Hyperemic Peak Research Articles

The prognostic utility of heart rate and blood pressure response to regadenoson stress

BackgroundAlthough heart rate response (HRR) to regadenoson stress has been shown to be a strong predictor of outcome, it has not been investigated in a large all-comers cohort. The prognostic utility of systolic blood pressure response (SBPR) has not been investigated in comparison with HRR. Methods and resultsIn a retrospective cohort of 10,227 patients undergoing regadenoson stress single-photon emission computed tomography myocardial perfusion imaging (MPI), HRR, and SBPR were calculated as 100×(peak hyperemia value–baseline value)/baseline value. During 35±21 months follow-up, 921 (8.8%) deaths were observed. The median HRR was 35% (interquartile range [IQR], 21% to 51%). The median SBPR was −9% (IQR, −17% to −2%). HRR and SBPR were independently associated with all-cause mortality with adjusted hazard ratio [HR] of .980 per 1% increment in HRR (CI, .977-.984) and .994 per 1% increment in SBPR (CI, .988-.999). Mortality rates increased with decreasing HRR quartile and SBPR tertile. HRR provided incremental prognostic value for all-cause mortality beyond clinical and imaging parameters (area under the curve [AUC] increase, .03; P<.001) and SBPR data (AUC increase, .11; P<0001). SBPR did not provide significant incremental prognostic value beyond clinical and imaging parameters or HRR data. We derived and validated HRR of <20% as a cut-off that can improve risk stratification beyond clinical and MPI findings. ConclusionAmong patients undergoing stress MPI, impaired HRR to regadenoson provided independent and incremental prognostic value for all-cause mortality beyond clinical, imaging, and SBPR data. SBPR positively correlates with HRR, but it does not provide incremental prognostic utility. HRR, but not SBPR, should be routinely reported and considered in assessing patients' overall risk. An abnormal HRR threshold of <20% can improve risk stratification.

An evaluation of the effects of localised skin cooling on microvascular, inflammatory, structural, and perceptual responses to sustained mechanical loading of the sacrum: A study protocol.

This study protocol aims to investigate how localised cooling influences the skin's microvascular, inflammatory, structural, and perceptual tolerance to sustained mechanical loading at the sacrum, evaluating factors such as morphology, physiology, and perceptual responses. The protocol will be tested on individuals of different age, sex, skin tone and clinical status, using a repeated-measure design with three participants cohorts: i) young healthy (n = 35); ii) older healthy (n = 35); iii) spinal cord injured (SCI, n = 35). Participants will complete three testing sessions during which their sacrum will be mechanically loaded (60 mmHg; 45 min) and unloaded (20 min) with a custom-built thermal probe, causing pressure-induced ischemia and post-occlusive reactive hyperaemia. Testing sessions will differ by the probe's temperature, which will be set to either 38°C (no cooling), 24°C (mild cooling), or 16°C (strong cooling). We will measure skin blood flow (via Laser Doppler Flowmetry; 40 Hz); pro- and anti-inflammatory biomarkers in skin sebum (Sebutape); structural skin properties (Optical Coherence Tomography); and ratings of thermal sensation, comfort, and acceptance (Likert Scales); throughout the loading and unloading phases. Changes in post-occlusive reactive hyperaemia will be considered as the primary outcome and data will be analysed for the independent and interactive effects of stimuli's temperature and of participant group on within- and between-subject mean differences (and 95% Confidence Intervals) in peak hyperaemia, by means of a 2-way mixed model ANOVA (or Friedman). Regression models will also be developed to assess the relationship between absolute cooling temperatures and peak hyperaemia. Secondary outcomes will be within- and between-subject mean changes in biomarkers' expression, skin structural and perceptual responses. This analysis will help identifying physiological and perceptual thresholds for the protective effects of cooling from mechanically induced damage underlying the development of pressure ulcers in individuals varying in age and clinical status.

Post-occlusive reactive hyperemia variables can be used to diagnose vascular dysfunction in hemorrhagic shock

