Reversible Ischemia Research Articles

Abstract 4138339: Abatacept prevents anti-PD-1-induced inflammatory heart failure development after myocardial ischemic injury in mice

Introduction: Immune checkpoint inhibitors (ICI), such as anti-PD-1 monoclonal antibodies are increasingly used in anti-cancer therapy. However, several cardiovascular adverse effects can occur with the use of ICIs, including new-onset heart failure. Hypothesis: We hypothesized that prior myocardial ischemic injury could exacerbate cardiac dysfunction and inflammation caused by anti-PD-1 treatment. Moreover, we investigated whether abatacept, a T-cell co-stimulation blocker, can prevent ICI-induced cardiac effects. Methods: To induce reversible cardiac ischemia, C57Bl/6J mice were treated with isoprenaline (ISOP group) or with PBS (CON group), followed by 16 weeks of recovery period. Following this, mice from both groups were divided into three further treatment groups: isotype control, anti-PD-1, or anti-PD-1 combined with abatacept, and were treated for two weeks, with three weekly intraperitoneal injections. Echocardiography was performed to evaluate cardiac function while myocardial inflammation was assessed by qRT-PCR and immunohistochemistry. Flow cytometry and Western blot were used to investigate changes occurring in the thymus. Results: Mice with normal heart function but with prior ischemic injury and anti-PD-1 treatment (ISOP + anti-PD-1) showed significantly decreased fractional shortening and cardiac index on echocardiography, while in animals with abatacept co-treatment (ISOP+anti-PD-1+abatacept) cardiac function was not altered. Increased immune cell infiltration was seen in the myocardium of the ISOP+anti-PD-1 treated group compared to CON animals, including T-cells and macrophages, with increased expression of pro-inflammatory cytokines, while co-treatment with abatacept ameliorated the inflammatory response. In the thymus, increased expression of PD-1 was found after abatacept co-treatment. Conclusion: Prior myocardial ischemic injury was associated with cardiac dysfunction and inflammation after anti-PD-1 treatment, which was ameliorated by abatacept co-treatment. Patients with prior cardiac ischemic events may be at greater risk for developing ICI-induced cardiotoxicity, including new-onset HF.

Abstract 4122369: Beyond Closure: A Case Report on Coronary Steal Syndrome by Previously Embolized Internal Mammary Artery Side Branch

Background: Internal mammary artery (IMA) side branch flow diversion post- coronary artery bypass grafting (CABG) and its role in coronary steal syndrome remains controversial. However, evident association persists when substantial side branches stem from the IMA, possibly due to relatively lower peripheral resistance as compared to higher coronary resistance. Intervention has shown promise in ameliorating reversible ischemia in these cases. Recanalization of previously occluded side branch is rare and has only been reported within a 6 month period. We report a case of recanalization of a previously occluded side-branch after 4 years with recurrence of symptoms. Case: A 63-year-old male underwent CABG with LIMA-LAD in 2020 and coil embolization of LIMA side branch for symptomatic coronary steal syndrome (figure 1). Angina recurred 3 years later, leading to right coronary artery stent placement. He now presents with palpitations and dyspnea on exertion. Vital signs and physical exam was unremarkable. ECG showed a normal sinus rhythm with no signs of ischemia. A 24-hour Holter showed significant polymorphic ventricular ectopy and episodes of sustained ventricular tachycardia (arrhythmic burden 12.4%). Transthoracic echocardiogram showed an ejection fraction of 71% and slightly decreased left ventricular global longitudinal strain (-16.6%). Decision-making: A diagnostic cardiac catheterization was performed which showed patency of bypass and stent with no signs of occlusion or restenosis, rather revealing a permeable, previously occluded side-branch (figure 2A) and resurgent coronary steal phenomenon. Repeat coiling was performed, achieving complete cessation of flow (figure 2B) and evident increased flow to the LAD. Resolution of symptoms was observed and post-procedure Holter showed normal sinus rhythm with no arrhythmic changes. Conclusion: Recanalization of an IMA side branch after complete occlusion with multiple coils is rare, particularly beyond 6 months. This appears to be the first reported case of the phenomenon, occurring after 4 years. Administration of heparin for recent stent placement, continuation of oral antiplatelet therapy and distal coil location may have contributed to restoration of flow, despite the presence of intraluminal coils. Repeat coiling proved successful in relieving symptoms.

