Coronary Bed Research Articles

The interplay between coronary microvascular resistance, arterial reservoir function and coronary flow reserve: unravelling the significance of high microvascular resistance

Abstract Background Beyond the observation that patients with low CFR indicating presence of coronary microvascular dysfunction (CMD) have an unfavourable prognosis compared to patients with preserved CFR, recent large multicentre trials [1-2] have shown that increased minimal hyperaemic microvascular resistance (HMR or IMR) ,neither on top of the low CFR nor alone, does not play a role as a prognostic factor for ischemia in nonobstructive coronary artery disease (INOCA) patients. Purpose This study investigates the pathophysiological interactive processes in CMD and no-CMD groups with high and low HMR taking into account potential adaptive mechanisms that alter arterial reservoir function [3] associated with microvascular resistance and systemic vasomotor response in INOCA patients. Methods Analysis was conducted on 312 unique unobstructed vessels (FFR>0.80) from 258 patients (73% male) enrolled in the DEFINE-FLOW [4] study. CFR and HMR were quantified using intracoronary Doppler and pressure measurements. Vessels were categorized into four groups based on high and low CFR and HMR using the best available cut-off values (2.5 for both). Arterial reservoir capacity (ARC) and related parameters [3] were quantified using reservoir-excess pressure (Preservoir and Pexcess) analysis of averaged aortic and distal coronary pressure waveforms in CMD (CFR<2.5) and no-CMD (CFR≥2.5) subgroups. (Figure 1-2) Results Compared to vessels without CMD, functional and structural CMD have increased Pexcess (p:0.007) and a rapid decline in diastolic pressure (DRCcoronary p<0.001, DRCaortic, p<0.05), indicating the ongoing systemic hemodynamic superfluous state despite locally suppressed resting blood flow in the structural CMD. Higher baseline microvascular resistance (BMR) was associated with increased reservoir pressure (r:0.302, p<0.001). The vessels with preserved CFR despite high HMR are characterised by uniquely increased ARC (p:0.014), effectively diminished Pexcess (p:0.010), which parallels the local (highest BMR p<0.001) and global (lowest DRCaortic, p<0.05) vasomotor response, that normalizes the systemic and local hyperperfusion, and ultimately regains an adequate flow reserve (CFR) (p<0.001). The high HMR in this group was mainly due to increased resting tonus unlike structural CMD, evident by the highest RRR (BMR/HMR).(p<0.001) (Figure 1-2) Conclusion(s) The high HMR despite preserved CFR vessels form a unique-adaptive group, characterised by substantially increased arterial reservoir capacity and effectively diminished Pexcess, by means of an adaptive vasomotor response which manifests locally in the coronary bed as pronouncedly augmented BMR & RRR, and globally as reduced DRC in the aortic pressure waveform. This adaptive myogenic response normalising resting flow and ongoing systemic and local hyperperfusion ultimately regains an adequate flow reserve (CFR).Figure 1.Methods and Main FindingsFigure 2.Visual Abstract

Early coronary artery atherosclerosis in humans is associated with attenuated coronary retention of klotho

Abstract Background Vascular aging is a key feature of cardiovascular disease. α-klotho (klotho) is a protein inversely associated with aging and may contribute to vascular repair. Lower levels of systemic klotho have been identified in humans with features of early and advanced coronary atherosclerosis. It remains unknown if circulating klotho is present within human coronary circulation and whether cardiovascular klotho retention correlates with atherosclerosis. Purpose The current study aimed to assess the presence of klotho within coronary circulation compared to systemic circulation and hypothesized that net coronary klotho retention is attenuated in patients with early age-related features of coronary artery disease (CAD). Methods A total of 42 patients that underwent clinically indicated coronary angiogram for chest pain that had no obstructive CAD underwent intravascular ultrasound (IVUS) assessment were retrospectively examined. Virtual histology assessed coronary plaque characteristics. Blood samples simultaneously collected from the proximal aorta and coronary sinus were used for klotho detection using enzyme-linked immunosorbent assay. The net gradient of klotho across cardiovascular circulation was calculated by multiplying the arteriovenous klotho gradient by basal coronary blood flow. A net positive gradient indicated less cardiovascular klotho retention; a net negative gradient indicated greater cardiovascular klotho retention. Results Overall, participants were age 54±10 years old and 76% were female. There were overall higher levels of klotho within the coronary sinus (median 0.49 ng/mL [0.15; 1.69]) compared to systemic circulation (median 0.30 ng/mL [0.16; 1.14]). Participant groups were determined by those with positive (n = 20) or negative (n = 22) cardiovascular retention of klotho. Both groups were similar in age (56 ±2 vs. 51 ±2 years old, p = 0.080), gender (72% vs. 80% female, p = 0.580), and had similar occurrences of traditional cardiovascular comorbidities. Those with less cardiovascular klotho retention in the coronary vascular bed had significantly greater degree of non-obstructive coronary artery plaque (Gensini score 3.5 vs. 0, p < 0.001) and had higher percent plaque burden (46% [35; 53] vs. 34% [28; 46], p = 0.044) than those with greater cardiovascular klotho retention. Conclusions Patients with early coronary atherosclerosis may be characterized by attenuated retention of klotho within coronary circulation. Moreover, humans appear to have higher circulating klotho in coronary circulation than in systemic circulation. The current study may support a role for mechanism or potential therapeutic target for klotho in coronary atherosclerosis in humans.

