Reliability and reproducibility of the venous excess ultrasound (VExUS) score, a multi-site prospective study: validating a novel ultrasound technique for comprehensive assessment of venous congestion.

Though the novel venous excess ultrasound (VExUS) score is increasingly used as a noninvasive means of venous congestion measurement, the inter-rater reliability (IRR), inter-user reproducibility (IUR), and utility of concurrent ECG have not been evaluated. We conducted a multicenter study of the IRR, IUR, and utility of ECG for VExUS interpretation between four attending physicians of diverse specialties, reporting the Kappa statistic (KS) and Intraclass Correlation Coefficient (ICC) for IRR and IUR for scans with and without ECG. Eighty-four paired VExUS exams from 42 patients, 60 of which had a concurrent ECG tracing, were interpreted. They showed substantial IRR, with a KS of 0.71 and ICC of 0.83 for the overall VExUS grade (p < 0.001), and IUR, with a KS 0.63 and ICC of 0.8. There was greater agreement among images with an ECG tracing. These results suggest that ECG-augmented VExUS may be a reliable and reproducible measure interpretable by clinicians with diverse backgrounds.

Near-Infrared Spectroscopy During Reactive Hyperemia for the Assessment of Lower Limb Vascular Function.

Vascular diseases of the lower limb contribute substantially to the global burden of cardiovascular disease and comorbidities such as diabetes. Importantly, microvascular dysfunction can occur prior to, or alongside, macrovascular pathology, and both potentially contribute to patient symptoms and disease burden. Here, we describe a non-invasive approach using near-infrared spectroscopy (NIRS) during reactive hyperemia, which provides a standardized assessment of lower limb vascular (dys)function and a potential method to evaluate the efficacy of therapeutic interventions. Unlike alternative methods, such as contrast-enhanced ultrasound, this approach does not require venous access or sophisticated image analysis, and it is inexpensive and less operator-dependent. This description of the NIRS method includes representative results and standard terminology alongside the discussion of measurement considerations, limitations, and alternative methods. Future application of this work will improve standardization of vascular research design, data collection procedures, and harmonized reporting, thereby enhancing translational research outcomes in the areas of lower limb vascular (dys)function, disease, and treatment.

Ultrasonographic assessment of pulmonary and Central venous congestion in experimental heart failure.

Pulmonary and systemic congestion as a consequence of heart failure are clinically recognized as alarm signals for clinical outcome and mortality. Although signs and symptoms of congestion are well detectable in patients, monitoring of congestion in small animals with heart failure lacks adequate noninvasive methodology yet. Here, we developed a novel ultrasonography-based scoring system to assess pulmonary and systemic congestion in experimental heart failure, by using lung ultrasound (LUS) and imaging of the inferior vena cava (Cava), termed CavaLUS. CavaLUS was established and tested in a rat model of supracoronary aortic banding and a mouse model of myocardial infarction, providing high sensitivity and specificity while correlating to numerous parameters of cardiac performance and disease severity. CavaLUS, therefore, provides a novel comprehensive tool for experimental heart failure in small animals to noninvasively assess congestion.NEW & NOTEWORTHY As thorough, noninvasive assessment of congestion is not available in small animals, we developed and validated an ultrasonography-based research tool to evaluate pulmonary and central venous congestion in experimental heart failure models.

Assessment of Endothelial Reactivity by Measurement of Vascular Material Response to Shear Stress: A Feasibility Study.