Cocaine-associated Chest Pain: Our Experience with Myocardial Markers and Stress Lexiscans

Abstract Background: Cocaine is a commonly abused recreational drug, leading to frequent emergency room visits. The aim of this study was to check the effect of cocaine on myocardial markers of injury and the stress myocardial imaging patterns. Materials and Methods: All patients with anginal chest pain or equivalents who tested positive for cocaine on urine drug screen with reversible myocardial ischemia on regadenoson stress myocardial perfusion imaging called lexiscans were included and their corresponding myocardial markers of injury and stress imaging were reviewed. Results: Thirty-four patients had tested positive for cocaine in urine, out of the 192 patients with reversible myocardial ischemia on stress testing. The percentage of cocaine-associated myocardial ischemia was up to 17.70% in our study. Creatine kinase-MB levels were above the normal reference value of 5 ng/mL in 72.7% of patients and the combined cardiac troponins by fourth-generation assays were above the detection levels (≥0.02 ng/mL for cardiac troponin I [cTnI] and ≥0.010 ng/mL for cardiac troponin T [cTnT]) in 50% of patients. None of our patients had severe reversible myocardial ischemia on lexicans, but rather minimal-to-mild reversible myocardial ischemia was seen in the majority (76.5%) of patients. cTnI elevation was significantly associated with minimal reversible myocardial ischemia on one-way analysis of variance (P < 0.05). Conclusion: Cocaine was associated with minimal-to-mild reversible myocardial ischemia on stress testing with significant elevation of cTnI.

A randomized, double-blind, placebo-controlled, mechanistic trial on the safety, tolerability and pharmacodynamics of ninerafaxstat in patients with angina and chronic coronary syndrome

Abstract Background/Introduction Symptoms of angina resulting from reversible myocardial ischemia in chronic coronary syndromes have a negative impact on quality of life. Metabolic alterations are a key feature of ischemia, including reduced ATP generation by mitochondrial oxidative phosphorylation, NAD+ depletion, anaerobic glycolysis, proton & lactate accumulation leading to contractile dysfunction. Ninerafaxstat is a novel cardiac mitotrope that shifts metabolism from fatty acids towards glucose utilization, optimizing myocardial energy production during ischemia. Purpose We aimed to investigate the safety, tolerability, impact on myocardial glucose utilization and preliminary anti-ischemic efficacy of ninerafaxstat administered for 8 weeks to patients with symptomatic chronic stable angina who were on anti-anginal therapy and had evidence of myocardial stress hypoperfusion using 15O-H2O PET imaging. Methods IMPROVE-Ischemia was an international, randomized, double-blind, placebo-controlled mechanistic trial comparing ninerafaxstat vs. placebo in patients with symptomatic chronic coronary syndrome. The primary endpoint was the safety and tolerability of ninerafaxstat. Key efficacy evaluations were undertaken at baseline and end-of-treatment (Week 8) including imaging core laboratory assessments of 15O-H2O PET perfusion rest and stress imaging to quantify absolute myocardial blood flow (MBF), dobutamine stress echo with contrast for evaluation of LV contractile response during demand stress using the wall motion score index (WMSI) and, in a subgroup of subjects, 18F-FDG-PET imaging of myocardial glucose metabolism. Results The study randomized 58 subjects (mean age 68.6±7.1 years) with symptomatic stable angina and inducible hypoperfusion from 4 sites across 3 countries (Denmark, Finland, Sweden). 22% had type 2 diabetes and 50% had undergone percutaneous and/or surgical coronary revascularization. The majority (68%) were on ≥2 (up to 4) regular anti-anginals. Ninerafaxstat was well tolerated without impact on systemic hemodynamics. At Week 8, ninerafaxstat significantly increased myocardial glucose utilization and, in those with dobutamine-induced deterioration in wall motion at baseline assessment (n=25, pre-specified subgroup), resulted in a ~50% improvement in mean and peak stress WMSI, without altering rest or hyperemic stress MBF (Table 1). Conclusion(s) Treatment with ninerafaxstat was well-tolerated and showed a neutral hemodynamic profile. Ninerafaxstat significantly increased myocardial glucose utilization consistent with its mechanism of action and improved myocardial contractile response to dobutamine stress in subjects with baseline stress inducible deterioration of wall motion. These findings support a direct, metabolically-mediated, anti-ischemic effect of ninerafaxstat on top of existing anti-anginal agents, supporting its further development in cardiac pathologies characterised by ischemia.

One-year results from the REDUCER-I multi-center real-world clinical trial of the treatment of refractory angina with the coronary sinus Reducer

