] relatively healthy adults. In the PA, compared with zero, NTG significantly increased diameter in all groups (YM: 0.29 ± 0.13, YF: 0.35 ± 0.26, OM: 0.30 ± 0.18, OF: 0.31 ± 0.14 mm), while control did not. The increase in VC only achieved significance in the OF (0.22 ± 0.31 mL/min/mmHg). In the MCA, compared with zero, NTG significantly increased diameter and VC in all groups (YM: 0.89 ± 0.30, 1.06 ± 1.28; YF: 0.97 ± 0.31, 1.84 ± 1.07; OM: 0.90 ± 0.42, 0.72 ± 0.99; OF: 0.74 ± 0.32, 1.19 ± 1.18, mm and mL/min/mmHg, respectively), while control did not. There were no age or sex differences or age-by-sex interactions for both the NTG-induced PA and MCA dilation and VC. In addition, PA and MCA dilation and VC responses to NTG were not related when grouped by age, sex, or as all subjects (r = 0.04-0.44, P > 0.05). Thus, peripheral and cerebral endothelial-independent VSMC function appears to be unaffected by age or sex, and variations in such VSMC function in one of these vascular beds are not reflected in the other.NEW & NOTEWORTHY To confidently explain peripheral and cerebral vascular dysfunction, it is essential to have a clear understanding of the endothelial-independent function of VSMCs across age and sex. By assessing endothelium-independent dilation using sublingual nitroglycerin, endothelial-independent VSMC function in the periphery (popliteal artery), and in the cerebral circulation (middle cerebral artery), was not different due to age or sex. In addition, endothelial-independent VSMC function in one of these vascular beds is not reflected in the other.

Post-partum myocardial ischemia due to intramuscular methylergonovine-induced coronary vasospasm: case report.

BACKGROUND: Methylergonovine is a vasoconstrictive agent historically used as a provocative agent in the lab for coronary vasospasm; it is also a first line uterotonic agent for management of postpartum hemorrhage. CASE PRESENTATION: A 29-year-old female with history of smoking and idiopathic thrombocytopenia received intramuscular methylergonovine after delivery of twins for intrauterine hemorrhage management. Subsequently, she had episodes of chest pain with high sensitivity Troponin I elevation to 1509 ng/L with accompanying septal T wave inversions, decreased left ventricular ejection fraction to 49% and basal septal wall hypokinesis. Computed tomography (CT) coronary angiogram showed patent coronary arteries and no coronary arterial dissection. The patient was conservatively managed with aspirin and metoprolol, and on follow up had fully recovered left ventricular function with resolution of wall motion abnormalities. Given this, coronary vasospasm due to intramuscular methylergonovine is the most likely cause of patient's chest pain and associated myocardial ischemia. CONCLUSIONS: Intramuscular, intrauterine, intravenous, and even oral methylergonovine can rarely cause coronary vasospasm leading to myocardial ischemia. Cardiologists caring for postpartum patients should be aware of these potential lethal complications; prompt identification and administration of sublingual nitroglycerin can prevent severe complications of arrythmias, heart block, or cardiac arrest.

Can Sublingual Nitrate Improve Visualization of Lower Limb Arteries on Computed Tomography Angiography?

OBJECTIVE: The aim of the study is to evaluate the role of sublingual nitrate in improving vessel visualization on peripheral computed tomography angiography (CTA). METHODS: Fifty patients clinically diagnosed with peripheral arterial disease of the lower limb were prospectively included in this study: Twenty-five underwent CTA after sublingual nitrate administration (nitrate group) and 25 without (non-nitrate group). Two blinded observers qualitatively and quantitatively assessed the data thus generated. The mean luminal diameter, intraluminal attenuation, site, and percentage of stenosis were evaluated in all segments. Assessment of collateral visualization at sites of significant stenosis was also done. RESULTS: Patients in the nitrate and non-nitrate groups were similar in age and sex characteristics ( P > 0.05).On subjective evaluation, there was significantly improved visualization of the femoropopliteal and tibioperoneal vasculature of the lower limb in the nitrate group compared with the non-nitrate group ( P < 0.05). Quantitative evaluation showed a statistically significant difference in the measured arterial diameters for all evaluated segments in the nitrate group versus the non-nitrate group ( P < 0.05). Intra-arterial attenuation was significantly greater for all segments in the nitrate group resulting in better contrast opacification in these studies. Collateral visualization around segments with more than 50% stenosis/occlusion was also better in the nitrate group. CONCLUSIONS: Our study suggests that nitrate administration before peripheral vascular CTA can improve visualization, especially in the distal segments by increasing the vessel diameter and intraluminal attenuation along with better delineation of the collateral circulation around stenotic areas. It may also improve the number of evaluable segments of vasculature in these angiographic studies.

