Peripheral Vascular Beds Research Articles

Intravascular Lithotripsy for Peripheral Artery Calcification: 30-Day Outcomes From the Disrupt PAD III Observational Study.

Intravascular lithotripsy (IVL) has shown promising safety and effectiveness in calcified peripheral artery disease (PAD) in large trials and small real-world experiences. Real-world evidence from a larger cohort is lacking, so we aimed to evaluate the real-world acute performance of IVL in the treatment of calcified PAD. The Disrupt PAD III Observational Study (OS) is a prospective, multicenter, single-arm study. Patients with claudication or critical limb-threatening ischemia (CLTI) and at least moderate calcification were eligible. Independent predictors of procedural outcomes were assessed by multivariable analysis. Between November 2017 and June 2021 across 30 global sites, 1373 patients with 1677 lesions (1531, 91.3% core lab evaluable) were enrolled. Diameter stenosis and lesion length was 80.6±17.6% and 93.5±74.3 mm, respectively. Target vessels included femoropopliteal (61%), iliac (15.8%), common femoral (10.7%), and infrapopliteal arteries (12.8%). Lesion characteristics included 31.1% chronic total occlusions (CTOs) and 19.3% long lesions (≥15 cm). At final assessment, residual stenosis was 23.8±11.3%, with 0.9% serious angiographic complications, no abrupt closures, distal embolization, no flow, or thrombotic events. Independent predictors of ≤30% residual stenosis were lesion length ≥15 cm (odds ratio [OR]=0.384), female sex (OR=1.850), age ≤75 years (OR=1.625), IVL balloon to artery ratio ≥1.0 (OR=1.538), and CTO lesions (OR=0.638). Lesion length ≥15 cm (OR=16.076) was an independent predictor of procedural complications. The Disrupt PAD III OS represents the largest assessment of IVL periprocedural outcomes in calcified PAD. It confirmed excellent procedural safety and effectiveness in complex lesions across multiple peripheral vascular beds. This final analysis of the PAD III OS represents the largest report of peripheral IVL utilization in daily clinical practice. The outcomes of this study indicate that previously reported procedural results in clinical trial settings can be translated to a broader patient population. Treatment with peripheral IVL in severely calcified stenotic lower limb lesions demonstrated consistent acute safety and stenosis reduction, even in complex patients across multiple vessel beds. In addition, the importance of proper IVL balloon sizing to achieve excellent acute stenosis reduction was confirmed by multivariate analysis.

ENDOVASCULAR ANGIOPLASTY FOR REPEATED REVASCULARIZATION OF THE ARTERIAL BED IN PATIENTS WITH RECURRENT CHRONIC ARTERIAL INSUFFICIENCY

Aim. To improve the results of repeated reconstruction of the great vessels in case of relapse of chronic arterial insufficiency by differentiated use of popliteal tibial autovenous bypass grafting and endovascular angioplasty for revascularization of the arteries of the leg. Materials and methods. The long-term results of surgical treatment of 522 patients were examined, including 353 patients with bilateral atherosclerotic occlusion of the aortic-femoral zone and 159 patients with unilateral occlusion of the ileo-femoral segment. At the primary surgical intervention, 98 patients were diagnosed with chronic arterial insufficiency (CAI) of stage II B, in 228 – CAI of stage III, in 196 – chronic critical ischemia of the lower extremities, stage III – IV. In the long-term postoperative period, 146 (27.97 %) late complications were diagnosed, of which 78 (56.1 %) had a relapse of chronic arterial insufficiency. In 36 patients, CAI stage II B was established, and in 42 – CAI stage III. Patients were re-operated in the period of 5.4 ± 1.9 years after primary revascularization. All men were 64.4 ± 3.1 years old. Results. The multilevel atherosclerotic lesions of the reconstructed arterial bed, cicatricial changes after the initial surgical intervention, progressive atherosclerotic lesions of the outflow tract required multi-story shunting operations. The success of shunting surgery depends on sufficient revascularization of the outflow paths – the arterial bed of the ankle segment. Revascularization of the distal arterial bed was achieved using popliteal-tibial autovenous bypass grafting (19 cases) and endovascular angioplasty (30 observations). To reduce peripheral vascular resistance and increase the volume of the peripheral vascular bed in 19 (63.3%) cases, endovascular balloon angioplasty of two tibial arteries was performed simultaneously. The postoperative period in 10 (12.8%) patients was complicated by the development of thrombosis of the reconstruction segment. In 7 cases, thrombosis of the reconstruction segment was eliminated. The using of popliteal-tibial autogenous bypass grafting and endovascular angioplasty during revascularization of the ankle segment provided satisfactory results in repeated reconstructive operations in 87.2 % of cases. Conclusions. For the revascularization of the lower leg arteries, the use of popliteal autovenous shunting and endovascular angioplasty provides 87.2% satisfactory results in repeated reconstructive operations for chronic arterial insufficiency relapse.