IntroductionLaser doppler flowmetry (LDF) allows non-invasive assessment of microvascular functions. The combination of LDF with an occlusion functional test enables study of post-occlusive reactive hyperemia (PORH), providing additional information about vasomotor function, capillary blood flow reserve, and the overall reactivity of the microvascular system. AimTo identify early alterations of PORH variables in the skin of a rat in hemorrhagic shock (HS). Material and methodsMale Wistar rats (n = 14) weighing 400–450 g were anesthetized with a combination of tiletamine/zolazepam (20 mg/kg) and xylazine (5 mg/kg). The animals breathed on their own, and were placed on a heated platform in the supine position. A PE-50 catheter was inserted into the carotid artery to measure the mean arterial pressure (MAP). The optical probe of the Laser Doppler device was installed on the plantar surface of the hind limb of a rat; a pneumatic cuff was applied proximal to the same limb. The occlusion time was 3 min. The following physiological variables were measured at baseline and 30 min after blood loss: MAP, mmHg; mean cutaneous blood flow (M, PU); cutaneous vascular conductance (CVC = M/MAP); peak hyperemia (Mmax, PU) and maximum cutaneous vascular conductance (CVCmax) during PORH. In the HS group (n = 7), 30 % of the estimated blood volume was taken within 5 min. There was no blood loss in the group of sham-operated animals (Sham, n = 7). The results are presented as Me [25 %;75 %]. The U-Mann-Whitney criterion was used to evaluate intergroup differences. Differences were considered statistically significant at p < 0.05. ResultsThe groups did not differ at baseline. Blood loss led to a significant decrease in MAP (43 [31;46] vs. 94 [84;104] mmHg), M (11.5 [16.9;7.8] vs 16.7 [20.2;13.9]) and Mmax (18.1 [16.4;21.8] vs. 25.0 [23.0;26.2]) in the HS group compared to the Sham group, respectively. At the same time, both CVC (0.25 [0.23;0.30] vs. 0.16 [0.14;0.21]) and CVCmax (0.55 [0.38;0.49] vs 0.24 [0.23; 0.29]) increased after blood loss in the HS group compared to the Sham group. Arterial blood gas analysis revealed metabolic lactic acidosis in the HS group. ConclusionIn this rat model of HS, alterations in cutaneous blood flow are manifested by a decrease in perfusion (M) and the intensity of PORH (Mmax) with a simultaneous increase in vascular conductance (CVC and CVCmax).

Residual Microvasuclar Dysfunction (RMVD) after percutaneous coronary intervention (PCI) assessed by stress- transthoracic Doppler echocardiography (S-TDE)

Abstract Background Microvascular dysfunction (MVD) has been increasingly acknowledged as a relevant cause of myocardial ischemia and worse prognosis. Coronary flow velocity reserve (CFVR), an integrated marker of coronary circulation, can be obtained noninvasively by stress-TDE. However, limited data is available regarding residual MVD (RMVD) of the target territory after percutaneous coronary intervention (PCI) assessed by stress- transthoracic Doppler echocardiography (S-TDE). Purpose This study aimed to investigate the echocardiographic predictors for RMVD after PCI assessed by S-TDE. Methods This study prospectively included 175 patients with chronic coronary syndrome who were scheduled for elective PCI at a single tertiary-care center between April 2019 and November 2022. All patients had anginal symptoms with de novo, functionally significant, proximal left anterior descending (LAD) lesions and underwent fractional flow reserve (FFR)-guided elective single vessel PCI for LAD. Exclusion criteria were patients with reduced left ventricular (LV) systolic function (ejection fraction &amp;lt; 50%), periprocedural myocardial infarction as defined by the fourth universal definition of myocardial infarction. Eligible patients underwent pre- (1 day before) and post-procedural (3 days after) LAD coronary flow assessments by S-TDE. Coronary flow velocity reserve (CFVR) was calculated as the ratio of the hyperemic peak diastolic flow velocity to the basal peak diastolic flow velocity. We also excluded the patients with suboptimal S-TDE imaging. We defined an RMVD after PCI as a post-PCI CFVR impairment (CFVR&amp;lt;2.0). Association between RMVD and echocardiographic parameters were evaluated. Results A total of 150 patients were included in the final analysis. RMVD was observed in forty-five (30.0%) patients after successful LAD PCI. Patients with RMVD had older age (74 [67-79] versus 72 [59-76], P=0.042) and lower estimated glomerular filtration rate (eGFR) (58.4 [37.6-75.1] mL/min/1.73m2 versus 65.9 [54.3-75.5] mL/min/1.73m2, P=0.045) than those without RMVD. Univariate logistic regression analyses revealed that higher age, lower eGFR, pre-PCI higher ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e’), shorter deceleration time of diastolic coronary flow (DDT) and lower pre-PCI CFVR were associated with post-PCI RMVD. Multivariate logistic regression analyses including age and eGFR as covariates showed higher E/e’ (adjusted odds ratio [OR] 1.13, 95% confidence interval [CI] 1.02-1.25, P=0.022), shorter DDT (OR 0.999, 95% CI 0.998-1.000, P=0.045) and lower pre-PCI CFVR (OR 0.336, 95% CI 0.165-0.683, P=0.003) were independently predictive of RMVD. Conclusions In patients with preserved LV ejection fraction who underwent successful elective FFR-guided PCI for LAD, pre-PCI LV diastolic dysfunction was associated with post-PCI residual microvascular dysfunction of LAD territory.