Impact of neonatal hyperoxia on the development of the coronary vascular bed: an experimental model for the study of cardiomyopathy associated with premature birth

Abstract Introduction Very preterm birth (PT; <32 weeks of gestation), nearly 2% of all births, leads to short-term complications such as bronchopulmonary dysplasia and retinopathy of prematurity that are driven by compromised organ vascular development. Adults born preterm display an increased risk of ischaemic cardiomyopathy and heart failure. Our group has shown that neonatal rats exposed to hyperoxia, simulating the PT neonatal conditions, develop cardiomyocytes hypertrophy, fibrosis and cardiac dysfunction, or Oxygen-Induced Cardiomyopathy (OIC). Whether cardiac changes also associate with alterations in vascular development in the left ventricle (LV) remains unknown. Purpose We hypothesized that neonatal exposure to hyperoxia impact the development of the LV vascular network. Methods Male pups were exposed to 80% O2 (OIC) or room air (CTRL) from day 3 (P3) to P10 of life. Hearts were collected at P10, 4- and 16 weeks. Arteriolar length and capillary density per cardiomyocyte were measured using stereology (elastin) and immunofluorescence (WGA, α-SMA, CD31). High-resolution 3D reconstruction of the vascular network was achieved by combining fluorescent labelling of coronaries (anti-α-SMA) and capillaries (anti-CD31) with a tissue-cleaning protocol (iDisco+), allowing detailed morphometric characterization of the vascular network. The expression of vascular endothelial growth factors and receptors (VEGFA, VEGFB, VEGFR 1 and 2, NRP1, and PIGF) were quantified by RT-qPCR and Western blots. Differences between groups were analyzed with Student's t-test (P < 0.05) (N = 6 per group). Results At P10, we observed a notable rise in the number of capillaries per cardiomyocyte (0.88 ± 0.05 vs. 0.62 ± 0.02 mm2) and a significant increase in VEGFA (+76%) and NRP1 (+38%) expression in the LV from OIC vs. CTRL rats. By 4 weeks, the OIC group showed a significant reduction in arteriolar length vs. CTRL (6.51 ± 0.76 vs. 9.77 ± 1.12 m/cm3), coupled with an increase in the number of capillaries per cardiomyocyte (1.11 ± 0.05 vs. 0.85 ± 0.03 mm2). VEGFA was decreased (-14%) and PLGF increased (+24%) in the LV of OIC rats. At 16 weeks, the OIC condition displayed a significant increase in the number of capillaries per cardiomyocyte (1.37 ± 0.03 vs. 0.98 ± 0.07 mm2) and a decrease in VEGFA (-23%), along with reduction in its receptors VEGFR1 (-27%), VEGFR2 (-20%) and NRP1 (-17%). Conclusion OIC resulting from neonatal hyperoxia exposure associates with vascular changes in the LV that persist to adulthood. These changes are characterized by a reduction in arteriolar length and an increase in the number of capillaries, accompanied by modulation of the expression of pro-angiogenic VEGFA and receptors. The impact of these vascular alterations on the susceptibility of the LV to ischemic or hypertension-related damage is to be explored. These findings suggest a crucial mechanistic pathway for understanding the risk of cardiac pathologies associated with preterm birth.

Mechanical right ventricular involvement is independent of right coronary arterial bed and has a prognostic impact in acute myocardial infarction complicated by cardiogenic shock