Microvascular dysfunction associated with reduced nailfold capillary density in patients with ischemia with no obstructive coronary artery disease

Abstract Funding Acknowledgements None. Introduction The impairment of microvascular function present in coronary microcirculation with chronic angina without obstructive coronary arteries. There are insufficient data in the literature regarding possible generalized microangiopathy in this population. Aim The aim of this study is to demonstrate whether patients with Angina with No Obstructive Coronary Artery Disease (ANOCA) compared to individuals without coronary microvascular dysfunction (CMD) are characterized by a different level of nailfold capillaroscopy abnormalities. Methods We examined 18 participants without CMD - non-CMD group [9 female, 50%, mean age: 54.4±8.1 years) and 26 patients with ANOCA - CMD group (22 female, 84,6%, mean age : 53.2±10.7 years). Functional coronary angiography was performed for the assessment of coronary microcirculation in all patients. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the left anterior descending coronary artery using a temperature/pressure sensor-tipped guidewire. In addition, the assessment of skin microcirculation was performed by capillaroscopy, a non-invasive technique to evaluate small vessels of the microcirculation in the nailfold, using stereomicroscope in all patients. Results In CMD group, mean CFR and IMR were 1.34±0.6 and 44.8±28, respectively. Out of the 26 MVD patients with abnormal CFR, 7 of them (27%) had a normal value of IMR, indicating functional microvascular dysfunction. On the other hand, 18 patients (69%) had an abnormal IMR, indicating structural microvascular dysfunction. Capillary density in patients with MVD was significantly decreased compared to the control group (7.6±2.2 vs 10.9±1.8 vessels/mm, p=0.04). The difference in capillary density between the two groups was statistically significant after adjustment for multiple comparisons (p<0.05). No significant difference was found in body mass index, renal function, medical history of dyslipidemia, diabetes mellitus and smoking status between the two groups (p<0.05). Conclusion Nailfold capillary density was reduced in ANOCA patients compared to control group. These data may provide new insights regarding possible generalized microangiopathy in CMD patients. These results suggest that there is an association between microcirculatory impairment at both heart and peripheral vascular bed level.

Changes in the Etiological Structure and Specifics When Choosing Antibacterial Therapy Against Infective Endocarditis in Pediatric Practice

Infective endocarditis in children is a rare disease, which often has an extremely serious prognosis. The most common risk factor for infective endocarditis in this category of patients is the history of congenital heart disease. At the same time, currently, the disruption of the integrity of the peripheral vascular bed is increasingly noted, among the predisposing causes, due to invasive diagnostic and therapeutic medical procedures, as well as severe somatic diseases. In accordance with the developed recommendations, the appointment of antibacterial therapy for infective endocarditis should be based on etiotropic orientation. Taking these circumstances into account, the article presents an overview of the data reflecting the issues of etiology and choice of antibacterial therapy for infective endocarditis in pediatric practice.

Clinical Significance of Altered Vascular Morphology and Function in Normotension.

To review current literature examining the presence of subclinical micro- and macrovascular alterations in normotensive individuals and their clinical significance in terms of hypertension prediction. Emphasis is placed on alterations that can be detected in peripheral vascular beds using non-invasive, easily applicable methodology, as these are in general easier to capture and evaluate in clinical practice compared to more complex invasive or functional tests. Arterial stiffness, increased carotid intima-media thickness, and altered retinal microvascular diameters predict the progression from the normotensive to the hypertensive state. By contrast, there is substantial lack of relevant prospective studies for skin microvascular alterations. Although conclusions regarding causality cannot be safely deduced from available studies, detection of morphological and functional vascular alterations in normotensive individuals emerges as a sensitive indicator of progression to hypertension and hence increased CVD risk. An increasing amount of evidence suggests that early detection of subclinical micro- and macrovascular alterations would be clinically useful for the early identification of individuals at high risk for future hypertension onset. Methodological issues and gaps in knowledge need to be addressed before detection of such changes could guide the development of strategies to prevent new-onset hypertension in normotensive individuals.