Can Significant Coronary Artery Disease Coexist With Transient Takotsubo Cardiomyopathy, and How Does Spasm Interrelate?

An 86-year-old woman being treated for metastatic breast cancer developed severe chest pain at rest during a follow-up visit at a hospital's outpatient oncology clinic. An electrocardiogram showed severe ST-segment elevation. The patient was given sublingual nitroglycerin and was transferred to the emergency department. Diagnostic coronary angiography revealed moderate coronary artery disease with calcific stenoses and transient spastic occlusion of the left anterior descending coronary artery. For this patient, sublingual nitroglycerin aborted the spastic event and apparent transient takotsubo cardiomyopathy. Chemotherapy can potentially cause endothelial dysfunction and increased coronary spasticity, which could result in takotsubo cardiomyopathy.

An acute bout of prolonged sitting blunts popliteal endothelium-independent dilation in young, healthy adults.

A single bout of prolonged uninterrupted sitting increases oxidative stress, reduces popliteal blood flow-induced shear stress, and diminishes endothelium-dependent, flow-mediated dilation (FMD). The FMD response is also influenced by the sensitivity of vascular smooth muscle cells to nitric oxide (i.e., endothelium-independent dilation), which is also attenuated by elevated oxidative stress. However, it is currently unknown whether prolonged sitting impacts popliteal endothelium-independent dilation responses, which may uncover a novel mechanism associated with sitting-induced vascular dysfunction. This study tested the hypothesis that prolonged sitting attenuates both popliteal FMD and endothelium-independent, nitroglycerin-mediated dilation responses (NMD, 0.4 mg sublingual dose). Popliteal blood flow (mL/min), relative FMD (%), and NMD (%) were assessed via duplex ultrasonography before and after a ∼3-h bout of sitting in 14 young, healthy adults (8♀; 22 ± 2 yr). Prolonged sitting attenuated resting blood flow (57 ± 23 to 32 ± 16 mL/min, P < 0.001), relative FMD (4.6 ± 2.8% to 2.2 ± 2.5%; P = 0.001), and NMD (7.3 ± 4.0% to 4.6 ± 3.0%; P = 0.002). These novel findings demonstrate that both endothelium-dependent and independent mechanisms contribute to the adverse vascular consequences associated with prolonged bouts of sitting.NEW & NOTEWORTHY We demonstrate that lower-limb vascular smooth muscle function is attenuated in young, healthy adults after an acute bout of prolonged sitting. These data indicate that prolonged sitting-induced vascular dysfunction involves both endothelium-dependent and -independent mechanisms.

Challenging the Hemodynamic Hypothesis in Heart Failure With Preserved Ejection Fraction: Is Exercise Capacity Limited by Elevated Pulmonary Capillary Wedge Pressure?

BACKGROUND: Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP should improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin to acutely lower PCWP during exercise in patients with HFpEF. METHODS: Thirty patients with HFpEF (70±6 years of age; 63% female) underwent 2 bouts of upright, seated cycle exercise dosed with sublingual nitroglycerin or placebo control every 15 minutes in a single-blind, randomized, crossover design. PCWP (right heart catheterization), oxygen uptake (breath × breath gas exchange), and cardiac output (direct Fick) were assessed at rest, 20 Watts (W), and peak exercise during both placebo and nitroglycerin conditions. RESULTS: PCWP increased from 8±4 to 35±9 mm Hg from rest to peak exercise with placebo. With nitroglycerin, there was a graded decrease in PCWP compared with placebo at rest (-1±2 mm Hg), 20W (-5±5 mm Hg), and peak exercise (-7±6 mm Hg; drug × exercise stage P=0.004). Nitroglycerin did not affect oxygen uptake at rest, 20W, or peak (placebo, 1.34±0.48 versus nitroglycerin, 1.32±0.46 L/min; drug × exercise P=0.984). Compared with placebo, nitroglycerin lowered stroke volume at rest (-8±13 mL) and 20W (-7±11 mL), but not peak exercise (0±10 mL). CONCLUSIONS: Sublingual nitroglycerin lowered PCWP during submaximal and maximal exercise. Despite reduction in PCWP, peak oxygen uptake was not changed. These results suggest that acute reductions in PCWP are insufficient to improve exercise capacity, and further argue that high PCWP during exercise is not by itself a limiting factor for exercise performance in patients with HFpEF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04068844.