TDE-derived impaired post-PCI Coronary flow velocity reserve predicts MACE in patients who underwent LAD PCI

Abstract Background Coronary flow velocity reserve (CFVR) can be obtained noninvasively by stress transthoracic Doppler echocardiography (S-TDE). However, prognostic significance of S-TDE-derived CFVR after percutaneous coronary intervention (PCI) remains unknown. Purpose This study aimed to investigate the relationship between post-PCI CFVR and major adverse cardiac event (MACE). Methods This study prospectively included 200 patients with stable coronary artery disease who were scheduled for elective PCI of de novo, single, functionally significant left anterior descending (LAD) lesions at a single tertiary-care center between April 2019 and November 2022. All patients underwent fractional flow reserve (FFR)-guided elective PCI. Exclusion criteria were patients with previous coronary artery bypass graft surgery, left main coronary artery disease and periprocedural myocardial infarction as defined by the fourth universal definition of myocardial infarction. Eligible patients underwent pre- (1 day before) and post-procedural (3 days after) LAD coronary flow assessments by stress-TDE. CFVR was calculated as the ratio of the hyperemic peak diastolic flow velocity to the basal peak diastolic flow velocity. We also excluded the patients with suboptimal S-TDE imaging. Association between post-PCI physiological parameters and MACE (composite of cardiac death, myocardial infarction, heart failure and target vessel revascularization) were evaluated. Results A total of 174 patients were included in the final analysis after successful LAD PCI. MACE occurred in twenty-one (12.0%) patients during the follow-up (1.9 [0.9-2.5] years). Clinical demographics were similar in patients with versus without MACE. Post-PCI S-TDE-derived CFVR was lower in patients with versus without MACE (P = 0.023), while post-PCI FFR values tended to be lower in patients with versus without MACE, albeit not significant (P = 0.077). Receiver-operating characteristic curve analysis revealed that the optimal cut-off values of post-PCI FFR and post-PCI CFVR values to predict MACE were 0.83 and 1.70, respectively. Significant differences in the MACE were detected according to post-PCI FFR (≤ 0.83 versus &amp;gt; 0,83: 17.9 % versus 6.7 %, P = 0.035) and post-PCI CFVR (&amp;lt; 1.70 versus ≥ 1.70: 33.3% versus 8.2%, P = 0.001). On a multivariable Cox-proportional hazard analysis, patients with post-PCI CFVR &amp;lt; 1.70 had an increased risk for MACE (adjusted hazard ratio [HR] 4.75, 95% confidence interval [CI] 1.98-11.38, P &amp;lt; 0.001), along with post-PCI FFR ≤ 0.83 (adjusted HR 2.78, 95% CI 1.07-7.20, P=0.035). Conclusions In patients who underwent successful elective PCI for LAD, S-TDE-derived impaired post-PCI CFVR and post-PCI FFR were independently associated with MACE.

Coronary Flow Reserve Changes after Angiotensin Receptor-Neprilysin Inhibitor Treatment in Heart Failure with Reduced Ejection Fraction.

Sacubitril/valsartan has been shown to reduce hospital admissions and even mortality for heart failure. In heart failure and acute coronary syndrome, the effects of sacubitril/valsartan have been studied, but the effect on coronary artery flow is not known. We aimed to understand the effect of sacubitril/valsartan on coronary artery flow by using echocardiographic coronary flow reserve (CFR). Thirty-six patients (17 ischemic and 19 non-ischemic) with heart failure with reduced ejection fraction (EF of < 40%) eligible for sacubitril/valsartan treatment and 21 normal controls were recruited. The study group and controls were similar with regard to gender, smoking status, and age distribution (p = 0.874, p = 0.709, and p = 0.765, respectively). Blood pressure, heart rate, 6-minute walk test (6MWT), N terminal pro B type natriuretic peptide (NT-pro-BNP) level, standard echocardiography, from where left anterior descending mid-distal flow was seen, baseline peak diastolic flow rate and 2 minutes after dipyridamole infusion, and hyperemic peak diastolic flow rate were measured, and CFR with echocardiography was assessed prior to and at 6 months after sacubitril/valsartan initiation. Baseline peak diastolic flow rate did not exhibit a significant difference at 6 months (p = 0.143), but hyperemic peak diastolic flow rate, CFR, EF (%), and 6MWD values were significantly increased (all p < 0.001), and New York Heart Association Functional Class, NT-pro-BNP (pg/mL), left ventricule end diastolic diameter (mm), and left ventricule end systolic diameter (mm) values were significantly decreased (all p < 0.001) after sacubitril/valsartan treatment. Sacubitril/valsartan significantly alters coronary blood flow, especially its dynamic features, in patients with heart failure with reduced ejection fraction.

Abnormal left ventricular subendocardial perfusion and diastolic function in women with obesity and heart failure and preserved ejection fraction

Purpose– Coronary microvascular dysfunction (CMD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Stress cardiovascular magnetic resonance (CMR) has been proposed as a non-invasive tool for detection of CMD. The aim of this study was to determine relationship between CMD and diastolic function in patients with HFpEF using a novel CMR technique.Methods– Patients with obesity and HFpEF without epicardial coronary artery disease (CAD) underwent Doppler echocardiography to measure diastolic function, followed by vasodilator stress CMR, using a single bolus, dual sequence, quantitative myocardial perfusion mapping to measure myocardial blood flow (MBF) at rest and at peak hyperemia. With this, myocardial perfusion reserve (MPR), global stress endocardial-to-epicardial (endo:epi) perfusion ratio, and total ischemic burden (IB, defined as myocardial segments with MBF < 1.94 mL/min/g) were calculated. Results are reported as median and interquartile range.Results– Nineteen subjects were enrolled (100% female, 42% Black). Median age was 64 [56–72] years. Global stress MBF was 2.43 ml/min/g [2.16–2.78] and global myocardial perfusion reserve (MPR) was 2.34 [2.07–2.88]. All had an abnormal subendocardial perfusion with an endo:epi of less than 1 (0.87 [0.81–0.90]). Regional myocardial hypoperfusion was detected in 14 (74%) patients with an IB of 6% [0-34.4]. Endo:epi ratio significantly correlated with IB (R=-0.510, p = 0.026) and measures of diastolic function (R = 0.531, p = 0.019 and R=-0.544, p = 0.014 for e’ and E/e’ respectively).Conclusion– Using a novel quantitative stress CMR myocardial perfusion mapping technique, women with obesity and HFpEF were found to have patterns of abnormal subendocardial perfusion which significantly correlated with measures of diastolic dysfunction.