Coronary microvascular disease is associated with decreased nailfold capillary density in patients with ischemia and no obstructive coronary arteries

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Existing data support that coronary microcirculation impairment is common in patients with angina pectoris without obstructive coronary artery disease. There are insufficient data in the literature regarding possible generalized microangiopathy in the above population. Purpose The aim of this study is to evaluate whether patients with coronary microvascular dysfunction (CMD) compared to individuals without angina are characterized by a different level of capillary density in the nailfold capillary microscopy. Methods We examined 21 patients [9 female, 39%, mean age: 61.2±9.9 years, mean office blood pressure (BP) : 139/86±18/10 mmHg] and 25 CMD patients (16 female, 64%, mean age : 57.9±4.8 years, average office BP: 127/77±18/10 mmHg). In the group of patients with chronic angina pectoris CMD was defined by a standardized systematic protocol in which coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the left anterior descending coronary artery using a temperature/pressure sensor-tipped guidewire. CMD patients were classified into 2 groups, the structural and the functional endotype, based on commonly used cut-offs (impaired CFR < 2.5, increased IMR ≥ 25). Functional CMD was defined as abnormal CFR in combination with normal IMR and structural CMD as abnormal CFR with abnormal IMR. In addition, the assessment of skin microcirculation was performed by capillaroscopy, a non-invasive technique to evaluate small vessels of the microcirculation in the nailfold, using stereomicroscope in all patients. Results In CMD group, mean CFR and IMR were 1.6 ± 0.9 and 43.9± 30 IU, respectively. Of the 25 patients with abnormal CFR, 8 (32%) had normal IMR consistent with functional CMD endotype, and 17 (68%) had abnormal IMR consistent with structural endotype. Capillary density in patients with CMD was significantly decreased compared to that of asymptomatic participants (9 vs 10.86 vessels/mm, p=0.04). The difference in capillary density between the two groups was statistically significant after adjustment for multiple comparisons (p<0.05). No significant difference was found in body mass index, renal function, medical history of dyslipidemia, diabetes mellitus and smoking status between the two groups (p<0.05). Conclusion Patients with CMD compared to individuals without angina are characterized by decreased nailfold capillary density. These results suggest that there is a correlation between microcirculatory impairment at the level of the coronary microcirculation and the peripheral vascular beds.

Impacts of respiratory fluctuations on cerebral circulation: a machine-learning-integrated 0–1D multiscale hemodynamic model

Objective. This study aims to accurately identify the effects of respiration on the hemodynamics of the human cardiovascular system, especially the cerebral circulation. Approach: we have developed a machine learning (ML)-integrated zero–one-dimensional (0–1D) multiscale hemodynamic model combining a lumped-parameter 0D model for the peripheral vascular bed and a one-dimensional (1D) hemodynamic model for the vascular network. In vivo measurement data of 21 patients were retrieved and partitioned into 8000 data samples in which respiratory fluctuation (RF) of intrathoracic pressure (ITP) was fitted by the Fourier series. ML-based classification and regression algorithms were used to examine the influencing factors and variation trends of the key parameters in the ITP equations and the mean arterial pressure. These parameters were employed as the initial conditions of the 0–1D model to calculate the radial artery blood pressure and the vertebral artery blood flow volume (VAFV). Main results: during stable spontaneous respiration, the VAFV can be augmented at the inhalation endpoints by approximately 0.1 ml s−1 for infants and 0.5 ml s−1 for adolescents or adults, compared to those without RF effects. It is verified that deep respiration can further increase the ranges up to 0.25 ml s−1 and 1 ml s−1, respectively. Significance. This study reveals that reasonable adjustment of respiratory patterns, i.e. in deep breathing, enhances the VAFV and promotes cerebral circulation.

Brain Glucose Sensing and the Problem of Relative Hypoglycemia.

"Relative hypoglycemia" is an often-overlooked complication of diabetes characterized by an increase in the glycemic threshold for detecting and responding to hypoglycemia. The clinical relevance of this problem is linked to growing evidence that among patients with critical illness, higher blood glucose in the intensive care unit is associated with higher mortality among patients without diabetes but lower mortality in patients with preexisting diabetes and an elevated prehospitalization HbA1c. Although additional studies are needed, the cardiovascular stress associated with hypoglycemia perception, which can occur at normal or even elevated glucose levels in patients with diabetes, offers a plausible explanation for this difference in outcomes. Little is known, however, regarding how hypoglycemia is normally detected by the brain, much less how relative hypoglycemia develops in patients with diabetes. In this article, we explore the role in hypoglycemia detection played by glucose-responsive sensory neurons supplying peripheral vascular beds and/or circumventricular organs. These observations support a model wherein relative hypoglycemia results from diabetes-associated impairment of this neuronal glucose-sensing process. By raising the glycemic threshold for hypoglycemia perception, this impairment may contribute to the increased mortality risk associated with standard glycemic management of critically ill patients with diabetes.