Flow-mediated dilation (FMD) evaluates the relative change in arterial diameter during hyperemia to assess the endothelial response due to a shear stimulus. However, conventional FMD measures diameter response alone and the alterations in the arterial wall's material properties during reactive hyperemia, which also influence dilation, go unaddressed. In this work, we examine the material response (MR) of the artery during reactive hyperemia using clinically relevant stiffness markers for the assessment of endothelial reactivity (ER). For this, we have developed an in-house brachial cuff control (BCC) system to continuously acquire brachial pressure which can be integrated with simultaneous measurement of brachial diameter and used to quantify the relative changes in wall property during hyperemia non-invasively. The assessment of endothelial reactivity using material response (ERAMR) was conducted on 20 healthy participants (12M/8F) and the results were compared with conventional FMD (FMD%). The mean pressure response gave an inverse trend to that of diameter response with varying magnitudes during reactive hyperemia (18.71% from baseline for diameter and 2.45% for pressure), there was a significant difference in the measurement of FMD and ERAMR (P < 0.05). The larger distribution of ERAMR compared to FMD% in box-plots further implies the inclusion of within-subject variations. Hence, ERAMR can be a potential estimate of ER, given the need for intensive validations in this line on larger cohorts.Clinical Relevance- This study demonstrates the independent role of arterial wall material properties to quantify endothelial reactivity in response to a shear stimulus.

Invasive physiologic assessment of coronary artery stenosis by resting full-cycle ratio and fractional flow reserve: a prospective observational study.

Resting full-cycle ratio (RFR), an alternative to fractional flow reserve (FFR) for evaluating intermediate coronary artery stenosis, helps reduce patients' time, cost, and discomfort. However, the validation data for RFR and FFR are lacking. We aimed to assess the diagnostic accuracy of RFR and FFR and evaluate effective decision-making for revascularization using their values. Patients subjected to an invasive physiological study for intermediate coronary artery stenosis in Yongin Severance hospital between October 2020 and April 2022 were prospectively and consecutively recruited. We evaluated the correlation between RFR and FFR measurements and the diagnostic performance of RFR (≤ 0.89) versus FFR (≤ 0.80). In all, 474 intermediate coronary stenosis lesions from 400 patients were evaluated using RFR and FFR values. There was a strong linear relationship between RFR and FFR (r = 0.75, 95% CI 0.70-0.78, p < 0.01). Comparing diagnostic performance between RFR and FFR, RFR demonstrated diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 85.0%, 80.0%, 86.7%, 67.1%, and 92.7%, respectively. We analyzed the RFR value in the hyperemia zone (0.86-0.93) according to positive (RFR: 0.86-0.89) and negative (RFR: 0.90-0.93) areas. PPV in positive area is 47.8% (95% Confidence Interval [CI]: 33.8% to 62.0%) and NPV in negative area is 87.7% (95% CI: 80.3% to 93.1%). Excellent correlation exists between RFR and FFR and the diagnostic value of RFR without hyperemia compared with FFR in establishing the accurate functional significance of coronary artery stenosis was shown. RFR alone could evaluate the functional significance of coronary artery stenosis without unnecessary hyperemia, except in the positive area.Trial registration: URL: http://trialsearch.who.int ; Unique identifier: KCT0005255.

Assessment of cerebral autoregulatory function and inter-hemispheric blood flow in older adults with internal carotid artery stenosis using transcranial Doppler sonography-based measurement of transient hyperemic response after carotid artery compression.

Unhealthy vascular aging promotes atherogenesis, which may lead to significant internal carotid artery stenosis (CAS) in 5 to 7.5% of older adults. The pathogenic factors that promote accelerated vascular aging and CAS also affect the downstream portion of the cerebral microcirculation in these patients. Primary treatments of significant CAS are eversion endarterectomy or endarterectomy with patch plasty. Factors that determine adequate hemodynamic compensation and thereby the clinical consequences of CAS as well as medical and surgical complications of carotid reconstruction surgery likely involve the anatomy of the circle of Willis (CoW), the magnitude of compensatory inter-hemispheric blood flow, and the effectiveness of cerebral microcirculatory blood flow autoregulation. This study aimed to test two hypotheses based on this theory. First, we hypothesized that patients with symptomatic and asymptomatic CAS would exhibit differences in autoregulatory function and inter-hemispheric blood flow. Second, we predicted that anatomically compromised CoW would associate with impaired inter-hemispheric blood flow compensation. We enrolled older adults with symptomatic or asymptomatic internal CAS (>70% NASCET criteria; n = 46) and assessed CoW integrity by CT angiography. We evaluated transient hyperemic responses in the middle cerebral arteries (MCA) after common carotid artery compression (CCC; 10 s) by transcranial Doppler sonography (TCD). We compared parameters reflecting autoregulatory function (e.g., transient hyperemic response ratio [THRR], return to baseline time [RTB], changes of vascular resistance) and inter-hemispheric blood flow (residual blood flow velocity). Our findings revealed that CAS was associated with impaired cerebral vascular reactivity. However, we did not observe significant differences in autoregulatory function or inter-hemispheric blood flow between patients with symptomatic and asymptomatic CAS. Moreover, anatomically compromised CoW did not significantly affect these parameters. Notably, we observed an inverse correlation between RTB and THRR, and 49% of CAS patients exhibited a delayed THRR, which associated with decreased inter-hemispheric blood flow. Future studies should investigate how TCD-based evaluation of autoregulatory function and inter-hemispheric blood flow can be used to optimize surgical techniques and patient selection for internal carotid artery revascularization.