Evaluation of left ventricular function in ischemia with non-obstructive coronary arteries: a research based on adenosine stress myocardial contrast echocardiography.

Patients with ischemia with non-obstructive coronary arteries (INOCA) have an increased risk of adverse cardiovascular events in the future, which is widespread but underdiagnosed. The purpose of this study is to explore the application value of adenosine stress myocardial contrast echocardiography (ASMCE) in INOCA disease, so that clinicians can early identify and intervene patients with left ventricular function subclinical impairment in INOCA. We enrolled 118 patients with INOCA by ASMCE and invasive coronary angiography (ICA), 97 of whom had complete data. The study population was divided into two subgroups depending on coronary flow velocity reserve (CFVR): impaired CFVR group (n = 34) and normal CFVR group (n = 63). Global longitudinal strain endocardial myocardial (GLSendo), mid-myocardial (GLSmid) and epicardial myocardial (GLSepi) increased after stress in both groups; transmural strain, wall motion scored index (WMSI) and myocardial perfusion scored index (MPSI) increased and FORCE decreased in impaired CFVR group after stress, but there was no difference in normal group before and after stress. There was no significant difference in left ventricular myocardial mechanical parameters, including ΔGLSendo, ΔGLSmid, ΔGLSepi, GLSendo-epi Reserve, Δpeak strain dispersion (PSD), PSD Reserve between the two groups, but ΔEF, strain reserve and left ventricular contractile reserve (LVCR) in the impaired CFVR group were lower than those in the normal CFVR group, while ΔWMSI and ΔMPSI were increased. CFVR can be a clinically valuable indicator in the ASMCE diagnosis of patients with microvascular angina pectoris in INOCA. In the evaluation of left ventricular function in INOCA patients, attention should be paid not only to myocardial deformation, but also to the dynamic changes of LVCR and myocardial perfusion during peak hyperemia.

Exercise capacity as a predictor of coronary microvascular dysfunction

Abstract Introduction Exercise capacity (EC) is an important prognostic test in patients with coronary artery disease (CAD). Positron-emission tomography (PET) is an important risk-stratifying tool to tailor management of patients with coronary artery disease. Purpose We aimed to assess EC in predicting positron emission tomography (PET) myocardial perfusion imaging (MPI) derived coronary flow reserve (CFR). Methods Consecutive patients who had clinically indicated PET MPI and EC were included. EC was defined based on peak metabolic equivalents (METS) achieved during exercise stress test. Myocardial blood flow (MBF) in ml/gm/min was obtained from dynamic PET MPI images at rest and peak hyperemia. The coronary flow reserve (CFR) was calculated as the ratio of stress to rest MBF of the left ventricle. Results The study population consisted of 511 patients who underwent PET MPI and EC testing (mean age 56 (±11), 71% male). Cardiovascular risk factors were prevalent (75% hypertensive, 82% dyslipidemic, 43% diabetics, 27% known CAD). Peak METS &amp;gt;6 was achieved in 81% of patients, and the CFR &amp;lt;2 was present in 27%. In multivariable logistic regression models adjusted for age, sex, cardiovascular risk factors (hypertension, diabetes, dyslipidemia) and medication use (angiotensin converting enzyme inhibitor/angiotensin receptor blocker, statins, beta-blockers), patients with peak METS &amp;gt;6 had a statistically significant lower odds of microvascular dysfunction (CFR &amp;lt;2: OR 0.43, 95% CI 0.26–0.71, p=0.001). Assessment of discrimination showed the model with CFR &amp;lt;2 had an incremental improvement of Harrell's C statistic over clinical variables (0.65 vs 0.69, p=0.02). Conclusion Our findings showed exercise capacity was a good predictor of CFR and microvascular coronary health over and above clinical variables. Further studies are needed to assess the prognostic interplay between EC and CFR. Funding Acknowledgement Type of funding sources: None.