DAILY EXERCISE DOES NOT ALTER CEREBRAL BLOOD FLOW REGULATION DURING TILT IN OLDER ADULTS AFTER TWO WEEKS OF BEDREST

Abstract Bedrest is associated with cardiovascular and cerebrovascular changes that are linked to a greater prevalence of orthostatic intolerance; however, much of what we know from bedrest trials comes from young adults. How older adults respond to extended periods of activity restriction is not well understood. The current work tested the hypothesis that impaired control of cerebral blood flow in older adults following bedrest could be attenuated by regular exercise. Twenty-two older adults (55-65 years, 11 women) participated in a randomized controlled trial involving 14 days of continuous 6-degree head-down bedrest. The cohort was randomized to an exercise intervention (EX), involving daily aerobic, high-intensity interval, and resistance training, or a control group (CON), involving passive manual therapy. Cerebral blood flow velocity, cardiac output, and arterial blood pressure were measured continuously during a passive 80-degree head-up tilt protocol for up to 15 minutes. Responses in the cerebral and peripheral vascular beds were quantified by vascular resistance (cerebral: resistance area product (RAP); peripheral: total peripheral resistance (TPR)). Following bedrest, both supine RAP and TPR were elevated (p< 0.01), with no effect of exercise training. In addition, the number of participants who could not complete 15 minutes of tilt increased from 3 to 15 (8 EX, 7 CON). In these non-finishers, RAP dropped ~20% and TPR dropped ~15% during the final 2 minutes of tilt, with no difference between groups. These data suggest that multimodal exercise training is insufficient to prevent changes in cardiovascular and cerebrovascular regulation in older adults observed during 14-day bedrest.

154 Ultrasound Visualizes Peripheral Vascular Dysfunction in Finger Pulp Blood Flow in Patients with Systemic Sclerosis

There are no reliable biomarkers of vascular severity or extension, so identification of patients with disabling or life-threatening vascular involvement is often difficult and too late. Best therapeutic effects include healing of ulcers and improvement of blood flow in pulmonary, renal and peripheral vascular beds in systemic sclerosis (SSc). Recent advance of medical devices enables precise recognition of small architectures, so that peripheral blood flow is used for one of individual identifications.

Current Cardiovascular Disease Risk Prediction Models Are Not Applicable in MDS Patients: Preliminary Results of a Prospective Observational Single-Centre Cohort Study

Background/aims Cardiovascular disease (CVD) is a leading cause of death in lower-risk Myelodysplastic syndrome (LR-MDS) patients and a shared pathobiology between MDS and CVD has been postulated. However, current evidence emanates only from retrospective cohorts suffering from crucial shortcomings. Prospective annotation can overcome these limitations and delineate the role of MDS as an independent risk factor for CVD. For this reason we conducted a prospective observational single-centre cohort study in LR-MDS patients. Methods Patients underwent thorough evaluation for CVD every 6 months. Cerebrovascular, peripheral and coronary vascular beds were assessed for atherosclerosis by ultrasound and coronary artery calcium (CAC), respectively. Cardiac structure and function was assessed by echocardiography. Multi-Ethnic Study of Atherosclerosis (MESA), Framingham (FRS) risk scores and serum markers of myocardial injury (Serum high-sensitivity troponin T, hsTnT), stress (N-terminal pro-B-type natriuretic peptide, NT-proBNP), and systemic inflammation (high-sensitivity C-reactive protein, hsCRP) were also estimated at each visit. Chi-square, Wilcoxon signed-ranks tests and Pearson's correlation coefficient were used as appropriate. Multiple linear regression was applied for modeling the relationship between a dependent and one or more independent variables. The level of statistical significance was set to P=0.05. Results Table 1 presents baseline characteristics of 26 patients included so far. There were no correlations of CAC, MESA and FRS with either MDS subtype or IPSS-R risk category after adjustment for preexisting CVD, age, sex, and transfusion dependence. In sharp contrast to the general population (Okwuosa, TM et al. JACC 2011), CAC score was not associated with FRS (p=0.7) and was disproportionately increased in low and very low FRS risk patients (Figure 1). Likewise, the number of affected vascular beds (AVB) did not correlate with FRS (p=0,51) (Figure 2), further suggesting that the current CVD risk prediction tools are inaccurate in MDS and arguing for an intrinsic tendency of MDS towards CVD development. A second and a third evaluation was available in 17 and 7 patients, respectively. All patients increased significantly the CAC score both at 6 months (p=0.04) and 1 year (p=0.003). The average increase from baseline was 26.2% at 6 months and 72.6% at 1 year, markedly higher than expected in the general population (McCullough PA et al. Arch Int Med 2009), and was marginally higher in transfusion dependent patients (p=0.049), but not associated with baseline MESA score, FRS, preexisting CVD, exposure to ESAS, statin therapy, sex. Finally, baseline NT-proBNP levels correlated strongly with CAC score P=0.001 (Figure 3) in line with numerous evidence showing that NT-proBNP can potentially serve as a predictor of CVD risk in both MDS and non-MDS individuals. Conclusion To our knowledge this is the first study in LR-MDS patients assessing longitudinally all critical parameters and providing objective measurements of subclinical atherosclerosis in all vascular beds. Our preliminary results indicate that the established CVD prediction models do not operate properly in LR-MDS patients and reinforce the notion of a pro-atherogenic role of MDS. Accurate assessment of CVD risk and prompt detection of subclinical cardiovascular disease in MDS patients will assist clinical decisions on the introduction of intensive monitoring and preventive use of CVD-specific interventions in these individuals. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Influence of beta-rhythm neurofeedback on the functional state of the cardiovascular system of athletes