Assessment of renal sympathetic control using invasive pressure and flow velocity measurements in humans.

Renal sympathetic innervation is important in the control of renal and systemic hemodynamics and is a target for pharmacological and catheter-based therapies. The effect of a physiological sympathetic stimulus using static handgrip exercise on renal hemodynamics and intraglomerular pressure in humans is unknown. We recorded renal arterial pressure and flow velocity in patients with a clinical indication for coronary or peripheral angiography using a sensor-equipped guidewire during baseline, handgrip, rest, and hyperemia following intrarenal dopamine (30 µg/kg). Changes in perfusion pressure were expressed as the change in mean arterial pressure, and changes in flow were expressed as a percentage with respect to baseline. Intraglomerular pressure was estimated using a Windkessel model. A total of 18 patients (61% male and 39% female) with a median age of 57 yr (range: 27-85 yr) with successful measurements were included. During static handgrip, renal arterial pressure increased by 15.2 mmHg (range: 4.2-53.0 mmHg), whereas flow decreased by 11.2%, but with a large variation between individuals (range: -13.4 to 49.8). Intraglomerular pressure increased by 4.2 mmHg (range: -3.9 to 22.1 mmHg). Flow velocity under resting conditions remained stable, with a median of 100.6% (range: 82.3%-114.6%) compared with baseline. During hyperemia, maximal flow was 180% (range: 111%-281%), whereas intraglomerular pressure decreased by 9.6 mmHg (interquartile range: 4.8 to 13.9 mmHg). Changes in renal pressure and flow during handgrip exercise were significantly correlated (ρ = -0.68, P = 0.002). Measurement of renal arterial pressure and flow velocity during handgrip exercise allows the identification of patients with higher and lower sympathetic control of renal perfusion. This suggests that hemodynamic measurements may be useful to assess the response to therapeutic interventions aimed at altering renal sympathetic control.NEW & NOTEWORTHY Renal sympathetic innervation is important in the homeostasis of systemic and renal hemodynamics. We showed that renal arterial pressure significantly increased and that flow decreased during static handgrip exercise using direct renal arterial pressure and flow measurements in humans, but with a large difference between individuals. These findings may be useful for future studies aimed to assess the effect of interventions that influence renal sympathetic control.

Pulmonary blood volume assessment from a standard cardiac rubidium-82 imaging protocol: impact of adenosine-induced hyperemia.