Case Report: Central retinal artery occlusion following sildenafil intake.

Purpose: To report a case of central retinal artery occlusion associated with sildenafil intake and briefly discuss its causative pathogenesis. Methods: A 50-year-old man with no premorbidities presented with symptoms of sudden severe visual field constriction in the left eye (LE). Best-corrected visual acuity in the LE was 20/25. Fundus examination and fluorescein angiography of the LE were suggestive of central retinal artery occlusion (CRAO) with cilioretinal artery sparing. Further investigation revealed that 100 mg of sildenafil had been taken for the first time three hours before the onset of symptoms. Results: The patient was treated promptly with intravenous acetazolamide, sublingual isosorbide dinitrate and ocular massage, but without visual recovery. No other associated systemic or local risk factors were found, and the case was classified as a potential complication of sildenafil. Conclusion: Although no direct link could be established, the aim of this report is to highlight the incidence and to consider this issue when evaluating any case of central retinal artery occlusion.

Effect of transradial catheterization and nifedipine on flow- and nitroglycerin-mediated dilations of distal and proximal radial artery.

OBJECTIVE: Radial artery (RA) dysfunction after transradial access intervention is not limited to the distal portion but can also occur in the proximal portion of RA. The aim of the present study was to assess the effect of sublingual nifedipine administrated prior to puncture on the endothelial function of distal and proximal RA. METHODS: Eighty-nine patients who underwent coronary angiography (CAG) were randomly assigned to the nifedipine group ( n = 45) or control group ( n = 44). The flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of distal and proximal RA were measured at baseline, 24 h, and 48 h after transradial angiography. RESULTS: Compared with the control group, the nifedipine group only limited the reduction of FMD in the distal RA at 24 and 48 h [6.52 ± 1.40% (24 h) vs. 5.85 ± 1.38% (24 h), P = 0.03; 7.41 ± 1.30% (48 h) vs. 6.65 ± 1.25% (48 h), P = 0.006], whereas FMD alterations in the proximal RA were not restored by nifedipine. Both groups were still lower than baseline values (11.66 ± 2.35% and 11.24 ± 2.22%). We observed similar effects of nifedipine on the NMD of the distal RA. CONCLUSION: Although transradial angiography-induced dysfunction was reported in both distal and proximal RA, nifedipine could help restore the distal endothelial function of the cannulated RA.

Pyridostigmine-induced coronary artery spasm in early-onset myasthenia gravis: a case presentation and review of the literature.

We present a case of pyridostigmine-induced coronary artery spasm in a woman with early-onset myasthenia gravis (MG) who suffered from acute chest discomfort a few days after pyridostigmine dose up-titration. Twelve-lead ECG demonstrated ST-segment elevation in inferior limb leads together with sinus arrest. Sublingual nitrate was immediately given, which rapidly relieved her symptoms concomitantly with the resolution of abnormal ECG findings. Coronary angiography showed normal coronary arteries reflecting the transient nature of the disease. A small dose of pyridostigmine was rechallenged under close monitoring in the coronary care unit and reproduced her chest discomfort. After the substitution of pyridostigmine with immunosuppressive agents and prescription of long-acting nitrate, she had no recurrence of chest discomfort, as well as well-controlled MG symptoms.

Coronary microvascular dysfunction is common in patients hospitalized with COVID-19 infection.