BACKGROUND: The study of the effects of urgent and long-term adaptation of the cardiovascular system of athletes under the influence of beta-rhythm neurofeedback expands its corrective and restorative potential for use in the practice of sports medicine and rehabilitation.
 AIMS: Study of the restorative and rehabilitation potential of the influence of beta-rhythm neurofeedback on the functional state of the cardiovascular system of athletes.
 MATERIAL AND METHODS: The course of neurofeedback on the beta rhythm of the brain consisted of 10 sessions, including a graphical and game version of the representation of the controlled parameter (beta rhythm) on the computer monitor screen, the success of controlling the beta rhythm with the specified conditions of voluntary muscle relaxation during the session was supported by visual and auditory biological feedback. Registration of indicators of the cardiovascular system was carried out before and after the 1st, 5th and 10th sessions of the course, the dynamics during the course and individual sessions is represented by the growth rate (%) of the indicators.
 RESULTS: A course of neurofeedback on the beta-rhythm of the brain of 10 sessions were young athletes (n=1020) aged 1821, representatives of cyclic, acyclic and game sports in the preparatory period of the training cycle.
 The effects of urgent adaptation in athletes at the 1st session of the neurofeedback course according to the beta-rhythm of the brain are reflected by positive changes in the strengthening of the vagal influence of the parasympathetic nervous system on the functional state of the cardiovascular system, expressed in a decrease in heart rate, systemic pressure, performance and pumping functions of the heart, in the transition of the type of regulation of blood circulation from the unfavorable hyperkinetic type to the physiological ― eukinetic ― type. At the same time, the load on the peripheral vascular bed increased, especially on its precapillary section.
 The effects of long-term adaptation at the 10th session of the neurofeedback course according to the beta-rhythm of the brain are represented by systemic rearrangements with an increased influence of the parasympathetic nervous system in the functioning of the cardiovascular system of athletes, reflected in the maximum decrease in heart rate throughout the course, in an equivalent decrease in systemic pressure, stabilization of performance and pumping function of the heart, achievement and preservation of the eukinetic type of regulation of blood circulation, achievement of a stable stable state of the central and peripheral vascular bed with a slight response to environmental factors.
 CONCLUSION: A course of neurofeedback on the beta-rhythm of the brain of 10 sessions helps to reduce stress in the functioning of the cardiovascular system of athletes by enhancing the vagal influences of the parasympathetic nervous system, has a positive effect on heart rate, systemic pressure, performance and pumping function of the heart; promotes the transition from an unfavorable hyperkinetic to a physiological eukinetic type of circulatory regulation; has a positive effect on adaptive changes in indicators of general and peripheral vascular resistance. The revealed effects of the course of neurofeedback on the beta-rhythm of the brain are of a pronounced corrective and restorative nature during the intense functioning of the cardiovascular system of athletes and can be used in sports rehabilitation and rehabilitation practice.

High-resolution Doppler ultrasound in systemic sclerosis: Analysis of digital arteries and nailfold microvasculature using 18-5 MHz and 33-9 MHz probes.

Newly developed Doppler techniques enable the sampling of slow vascular flows and the extrapolation of spectral parameters in distal arterioles. The aim of this study was to investigate the role of spectral analysis performed by means of ultra-high frequency ultrasound (US) in the evaluation of the peripheral vascular bed of systemic sclerosis (SSc) patients. Both hands of 33 patients affected by diffuse cutaneous SSc and 34 volunteers were evaluated with a US machine equipped with 33-9MHz and 18-5MHz transducers. Proximal resistive index and the peak systolic velocity (pRI and pPSV, respectively), were calculated at the level of the second interdigital artery. The distal resistive index (dRI) was calculated at the level of a nailfold arteriole of the third finger. All SSc patients had been previously divided into 4 subgroups according to their nailfold videocapillaroscopic (NVC) patterns following accepted criteria. SSc patients showed a significantly slower systolic velocity at the level of the second interdigital artery (pPSV [SD]=8.38 [3]cm/s vs pPSV [SD]=11.14 [4.5]cm/s; P= .005) and a higher dRI (dRI [SD]=0.65 (0.14) vs dRI [SD]=0.57 [0.11); P= .0115). No differences were found between the pRI values measured in the SSc patients and those of the controls (pRI [SD]=0.76 [0.11] vs pRI [SD]=0.73 [0.12]; P= .359]. The subgroup analysis did not show any significant difference when pPSV, pRI and dRI were compared among NVC morphological patterns. High-resolution Doppler analysis of digital distal arterioles may disclose subtle abnormalities in the downstream microvasculature of SSc patients that could be missed when the examination is performed at a more proximal level and/or using lower Doppler frequencies.