Abstract Background In Acute Myocardial Infarction complicated by Cardiogenic Shock(AMI-CS), understanding the implications of right ventricular involvement (RVi) is crucial for refining risk stratification and optimizing management. Purpose Distinguish the prognosis in RVi at baseline(RVB) and persistent(RVP) in AMI-CS Methods 357 patients with AMI-CS+PAC serial measures at 0, 6, 12, 24h. RVi was defined as the presence of all 4 criteria PAPI<1; RVSWi≤4.08; RAP≥15 mmHg; and PVC/PCP≥0.86 and persistent as the presence of the 4 criteria at 4 time points. For hemodynamic measures, repeated measures ANOVA; and KM curves and Cox regression were performed. Results 300 without vs 57 with RVB. Additionally, 344 without vs 13 had RVP. Killip-Kimball classification showed a higher significant association with both RVB(P=0.042). A higher percentage of RVB received vasopressin(P=0.008), and there was a significant association with levosimendan use(P=0.009) in RVP. The higher MODS score, RVB(P=0.017) and RVP(P=0.029). The number of vasoactives was higher in RVB(P=0.031) RVP(P=0.009). Finally, the phenotypic characterization revealed a significant association with RVB(P=0.001) and RVP(P=0.032) more cardio-metabolic. The SCAI-CSWG classification indicated a higher proportion in the E category for both RVB(P=0.046) and not significant in RVP(P=0.405). Overall, mortality rates did not differ significantly between in RVB(P=0.174) or RVP(P=0.117), although there was a trend towards higher mortality in patients with RVi. Age, sex, DM, HTN, previous MI, PCI, CABG, stroke, and type of MI, primary reperfusion, LVEF, and laboratory parameters did not differ. RVB had higher heart rate(P=0.036), RAP, PASP(both P<0.001), lower SBP(P=0.049), cardiac output(P=0.004), index(P=0.001), power(P=0.012), power index(P=0.002), CPI(RAP), perfusion pressure, PAPi(both P<0.001), Stroke volume(SV, P=0.001), SVi(P<0.001), LVSWi(P=0.001), and RVSWi(P<0.001). RVP higher RAP(<0.001), and lower cardiac output(P=0.008), index(P=0.005), power(P=0.034), power index(P=0.029), CPI(RAP)(P=0.002), perfusion pressure(P=0.035), PAPi(P<0.001), SV(P=0.018), SVi(P=0.011), LVSWi(P=0.034) RVSWi(P<0.001). Importantly interaction between group*time was found in RVB in RAP(P<0.001), mPAP(P=0.038), perfusion pressure(P=0.002) and RVSWi(P<0.001) and in RVP in SV(P=0.014), SVi(P=0.013) and LVSWi(P=0.028) suggest that RVi had different hemodynamic response. For RVB a reduction of -4.16 days in survival time (-7.79, -0.54, P=0.024); Logrank P=0.035. Similarly, for RVP demonstrated a significant reduction of -7.27 days (-14.08, -0.47, P=0.036); Logrank P=0.017. No significant of the culprit artery in RVB, RVP (P>0.05) was observed. RVB and RVP was strongly associated with a higher prevalence of RVi (STe-V3/4R) on ECG (35.1 vs. 11.7%, and 61.5 vs. 13.7%, P<0.001). Conclusion In AMI-CS, RVi, whether baseline or persistent, is associated with distinct hemodynamic profiles and a trend toward higher mortality.Figure 1.Hemodynamics of RVB(A-C) & RVP(D-F)Figure 2.Survival of RVB, RVP (A, B) & HR(C)

Patients with STEMI after Revascularization: Is There a Relationship Between Coronary Artery Lesion and Renal Function?

The aim. To establish the relationship between coronary bed lesions and glomerular filtration rate (GFR) calculated on the basis of creatinine, cystatin C and urine albumin-creatinine ratio in patients with ST-elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention. Materials and methods. We examined 286 patients with STEMI, aged 39 to 87 years (mean age 62.8 ± 9.8, median age 64, interquartile range 56 to 71 years), 202 (70.6%) were men and 84 (29.4%) were women. All the patients underwent general clinical tests, coronary angiography with subsequent percutaneous coronary intervention, and echocardiography. Results. The most frequent infarct-related coronary artery (CA) was the anterior interventricular branch of the left coronary artery in the proximal and middle segments, and the right coronary artery in the proximal segment. In general, there was no significant difference in the number of affected CAs among the examined patients. The division of patients into groups according to the level of GFR, determined both on the basis of creatinine and cystatin C, did not reveal significant differences in the distribution of infarct-related CAs. At the same time, the number of patients with multivessel lesions significantly increases with decreased GFR. Depending on the level of the urinary albumin-to-creatinine ratio, a significant increase in the number of patients with two- and multivessel lesions of the CAs was noted. Conclusions. Close correlations between multivessel lesions of CAs and gender, age, urinary albumin-to-creatinine ratio, GFR, left and right atrial size, duration of history of hypertension and diabetes mellitus, presence of II-III degree atrioventricular block and mortality were established.

A Routine Coronary Angiography before Carotid Endarterectomy as an Example of Interdisciplinary Work: The Immediate Results of the Surgery.