BACKGROUND AND AIMS: Microvascular disease is considered as one of the main drivers of morbidity and mortality in severe COVID-19, and microvascular dysfunction has been demonstrated in the subcutaneous and sublingual tissues in COVID-19 patients. The presence of coronary microvascular dysfunction (CMD) has also been hypothesized, but direct evidence demonstrating CMD in COVID-19 patients is missing. In the present study, we aimed to investigate CMD in patients hospitalized with COVID-19, and to understand whether there is a relationship between biomarkers of myocardial injury, myocardial strain and inflammation and CMD. METHODS: 39 patients that were hospitalized with COVID-19 and 40 control subjects were included to the present study. Biomarkers for myocardial injury, myocardial strain, inflammation, and fibrin turnover were obtained at admission. A comprehensive echocardiographic examination, including measurement of coronary flow velocity reserve (CFVR), was done after the patient was stabilized. RESULTS: Patients with COVID-19 infection had a significantly lower hyperemic coronary flow velocity, resulting in a significantly lower CFVR (2.0 ± 0.3 vs. 2.4 ± 0.5, p < .001). Patients with severe COVID-19 had a lower CFVR compared to those with moderate COVID-19 (1.8 ± 0.2 vs. 2.2 ± 0.2, p < .001) driven by a trend toward higher basal flow velocity. CFVR correlated with troponin (p = .003, r: -.470), B-type natriuretic peptide (p < .001, r: -.580), C-reactive protein (p < .001, r: -.369), interleukin-6 (p < .001, r: -.597), and d-dimer (p < .001, r: -.561), with the three latter biomarkers having the highest areas-under-curve for predicting CMD. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with COVID-19 and is related to the severity of the infection. CMD may also explain the "cryptic" myocardial injury seen in patients with severe COVID-19 infection.

High-resolution non-contrast free-breathing coronary cardiovascular magnetic resonance angiography for detection of coronary artery disease: validation against invasive coronary angiography.

BACKGROUND: Coronary artery disease (CAD) is the single most common cause of death worldwide. Recent technological developments with coronary cardiovascular magnetic resonance angiography (CCMRA) allow high-resolution free-breathing imaging of the coronary arteries at submillimeter resolution without contrast in a predictable scan time of ~ 10 min. The objective of this study was to determine the diagnostic accuracy of high-resolution CCMRA for CAD detection against the gold standard of invasive coronary angiography (ICA). METHODS: Forty-five patients (15 female, 62 ± 10 years) with suspected CAD underwent sub-millimeter-resolution (0.6 mm3) non-contrast CCMRA at 1.5T in this prospective clinical study from 2019-2020. Prior to CCMR, patients were given an intravenous beta blockers to optimize heart rate control and sublingual glyceryl trinitrate to promote coronary vasodilation. Obstructive CAD was defined by lesions with ≥ 50% stenosis by quantitative coronary angiography on ICA. RESULTS: The mean duration of image acquisition was 10.4 ± 2.1 min. On a per patient analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 95% (75-100), 54% (36-71), 60% (42-75) and 93% (70-100), respectively. On a per vessel analysis the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 80% (63-91), 83% (77-88), 49% (36-63) and 95% (90-98), respectively. CONCLUSION: As an important step towards clinical translation, we demonstrated a good diagnostic accuracy for CAD detection using high-resolution CCMRA, with high sensitivity and negative predictive value. The positive predictive value is moderate, and combination with CMR stress perfusion may improve the diagnostic accuracy. Future multicenter evaluation is now required.

Impact of Sublingual Nitroglycerin on the Assessment of Computed Tomography-derived Fractional Flow Reserve: An Intraindividual Comparison Study.

OBJECTIVE: The aim of this study was to investigate the impact of nitroglycerin (NTG) on the assessment of computed tomography-derived fractional flow reserve (CT-FFR). MATERIALS AND METHODS: Seventy-seven patients with suspected coronary artery disease were recruited, and they underwent computed tomography angiography (CCTA) before and after NTG administration. The CT-FFRs were compared at 2 CCTAs. The difference was compared using the Wilcoxon signed rank test. Patients were divided into normal and stenosis groups according to CCTA results. Vessels in the stenosis group were further divided into different groups based on coronary artery calcium score (CACS) and stenosis degree. The poststenotic CT-FFR differences before and after NTG (DCT-FFR) were calculated to evaluate the impact of stenosis degree and CACS. Terminal CT-FFRs derived from CCTAs before and after NTG in total and vessel-specific levels were compared in the normal group. RESULTS: Of 47 patients in the stenosis group, poststenotic CT-FFR was significantly increased after NTG at per-vessel level. By taking CT-FFR of 0.75 or lower as the threshold, 5 and 4 patients showed abnormal CT-FFR before and after NTG, respectively. No significant differences were noted among the various stenosis degree and CACS groups regarding DCT-FFR. Of 30 patients in the normal group, terminal CT-FFR was significantly increased after NTG in total level and vessel-specific level of left anterior descending and right coronary artery, but not in the left circumflex. CONCLUSIONS: Both post lesion and distal vessel CT-FFR significantly improved after the administration of GTN with the degree of change not affected by stenosis severity or CACS.