Arterial Baroreceptor Denervation Enhances Muscle Metaboreflex Induced Increases in Effective Arterial Elastance Without Worsening Stoke Work During Dynamic Exercise in Heart Failure

Optimal energy transfer from the left ventricle to the systemic circulation is paramount to the maintenance of workload performance during exercise. This interaction between the heart and circulation is quantified by the ventricular‐vascular coupling relationship which is the ratio of direct assessments of arterial and ventricular elastance. During exercise, increases in both arterial and ventricular elastance occur as a result of sympatho‐excitatory efferent responses brought about by activation of metabosensitive skeletal muscle afferents ‐ termed the muscle metaboreflex. In heart failure, ventricular elastance is reduced and arterial elastance is increased causing ventricular‐vascular uncoupling at rest and further sympatho‐activation elicited by the muscle metaboreflex worsens this relationship through profound systemic vasoconstriction. Recent studies have concluded that the arterial baroreflex substantially buffers vasoconstriction within peripheral vascular beds. In heart failure, the arterial baroreflex buffering capacity is significantly reduced and muscle metaboreflex induced vasoconstriction is enhanced. To what extent this shift in metaboreflex control of peripheral sympathetic tone affects ventricular‐vascular coupling is unknown. We examined the effect of sino‐aortic baroreceptor denervation (SAD) on the ventricular‐vascular relationship at rest and during moderate dynamic exercise (6.4 km/h 10% grade) in chronically instrument conscious canines before and after the induction of heart failure to determine whether loss of baroreflex buffering engendered further uncoupling of the ventricular‐vascular relationship in heart failure. Increases in effective arterial elastance (Ea), were significantly enhanced during muscle metaboreflex activation after SAD (0.5 ± 0.1 mmHg/ml to 2.0 ± 0.4 mmHg/mL). Furthermore, SAD elicited a significant increase in the ability to improve stroke work during muscle metaboreflex activation (2.7 ± 0.1 L*mmHg to 3.5 ± 0.1 L*mmHg) suggesting that even without the arterial baroreflex muscle metaboreflex activation in healthy subjects maintains ventricular‐vascular coupling. In heart failure, SAD elicited a 2‐fold increase in Ea during muscle metaboreflex activation (0.9 ± 0.2 mmHg/ml to 1.8 ± 0.2 mmHg/ml). Stroke work did not improve during muscle metaboreflex activation in heart failure with SAD. Thus, enhanced increases in Ea are likely not matched by ventricular elastance thereby exacerbating the already uncoupled ventricular‐vascular relationship. We conclude that the arterial baroreflex actively restrains increases in Ea and stroke work during muscle metaboreflex activation and SAD does not appear to significantly impact the ventricular‐vascular relationship in healthy subjects. In heart failure, the arterial baroreflex retains some degree of restraint over metaboreflex induced increases in Ea and thus is likely a mechanism which prevents worsening of the already impaired energy transfer from the left ventricle to the systemic circulation.

Intravascular Lithotripsy-Assisted Carotid Stent Expansion

Carotid artery stenting has been demonstrated to effectively reduce the risk of stroke in appropriately selected patients. Its application has remained limited in the setting of heavily calcified plaque. Atherectomy has been used in peripheral vascular beds to overcome this limitation; however, the embolic risks associated with atherectomy are too great for the carotid space. We have present the use of intravascular lithotripsy to safely overcome the complications associated with severely calcified carotid lesions.

Impaired coagulation, liver dysfunction and COVID-19: Discovering an intriguing relationship.