The aim: to evaluate the incidence of obstructive lesions of the coronary arteries during routine coronary angiography (CAG) before carotid endarterectomy (CEA) and the incidence of perioperative complications. Materials and Methods: We examined a continuous sample of 498 patients before CEA who underwent an invasive evaluation of the coronary bed during CAG. Depending on the hemodynamic significance of coronary artery lesions, the patients were divided into three groups: group I-obstructive coronary artery disease (≥70%) (n = 309, 62.0%); group II-non-obstructive lesions of the coronary arteries (<70%) (n = 118, 23.7%); group III-intact coronary arteries (n = 71, 14.3%). The groups were compared with each other according to the data of the preoperative examination (clinical and anamnestic parameters, laboratory data and results of echocardiography), as well as according to the immediate results of the operation. In the hospital period, adverse cardiovascular events were assessed: death, myocardial infarction (MI), stroke, arrhythmias, atrial fibrillation or flutter (AF/AFL) and combined endpoint. Results: The groups differed significantly in the presence of symptoms of angina pectoris, myocardial infarction and myocardial revascularization procedures in their medical history and in the presence of chronic ischemia of the lower extremities. However, in the group of intact coronary arteries, the symptoms of angina were in 14.1% of patients, and a history of myocardial infarction was in 12.7%. Myocardial revascularization before CEA or simultaneously with it was performed in 43.0% of patients. As a result, it was possible to reduce the number of perioperative cardiac complications (mortality 0.7%, perioperative myocardial infarction 1.96%). Conclusions: The high incidence of obstructive lesions in the coronary arteries in our patients and the minimum number of perioperative complications favor routine CAG before CEA.

Chronic acetylcholinesterase inhibition reduces the effects of physical training on ventricular contractility and coronary bed reactivity in hypertensive rats

Systemic arterial hypertension is accompanied by autonomic impairments that, if not contained, promotes cardiac functional and morphological damages. Pyridostigmine bromide (PYR) treatment results in positive effects on autonomic control and beneficial cardiac remodeling. These findings were also observed after aerobic physical training (APT). However, little is known about PYR effects on left ventricular contractility, mainly when it is combined with APT. We aimed to investigate the effects of chronic acetylcholinesterase inhibition on cardiac autonomic tone balance, coronary bed reactivity, and left ventricular contractility in spontaneously hypertensive rats (SHR) submitted to APT. Male SHR (18 weeks) were divided into two groups (N = 16): untrained and submitted to APT for 14 weeks (18th to 32nd week). Half of each group was treated with PYR (15 mg/kg/day) for two weeks (31st to 32nd week). The experimental protocol consisted of recording hemodynamic parameters, double autonomic blockade with atropine and propranolol, and assessment of coronary bed reactivity and ventricular contractility in isolated hearts using the Langendorff technique. PYR and APT reduced blood pressure, heart rate, and sympathetic influence on the heart. The Langendorff technique showed that APT increased coronary perfusion pressure and left ventricle contractility in response to coronary flow and β-agonist administration. However, treatment with PYR annulled the effects of APT. In conclusion, although chronic treatment with PYR reduces cardiac sympathetic tonic influence, it does not favor coronary bed reactivity and cardiac contractility gains. PYR treatment in the trained SHR group nullified the coronary vascular reactivity and cardiac contractility gains.

Pericytes in the brain and heart: functional roles and response to ischemia and reperfusion.

In the last 20 years there has been a revolution in our understanding of how blood flow is regulated in many tissues. Whereas it used to be thought that essentially all blood flow control occurred at the arteriole level, it is now recognised that control of capillary blood flow by contractile pericytes plays a key role both in regulating blood flow physiologically and in reducing it in clinically-relevant pathological conditions. In this article we compare and contrast how brain and cardiac pericytes regulate cerebral and coronary blood flow, focusing mainly on the pathological events of cerebral and cardiac ischemia. The cerebral and coronary capillary beds differ dramatically in morphology, yet in both cases pericyte-mediated capillary constriction plays a key role in restricting blood flow after ischemia and possibly in other pathological conditions. We conclude with suggestions for therapeutic approaches to relaxing pericytes, which may prove useful in the long term for reducing pericyte-induced ischemia.

Strengthening cardiac services in Faridabad District: A facility mapping exercise to explore implementation of a hub-and-spoke model.