Abstract Background/Introduction Patients with refractory angina have chronic symptoms due to reversible ischemia which are inadequately controlled with optimal medical therapy or interventional treatments. These patients suffer from a poor quality of life and place a significant strain on the health care system due to their frequent rehospitalizations. The coronary sinus (CS) Reducer is a stainless-steel hour-glass shaped mesh stent that creates a focal narrowing in the lumen of the CS resulting in improved microvascular resistance and redistribution of myocardial blood flow. Purpose The COSIRA randomized controlled trial showed the Reducer is a safe and effective treatment for refractory angina with patients having significant improvements in Canadian Cardiovascular Society (CCS) class and other measures of quality of life. The REDUCER-I post-market study evaluated the long-term outcomes with the Reducer in a large and challenging ‘real-world’ cohort. Methods REDUCER-I is a multicenter, non-randomized study conducted across 26 medical centers in Europe. At one year, device effectiveness was assessed by improvement in CCS grade as compared to baseline and device safety was assessed by Major Adverse Cardiac Events (MACE). Secondary endpoints included six-minute walk tests, EQ-5D-5L tests, and Seattle Angina Questionnaires (SAQ). Subjects were followed at 30 days, 6 months, and annually through five years. Results The as-treated population includes a total of 371 patients who received a Reducer implant (78.7% (292/371) male, 47.2% (175/371) diabetic, 73.9% (274/371) post-revascularization). The one-year Kaplan-Meier overall MACE rate post-implant was 7.1% (95% CI [4.9, 10.4]). There were nine deaths within the first 365 days, one death was due to unknown causes and eight deaths were adjudicated to as not being device- or procedure-related. At 12 months, 70.0% (205/293) of patients improved by ≥1 CCS class. At baseline, 72.2% (232/363) of patients were CCS class III/IV and this proportion decreased to 18.1% (54/298) at 12 months (P<0.0001). The patients’ baseline six-minute walk distance was 327.5±116.1m which improved by a mean of 30.8±81.8m at 12 months (p<.0001). In the year prior to Reducer implant, 33.3% (88/264) of the patients had at least one visit to the emergency department compared to 11.7% (31/264) in the year after Reducer implant (p<.0001). The significant improvements in CCS class and SAQ-QoL were sustained through 3 years (Figure). Conclusion In this 12-month analysis of the REDUCER-I study, patients with refractory angina treated with the CS Reducer had low MACE rates and showed significant and sustained improvements in angina, QoL, functional capacity, and need for rehospitalization.

Outcomes of Proximal Hybrid Arterial Reconstruction in Combination with Simultaneous Amputation in Dry Atherosclerotic Gangrene of Toes

INTRODUCTION: When treating atherosclerotic gangrene of the lower limb (LL), the surgeon faces the questions about the reasonability of vascular reconstruction and the optimal timing of amputation after surgery on the LL arteries. The answer to these questions is given by assessing the state of the microvasculature of the operated limb. With sufficient development of the microvasculature and good collateral circulation, it is possible to perform a simultaneous amputation after proximal reconstruction. In this situation, a clear demarcation of the zone of necrosis and reversible ischemia is required, which can be realized by the method of ultraviolet luminescence spectroscopy. AIM: To analyze the results of hybrid reconstructions on the LL arteries with multilevel diffuse atherosclerotic lesions and dry gangrene of toes (DGT). MATERIALS AND METHODS: A prospective, controlled, non-randomized study included 29 patients suffering from critical ischemia of the lower limbs and having DGT, who were operated on in the amount of hybrid arterial reconstruction. The patients were divided into two groups: patients of group 1 (n = 14) underwent restoration of the main blood flow at the level of the iliofemoral arterial segment using a hybrid method, with simultaneous minor amputation of LL at various levels; patients of group 2 (control group, n = 15) underwent a simultaneous proximal and distal hybrid operation, providing main blood flow through at least one of the lower leg arteries, followed by a minor amputation of the lower leg at various levels over the next 4–5 days. RESULTS: There were no statistically significant differences in the groups in the degree of decrease in luminescence intensity after vascular surgery. A histological examination of intraoperative preparations of DGT revealed necrosis of the cellular microenvironment at luminescence amplitude (1.0 ± 0.05) × 105 photons at 410 nm frequency. At luminescence amplitude not exceeding this level, signs of necrobiosis were noted. Luminescence level of ≥ 1.0 × 105 photons was used as the amputation boundary. In the case of an uncomplicated vascular stage of the operation, a comparable decrease in the conventional amputation boundary was noted in the study groups. In the early postoperative period, in patients of group 1, the level of inflammation markers, average number of bed-days, and the number of thrombotic complications were lower than in the control group (p 0.05). A strong correlation was recorded between the morphological signs of the acute phase of inflammation and the intensity of chemiluminescence (r = 0.7, p 0.005). CONCLUSION: In patients with DGT, at a luminescence amplitude on the lower leg and foot not exceeding 1.0 × 105 photons at 410 nm frequency and 0.7 × 105 photons at 450 nm frequency, an effective treatment method is restoration of the main blood flow in the iliofemoral segment using a hybrid method with simultaneous minor amputation at various levels of the foot. This luminescence level is the conventional boundary between necrotic changes and reversible ischemia (necrobiosis) of the soft tissues of the LL.