BACKGROUND: This study aimed to assess the feasibility of estimating the pulmonary blood volume noninvasively using standard Rubidium-82 myocardial perfusion imaging (MPI) and characterize the changes during adenosine-induced hyperemia. METHODS: This study comprised 33 healthy volunteers (15 female, median age = 23 years), of which 25 underwent serial rest/adenosine stress Rubidium-82 MPI sessions. Mean bolus transit times (MBTT) were obtained by calculating the time delay from the Rubidium-82 bolus arrival in the pulmonary trunk to the arrival in the left myocardial atrium. Using the MBTT, in combination with stroke volume (SV) and heart rate (HR), we estimated pulmonary blood volume (PBV = (SV × HR) × MBTT). We report the empirically measured MBTT, HR, SV, and PBV, all stratified by sex [male (M) vs female (F)] as mean (SD). In addition, we report grouped repeatability measures using the within-subject repeatability coefficient. RESULTS: Mean bolus transit times was shortened during adenosine stressing with sex-specific differences [(seconds); Rest: Female (F) = 12.4 (1.5), Male (M) = 14.8 (2.8); stress: F = 8.8 (1.7), M = 11.2 (3.0), all P ≤ 0.01]. HR and SV increased during stress MPI, with a concomitant increase in the PBV [mL]; Rest: F = 544 (98), M = 926 (105); Stress: F = 914 (182), M = 1458 (338), all P < 0.001. The following test-retest repeatability measures were observed for MBTT (Rest = 17.2%, Stress = 17.9%), HR (Rest = 9.1%, Stress = 7.5%), SV (Rest = 8.9%, Stress = 5.6%), and for PBV measures (Rest = 20.7%, Stress = 19.5%) CONCLUSION: Pulmonary blood volume can be extracted by cardiac rubidium-82 MPI with excellent test-retest reliability, both at rest and during adenosine-induced hyperemia.

Intraobserver Repeatability Assessment of the S390L Firefly WDR Slitlamp in Patients With Dry Eye Disease: Objective, Automated, and Noninvasive Measures.

OBJECTIVES: To assess the intraobserver repeatability of automated, objective, and noninvasive measures obtained with the S390L Firefly WDR slitlamp. METHODS: This cross-sectional study included 50 eyes of patients with dry eye disease with a mean age of 55.06±12.96 years. Three consecutively repeated measures of the following variables were obtained: first noninvasive break-up time (F-NIBUT), average noninvasive break-up time (A-NIBUT), tear meniscus height, tear meniscus area (TMA), nasal ciliary hyperemia (NCIH), temporal ciliary hyperemia (TCIH), nasal conjunctival hyperemia (NCOH), temporal conjunctival hyperemia (TCOH), upper loss area meibomian gland (U-LAMG), lower loss area meibomian gland (L-LAMG), upper meibomian gland dysfunction grade (U-MGD grade), and lower meibomian gland dysfunction grade (L-MGD grade). Intraobserver repeatability was estimated with coefficient of variation (CoV), intrasubject standard deviation (SD) (S w ), and Bland-Altman plots. RESULTS: All variables showed no statistically significant differences in the repeated-measures analysis except for L-MGD grade ( P =0.045). F-NIBUT and A-NIBUT obtained the highest CoV with an average value of 0.48±0.41 [0.02-1.00] and 0.34±0.25 [0.02-1.00], respectively. The remaining variables showed CoVs between 0.04±0.11 [0.00-0.43] and 0.18±0.16 [0.00-0.75]. A-NIBUT, TMA, NCOH, and L-LAMG obtained an S w of 2.78s, 0.21 mm 2 , <0.001, and 4.11%, respectively. Bland-Altman plots showed a high level of agreement between pairs of repeated measures. CONCLUSION: The S390L Firefly WDR slitlamp has moderate intraobserver repeatability for F-NIBUT and A-NIBUT, which suggests that F-NIBUT and A-NIBUT are tests with high variability. The remaining variables show satisfactory intraobserver repeatability.

Contrast-enhanced cine MR sequences in the assessment of myocardial hyperemia in acute myocarditis: can they help? A feasibility study.