Background & objectives Improving access to acute cardiac care requires remodelling of existing health systems into a service delivery network with an anchor establishment (Hub) offering a full array of services, complemented by spoke establishments that offer limited services. We assessed the availability of cardiac services in the district of Faridabad in the northern State of Haryana, India and explored the feasibility and challenges of implementing a hub-and-spoke model. Methods In 2019-2020, we listed all the facilities in private and public sectors in the study-district and mapped their geocoordinates with the help of QGIS (Quantum Geographic Information System) software version 3.20. After consent, we assessed the availability of specific cardiac care-related inputs (medicines, technologies and staff) using a checklist by enquiring from the hospital staff. Each facility was classified as L1 (No ECG) to L5 (cardiac catheterization) as per the national guidelines for the management of ST-elevation myocardial infarction (STEMI). Results There were 109 health facilities (66% private) in the district, 1.6 cardiologists and 5.4 coronary care unit beds per 100,000 population (94% private). Only one district hospital running in a public-private partnership mode at the L5 level provided any cardiac services. Private facilities were providing a range of services with a considerable number of them functional at L5. The higher-level facilities were concentrated in the central and urban parts of the district. Only 46 per cent of the ambulances had oxygen cylinders and 14.7 per cent had defibrillators. Interpretation & conclusions Implementation of a hub-and-spoke model for cardiac care in Faridabad district will require significant strengthening of public health services, development of a private-sector participation model, and strengthening of ambulance services.

Features of Coronary Atherosclerosis in Patients with Coronary Artery Disease Residing in the Far North

Aim: To evaluate the features of coronary artery disease (CAD) in patients in the Far North and determination of the potential impact of extreme climatic factors on the development of coronary atherosclerosis. Material and Methods. Using the “Register of performed coronary angiography operations”, 5,679 patients with coronary artery disease were selected, who underwent coronary angiography at the Tyumen Cardiology Research Center. The main study group consisted of 2,590 patients permanently residing in the YamaloNenets Autonomous Okrug and 3,089 patients residing in the South of the Tyumen Region. Results. Patients with permanent residence in the Yamalo-Nenets Autonomous Okrug were on average younger (53.20 ± 7.49 versus 56.79 ± 8.34 years, p &lt; 0.001), men were more common among them. In the extreme North there were more smokers (40.7 vs. 32.0%, p &lt; 0.001) and alcohol users (19.7 vs.15.0%, p &lt; 0.001), and more frequent myocardial infarction in anamnesis (57.1 vs. 48.2%, p &lt; 0.001). At the same time, in patients permanently residing in the South of the Tyumen Region, a burdened hereditary history of CAD was more often determined, and the frequency of arterial hypertension and dyslipidemia was higher. In groups balanced by baseline clinical and demographic characteristics, including CAD risk factors, patients from the Yamal-Nenets Autonomous Okrug had more frequent lesions of the three main coronary arteries: anterior descending artery (42 vs. 35%, p &lt; 0.001), circumflex artery (25 vs. 23%, p = 0.038) and right coronary artery (42 vs. 38%, p = 0.007). It should be noted that in balanced groups in patients permanently residing in the Far North, occlusive lesions of the coronary arteries were statistically significantly more likely to be determined (54 vs. 47%, p &lt; 0.001). Also, between the compared groups, statistically significant differences were found in the type of left ventricle (LV) myocardial remodeling, but these differences were not determined in the balanced groups. Also, in the group of patients permanently residing in the Far North, there was a trend towards a decrease in the LV ejection fraction (53.6 ± 8.6% vs. 54.2 ± 8.7, p = 0.074).Conclusion. In patients with verified coronary artery disease living in the Far North, a more frequent and pronounced atherosclerotic lesion of the coronary bed is determined. These pathological changes are probably due to the complex impact of unfavorable natural and climatic environmental factors.

Intracoronary adenosine compared with adrenaline and verapamil in the treatment of no-reflow phenomenon following primary PCI in STEMI patients

Backgroundno-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI). Methods108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay. ResultsThe study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups. ConclusionLocal delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine.

#2851 Effects of dialysis on various microcirculatory beds in end-stage kidney disease (ESKD): a systematic review and meta-analysis