Secondary Prevention Program through Hybrid Tele-Cardiac Rehabilitation using a Combination of Vigorous-intensity Interval Training and Low-Intensity Home-based Exercise in Patient with Refractory Angina Post-Percutaneous Coronary Intervention

Background: Refractory angina (RA) refers to symptoms lasting >3 months due to reversible ischemia occurring with coronary artery disease, which cannot be controlled by increased medical therapy or revascularization including percutaneous coronary intervention (PCI). It may result in a significant impact on patient outcomes such as exercise limitation, biopsychosocial disorders, and decreased quality of life. Participation of patients with RA in cardiac rehabilitation (CR) reduces angina frequency and increases exercise capacity. Exercise-based CR also improves endothelial function, reduces oxidative stress and arterial stiffness, and improves myocardial perfusion. CR is also known as a secondary prevention program with the main goal to help patients return to their normal activities by increasing their functional capacity and preventing long-term complications. Case illustration: A 64-year-old male has undergone PCI and experienced RA. This patient was given a CR program to increase his functional capacity as a secondary prevention of cardiovascular disease through a center-based combined with a home-based CR program. Aerobic exercise given was hospital-based vigorous-intensity interval training and low-intensity home-based exercise. Problems found were refractory angina that often appeared during activity, and low cardiorespiratory endurance or muscular fitness. Angina symptoms and hand grip strength improved after 2 weeks, even though muscular fitness classification was still poor. During the program, he could achieve the exercise heart rate target without any symptoms. After 4 weeks, hand grip strength and physical activity were improved, and an exercise test revealed no symptoms during the test, appropriate hemodynamic response, and good fitness classification. However, there were still frequent VES with couplet episodes, so the patient was still classified as high-risk stratification. Although risk stratification was still high, the patient was allowed to enter phase III CR, with the prescription of moderate-intensity aerobic, low-intensity resistance, flexibility, and breathing exercises. These exercises were given based on recommendations for the average adult to maintain his level of physical activity and promote lifelong healthy behavior. Conclusion: Hybrid tele-cardiac rehabilitation through a combination of vigorous-intensity interval training and low-intensity home-based exercise in a patient with refractory angina post-PCI improved functional capacity as a key component for the prevention of long-term cardiac or non-cardiac complications.

Controlled Reversible Visceral Arterial Ischemia, Venous Congestion and Combined Malperfusion via Midline Laparotomy in Rats.

Besides sepsis and malignancy, malperfusion is the third leading cause of tissue degradation and a major pathomechanism for various medical and surgical conditions. Despite significant developments such as bypass surgery, endovascular procedures, extracorporeal membrane oxygenation, and artificial blood substitutes, tissue malperfusion, especially of visceral organs, remains a pressing issue in patient care. The demand for further research on biomedical processes and possible interventions is high. Valid biological models are of utmost importance in enabling this kind of research. Due to the multifactorial aspects of tissue perfusion research, which include not only cell biology but also vascular microanatomy and rheology, an appropriate model requires a degree of biological complexity that only an animal model can provide, rendering rodents the obvious model of choice. Tissue malperfusion can be differentiated into three distinct conditions: (1) isolated arterial ischemia, (2) isolated venous congestion, and (3) combined malperfusion. This article presents a detailed step-by-step protocol for the controlled and reversible induction of these three types of visceral malperfusion via midline laparotomy and clamping of the abdominal aorta and caval vein in rats, underscoring the significance of precise surgical methodology to guarantee uniform and dependable results. Prime examples of possible applications of this model include the development and validation of innovative intraoperative imaging modalities, such as Hyperspectral Imaging (HSI), to objectively visualize and differentiate malperfusion of gastrointestinal, gynecological, and urological organs.

Prior cardiac ischemic injury exacerbates immune checkpoint inhibitor-induced cardiotoxicity

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Momentum grant of the Hungarian Academy of Sciences Introduction Immune checkpoint inhibitors (ICI), such as monoclonal antibodies targeting programmed death ligand-1 (PD-1), revolutionized cancer treatment. However, they can lead to several cardiovascular adverse effects, ranging from mild cardiac dysfunction to fulminant, lethal myocarditis. Nevertheless, the mechanisms and risk factors behind the diverse forms of ICI-induced cardiotoxicity are not entirely understood currently. Purpose In this study, we hypothesized that a prior cardiac ischemic injury, leading to acute immune cell infiltration and activation, but without subsequent heart failure, can exacerbate the cardiotoxicity and cardiac inflammation caused by anti-PD-1 monoclonal antibodies. Furthermore, we aimed to investigate in our mouse model whether abatacept, an inhibitor of T-cell co-stimulation, can ameliorate ICI-induced cardiac effects. Methods First, we treated 8 weeks-old C57BL/6J mice with isoprenaline (ISOP group, 160 mg/kg, n = 43) or with its solvent (CON group, n = 38), to induce reversible cardiac ischemia. Validation of the ischemic injury was performed in 6 randomly selected animals from each group two days after the treatment with histology and echocardiography. After this, the animals underwent 16 weeks of recovery period, followed by echocardiography to confirm cardiac functional recovery. Here, mice from both groups were randomized to three further treatment groups: isotype control, anti-PD-1 alone, or anti-PD-1 combined with abatacept and were treated for two weeks, with three weekly intraperitoneal injections (immune checkpoint inhibition phase). Echocardiography, qRT-PCR and histology was performed to evaluate cardiac function and inflammation. Results Two days after the initial ISOP treatment, mice displayed significant reduction in ejection fraction and infiltration of inflammatory cells were seen on histology. During the recovery period, 8 mice from the ISOP group and one mouse from the CON died. After the immune checkpoint inhibition phase, mice with prior ischemic injury and anti-PD-1 treatment (ISOP + anti-PD-1 alone) showed significant cardiac dysfunction on echocardiography, while animals with abatacept treatment (ISOP+anti-PD-1+abatacept) showed normal cardiac function. With qRT-PCR and histology, increased infiltration of T-cells and macrophages was seen in the myocardium of the ISOP+anti-PD-1 treated group compared to CON animals, with increased expression of pro-inflammatory cytokines, including Il17a, Il23 and Ifng. However, no cardiac infiltration was seen in mice without prior ischemic injury and the pro-inflammatory cytokine response was less pronounced as well. Conclusions Prior cardiac ischemic injury without overt cardiac dysfunction exacerbates cardiac inflammation and cardiotoxicity induced by anti-PD-1 immune checkpoint inhibition therapy. Patients with pre-existing ischemic heart disease may be at greater risk for developing ICI-induced severe cardiac adverse events.Hypothesis