The study was designed to assess the accuracy of contrast-enhanced balanced steady-state free precession (cine-SSFP) CMR imaging sequences to exhibit myocardial hyperemia in acute myocarditis, which has for a long time been investigated in some centers using early gadolinium enhancement (EGE) sequence. Contrast-enhanced cine-SSFP (CESSFP) sequences were compared to precontrast cine-SSFP sequences to calculate the early cine-contrast enhancement in 36 consecutive patients with acute myocarditis and 36 controls matched for age and gender. Four-chamber views images were obtained in each subject before and after gadolinium injection. Absolute and relative left ventricular myocardial enhancement of the overall myocardium, then separately of the lateral wall and interventricular septum was analyzed in telediastole. Myocarditis patients displayed higher cine-SSFP absolute enhancement than controls (overall left ventricular myocardium 2.38 ± 0.33 vs 1.84 ± 0.31; lateral wall 2.45 ± 0.35 vs 1.83 ± 0.32; and septum 2.26 ± 0.29 vs 1.82 ± 0.29, p < 0.0001 for all). Less significant differences were observed for the relative enhancement (p < 0.05 for all). Using ROC curves, the optimal threshold value of absolute enhancement to diagnose acute myocarditis was 2.05 (sensitivity: 86%; specificity: 81%). Given the simplicity of use, contrast-enhanced cine-SSFP sequences should be used as an additional diagnostic tool to detect hyperemia in acute myocarditis patients.

Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19).

Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12-15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH). A multiplex biometric immunoassay panel was used to assess 48 serum cytokines and chemokines. Twenty patients and 14 control volunteers were enrolled. The areas under the curves of vasodilation induced by LTH were significantly increased after recovery (P=0.009) and were not different from values obtained in healthy volunteers (P = 0.85). The peak microvascular flow during LTH did also significantly increase (P = 0.02), and was not different form values obtained in healthy volunteers (P = 0.55). Several cytokines displayed significantly reduced serum concentrations after recovery from COVID-19. In conclusion, endothelium-dependent systemic microvascular reactivity improved after recovery from COVID-19 in patients with cardiovascular diseases, in parallel with a reduction in the levels of several serum cytokines and chemokines involved in the regulation of vascular function and inflammation.

Myocardial mass affects diagnostic performance of non-hyperemic pressure-derived indexes in the assessment of coronary stenosis.

Background Several non-hyperemic pressure-derived Indexes (NHPI) have been introduced for the assessment of coronary stenosis, showing a good correlation with fractional flow reserve (FFR). Notably, either the assessment of NHPI during adenosine administration (NHPIADO) or the Hybrid Approach (NHPIHA), combining NHPI with FFR, have been showed to increase the accuracy of such indexes. It remains unclear whether diagnostic performance might be affected by the extent of the subtended myocardial mass. METHODS: We enrolled consecutive patients with an intermediate coronary stenosis assessed with NHPI and FFR. NHPI were also measured during adenosine (ADO) administration (NHPIADO). The amount of jeopardized myocardium was assessed using the Duke Jeopardy Score (DJS). With FFR as reference, we assessed the accuracy of NHPI, NHPIADO and NHPIHA according to the extent of the subtended myocardium. RESULTS: One-hundred-seventy stenoses from 151 patients were grouped according to the DJS as follows: A) Small Extent (SE, n = 82); B) Moderate Extent (ME, n = 53); C) Large Extent (LE, n = 35). As compared with FFR, NHPI showed a significantly different accuracy, as assessed by the Youden's index, according to the extent of the jeopardized myocardium (SE: 0.39 ± 0.05, ME: 0.68 ± 0.06, LE: 0.28 ± 0.06, p < 0.001). Conversely, both the NHPIADO (SE: 0.76 ± 0.02, ME: 0.88 ± 0.02, LE: 0.82 ± 0.02, p = 0.72) and NHPIHA (SE: 0.82 ± 0.07, ME: 0.84 ± 0.02, LE: 0.88 ± 0.02, p = 0.70) allowed for a better diagnostic accuracy regardless of the amount of myocardium subtended. CONCLUSIONS: Diagnostic performance of NHPI might be affected by the extent of myocardial territory subtended by the coronary stenosis. A hybrid approach might be useful to overcome this limitation.

Understanding the Basis for Hyperemic and Nonhyperemic Coronary Pressure Assessment.

