Mixture of Doxycycline, ML-7 and L-NAME Restores the Pro- and Antioxidant Balance during Myocardial Infarction-In Vivo Pig Model Study.

The restoration of blood flow to the ischemic myocardium inflicts ischemia/reperfusion (I/R) heart injury (IRI). The main contributors to IRI are increased oxidative stress and subsequent excessive production of ROS, increased expression of NOS and peroxinitate, activation of MMPs, and enhanced posttranslational modifications of contractile proteins, which make them more susceptible to proteolytic degradation. Since the pathophysiology of IRI is a complex issue, and thus, various therapeutic strategies are required to prevent or reduce IRI and microvascular dysfunction, in the current study we proposed an innovative multi-drug therapy using low concentrations of drugs applied intracoronary to reach microvessels in order to stabilize the pro- and antioxidant balance during a MI in an in vivo pig model. The ability of a mixture of doxycycline (1 µM), ML-7 (0.5 µM), and L-NAME (2 µM) to modulate the pro- and antioxidative balance was tested in the left ventricle tissue and blood samples. Data showed that infusion of a MIX reduced the total oxidative status (TOS), oxidative stress index (OSI), and malondialdehyde (MDA). It also increased the total antioxidant capacity, confirming its antioxidative properties. MIX administration also reduced the activity of MMP-2 and MMP-9, and then decreased the release of MLC1 and BNP-26 into plasma. This study demonstrated that intracoronary administration of low concentrations of doxycycline in combination with ML-7 and L-NAME is incredibly efficient in regulating pro- and antioxidant balance during MI.

Current role of intravascular imaging in percutaneous treatment of calcified coronary lesions.

Percutaneous treatment of calcified coronary lesions is still a challenge in modern interventional cardiology practice. Coronary angiography is limited to the precise and quantitative assessment of calcium in coronary arteries. Intracoronary imaging (ICI) modalities, including optical coherence tomography (OCT) and intravascular ultrasound (IVUS), produce a very detailed image of calcifications and could help in proper percutaneous treatment. Intracoronary imaging indicates the need to use additional tools and improves the final effect of an intervention. Drawing on the already published literature, the authors focused on the qualification of patients to the procedure, conduct and result of interventional procedures involving calcified lesions supported by ICI. The article shows the advantages and disadvantages of both ICI methods in general and especially in calcified lesions. Currently available tools dedicated to dealing with coronary calcium and helping to meet optimal stent implantation criteria are also described. This article reviews the data on ICI implementation in daily clinical practice to improve the results of percutaneous interventions, and indicates further directions.

Outcomes for patients with implanted cardioverter-defibrillators admitted to the Emergency Department due to electrical shock during the pre-pandemic and COVID-19 era.

BACKGROUND: Implantable cardioverter-defibrillators (ICD)/cardiac resynchronization therapy with defibrillation (CRT-D) recipients may be susceptible to the arrhythmic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. AIMS: We aimed to evaluate characteristics and outcomes of patients hospitalized for ICD/CRT-D shocks during the pandemic compared to the pre-pandemic period. METHODS: This retrospective study analyzed medical records of patients hospitalized for ICD/CRT-D shock in the pre-pandemic (January 1, 2018-December 31, 2019) and pandemic periods (March 4, 2020-March 3, 2022). Survival data were obtained on October 24, 2022. RESULTS: In total, 198 patients (average age 65.6 years) had 138 pre-pandemic and 124 pandemic visits. Of these patients, 115 were hospitalized during pre-pandemic, 108 during the pandemic, and 25 in both periods. No significant differences were noted in age, sex, number of shocks, or appropriateness of therapy between these periods. During the pandemic, during 14 hospital stays of patients with SARS-CoV-2, 8 (57.1%) received electrical shocks, compared to 12 (10.9%) with negative SARS-CoV-2 tests (P <0.001). The in-hospital mortality rate was 2 of 115 patients hospitalized during the pre-pandemic and 7 of 108 during pandemic periods (4 patients with and 3 without SARS-CoV-2 [P = 0.10]). During the follow-up, there were 66 deaths. Cox regression analysis showed that survival decreased with age and heart failure decompensation in medical history but increased with higher ejection fraction. The pandemic alone was not a survival predictor. However, SARS-CoV-2 infection, older age, and heart failure decompensation in medical history predicted worse outcomes during the pandemic period. CONCLUSIONS: The pandemic did not increase the number of hospital visits due to ICD/CRT-D discharges. SARS-CoV-2 infection predicts increased mortality in patients with ICD/CRT-D shocks.