Evaluation of functional significance of intermediate coronary artery lesions noninvasively by tissue doppler echocardiography and single photon emission computed tomography versus invasively by IFR

Background: Myocardial perfusion imaging by single photon emission computed tomography (MPI–SPECT) is noninvasive test that can give an important information for the diagnosis of coronary artery disease (CAD), detect reversible ischemia, quantify defect sizes and help in clinical decisions of interventions as well as assessment of disease prognosis. Tissue Doppler imaging (TDI) emerged as a potential modality for assessing systolic and diastolic LV performance. Strain doppler echocardiography (SDE) is a new tool for measuring regional myocardial deformation excluding the effect of adjacent myocardial tissue. The development of Instantaneous wave-free Ratio (IFR) as a relatively new invasive method for physiological assessment of coronary lesions without the use of pharmacologic hyperemic agents is the golden standard test for assessment of intermediate coronary lesions and guiding the revascularization decision. Methods: This Cross-sectional study was done was conducted on 50 cases with intermediate coronary artery lesions admitted at the Cardiology departments in Benha University, Kobry Elkobba Military Hospital and Air Force Specialized Hospital. All groups were subjected to history and clinical examination, cardiac examination, 12 lead ECG, 2D echocardiography, routine laboratory investigations, coronary angiography with evaluation of intermediate lesion by IFR then TDI and SDE for evaluation the regional myocardial deformation of the segments supplied by the same coronary artery, after that 99mTc-sestamibi (MIBI) SPECT imaging was done to quantify defect size and finally correlation was done between results of IFR, TDI and SPECT to guide the revascularization decision. Results: Pearson’s correlation analysis showed that; Gated single-photon emission computed moderate and severe Ischemia, Sm-velocity, WMSI, DT, had a highly significant positive correlation with IFR value (p < 0.001). E/A ratio, Mean E/e’ velocity ratio, FS, LVEF and LV GLS had a highly significant negative correlation with IFR value (p < 0.001). Conclusions: Instantaneous wave-free Ratio (IFR) modality is a reliable measure to guide functional significance of the intermediate coronary artery lesions for decision making and guiding plan of management. But it is an expensive and invasive modality. On the other hand, SPECT and tissue doppler modalities showed high sensitivity and specificity in the same group of patients with less expensive, non-invasive and no contrast use advantages.

Seizure and regadenoson: An underestimated concern

For 15 years, regadenoson, a selective adenosine 2A (A2A) receptor agonist, has been largely used as a pharmacologic stress agent in myocardial perfusion studies. It acts by increasing coronary blood flow. It has been shown to be non-inferior to adenosine for the detection of reversible myocardial ischemia. Regadenoson has several advantages, including less serious adverse effects, better tolerance and easier practical administration. However, specific adverse effects on the central nervous system, although rarely reported, can provocoke seizure through A2A receptor activation. We report here a case of regadenoson-associated-seizure and review the relevant literature. A 73-year-old male with a past medical history of hypertension, atrial fibrillation, stroke, hemodialysis and type 2 diabetes was referred for evaluation of hypokinesia of the apical segments. He had an unique episode of epilepsia in 2008. Less than one minute after regadenoson injection, he had a partial tonic-clonic seizure of the right upper and lower limbs, which lasted for 30seconds and resolved spontaneously. This case report is a reminder that this under-diagnosed adverse effect must be taken into consideration when using regadenoson for cardiac stress testing.

A budget impact model and a cost-utility analysis of reducer device (Neovasc) in patients with refractory angina.