Coronavirus disease 2019 (COVID-19) is, at present, one of the most relevant global health problems. In the literature hepatic alterations have been described in COVID-19 patients, and they are mainly represented by worsening of underlying chronic liver disease leading to hepatic decompensation and liver failure with higher mortality. Several potential mechanisms used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to cause liver damage have been hypothesized. COVID-19 primary liver injury is less common than secondary liver injury. Most of the available data demonstrate how liver damage in SARS-CoV-2 infection is likely due to systemic inflammation, and it is less likely mediated by a cytopathic effect directed on liver cells. Moreover, liver alterations could be caused by hypoxic injury and drugs (antibiotics and non-steroidal anti-inflammatory drugs, remdesivir, tocilizumab, tofacitinib and dexamethasone). SARS-CoV-2 infection can induce multiple vascular district atherothrombosis by affecting simultaneously cerebral, coronary and peripheral vascular beds. Data in the literature highlight how the virus triggers an exaggerated immune response, which added to the cytopathic effect of the virus can induce endothelial damage and a prothrombotic dysregulation of hemostasis. This leads to a higher incidence of symptomatic and confirmed venous thrombosis and of pulmonary embolisms, especially in central, lobar or segmental pulmonary arteries, in COVID-19. There are currently fewer data for arterial thrombosis, while myocardial injury was identified in 7%-17% of patients hospitalized with SARS-CoV-2 infection and 22%-31% in the intensive care unit setting. Available data also revealed a higher occurrence of stroke and more serious forms of peripheral arterial disease in COVID-19 patients. Hemostasis dysregulation is observed during the COVID-19 course. Lower platelet count, mildly increased prothrombin time and increased D-dimer are typical laboratory features of patients with severe SARS-CoV-2 infection, described as “COVID-19 associated coagulopathy.” These alterations are correlated to poor outcomes. Moreover, patients with severe SARS-CoV-2 infection are characterized by high levels of von Willebrand factor with subsequent ADAMTS13 deficiency and impaired fibrinolysis. Platelet hyperreactivity, hypercoagulability and hypofibrinolysis during SARS-CoV-2 infection induce a pathological state named as “immuno-thromboinflammation.” Finally, liver dysfunction and coagulopathy are often observed at the same time in patients with COVID-19. The hypothesis that liver dysfunction could be mediated by microvascular thrombosis has been supported by post-mortem findings and extensive vascular portal and sinusoidal thrombosis observation. Other evidence has shown a correlation between coagulation and liver damage in COVID-19, underlined by the transaminase association with coagulopathy, identified through laboratory markers such as prothrombin time, international normalized ratio, fibrinogen, D-dimer, fibrin/fibrinogen degradation products and platelet count. Other possible mechanisms like immunogenesis of COVID-19 damage or massive pericyte activation with consequent vessel wall fibrosis have been suggested.

Calcific Plaque Modification by Acoustic Shockwaves: Intravascular Lithotripsy in Cardiovascular Interventions.

To provide a review of recent literature on the treatment of moderate-to-severe calcification in coronary and peripheral vasculature with intravascular lithotripsy (Shockwave Medical, Santa Clara, CA). Moderate-to-severe calcific plaques constitute a significant proportion of lesions treated with transcatheter interventions in the coronary and peripheral vascular beds and portend lower procedural success rates, increased periprocedural major adverse events, and unfavorable long-term clinical outcomes compared to non-calcific plaques. Intravascular lithotripsy (IVL) is a new technique that uses acoustic shock waves in a balloon-based system to induce fracture in the calcium deposits to facilitate luminal gain and stent expansion. IVL demonstrated high procedural success and low complication rates in the management of moderate-to-severe calcification in coronary and peripheral vascular beds and led to large luminal gain by modification of calcific plaque as assessed by optical coherence tomography. Further studies will determine the role of IVL in an integrated, protocolized approach to the treatment of severely calcified plaques in the coronary and peripheral vascular beds.

Комплексный подход к лечению неоперабельных пациентов с критической ишемией нижних конечностей и сахарным диабетом: результаты и перспективы

INTRODUCTION: The question of the optimal methods of conservative treatment of patients with critical lower limb ischemia (CLLI) and diabetes mellitus (DM) is still open. AIM: To evaluate the long-term results of therapeutic treatment of patients with CLLI and DM whose peripheral vascular bed is unsuitable for reconstruction, or who refused surgical treatment for different reasons, and to determine effectiveness of additional angiogenesis in this group of patients. MATERIALS AND METHODS: The work involved 65 patients with CLLI and DM who were divided to 2 groups. The control group of patients (40 individuals) received a course of conventional therapy. In the study group (25 individuals), additional exogenous stimulation of angiogenesis was used with angiogenic vascular endothelial growth factor. Subsequently, instrumental parameters of limb perfusion were assessed within 6 months, and in the long-term period (5 years), limb preservation and mortality in this group. RESULTS: Exogenous stimulation of angiogenesis permits to improve the following 6-month treatment results (8% of deaths and 20% of amputations in the study group versus 15% of deaths and 42.5% of amputations in the same period in the control group), and permits to maintain this trend within 5 years of follow-up (64% of deaths and 72% of amputations in the study group versus 80% of deaths and 87.5% of amputations in the control group). Reliable differences between the groups in the frequency of amputations were observed on visits in 6 months (p = 0.041) and in 1 year of follow-up (p = 0.048). According to instrumental data, the best parameters in terms of the painless walking distance (p = 0.032) and transcutaneous oxygen tension were obtained in the study group by 6 months of follow-up (p = 0.028). CONCLUSIONS: Therapeutic angiogenesis improves the results of treatment of patients with CLLI and diabetes mellitus, especially in 6 months — 2 years interval, however, conservative therapy still demonstrates unsatisfactory results of treatment in the near and in the long terms.