Clinical Application of Non-Contrast-Enhanced Dixon Water-Fat Separation Compressed SENSE Whole-Heart Coronary MR Angiography at 3.0 T With and Without Nitroglycerin.

BACKGROUND: 3.0 T non-contrast-enhanced nitroglycerin (NTG)-assisted whole-heart coronary magnetic resonance angiography (MRA) employing Dixon water-fat separation and compressed SENSE (CS-SENSE) acceleration is a promising method for diagnosing coronary artery disease (CAD). PURPOSE: To evaluate the diagnostic performance of this technique for detecting clinically-relevant (≥50% diameter reducing) CAD and to evaluate the difference in NTG-induced coronary vasodilation between patients with and without clinically-relevant CAD. STUDY TYPE: Prospective. POPULATION: Sixty-six patients with suspected CAD. FIELD STRENGTH/SEQUENCE: 3.0 T; CSSENSE, Dixon water-fat separation, three-dimensional segmented turbo field gradient-echo sequence for whole-heart coronary MRA. ASSESSMENT: Overall image quality of coronary MRA was calculated on the basis of all visible coronary segments. The diagnostic performance of coronary MRA for detecting a ≥50% reduction in coronary artery diameter with and without NTG was compared using X-ray coronary angiography (CAG) as the reference. According to CAG, patients were divided into a non-clinically-relevant CAD group and clinically-relevant CAD group, and the difference in NTG-induced vasodilation between the groups was evaluated. STATISTICAL TESTS: Unpaired/paired Student's t-test, Mann-Whitney U test, paired Wilcoxon signed-rank test, χ2 test, McNemar test. A two-tailed P value <0.05 was considered significant. RESULTS: Overall image quality was increased significantly in the coronary MRA images after NTG. The diagnostic performance of the non-NTG vs. NTG-assisted coronary MRA was as follows on a per-patient basis: sensitivity 94.3% vs. 94.3%, specificity 64.5% vs. 83.9%, positive predictive value 75.0% vs. 86.8%, negative predictive value 90.9% vs. 92.9%, and accuracy 80.3% vs. 89.4%, respectively. NTG-induced vasodilation was significantly lower in the clinically-relevant CAD group than in the non-clinically-relevant CAD group (13.7 ± 8.1% vs. 24.1 ± 16.3%). DATA CONCLUSION: Non-contrast Dixon water-fat separation CS-SENSE coronary MRA at 3.0 T can noninvasively detect clinically-relevant CAD and sublingual NTG improved performance. Combining pre- and post-NTG coronary MRA may provide a simple noninvasive and nonionizing test to evaluate coronary vasodilation function. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

IMPROvE-CED Trial: Intracoronary Autologous CD34+ Cell Therapy for Treatment of Coronary Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED. METHODS: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×105 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone. RESULTS: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [-18.0 to 32.4] to 57.6 [16.3-98.3]%; P=0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P=0.00018), and sublingual nitroglycerin use/day (1 [0.4-3.5] to 0 [0-1], Wilcoxon signed-rank test, P=0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED. CONCLUSIONS: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03471611.

Impaired endothelium-dependent and endothelium-independent systemic vasodilatory reserve in pulmonary hypertension regardless the clinical group: A generalized dysfunction beyond the pulmonary arteries?

OBJECTIVE: Endothelium-dependent (ED) and endothelium-independent (EI) flow-mediated vasodilatation (FMD) have been used as measures of systemic arterial vasodilatory reserve. In this study, we aimed to assess both ED-FMD and EI-FMD in different groups with pulmonary hypertension (PH), and to investigate the relationship of these measures with clinical, echocardiographic, and invasive parameters of diseases severity and targeted treatment status. METHODS: Our study population comprised 41 patients with PH [28 (68.2%) women, age 46.3±19.6 years] including idiopathic pulmonary arterial hypertension, Eisenmenger syndrome, and chronic thromboembolic PH in whom diagnosis were confirmed in accordance with current guidelines and 17 age and sex-matched healthy controls. The brachial artery (BA) was used for assessment of FMD with Duplex ultrasound, and serial changes in diameter were recorded at baseline, 1, and 3 minutes after termination of 2-minute external occlusive compression for ED-FMD, and after sublingual intake of glycerol trinitrate for EI-FMD, respectively. RESULTS: Compared with controls, overall the PH group showed significantly lower ED-FMD (0.65±0.21 vs. 0.30±0.23 and 0.65±0.18 vs. 0.24±0.21) and EI-FMD (0.67±0.15 vs. 0.37±0.25 and 0.75±0.20 vs. 0.32±0.24) responses at 1st and 3rd min (p<0.001 for all). All these changes in the values of ED-FMD and EI-FMD were comparable among the PH subgroups. Neither ED-FMD nor EI-FMD were correlated with measures of PH severity and targeted therapy (TT) status (p>0.05). CONCLUSION: Our results suggest an impaired BA vasodilatory reserve in patients with PH regardless of the clinical subgroup. Although these findings seem to be consistent with systemic dysfunction, acute FMD may not reflect the severity of PH and cannot be used as a potential surrogate for outcome in this setting.