Coronary microvascular health in patients with prior COVID-19 infection and no known CAD

Abstract Introduction Although most patients recovering from acute COVID-19 infection have complete resolution of symptoms, some have cardiopulmonary symptoms lingering long after the acute phase of the disease. One proposed mechanism involves chronicity of COVID-19 associated with myocarditis and endotheliopathy. Purpose To determine the coronary microvascular health of patients with prior COVID-19 and no known coronary artery disease (CAD) using positron emission tomography (PET). Methods Cases consisting of patients without known CAD but previous COVID-19 infection who had clinically indicated PET imaging were matched 1:4 on clinical and cardiovascular risk factors to controls having no prior COVID-19 infection. Myocardial blood flow (MBF) in ml/gm/min was obtained from dynamic images at rest and peak hyperemia. The coronary flow reserve (CFR) was calculated as the ratio of stress to rest MBF of the left ventricle. Coronary microvascular dysfunction (CMD) was defined as CFR&amp;lt;2. Results The study population consisted of 315 patients, 25% (n=80) of which had prior COVID-19 infection (mean±SD age 64±11 years, 46% men). The median (IQR) number of days between COVID-19 infection and PET imaging was 190 (85–268) days. After adjusting for age, gender and cardiovascular risk factors, patients with prior COVID-19 and no known CAD had a statistically significant higher odds of having a CFR &amp;lt;2 (OR 4.9, 95% CI 2.3–10.1 p&amp;lt;0.001) and CFR &amp;lt;2 normalized to patient's rate-systolic blood pressure product (OR 2.8, 95% CI 1.6–5.0 p=0.001). The annualized event rate for the composite outcome of all-cause death, myocardial infarction, admission for heart failure exacerbation and late revascularization was higher in cases vs controls and in those with CMD. Conclusion Our analysis showed that patients with prior COVID-19 and no known CAD had higher rates of CMD, and that the presence of CMD was associated with higher risk of incident cardiovascular events. Funding Acknowledgement Type of funding sources: None.

Incremental prognostic value of digital positron emission tomography derived myocardial flow reserve: A prospective cohort study

BackgroundPositron Emission Tomography (PET) Myocardial Perfusion Imaging (MPI) is a robust diagnostic and prognostic test in patients with suspected or known coronary artery disease (CAD). We aimed to assess the incremental prognostic value of myocardial flow reserve (MFR) using the latest generation of digital PET scanners. MethodsConsecutive patients with clinically indicated PET MPI for suspected or known CAD were included. Myocardial blood flow (MBF) in ml/min/g was obtained from dynamic images at rest and peak hyperemia, and the myocardial flow reserve (MFR) was calculated as the ratio of stress to rest MBF. Patients were followed from the date of PET imaging for the occurrence of the primary outcome (composite of all-cause death, myocardial infarction, and Percutaneous Coronary Intervention or Coronary Artery Bypass Graft occurring >90 days after imaging). Nested multivariable Cox regression models were used to assess the incremental prognostic role of MFR over traditional risk factors and PET relative perfusion parameters. ResultsThe final cohort consisted of 3534 patients (mean age 67 ± 12 years, 48% female, 67% Caucasian, 53% obese, 55% hypertension, 32% diabetes, 42% dyslipidemia). During a median follow-up of 8.5 (3.0–15.4) months, 229 patients (6.5%, 6.4 per 1000 person-years) experienced the primary outcome. In nested multivariable Cox models, impaired MFR (MFR < 2) was significantly associated with the primary outcome (HR 2.9, 95% CI 2.0–4.1, p < 0.001) and significantly improved discrimination (Harrell's C 0.77, p = 0.002). ConclusionMFR derived from digital PET scanners has an independent and incremental prognostic role in patients with suspected or known CAD.

An examination of the relationship among plasma brain derived neurotropic factor, peripheral vascular function, and body composition with cognition in midlife African Americans/Black individuals.

African American/Black individuals have been excluded from several lines of prominent neuroscience research, despite exhibiting disproportionately higher risk factors associated with the onset and magnitude of neurodegeneration. Therefore, the objective of the current investigation was to examine potential relationships among brain derived neurotropic factor (BDNF), peripheral vascular function, and body composition with cognition in a sample of midlife, African American/Black individuals. Midlife adults (men: n = 3, 60 ± 4 years; women: n = 9, 58 ± 5 years) were invited to complete two baseline visits separated by 4 weeks. Peripheral vascular function was determined by venous occlusion plethysmography, a dual-energy X-ray absorptiometry was used to determine body composition, and plasma was collected to quantify BDNF levels. The CNS Vital Signs computer-based test was used to provide scores on numerous cognitive domains. The principal results included that complex attention (r = 0.629) and processing speed (r = 0.734) were significantly (p < 0.05) related to the plasma BDNF values. However, there was no significant (p > 0.05) relationship between any vascular measure and any cognitive domain or BDNF value. Secondary findings included the relationship between lean mass and peak hyperemia (r = 0.758) as well as total hyperemia (r = 0.855). The major conclusion derived from these results was that there is rationale for future clinical trials to use interventions targeting increasing BDNF to potentially improve cognition. Additionally, these results strongly suggest that clinicians aiming to improve cognitive health via improvements in the known risk factor of vascular function should consider interventions capable of promoting the size and function of skeletal muscle, especially in the African American/Black population.