Acute arterial events across all vascular territories in the FOURIER trial

Abstract Background In the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trial, adding the PCSK9 inhibitor evolocumab to statin therapy reduced low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk. Although atherosclerotic coronary, cerebrovascular, and peripheral vascular events share a related pathobiology, the effect of aggressive LDL-C lowering with PCSK9 inhibition on the risk of acute arterial events across all three vascular beds is not well-described. Purpose To assess the efficacy of evolocumab on acute arterial events in all vascular territories including coronary, cerebral, and peripheral vascular beds. Methods In the FOURIER trial, patients (n=27,564) with stable atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on a statin were randomly assigned to evolocumab versus placebo and followed for a median of 2.2 years (1.8–2.5). Acute arterial events were defined as a composite of coronary (coronary heart disease [CHD] death, myocardial infarction [MI], or urgent coronary revascularization), cerebrovascular (ischemic stroke, transient ischemic attack [TIA], or urgent cerebral revascularization), or peripheral vascular (acute limb ischemia, major amputation, or urgent peripheral revascularization) events. Cox proportional-hazard models were used to assess the efficacy of evolocumab on these outcomes. Landmark and total event analyses were also done. Results Of the 2,210 first acute arterial events occurring during follow-up, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced the risk of a first acute arterial event by 19% (HR 0.81, 95% CI 0.74–0.88; P<0.001), with significant individual reductions in acute coronary (HR 0.83; 95% CI 0.75–0.91; P<0.001), acute cerebrovascular (HR 0.77; 95% CI 0.65–0.92; P=0.004), and acute peripheral vascular (HR 0.58; 95% CI 0.38–0.88; P=0.01) events (Figure, top). The magnitude of the risk reduction with evolocumab tended to increase over time, with a 16% reduction (HR 0.84; 95% CI 0.75–0.96) in the first year followed by a 24% reduction (HR 0.76; 95% CI 0.67–0.85) thereafter (Figure, bottom). There were 3,780 total acute arterial events (first plus recurrent), with a 22% reduction with evolocumab (incidence rate ratio [RR] 0.78; 95% CI 0.70–0.87). Evolocumab prevented 496 total acute arterial events as compared to 222 first events. Conclusions The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced the risk of acute arterial events across all vascular territories with a robust effect over time. These findings indicate a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The FOURIER trial was supported by Amgen.

Effect of evolocumab on acute arterial events across all vascular territories : results from the FOURIER trial

We assessed the impact of the proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor evolocumab on acute arterial events across all vascular territories, including coronary, cerebrovascular, and peripheral vascular beds, in patients with established atherosclerotic cardiovascular disease (ASCVD). In the FOURIER trial, 27 564 patients with stable ASCVD on statin therapy were randomly assigned to evolocumab or placebo. Acute arterial events were a composite of acute coronary (coronary heart disease death, myocardial infarction, or urgent coronary revascularization), cerebrovascular (ischaemic stroke, transient ischaemic attack, or urgent cerebral revascularization), or peripheral vascular (acute limb ischaemia, major amputation, or urgent peripheral revascularization) events. Of the 2210 first acute arterial events, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced first acute arterial events by 19% (hazard ratio [HR] 0.81 [95% confidence interval 0.74-0.88]; P < 0.001), with significant individual reductions in acute coronary (HR 0.83 [0.75-0.91]), cerebrovascular (HR 0.77 [0.65-0.92]), and peripheral vascular (HR 0.58 [0.38-0.88]) events. There were 3437 total events (first plus recurrent), with evolocumab reducing total events by 24% (incidence rate ratio 0.76 [0.69-0.85]). The magnitude of reduction in acute arterial events with evolocumab numerically increased over time, with a 16% reduction (HR 0.84 [0.75-0.95]) in the first year followed by a 24% reduction (HR 0.76 [0.67-0.85]) thereafter. The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced acute arterial events across all vascular territories with a robust effect over time, indicating a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.