Anticoagulation for Atrial Fibrillation in Acute Coronary Syndrome Survivors Reduces Major Cardiovascular Events and Mortality.

The prevalence of atrial fibrillation (AF) in acute coronary syndrome (ACS) patients is increasing. Data on outcomes of anticoagulation in ACS patients with AF are lacking.The aim of our study was to investigate the prevalence of stroke, myocardial infarction, bleeding complications, and all-cause mortality in this population.PL-ACS and AMI-PL registries gather an all-comer population of ACS patients in Poland, exceeding half a million records. We have selected ACS survivors with concomitant AF on admission, divided them into subgroups with regard to the administered anticoagulation, and followed up with them for a 12-month period (n = 13,973). Subsequently, groups were propensity score matched for age, sex, ejection fraction, diabetes, heart failure, renal impairment, and type of ACS.The study population was divided with regard to the administration of anticoagulation. Anticoagulation was prescribed in 2,466 patients (17.6%). The (D)OAC+ patients were younger; however, comorbidities were more prevalent in this group. The 12-month follow-up showed that the (D)OAC+ patients had significantly lower rates of all-cause mortality, myocardial infarction, and ischemic stroke, with no significant increase in bleeding events. After matching, the study groups consisted of 2,194 patients each and showed no differences in baseline characteristics. The outcomes of the 12-month observation were similar to the findings before matching.This all-comer national registry analysis shows that the use of guideline-recommended therapy and anticoagulation in ACS survivors with AF is associated with a lower rate of all-cause mortality, recurrent myocardial infarction, and ischemic stroke.

Multicenter registry of Impella-assisted high-risk percutaneous coronary interventions and cardiogenic shock in Poland (IMPELLA-PL).

BACKGROUND: Impella is a percutaneous mechanical circulatory support device for treatment of cardiogenic shock (CS) and high-risk percutaneous coronary interventions (HR-PCIs). IMPELLA-PL is a national retrospective registry of Impella-treated CS and HR-PCI patients in 20 Polish interventional cardiological centers, conducted from January 2014 until December 2021. AIMS: We aimed to determine the efficacy and safety of Impella using real-world data from IMPELLA-PL and compare these with other registries. METHODS: IMPELLA-PL data were analyzed to determine primary endpoints: in-hospital mortality and rates of mortality and major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months post-discharge. RESULTS: Of 308 patients, 18% had CS and 82% underwent HR-PCI. In-hospital mortality rates were 76.4% and 8.3% in the CS and HR-PCI groups, respectively. The 12-month mortality rates were 80.0% and 18.2%, and post-discharge MACCE rates were 9.1% and 22.5%, respectively. Any access site bleeding occurred in 30.9% of CS patients and 14.6% of HR-PCI patients, limb ischemia in 12.7% and 2.4%, and hemolysis in 10.9% and 1.6%, respectively. CONCLUSIONS: Impella is safe and effective during HR-PCIs, in accordance with previous registry analyses. The risk profile and mortality in CS patients were higher than in other registries, and the potential benefits of Impella in CS require investigation.

The effects of P2Y12 adenosine receptors' inhibitors on central and peripheral chemoreflexes.

Introduction: The most common side effect of ticagrelor is dyspnea, which leads to premature withdrawal of this life-saving medication in 6.5% of patients. Increased chemoreceptors' sensitivity was suggested as a possible pathophysiological explanation of this phenomenon; however, the link between oversensitization of peripheral and/or central chemosensory areas and ticagrelor intake has not been conclusively proved. Methods: We measured peripheral chemoreceptors' sensitivity using hypoxic ventilatory response (HVR), central chemoreceptors' sensitivity using hypercapnic hyperoxic ventilatory response (HCVR), and dyspnea severity before and 4 ± 1 weeks following ticagrelor initiation in 11 subjects with chronic coronary syndrome undergoing percutaneous coronary intervention (PCI). The same tests were performed in 11 age-, sex-, and BMI-matched patients treated with clopidogrel. The study is registered at ClinicalTrials.com at NCT05080478. Results: Ticagrelor significantly increased both HVR (0.52 ± 0.46 vs. 0.84 ± 0.69 L min-1 %-1; p < 0.01) and HCVR (1.05 ± 0.64 vs. 1.75 ± 1.04 L min-1 mmHg-1; p < 0.01). The absolute change in HVR correlated with the change in HCVR. Clopidogrel administration did not significantly influence HVR (0.63 ± 0.32 vs. 0.58 ± 0.33 L min-1%-1; p = 0.53) and HCVR (1.22 ± 0.67 vs. 1.2 ± 0.64 L min-1 mmHg-1; p = 0.79). Drug-related dyspnea was reported by three subjects in the ticagrelor group and by none in the clopidogrel group. These patients were characterized by either high baseline HVR and HCVR or excessive increase in HVR following ticagrelor initiation. Discussion: Ticagrelor, contrary to clopidogrel, sensitizes both peripheral and central facets of chemodetection. Two potential mechanisms of ticagrelor-induced dyspnea have been identified: 1) high baseline HVR and HCVR or 2) excessive increase in HVR or HVR and HCVR. Whether other patterns of changes in chemosensitivities play a role in the pathogenesis of this phenomenon needs to be further investigated.