Preprocedural transthoracic Doppler echocardiography to identify stenosis associated with increased coronary flow after revascularisation

The benefit of percutaneous coronary intervention (PCI) has been reported to be associated with functional stenosis severity defined by fractional flow reserve (FFR). This study aimed to investigate the predictive ability of preprocedural transthoracic Doppler echocardiography (TDE) for increased coronary flow. A total of 50 left anterior descending arteries (LAD) that underwent TDE examinations were analysed. Hyperaemic LAD diastolic peak velocity (hDPV) was used as a surrogate of volumetric coronary flow. The increase in coronary flow was evaluated by the metric of % hDPV-increase defined by 100× (post-PCI hDPV-pre-PCI hDPV)/pre-PCI hDPV. The two groups divided by the median value of % hDPV-increase were compared, and the determinants of a significant coronary flow increase defined as more than the median % hDPV-increase were explored. After PCI, FFR values improved in all cases. hDPV significantly increased from 53.0 to 76.0 mm/s (P < 0.01) and the median % hDPV-increase was 45%, while hDPV decreased in 10 patients. On multivariable analysis, pre-PCI FFR and hDPV were independent predictors of a significant coronary flow increase. Preprocedural TDE-derived hDPV provided significant improvement of identification of lesions that benefit from revascularisation with respect to significant coronary flow increase.

Elevated circulating endothelial microparticles (EMPs) in prepubertal children born preterm.

Endothelial microparticles (EMPs) act as early biomarkers of endothelial activation and damage. No studies have investigated EMPs in preterm-born individuals. Sixty-three preterm-born children and 52 children born full-term (controls) were studied. Circulating CD62E(+), CD144(+), and CD31(+)/CD42b(-) EMPs were measured in preterm-born children compared to controls; possible associations with cardiovascular risk factors and endothelial function parameters were also assessed. Circulating CD62E(+), CD144(+), and CD31(+)/CD42b(-) EMPs were significantly higher in preterm-born children compared to controls (p = 0.003, p < 0.001, and p < 0.001, respectively). Preterm birth was recognized as an independent predictor of each EMP subpopulation studied; moreover, the mean pressure and velocity of pulmonary artery were independently correlated with CD62E(+) (β = 0.20, p = 0.04) and CD144(+) EMPs (β = 0.22, p = 0.02), respectively, whereas age (β = 0.21, p = 0.03) and being born SGA (β = 0.26, p = 0.01) correlated independently with CD31(+)/CD42b(-) EMPs in the study population. Furthermore, diastolic blood pressure (β = 0.24, p = 0.04), being born SGA (β = 0.24, p = 0.04) and the hyperemic peak velocity of the brachial artery (β = -0.65, p = 0.02) were independently associated with CD31(+)/CD42b(-) EMPs in the preterm-born group. Circulating EMPs were higher in preterm-born children compared to children born full-term. Whether EMPs could act, in clinical practice, as a complementary tool for non-invasive evaluation of endothelium in preterm-born children, remains under investigation. Circulating endothelial microparticles (EMPs) are small membrane vesicles released from endothelial cells and they act as novel biomarkers of endothelial activation and damage. No studies have investigated circulating EMPs in preterm-born individuals. Circulating EMPs were significantly higher in prepubertal preterm-born children compared to children born at term. In the preterm-born group, the hyperemic peak velocity of the brachial artery was independently associated with CD31(+)/CD42b(-) EMPs. Whether assessment of circulating EMPs could act, in clinical practice, as a complementary tool for non-invasive evaluation of endothelium in preterm-born children, remains to be defined in future investigations.

Impact of aging on the effects of intracoronary adenosine, peak hyperemia and its duration during fractional flow reserve assessment.

Functional assessment of coronary stenoses is crucial for determining the correct therapeutic strategy. Age-related modifications in cardiovascular function could alter the functional significance of an intermediate coronary lesion. Therefore, the aim of the present study was to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease. We included patients undergoing coronary angiography at our Division of Cardiology from June 2008 to February 2019 for elective indication or recent acute coronary syndrome and receiving FFR assessment for an intermediate coronary stenosis (angiographic 40-70% stenoses). FFR measurement was performed by pressure-recording guidewire (Prime Wire; Volcano Imaging System Philips Healthcare, San Diego, California, USA), after induction of hyperemia with intracoronary boluses of adenosine (from 60 to 720 μg, with dose doubling at each step). We included in our study 276 patients, undergoing FFR evaluation on 314 lesions, that were divided according to age (< or ≥70 years). Elderly patients displayed a higher cardiovascular risk profile and received more often specific therapy. We found significantly higher FFR values and lower Delta FFR and time to recovery in patients with age ≥70 years old even with high-dose adenosine. Elderly patients showed a trend in lower percentage of positive FFRs, especially with high-dose (P = 0.09). Overall, any FFR ≤ 0.80 was observed in 33.5% of younger patients and 21.1% of patients ≥70 years (P = 0.02). Results were confirmed after correction for baseline differences [adjusted odds ratio (95% confidence interval) = 0.60 (0.33-1.09), P = 0.08]. This is one of the first studies investigating the impact of age on the measurement of FFR with high-dose adenosine. Patients with age >70 years old with intermediate CAD are more likely to have higher FFR values and lower duration of hyperemia after adenosine boluses, as compared with younger patients.