Abstract Background and Aims Microcirculatory dysfunction is common in ESKD-patients and may play a pivotal role in their cardiovascular burden. Besides traditional and chronic-kidney-disease (CKD)-specific risk factors, dialysis itself might contribute to the dysfunction of the microcirculation (MC). Although an intradialytic fall in systemic blood pressure (BP) may directly influence the microcirculatory perfusion, vascular beds in different organs may not react uniformly. This systematic review and meta-analysis evaluated the acute impact of hemodialysis (HD) and hemodiafiltration (HDF) on the MC in various vascular beds. Methods Pubmed and Embase databases were systematically explored until June 2023 by two independent researchers. All observational and interventional studies in ESKD patients that reported dialysis-induced alterations of the MC, measured at the cutaneous, sublingual, retinal, muscle or coronary beds were eligible. Dialysis-induced changes were extracted and pooled, using a fixed-effects meta-analysis when the studies were reasonably homogeneous in terms of outcomes and methodology. Results 17 Studies with 493 participants were included. Virtually all patients (99.8%) were treated with HD. No eligible studies on coronary or muscle MC were identified. Cutaneous MC was investigated in 7 studies, showing a mean reduction in transcutaneous oxygen pressure of −7.9 mmHg (95% CI −10.5 to –5.3, n = 4 studies) and a mean reduction in blood flow of −0.9 arbitrary units (95% CI −1.2 to −0.6, n = 3 studies). Cutaneous vasoreactivity was diminished in 2 out of 3 studies (reactive maximum microvascular hyperemia: −36% (p &amp;lt; 0.05); time to reach baseline skin temperature after standardized cooling: 65.6 seconds (p-value not reported); vs. no significant change in post-ischemic maximal flow (2.5, p = not significant (N.S.)). Sublingual MC was assessed in 3 studies, showing a mean decrease in microvascular flow index of −0.6 in small microvessels (vessel diameter (VD) &amp;lt;20-25 µm, 95% CI −1.0 to −0.2, n = 3 studies), but no significant change in proportion of perfused vessels (−0.5%, 95% CI −1.2 to 0.2, n = 2 studies). One study showed a significant reduction in sublingual perfused vessel density after treatment (VD &amp;lt;20 µm: −1.6 ± 3.1, p &amp;lt; 0.05; VD &amp;gt;20 µm: −0.6 ± 1.1, p &amp;lt; 0.05), whereas total vessel density was unaffected in another study (VD &amp;lt;20 µm: 0.5, p = N.S.). Retinal MC was investigated in 7 studies, showing that the perfused vessel density (PVD) remained unchanged in both the superficial and deep capillary plexus (PVD SCP −0.48, 95% CI (−0.99; 0.03); PVD DCP −0.48, 95% CI (−1.18; 0.23), n = 4 studies). One study reported a decreased PVD at the outer retina (−1.3 ± 5.7, p &amp;lt; 0.05), while conflicting results were observed in 2 studies (0.1, p = N.S.; vs. −2.9 ± 4.3, p &amp;lt; 0.001), reporting the PVD at the choriocapillaris level. One study found no change in retinal blood flow (0.4, p = N.S.). With regard to vessel diameter changes, an increase in retinal venular diameter was observed in 3 studies (retinal venular diameter: 11.2 µm, p = 0.002; central retinal vein equivalent: 12.7 µm, p &amp;lt; 0.001; retinal vessel diameter: 4.4, p &amp;lt; 0.01), and one study described impaired venular dilatation in response to flicker light (−4.0, p = 0.04). Conclusions Hemodialysis induces microvascular dysfunction in different organs, but its impact varies between vascular beds. Microvascular perfusion was most significantly impaired in the cutaneous and sublingual regions, whereas the retinal microcirculatory perfusion remained unaltered. Literature on the effect of hemodiafiltration on the MC is lacking.

Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: A multicenter systematic review and meta-analysis.

With heavily calcified coronary and peripheral artery lesions, lesion preparation is crucial before stent placement to avoid underexpansion, associated with stent thrombosis or restenosis and patency failure in the long-term. Intravascular lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, making it to a promising tool for patients with severe calcification in coronary bed. The aim of the study is to systematically review and summarize available data regarding the safety and efficacy of IVL for lesion preparation in severely calcified coronary arteries before stenting. This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL before stent implantation. The diameter of the vessel lumen before and after IVL, as well as stent implantation, were analyzed. The occurrence of major adverse cardiovascular events (MACE) was assessed using a random-effects model. This meta-analysis comprised 38 studies including 2977 patients with heavily calcified coronary lesions. The mean age was 72.2 ± 9.1 years, with an overall IVL clinical success of 93% (95% confidence interval [CI]: 91%-95%, I2 = 0%) and procedural success rate of 97% (95% CI: 95%-98%, I2 = 73.7%), while the in-hospital and 30-days incidence of MACE, myocardial infarction (MI), and death were 8% (95% CI: 6%-11%, I2 = 84.5%), 5% (95% CI: 2%-8%, I2 = 85.6%), and 2% (95% CI: 1%-3%, I2 = 69.3%), respectively. There was a significant increase in the vessel diameter (standardized mean difference [SMD]: 2.47, 95% CI: 1.77-3.17, I2 = 96%)and a decrease in diameter stenosis (SMD: -3.44, 95% CI: -4.36 to -2.52, I2 = 97.5%) immediately after IVL application, while it was observed further reduction in diameter stenosis (SMD: -6.57, 95% CI: -7.43 to -5.72, I2 = 95.8%) and increase in the vessel diameter (SMD: 4.37, 95% CI: 3.63-5.12, I2 = 96.7%) and the calculated lumen area (SMD: 3.23, 95% CI: 2.10-4.37, I2 = 98%), after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated to be 1.27 ± 0.6and 1.94 ± 1.1 mm, respectively. Periprocedural complications were rare, with just a few cases of perforations, dissection, or no-reflow phenomena recorded. IVL seems to be a safe and effective strategy for lesion preparation in severely calcified lesions before stent implantation in coronary arteries. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.