Despite the now routine integration of invasive physiologic systems into coronary catheter laboratories worldwide, it remains critical that all operators maintain a sound understanding of the fundamental physiologic basis for coronary pressure assessment. More specifically, performing operators should be well informed regarding the basis for hyperemic (ie, fractional flow reserve) and nonhyperemic (ie, instantaneous wave-free ratio and other nonhyperemic pressure ratio) coronary pressure assessment. In this article, we provide readers a comprehensive history charting the inception, development, and validation of hyperemic and nonhyperemic coronary pressure assessment.

Peripheral arterial elasticity changes derived by volume-oscillometry in reaction to hyperemia as a possible assessment of flow-mediated vasodilatation.

The flow-mediated dilation (FMD) test is commonly utilized and is the only technique for the assessment of vascular endothelial cell function. With this test, the augmentation of a brachial artery diameter following reactive hyperemia is measured precisely using ultrasonography by a skilled operator. This is a hospital-only test, and would be more useful if conveniently performed at home. This paper describes a first approach for studying the impact of changes in peripheral arterial elasticity, with prospects towards possible assessment of functional reactivity. A recently developed smartphone-based instrument was used to measure elastic properties of finger and radial arteries, related to stiffness and vasodilatation, as a function of distending pressure derived by photo-plethysmographic volume-oscillometry. Elasticity changes in both arteries before and after a 5-min supra-systolic upper-arm cuff occlusion were successfully obtained in 15 normal volunteers. The index-values of stiffness and vasodilatation showed, respectively, a significant decrease and increase (p < 0.01), demonstrating clearly the expected elasticity changes with hyperemia, which could be consistent with the clinically-stated reaction in an FMD test. The results suggest that this method could easily provide important information of both elasticity and vasodilatation. It appears promising as a convenient assessment method to contribute to arteriosclerotic cardiovascular screening.

Assessment of microvascular function using a novel technique Flow Mediated Skin Fluorescence (FMSF) in patients with diabetic kidney disease: A preliminary study.

BACKGROUND: Diabetic kidney disease (DKD) plays an important role in morbidity and mortality in patients with diabetes mellitus. The pathogenesis of this microangiopathy is mainly due to impaired vascular endothelial function. The Flow Mediated Skin Fluorescence (FMSF) method is an innovative, non-invasive tool for assessing the microcirculation function (especially microcirculatory response to hypoxia), also in patients with complications of diabetes mellitus (DM). MATERIAL AND METHODS: The study was conducted at the Medical University of Lodz, Poland. Total of 84 volunteers including 30 patients with DKD, 33 patients with DM without complications, and 21 healthy subjects underwent microvascular function assessments using FMSF. This technique measures changes in the intensity of nicotinamide adenine dinucleotide (NADH) fluorescence from the skin on the forearm as a function of time, in response to blocking and releasing blood flow in the forearm. In this study we asses two key parameters: Reactive Hyperemia Response (RHR) and Hypoxia Sensitivity [log(HS)] to characterize vascular circulation in patients with DKD and their response to transient ischemia. RESULTS: The patients with low reactive hyperemic response (the RHR parameter) had a significantly higher sCr than patients with moderate and high RHR value (p < 0.001, p < 0.05, respectively) and a significantly lower eGFR than the patients with moderate and high RHR parameter (p < 0.001, p < 0.01, respectively). The patients with very low and low log(HS) values had a significantly higher sCr than the patients with high log(HS) (p < 0.001, p < 0.01, respectively), and a significantly lower eGFR than the patients with high log(HS) parameter (p < 0.001, p < 0.01, respectively). The patients with very low log(HS) had a significantly higher sCr and a significantly lower eGFR than the patients with moderate (p < 0.05, p < 0.01, respectively). The mean value of the RHR parameter was significantly lower in DKD patients (18.31 ± 5.06 %) compared to both healthy subjects (34.37 ± 8.18 %, p < 0.001) and DM without complications subgroup (28.75 ± 7.12 %, p < 0.001). Similar trends were noted with the mean value of log(HS) parameter in DKD subgroup (1.03 ± 0.5) vs. healthy subjects (1.59 ± 0.53, p < 0.001), and vs. DM without complications subgroup (1.73 ± 0.52, p < 0.001). We observed a significant inverse correlation between the RHR parameter and serum creatinine (sCr) and a significant positive correlations with eGFR (R =  -0.3; p < 0.05, R = 0.61; p < 0.001, respectively). We found also a significant negative correlations of the log(HS) measure with sCr and a significant positive correlations with eGFR (R = -0.33; p < 0.01, R = 0.55; p < 0.001, respectively). We observed also a significant inverse correlation between the RHR and log(HS) parameters and advanced glycation end products (AGEs) (R = -0.6; p < 0.001, R = -0.32; p < 0.01, respectively). The AGEs parameter was also a significantly higher in patients with low RHR parameter than in patients with moderate (p < 0.01) and high (p < 0.001). CONCLUSIONS: The FMSF technique makes it possible to identify impairments of the microvascular function in patients with DKD. This study confirms that the simple two-parametric approach diagnostic tool perfectly characterizes the state of the microvascular system in diabetic patients with impaired renal function. These preliminary results require further validation in a larger patients cohort.