Przepływ w gałęzi przedniej zstępującej lewej tętnicy wieńcowej u pacjentów z marskością wątroby

Introduction. Although cardiac function appears normal in patients with cirrhosis at rest, cardiac function deteriorates in these patients under stress conditions. Decreased cardiac function against stress may be due to coronary microvascular dysfunction in these patients. In this study, we aimed to evaluate coronary microvascular dysfunction in patients with cirrhosis by measuring coronary flow reserve (CFR) by transthoracic echocardiography. Materials and methods. Thirty-eight patients with cirrhosis and 32 healthy subjects (as control group) were examined. In addition to standard two-dimesional (2D) and Doppler echocardiography, coronary flow velocity was measured by pulsed-wave Doppler from the middle to the distal part of the left anterior descending artery at the beginning and after dipyridamole infusion in the hyperemic state. CFR was measured as the ratio of hyperemic peak diastolic flow rate to basal peak diastolic flow rate. Results. CFR was significantly lower in the cirrhosis group than in the control group (2.01 ± 0.31 and 2.84 ± 0.62; p Conclusions. Impaired CFR in patients with cirrhosis promotes coronary microvascular dysfunction. The coronary microvascular dysfunction can potentially contribute to the development of cirrhotic cardiomyopathy.

Blood oxygenation level-dependent cardiovascular magnetic resonance of the skeletal muscle in healthy adults: Different paradigms for provoking signal alterations.

Stress blood oxygenation level-dependent (BOLD) cardiovascular magnetic resonance allows for quantitative evaluation of blood flow reserve in skeletal muscles. This study aimed to prospectively compare three commonly used skeletal BOLD cardiovascular magnetic resonance paradigms in healthy adults: gas inhalation, cuff compression-induced ischemia and postocclusive reactive hyperemia, and exercise. Twelve young (22 ± 0.9 years) and 10 elderly (58 ± 5.0 years) healthy subjects underwent BOLD cardiovascular magnetic resonance under the three paradigms. signal intensity time curves were generated and quantitative parameters were calculated. Meanwhile, stress transcutaneous oxygen pressure measurements were obtained as comparison. Measurement reproducibility was assessed with intraclass correlation coefficients. Differences in the BOLD variation, the correlation with transcutaneous oxygen pressure, and the age-related change between paradigms were statistically analyzed. Minimum ischemic value and maximum hyperemic peak value showed the highest interobserver and interscan reproducibilities (intraclass correlation coefficient >0.90). The plantar dorsiflexion exercise paradigm elicited the largest BOLD variation (15.48% ± 10.56%), followed by ischemia (8.30% ± 6.33%). Negligible to weak changes were observed during gas inhalation. Correlations with transcutaneous oxygen pressure measurements were found in the ischemic phase (r = 0.966; P < .001) and in the postexercise phase (r = -0.936; P < .001). Minimum ischemic value, maximum hyperemic peak value, maximum postexercise value, and slope of postexercise signal decay showed significant differences between young and elderly subjects (P < .01). Ischemia and reactive hyperemia have superior reproducibility, and exercise could induce the largest variation. Key parameters from the two paradigms show age-related differences.

Evaluation of Patterns and Correlations of the Degree of Conjunctival Hyperemia Induced by Omidenepag Isopropyl 0.002% and Ripasudil 0.4.

Purpose: To evaluate the pattern of conjunctival hyperemia induced by omidenepag isopropyl 0.002% and ripasudil 0.4%, and its correlation with the degree of hyperemia.Subjects and Methods: We previously reported the time course of conjunctival hyperemia induced by administering one drop of omidenepag isopropyl to one eye and one drop of ripasudil to the other eye in 34 healthy subjects (mean age: 29.7 years; 22 females, 12 males). We assessed the degree of hyperemia by slit-lamp photography of the frontal and temporal conjunctiva 0, 15, 30, 60, 120, 180, and 360 min after the administration of one drop of omidenepag isopropyl and ripasudil. The data were used to compare the frontal photographs before and at the peak of hyperemia according to the clinical hyperemia score (0-3) and classify the pattern of developing hyperemia due to both drugs. We also examined the correlation between the degree of hyperemia by comparing the images captured at the peak of hyperemia in both groups, using clinical hyperemia score and “percent coverage” of conjunctival hyperemia by using an automated hyperemia analysis software program; this program provides the pixel coverage of the conjunctival vessels in the region of interest. Results: There were significant differences in the developmental pattern of hyperemia between omidenepag isopropyl-administered and ripasudil-administered eyes (P<0.001, χ2 test), with dilation of large blood vessels only (N=2 vs. 1, respectively), small blood vessels only (N=17 vs. 5), both large and small blood vessels (N=8 vs. 27), and no change (N=6 vs. 0). The degree of hyperemia between the two groups was positively correlated with the hyperemia score (rs=0.344, P=0.055) in the frontal conjunctival photographs and the percent coverage of conjunctival blood vessels (r=0.510, P=0.003) in the temporal conjunctival photographs.Conclusions: The pattern of conjunctival hyperemia induced by omidenepag isopropyl predominantly involved small blood vessels, whereas that of ripasudil involved both large and small blood vessels. The eyes that were hyperemic with omidenepag isopropyl also tended to be hyperemic with ripasudil.