Diagnosis and Management of Congenital Coronary Artery Fistulas in Adults.

This review describes the presentation, diagnosis, and management of congenital coronary artery fistulas (CAFs) in adults. CAFs are classified as coronary-cameral or coronary arteriovenous fistulas. Fistulous connections at the distal coronary bed are more likely to be aneurysmal with higher risk of thrombosis and myocardial infarction (MI). Medium-to-large or symptomatic CAFs can manifest as ischemia, heart failure, and arrhythmias. CAF closure is recommended when there are attributable symptoms or evidence of adverse coronary remodeling. Closure is usually achievable using transcatheter techniques, though large fistulas may require surgical ligation with bypass. Given their anatomic complexity, cardiac CT with multiplanar 3-D reconstruction can enhance procedural planning of CAF closure. Antiplatelet and anticoagulation are essential therapies in CAF management. CAFs are rare cardiac anomalies with variable presentations and complex anatomy. CAF management strategies include indefinite medical therapy, percutaneous or surgical CAF closure, and lifelong patient surveillance.

Physical exercise is essential for increasing ventricular contractility in hypertensive rats treated with losartan.

The treatment of hypertensive patients with losartan is very common. Despite the reduction in blood pressure, its effects on cardiac contractility and sympathetic autonomic drive are still controversial. In turn, aerobic physical training (APT) also presents an important therapeutic option, providing significant improvements in cardiovascular autonomic control, however little is known about its effects on cardiac contractility, especially when associated with losartan. Therefore, we investigated in spontaneously hypertensive rats (SHR) the effects of losartan and APT on cardiac hemodynamics and functionality, with emphasis on autonomic tonic balance and cardiac contractility. Sixty-four SHR (18 weeks old) were divided into four groups (N = 16): vehicle; vehicle submitted to APT through swimming for 12 weeks; treated with losartan (5 mg·kg-1·d-1) for 12 weeks; and treated with losartan associated with APT. The groups were submitted to cardiac morphological and functional analysis by echocardiography; double blockade of cardiac autonomic receptors with atropine and propranolol; and coronary bed reactivity and left ventricular contractility analyses by the Langendorff technique. APT improved functional parameters and autonomic balance by reducing sympathetic drive and/or increasing vagal drive. In contrast, it promoted a concentric remodeling of the left ventricle (LV). Treatment with losartan reduced sympathetic autonomic drive and cardiac morphological parameters, but there were no significant gains in cardiac functionality and contractility. When combined, the concentric remodeling of the LV to APT was abolished and gains in cardiac functionality and contractility were observed. Our findings suggest that the effects of losartan and APT are complementary and should be applied together in the treatment of hypertension. In spontaneously hypertensive rats, the combination of aerobic physical training with losartan treatment was crucial to greater blood pressure reductions and an increase in left ventricular contractility. Furthermore, losartan treatment prevented the concentric left ventricular remodeling caused by aerobic physical training.

Cardioprotection with levocarnitine intracoronary administration during percutaneous coronary interventions

Currently, the number of percutaneous coronary interventions (PCI) performed in acute and chronic forms of coronary heart disease continues to grow: every year their number reaches at least 5,000,000 worldwide, and more than 200,000 of them in Russia. The main causes of postoperative mortality are perioperative myocardial infarction and acute heart failure due to inadequate protection of the myocardium from ischemia/reperfusion under conditions of balloon expansion and stenting of the affected coronary arteries. The review presents experimental and clinical literature data on the successful use of levocarnitine for cardioprotection in patients with various forms of coronary heart disease and patients with chronic heart failure, both with intravenous administration and as part of a cardioplegic solution during heart surgery. The intracoronary route of administration of levocarnitine solution during PCI in high-risk patients (elderly and senile patients, with multivessel lesions of the coronary bed, difficulties in conducting the intervention) is substantiated. The description of two clinical cases of the use of the technique in elderly patients with acute forms of coronary heart disease with multivessel lesion is given. The postoperative period proceeded without complications with smooth dynamics of biomarkers (troponin I, total creatinephosphokinase, MB-fraction of creatinephosphokinase, lactate dehydrogenase), ischemic ECG shifts were little pronounced. The expected results of the application of the technique are a reduction in intraoperative and postoperative complications of ischemia/ reperfusion and an increase in the effectiveness of the clinical results of PCI in high-risk patients.

Epicardium and Coronary Vessels.