Assessment of Intracoronary Adenosine-Induced Hyperemia in Patients with Atrial Fibrillation in Comparison with Patients in Sinus Rhythm.

BACKGROUND: Fractional flow reserve (FFR) is routinely used to evaluate coronary stenosis in patients with atrial fibrillation (AF), although no studies currently address its reliability in this particular population. The clinical impact of correct assessment of coronary stenosis in AF is particularly high in light of the antithrombotic therapy imposed by both AF and coronary stenting. OBJECTIVES: Given the hemodynamic variability and microvascular dysfunction described in AF, the aim of this study was to evaluate the hyperemic response to intracoronary adenosine in AF in comparison with sinus rhythm (SR). METHODS AND RESULTS: This retrospective study included 36 patients in AF and 36 patients in SR. The hyperemic curves were derived in a subset of patients where the required information was available (n = 16 AF, n = 10 SR). AF patients presented a hyperemic response after intracoronary administration of adenosine, which was equivalent to SR in terms of magnitude and time to maximal hyperemia. CONCLUSION: There is equivalent hyperemic response in FFR-guided revascularization in AF versus SR population. Our findings support the use of FFR in evaluating intermediate coronary stenosis in AF.

Bioactive adrenomedullin for assessment of venous congestion in heart failure.

AIMS: Bioactive adrenomedullin (bio-ADM) is a vascular-derived peptide hormone that has emerged as a promising biomarker for assessment of congestion in decompensated heart failure (HF). We aimed to evaluate diagnostic and prognostic performance of bio-ADM for HF in comparison to amino-terminal pro-B-type natriuretic peptide (NT-proBNP), with decision thresholds derived from invasive haemodynamic and population-based studies. METHODS AND RESULTS: Normal reference ranges for bio-ADM were derived from a community-based cohort (n = 5060). Correlations with haemodynamic data were explored in a cohort of HF patients undergoing right heart catheterization (n = 346). Mortality and decision cutoffs for bio-ADM was explored in a cohort of patients presenting in the ER with acute dyspnoea (n = 1534), including patients with decompensated HF (n = 570). The normal reference range was 8-39 pg/mL. The area under the receiver operating characteristic curve (AUROC) for discrimination of elevated mean right atrial pressure (mRAP) and pulmonary arterial wedge pressure (PAWP) was 0.74 (95% CI = 0.67-0.79) and 0.70 (95% CI = 0.64-0.75), respectively, with optimal bio-ADM decision cutoff of 39 pg/mL, concordant with cubic spline analyses. NT-proBNP discriminated PAWP slightly better than mRAP (AUROC 0.73 [95% CI = 0.68-0.79] and 0.68 [95% CI = 0.61-0.75]). Bio-ADM correlated with (mRAP, r = 0.55) while NT-proBNP correlated with PAWP. Finally, a bio-ADM decision cutoff of 39 pg/mL associated with 30 and 90 day mortality and conferred a two-fold increased odds of HF diagnosis, independently from NT-proBNP. CONCLUSIONS: Bio-ADM tracks with mRAP and associates with measures of systemic congestion and with mortality in decompensated HF independently from NT-proBNP. Our findings support utility of bio-ADM as a biomarker of systemic venous congestion in HF and nominate a decision threshold.