Refractory angina (RA) is a chronic condition characterized by the presence of debilitating angina symptoms due to established reversible ischemia in the presence of obstructive coronary artery disease (CAD). Treatments for this condition have undergone major developments in recent decades; however, the treatment for RA remains a challenge for medicine. In this sense, the Coronary Sinus Reducer System (CSRS) stands as the last line of therapy for ineligible patients for revascularization with reversible ischemia. The purpose of this report is to evaluate the potential burden on the National Health Service (NHS) and measure the health effects in terms of both quantity (life years) and quality-of-life aspects related to the reducer. Two different economic evaluation models were developed as part of the analysis. The budget impact was developed to estimate the potential burden on the NHS from incremental uptake of the use of the reducer in the target population. The utility cost analysis compares and evaluates the quality of life and health resource use and costs between the two alternatives, based on the research of Gallone et al. A deterministic and probabilistic sensitivity analysis was carried out to characterize the uncertainty around the parameters of the model. In the budget impact analysis (BIA), the reducer is shown to be more expensive in the first 2 years of the model, due to the gradual uptake in the market and the cost of the device. Starting from the third year, assuming maintenance of effectiveness, there are savings in terms of resource absorption in direct healthcare costs arising from hospitalizations, emergency department accesses, coronarography, and visits avoided. The BIA and cost-effectiveness model show that the reducer device, despite an increase in resources absorbed in the first years of implementation and use, has the potential to result in increased quality of life in patients with RA. These costs are largely offset in the short term by the improved clinical outcomes achievable leading to savings from the third year onward in the BIA and a dominance ratio in the cost-utility analysis.

Todas as Provas de Esforço Devem Ser Limitadas por Sintomas e não por se Atingir 85% da Frequência Cardíaca Teórica

Except for situations of acute myocardial infarction before hospital discharge, the exercise test should always be limited by symptoms, signs or exhaustive muscle fatigue and not by reaching 85% of the maximum theoretical heart rate. One of the objectives of the test is to reproduce symptoms and evaluate whether, simultaneously or not, signs of reversible ischemia appear on stress ECG, changes in rhythm or blood pressure, which presupposes not performing submaximal tests. A submaximal test does not allow maximum aerobic capacity calculation, an important prognostic factor whether in asymptomatic individuals or patients with ischemic heart disease. The greater adrenergic stimulation caused by high intensity effort, especially when the maximum aerobic capacity has been exceeded, can be decisive for the induction of potentially malignant arrhythmias when the aim is to stratify risk in certain heart diseases.

Intracoronary electrocardiogram detects coronary microvascular dysfunction and ischemia in patients with no obstructive coronary arteries disease

Coronary microvascular dysfunction (CMD) is the leading cause of ischemia with no obstructive coronary arteries disease (INOCA) disease. Diagnosis of CMD relies on surrogate physiological indices without objective proof of ischemia. Intracoronary electrocardiogram (icECG) derived hyperemic indices may accurately and objectively detect CMD and reversible ischemia in related territory. INOCA patients with proven ischemia by myocardial perfusion scan (MPS) and completely normal coronary arteries underwent simultaneous intracoronary electrophysiological (icECG) and physiological (intracoronary Doppler) assessment in all 3 coronary arteries during rest and under adenosine induced hyperemia. Sixty vessels in 21 patients were included in the final analysis. All patients had at least one vessel with abnormal CFR. 41 vessels had CMD (CFR < 2.5), of which 26 had increased microvascular resistance (structural CMD, HMR > 1.9 mmHg.cm-1.s) and 15 vessels had CMD (CFR < 2.5) with normal microvascular resistance (functional CMD, HMR <= 1.9 mmHg.cm-1.s). Only one-third of the patients (n = 7) had impaired CFR < 2.5 in all 3 epicardial arteries. Absolute ST shift between hyperemia and rest (∆ST) has shown the best diagnostic performance for ischemia (cut-off 0.10 mV, sensitivity: 95%, specificity: 72%, accuracy: 80%, AUC: 0.860) outperforming physiological indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002). In INOCA patients, CMD involves coronary artery territories heterogeneously. icECG can accurately detect CMD causing perfusion abnormalities in patients with INOCA outperforming physiological CMD markers, by demonstrating actual ischemia instead of predicting the likelihood of inducible ischemia based on violated surrogate thresholds of blunted flow reserve or increased minimum microvascular resistance. In 21 INOCA patients with coronary microvascular dysfunction (CMD) and myocardial perfusion scan proved ischemia, hyperemic indices of intracoronary electrocardiogram (icECG) have accurately detected vessel-specific CMD and resulting perfusion abnormalities & ischemia, outperforming invasive hemodynamic indices. Absolute ST shift between hyperemia and rest (∆ST) has shown the best classification performance for ischemia in no Obstructive Coronary Arteries (AUC: 0.860) outperforming Doppler derived CMD indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002).icECG can be used to diagnose CMD causing perfusion defects by demonstrating actual reversible ischemia at vessel-level during the initial CAG session, obviating the need for further costly ischemia tests. GOV: NCT05471739.