Vasodilatation by carbon dioxide and sodium nitroglycerin reduces compliance of the cerebral arteries in humans.

NEW FINDINGS: What is the central question of this study? Vascular compliance importantly contributes to the regulation of cerebral perfusion and complex mechanisms are known to influence compliance of a vascular bed: while vasodilatation mediates changes in vascular resistance, does it also affect compliance, particularly in the cerebral vasculature? What is the main finding and its importance? Cerebral vasodilatation, elicited by hypercapnia and sodium nitroglycerin administration, reduced cerebrovascular compliance by approximately 26% from baseline. This study provides new insight into mechanisms mediating cerebrovascular compliance. ABSTRACT: Changes in vascular resistance and vascular compliance contribute to the regulation of cerebral perfusion. While changes in vascular resistance are known to be mediated by vasodilatation, the mechanisms contributing to changes in vascular compliance are complex. In particular, whether vasodilatation affects compliance of the vasculature within the cranium remains unknown. Therefore, the present study examined the impact of two vasodilatation pathways on cerebrovascular compliance in humans. Fifteen young, healthy adults (26 ± 5 years, seven females) completed two protocols: (i) sublingual sodium nitroglycerin (SNG; 0.4 mg) and (ii) hypercapnia (5-6% carbon dioxide gas mixture for 4 min). Blood pressure waveforms (finger photoplethysmography) and middle cerebral artery blood velocity waveforms (transcranial Doppler ultrasound) were input into a modified Windkessel model and an index of cerebrovascular compliance (Ci) was calculated. During the SNG protocol, Ci decreased 24 ± 17% from baseline ((5.0 ± 2.3) × 10-4  cm s-1  mmHg-1 ) to minute 10 ((3.6 ± 1.2) × 10-4  cm s-1  mmHg-1 ; P = 0.009). During the hypercapnia protocol, Ci decreased 28 ± 9% from baseline ((4.4 ± 1.9) × 10-4  cm s-1  mmHg-1 ) to minute 4 ((3.1 ± 1.4) × 10-4  cm s-1  mmHg-1 ; P < 0.001). Cerebral vasodilatory stimuli induced by nitric oxide and carbon dioxide mechanisms reduced compliance of the cerebral vascular bed by approximately 26% from supine baseline values.

Muscle blood flow is independent of conduit artery diameter following prior vasodilation in males.

At the onset of exercise in humans, muscle blood flow (MBF) increases to a new steady-state that closely matches the metabolic demand of exercise. This increase has been attributed to "contraction-induced vasodilation," comprised of the skeletal muscle pump and rapid vasodilatory mechanisms. While most research in this area has focused on forearm blood flow (FBF) and vascular conductance, it is possible that separating FBF into diameter and blood velocity can provide more useful information on MBF regulation downstream of the conduit artery. Therefore, we attempted to dissociate the matching of oxygen delivery and oxygen demand by administering glyceryl tri-nitrate (GTN) prior to handgrip exercise. Eight healthy males (29 ± 9 years) performed two trials consisting of two bouts of rhythmic handgrip exercise (30 contractions·min-1 at 5% of maximum) for 6 min, one for each control and GTN (0.4 mg sublingual) condition. Administration of GTN resulted in a 12% increase in resting brachial artery diameter that persisted throughout the duration of exercise (CON: 0.50 ± 0.01 cm; GTN: 0.56 ± 0.01 cm, p < 0.05). Resting FBF was greater following GTN administration compared to control (p < 0.05); however, differences in FBF disappeared following the onset of muscle contractions. Our results indicate that the matching of FBF to oxygen demand during exercise is not affected by prior vasodilation, so that any over-perfusion is corrected at the onset of exercise. Additionally, our findings provide further evidence that the regulation of vascular tone within the microvasculature is independent of the conduit artery diameter.