Heat therapy reduces blood pressure and circulating endothelin‐1 levels, but does not improve walking performance or vascular function in patients with symptomatic peripheral artery disease

INTRODUCTIONPatients with peripheral artery disease (PAD) are at a heightened risk of cardiovascular events and have markedly reduced vascular function and exercise tolerance. Heat therapy (HT) has emerged as a practical treatment to improve cardiovascular health in young individuals as well in patients with overt cardiovascular disease. We recently reported that a single 90 min session of HT applied to the legs of patients with PAD using water‐circulating trousers increases popliteal artery blood flow and reduces blood pressure and the circulating levels of the potent endogenous vasoconstrictor endothelin‐1 (ET‐1). The objective of the present study was to test the hypothesis that the repeated exposure to leg HT would lower blood pressure and ET‐1 levels and improve walking performance and conduit artery and cutaneous vascular function in patients with symptomatic PAD.METHODSThirty‐two patients with symptomatic PAD (Age: 68± 8 years; Ankle‐brachial index: 0.67 ± 0.1) were assigned using a balanced randomized design to undergo 90 min of HT (48°C) or a thermoneutral treatment (33°C) 3 times per week for 6 consecutive weeks. The following outcomes were assessed at baseline and 3 and 6 weeks after the intervention: 1) resting ankle‐brachial index, 2) post‐occlusive reactive hyperemia in the popliteal artery (phase contrast magnetic resonance imaging), 3) leg cutaneous thermal hyperemia (laser Doppler flowmetry), 4) resting blood pressure every 5 min for 70 min, 5) 6‐min walk distance and 6) serum levels of ET‐1 and total nitrate (NOx).RESULTSParticipants completed 17.7 ± 0.6 treatment sessions, resulting in a compliance rate of 98.7%. In the group exposed to HT, systolic blood pressure (SBP) decreased from baseline by ~3 mmHg at 6 weeks, while in the control group SBP increased by ~1 mmHg. A significant group by time interaction was observed for the changes in SBP from baseline to 6 weeks (p=0.0049) with significant group differences at 20 min (Change in SBP: Control: 6.27 ± 15.5 vs. HT: −7.60 ± 13.6 mmHg, p=0.015) and 60 min (Change in SBP: Control: 4.13 ± 15.1 vs. HT: −7.33 ± 13.7 mmHg, p=0.0386). Similarly, serum ET‐1 levels decreased by ~15% from baseline to week 6 following exposure to HT, while a ~6% increase in this parameter occurred in the control group (Change in ET‐1: Control: 0.16 ± 0.6 vs. HT: −0.30 ± 0.4 pg/mL, p=0.035 – one outlier removed). Resting ABI, diastolic BP, 6MWT distance, hyperemic peak flow and cutaneous thermal hyperemia were not different between groups.CONCLUSIONExposure to repeated HT reduces systolic blood pressure and ET‐1 levels in patients with symptomatic PAD. These findings indicate that HT may be a practical and accessible nonpharmacological tool to reduce cardiovascular risk in PAD patients.Support or Funding InformationAmerican Heart Association Scientist Development grant (16SDG27600003).

Prognostic value of heart rate reserve is additive to coronary flow velocity reserve during dipyridamole stress echocardiography

During dipyridamole stress echocardiography (SE), a blunted heart rate reserve (HRR) is a prognostically unfavourable sign of cardiac autonomic dysfunction. To assess the prognostic meaning of HRR and coronary flow velocity reserve (CFVR). The study group comprised 2149 patients (1236 men; mean age 66±12 years) with suspected (n=1280) or known (n=869) coronary artery disease and without inducible regional wall motion abnormalities (RWMA) during dipyridamole SE (0.84mg/kg in 6min). We assessed CFVR of the left anterior descending artery with pulsed-wave Doppler as the ratio between hyperaemic peak and basal peak diastolic flow velocities (abnormal value≤2.0). HRR was calculated as the peak/resting ratio of heart rate from a 12-lead electrocardiogram (abnormal value≤1.22). All patients were followed up. CFVR and HRR were abnormal in 520 (24%) and 670 (31%) patients, respectively. There was a positive linear correlation between CFVR and HRR (r=0.30; P<0.0001). During a median follow-up of 22 months (1st quartile 12 months, 3rd quartile 35 months), 75 (6%) patients died. The annual mortality was 1.6% in the overall population, 0.5% in the 1224 (57%) patients with normal CFVR and HRR, 1.7% in the 405 (19%) patients with abnormal HRR only, 3.6% in the 255 (12%) patients with abnormal CFVR only, and 6.2% in the 265 (12%) patients with abnormal CFVR and HRR. HRR is weakly related to CFVR, and a blunted HRR usefully complements RWMA and CFVR for prediction of outcome with dipyridamole SE. The patient without inducible RWMA is still at intermediate risk, but the risk is low with concomitant preserved CFVR, and very low with concomitant normal HRR.