Efficacy and safety evaluation of Ginkgo biloba dropping pill (GBDP) on stable angina pectoris complicated with depression: A placebo-controlled, randomized, double-blind, multicenter study

BackgroundStable angina pectoris (SAP) is a clinical condition characterized by reversible and temporary myocardial ischemia and hypoxia. A majority of SAP patients also experience depressive disorders, which adversely affect their disease prognosis and overall quality of life. However, the clinical utility of existing antidepressants is constrained by their side effects. Ginkgo biloba dropping pill (GBDP), a Chinese patented medication, has demonstrated efficacy in the treatment of both coronary heart disease and mental disorders. This prospective, randomized, double-blind, multicenter clinical trial aimed to assess the effectiveness and safety of GBDP as an adjuvant therapy for SAP complicated by depression. MethodsParticipants were randomly assigned in a 1:1 ratio to receive either GBDP or a placebo (5 pills, three times a day) in addition to standard therapy for a duration of 12 weeks. The Seattle Angina Questionnaire (SAQ) was administered every 4 weeks during the treatment, and angina event frequency was assessed weekly. The 36-item Short-Form (SF-36) and Hamilton Depression Scale (HAMD) scores were measured both before and after the treatment. ResultsOut of the 72 patients, 68 (n = 34 per group) completed the entire study. At the first visit (4 weeks ± 3 days), the SAQ-Angina Stability score in the GBDP group was significantly higher than that in the placebo group (p < 0.05). While the average weekly frequency of angina episodes in the placebo group notably increased after 12 weeks of treatment (p < 0.05), it displayed an improving trend in the GBDP group (p > 0.05). By the endpoint, each subcategory score of SF-36 in the GBDP group exhibited significant improvement compared to baseline (p < 0.05). The comparison of score improvement between the two groups revealed that the SF-PCS score of the GBDP group was higher than that of the placebo group (p < 0.05). HAMD scores in both groups significantly increased after treatment (p < 0.05). No discernible difference in the incidence of adverse reactions was observed between the two groups (p > 0.05). ConclusionIn patients with SAP complicated by depression, GBDP, when combined with standard treatment, rapidly and safely alleviates angina pectoris symptoms. It demonstrates therapeutic potential in enhancing the quality of life and alleviating depressive symptoms.

Quantitative and qualitative comparison of Rubidium-82 and Oxygen-15 water cardiac PET

BackgroundDifferences in tracer characteristics may influence the interpretation of positron emission tomography myocardial perfusion imaging (MPI). We compare the reading of MPIs with a low-extraction retention tracer (82Rb) and a high-extraction non-retention tracer (15O-water) in a selected cohort of patients with known coronary artery disease (CAD). MethodsThirty-nine patients with known CAD referred to 82Rb MPI due to angina underwent rest and stress imaging with both tracers and experienced MPI readers provided blinded consensus reads of all studies. In addition, a comparison of regional and global quantitative measures of perfusion was performed. ResultsThe results showed 74 % agreement in the reading of 82Rb and 15O-water MPI for regional reversible ischemia and global disease, and 82 % agreement for regional irreversible ischemia. The 15O-water MPI identified more cases of global disease (n = 12 (15O-water) vs n = 4 (82Rb), p = 0.03), whereas differences in reversible ischemia (n = 22 vs n = 16, p = 0.11) and, irreversible ischemia (n = 8 vs n = 11, p = 0.45) were not significant. The correlation between myocardial blood flow measured using the two tracers was similar to previous studies (R2 = 0.78) with wide limits of agreement (−0.93 to 0.84 ml/g/min). ConclusionsAgreement between consensus readings of 82Rb and 15O-water MPI was good in patients with known CAD. In this limited size study, no significant differences in the identification of reversible and irreversible ischemia found, whereas 15O-water MPI had a higher positive rate for suspected global disease.

Nourin miRNAs: novel biomarkers highly expressed in unstable angina patients with normal ECG and negative hs-troponin and dropped post percutaneous coronary intervention