Nurse-Provided Lung and Inferior Vena Cava Assessment in Patients With Heart Failure.

BACKGROUND: Residual congestion detected using handheld ultrasound may be associated with increased risk of readmission and death after hospitalization for acute decompensated heart failure (ADHF). However, effective application necessitates routine use by nonexperts delivering clinical care. OBJECTIVES: The objective of this study was to determine the ability of heart failure (HF) nurses to deliver a predischarge lung and inferior vena cava (IVC) assessment (LUICA) to predict 90-day outcomes. METHODS: In this multisite, prospective, observational study, HF nurses scanned 240 patients with ADHF (median age: 77 years; 56% men) using a 9-zone LUICA protocol. Obtained images were reviewed by independent nurses who were blinded to clinical characteristics and outcomes. Based on a B-line cut-off of 10, patients were dichotomized as congested (n = 115) or not congested (n = 125). RESULTS: Congested patients were more likely to have previous cardiac operations, long-standing HF (>6 months), and renal impairment. At 90 days, HF readmission or mortality occurred in 42 congested patients (37%) compared with 18 noncongested patients (14%). Pulmonary congestion increased at 30-day (OR: 3.86; 95% CI: 1.65-8.99; P < 0.01) and 90-day (OR: 3.42; 95% CI: 1.82-6.4; P < 0.01) HF readmission or mortality risk and 90-day mortality (OR: 5.18; 95% CI: 1.44-18.69; P < 0.01). Pulmonary congestion increased the 90-day odds of HF readmission and/or death by 3.3- to 4.2-fold (P < 0.01), independent of demographics, HF characteristics, comorbidities, and event risk score. Over 90 days, days alive out of hospital were fewer (78.3 ± 21.4 days vs 85.5 ± 12.4 days; P < 0.01) in congested patients. CONCLUSIONS: LUICA can be a powerful tool for detection of predischarge residual congestion. HF nurses can obtain images and provide diagnostic reports that are predictive of ADHF outcomes.

Noninvasive assessment of foot perfusion in cholesterol-fed rabbits using dynamic volume perfusion CT with an upslope method.

To evaluate the feasibility of dynamic foot volume CT with the upslope method and to demonstrate macrovascular reactivity and microvascular perfusion during cuff-induced reactive hyperemia state in cholesterol-fed rabbits. 30 New Zealand male rabbits were divided into 2 groups: dietary hypercholesterolemia (n = 10) and normal diet control (n = 20). To measure for macrovascular reactivity, perfusion parameters of the left posterior tibial artery was measured at baseline and at reactive hyperemia state. For the evaluation of microvascular perfusion, color-coded perfusion map of the plantar dermis was generated for perfusion CT scan by an in-house developed dedicated analysis software based on upslope method. Dermal perfusion values were measured and analyzed before and after cuff-induced reactive hyperemia. Foot dynamic volume CT with the upslope method demonstrated significant impairment of both macrovascular reactivity and microvascular perfusion in cholesterol-fed rabbits without significant macrovascular lesions during cuff-induced reactive hyperemia (CRH) state. Arterial time-to-peak of cholesterol-fed rabbits failed to show acceleration while chow-fed rabbits showed significant decrease in time. Microvascular perfusion calculated by perfusion value (P < 0.01) and perfusion ratio (P = .014) showed decreased microvascular perfusion in cholesterol-fed rabbits compared to chow-fed rabbits during CRH state. Post-CT pathologic examination revealed decreased endothelial cell density in cholesterol-fed rabbits (P < 0.001). Foot perfusion CT using upslope method provides perfusion parameters for large arteries and a perfusion map of the foot during cuff-induced reactive hyperemia in cholesterol-fed rabbits. It may be a useful tool to assess microvascular reactivity in patients with peripheral artery disease but no apparent macrovascular lesions.