Congenital anomalies and acquired diseases of the coronary blood vessels are of great clinical relevance. The early diagnosis of these conditions remains, however, challenging. In order to improve our knowledge of these ailments, progress has to be achieved in the research of the molecular and cellular mechanisms that control development of the coronary vascular bed. The aim of this chapter is to provide a succint account of the key elements of coronary blood vessel development, especially in the context of the role played by the epicardium and epicardial cellular derivatives. We will discuss the importance of the epicardium in coronary blood vessel morphogenesis, from the contribution of the epicardially derived mesenchyme to these blood vessels to its role as an instructive signaling center, attempting to relate these concepts to the origin of coronary disease.

Cytokine profile in middle-aged men with acute and chronic coronary syndrome and its relation with coronary bed lesion severity

Cytokine profile in middle-aged men with acute and chronic coronary syndrome and its relation with coronary bed lesion severity

THE STATE OF THE CORONARY BED IN CORONARY HEART DISEASE IN PATIENTS WITH HYPOTHYROIDISM

Hypothyroidism is a significant aggravating factor for coronary heart disease (CHD). However, there are no practical recommendations for the management of this group to date. The main method of assessing the severity of coronary artery disease is a morphological assessment of the condition of the coronary arteries. The aim. To carry out comparative assessment of clinical parameters, including the state of the coronary bed in patients with coronary artery disease with newly diagnosed (without hormone replacement therapy) and primary manifest hypothyroidism compared with patients with coronary artery disease without hypothyroidism. Materials and methods. Two hundred and forty patients with CHD were examined. The study group included 90 patients with coronary heart disease and hypothyroidism, the comparison group consisted of 150 patients with coronary artery disease without thyroid pathology. A comprehensive examination of patients, including coronary angiography, was performed. The frequency of cases and characteristics of lesions of the coronary bed, the volume of interventions were assessed. The analysis of the obtained data was carried out in Statistica 10.0 (StatSoft Inc., USA). Results. In the study group (CHD and hypothyroidism), a statistically significantly increased level of myoglobin, a change in lipid profile parameters in relation to patients with CHD without hypothyroidism was found. In the group of patients with coronary artery disease and hypothyroidism, a predominance of the frequency of multivessel lesions of the coronary bed was revealed. The volume of surgical interventions between the examined patients did not reveal significant differences. Conclusion. Patients with coronary heart disease and hypothyroidism should be considered as a group of additional cardiovascular risk and require a more careful approach. It is possible to prescribe higher dosages of statins.

Reduced trans-myocardial extraction of endothelin-1 in cardiac allograft vasculopathy

Abstract Introduction Cardiac allograft vasculopathy (CAV) is a major cause of graft failure due to microvascular dysfunction and ischaemia following heart transplant. Endothelin-1 (ET-1) is an endothelium derived vasoconstrictor peptide with multiple adverse effects including vascular smooth muscle proliferation and pro-inflammatory signalling. Elevated circulating ET-1 has been associated with accelerated CAV. We assessed the trans-myocardial gradient (TMG: coronary sinus minus coronary artery concentration: negative=extraction, positive=secretion) of ET-1 in heart transplant patients to determine correlations with angiographic, Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) features of CAV. Methods 23 patients underwent invasive coronary angiography, 3-vessel grey scale IVUS (Opticross, 60mHz, Boston Scientific) and OCT (Dragonfly, Abbott Vascular) to define morphological features of vasculopathy 18±3 months post-transplant. Paired blood samples were obtained from the guide catheter and coronary sinus at the time of coronary imaging. Plasma was analysed using specific enzyme-linked immunosorbent assay for ET-1 peptide quantification. Survival was determined 98±5 months after initial assessment. Results ET-1 TMG distribution was mostly in the negative range reflecting net extraction across the coronary vascular bed (median [IQR]: -0.23 [-0.54, -0.02] pg/ml). However, vessels with more severe CAV demonstrated significantly more positive TMG i.e. less ET-1 trans-myocardial extraction (IVUS Stanford Grade IV: -0.05 [-0.21, 0.13] pg/ml versus Stanford Grade I-III: -0.31 [-0.64, -0.11] pg/ml, p = 0.01). ET-1 TMG was positively correlated with mean intimal thickness on both IVUS and OCT (IVUS: Kendall’s tau-b = 0.254, p=0.02 and OCT: Kendall’s tau-b = 0.344, p&amp;lt;0.0001). Patients who died had net ET-1 secretion compared with surviving patients (died: 0.21 [0.19 - 0.24] versus surviving: -0.28 [-0.52, -0.17], p = 0.01). Conclusions In heart transplant patients, coronary arteries with more intimal thickening had less trans-myocardial extraction, and more secretion of ET-1. ET-1 secretion in CAV may mediate the distal microvascular dysfunction commonly seen in this condition. These findings suggest a rationale for testing ET-1 receptor antagonists as a treatment for CAV.ET-1 TMG and IVUS Stanford Grade of CAVET-1 TMG and OCT derived MIT