Abstract Background We recently reported that Nourin-dependent miR-137 and miR-106b can identify reversible myocardial ischemia in chest pain patients with a confirmed diagnosis of chronic stable chronic artery disease (CAD) and unstable angina (UA). These patients showed normal resting ECG and hs-cTnI below the clinical decision (&amp;lt;99th of URL). Normal, low-grade, baseline expression levels of Nourin miRNAs were detected in healthy subjects and in non-cardiac chest pain patients with hs-cTnI &amp;lt;99th URL. Purpose 1) To confirm the upregulation of Nourin miRNAs in chest pain patients with normal resting ECG and hs-cTnI &amp;lt; 99th URL, who are suspected of having UA; 2) whether Nourin miRNA expression levels change after relieving myocardial ischemia by PCI; and 3) whether there is an association between severity of chest of pain and Nourin miRNA expression levels prior to PCI. Methods This study enrolled 36 consecutive chest pain patients with normal resting ECGs and hs-cTnI &amp;lt;99th URL, from two large referral centers in Egypt. All enrolled patients had a single vessel disease with significant coronary stenosis (&amp;gt;70%) during diagnostic coronary angiography that was treated by PCI using standard techniques. The gene expression levels of miR-137 and miR-106b were measured in serum samples collected prior to PCI, as well as 12 hours and 24 hours post PCI. The angina class was evaluated at presentation, discharge, and after 4 weeks to verify angina relief. Results All patients (n=36) underwent successful PCI. Gene expression levels of miR-137 and miR-106b were significantly upregulated prior to PCI (mean ± SD: miR-137 = 355±150 and miR-106b =317±122) compared to healthy subjects (n=16) who showed minimal expression levels ranged from 0.615 to 1.05 (P &amp;lt;0.0001). Levels of both biomarkers dropped by 50% (12 hours) and 65% (24 hours) post PCI (P &amp;lt;0.05) (Figure 1). The expression levels of Nourin miRNAs did not associate with the Canadian class levels of angina severity. All patients were asymptomatic at discharge, while 84% remained asymptomatic after 4 weeks. Conclusions This study: 1) confirms that Nourin miR-137 and miR-106b can identify myocardial ischemia in patients presenting with unstable angina; 2) confirms that these two novel molecular biomarkers are elevated during myocardial ischemia, in the absence of myocardial injury; and 3) for the first time, we report a significant drop of Nourin miRNA expression levels post PCI, with myocardial ischemia relief.

Abstract 16128: The Winslow Pathway and Internal Mammary Artery Harvesting in Patients With Aortoiliac Occlusive Disease

Introduction We present a case where the left Internal Mammary Artery (IMA) was not a straightforward choice as the grafted vessel in a patient undergoing Coronary Artery Bypass Grafting (CABG). Case Presentation Patient was a 66 years old female with Hypertension, Hyperlipidemia, hypothyroidism, and tobacco use disorder. Evaluation for a motor vehicle accident secondary to a syncopal episode, and intermittent chest tightness over the past few months, showed ST depressions on ambulatory electrocardiographic monitoring, reversible ischemia in the anterior and apical walls on Exercise Stress Test and severe multivessel coronary artery disease involving the distal main left coronary artery and its branches on Coronary Angiography. CABG was advised. Preoperative peripheral angiogram showed bilateral common iliac artery occlusion, precluding IABP placement. Selective angiography of the left IMA showed the left IMA to be the major vessel supplying collateral circulation to the left iliac system. Patient subsequently underwent CABG with bilateral Saphenous Vein Harvest. Discussion IMA harvesting in patients with Aortoiliac Occlusive Disease (AOD) with prominent collaterals through the subclavian-IMA-inferior epigastric-external iliac pathway, AKA the Winslow Pathway (WP), can result in limb threatening ischemia, and elective IMA angiography and/or doppler flow evaluation before CABG can help identify this important collateral pathway. Alternative approaches in patients with AOD include simultaneous coronary and peripheral revascularization, completely avoiding IMA harvesting or in some cases, angioplasty, although there is no consensus thus far.

Primary versus iatrogenic (post-PCI) coronary microvascular dysfunction: a wire-based multimodal comparison

BackgroundAlthough there are studies examining each one separately, there are no data in the literature comparing the magnitudes of the iatrogenic, percutaneous coronary intervention (PCI)-induced, microvascular dysfunction (Type-4 CMD) and...

In vivo study of the utility of selective intra-arterial injection of thiopental for neuroprotection in reversible cerebral ischemia.

Neuroprotective agents are needed to reduce cerebral damage during surgical or neurointerventional procedures including stroke patients. To evaluate if thiopental can be used as a neuroprotective agent when injected intra-arterially in a transient ischemia model. In total, 24 rabbits were studied as four groups of six animals. Group 1 served as the control group. In group 2, transient ischemia was obtained by intracarotid administration of degradable starch microspheres (DSM). Group 3 was administered thiopental intra-arterially via the carotid artery. Group 4 (experimental group) received both thiopental and DSM intra-arterially. DSM and thiopental were administered through a microcatheter placed into the common carotid artery via the central ear artery access. After sacrifice, apoptotic cells in the cerebral tissues of the animals were evaluated in H&E and TUNEL stained slides. There was a significant increase in the number of apoptotic glial or neuronal cells in group 2 compared to the control group and group 3. The mean number of both the apoptotic neuronal cells (6.8 ± 2.1 vs. 2.5 ± 1.3, P < 0.001) and the apoptotic glial cells (9.4 ± 3.1 vs. 4.6 ± 1.6, P < 0.001) were higher in group 2 compared to group 4. In addition, a higher level of neurological improvement was observed in group 4 compared to group 2 based on neurological assessment score. The intra-arterial administration of thiopental has a protective effect on both glial and neuronal cells during temporary cerebral ischemia in low doses.