Catheter-directed mechanical aspiration thrombectomy in a real-world pulmonary embolism population: a multicenter registry.

AIMS: High- (HR) and intermediate-high risk (IHR) pulmonary embolisms (PEs) are related to high early mortality and long-term sequelae. We aimed to describe clinical outcomes and adverse events in IHR and HR pulmonary embolism (PE) treated with catheter-directed mechanical thrombectomy (CDMT) in a real-world population. METHODS AND RESULTS: This study is a multicenter, prospective registry enrolling 110 PE patients treated with CDMT between 2019 and 2022. The CDMT was performed using the 8F Indigo (Penumbra, Alameda, CA, USA) system bilaterally in pulmonary arteries (PAs). The primary safety endpoints included device or PE-related death during the 48-h after CDMT, procedure-related major bleeding, or other major adverse events. Secondary safety outcomes were all-cause mortality during hospitalization or the follow-up. The primary efficacy outcomes were the reduction of PA pressures and change in the right-to-left ventricular (RV/L) ratio assessed in the imaging 24-48 h after the CDMT.71.8% of patients had IHR PE and 28.2% HR PE. 11.8% of patients had a failure and 34.5% had contraindications to thrombolysis, and 2.7% had polytrauma. There was 0.9% intraprocedural death related to RV failure and 5.5% deaths within the first 48 h. CDMT was complicated by major bleeding in 1.8%, pulmonary artery injury in 1.8%, and ischaemic stroke in 0.9%. Immediate haemodynamic improvements included a 10.4 ± 7.8 mmHg (19.7%) drop in systolic PAP (P < 0.0001), a 6.1 ± 4.2 mmHg (18.8%) drop in mean PAP, and 0.48 ± 0.4 (36%) drop in RV/LV ratio (P < 0.0001). CONCLUSION: These observational findings suggest that CDMT may improve hemodynamics with an acceptable safety profile in patients with IHR and HR PE.

Role of catheter-directed therapies in the treatment of acute pulmonary embolism. Expert opinion of the Polish PERT Initiative, Working Group on Pulmonary Circulation, Association of Cardiovascular Interventions, and Association of Intensive Cardiac Care of the Polish Cardiac Society.

Thanks to advances in interventional cardiology technologies, catheter-directed treatment has become recently a viable therapeutic option in the treatment of patients with acute pulmonary embolism at high risk of early mortality. Current transcatheter techniques allow for local fibrinolysis or embolectomy with minimal risk of complications. Therefore, these procedures can be considered in high-risk patients as an alternative to surgical pulmonary embolectomy when systemic thrombolysis is contraindicated or ineffective. They are also considered in patients with intermediate-high-risk pulmonary embolism who do not improve or deteriorate clinically despite anticoagulation. The purpose of this article is to present the role of transcatheter techniques in the treatment of patients with acute pulmonary embolism. We describe current knowledge and expert opinions in this field. Interventional treatment is described in the broader context of patient care organization and therapeutic modalities. We present the organization and responsibilities of pulmonary embolism response team, role of pre-procedural imaging, periprocedural anticoagulation, patient selection, timing of intervention, and intensive care support. Currently available catheter-directed therapies are discussed in detail including standardized protocols and definitions of procedural success and failure. This expert opinion has been developed in collaboration with experts from various Polish scientific societies, which highlights the role of teamwork in caring for patients with acute pulmonary embolism.

Aneurysm Sac Pressure during Branched Endovascular Aneurysm Repair versus Multilayer Flow Modulator Implantation in Patients with Thoracoabdominal Aortic Aneurysm.

Open thoracoabdominal repair is the gold standard in the TAAA treatment. However, there are endovascular techniques, that sometimes may be an alternative, such as branched endovascular aneurysm repair (BEVAR) or implantation of the multilayer flow modulator (MFM). In this study, we aimed to assess differences in the aneurysm sac pressure (ASP) between patients undergoing BEVAR and MFM implantation. The study included 22 patients with TAAA (14 patients underwent BEVAR, while eight MFM implantation). The pressure sensor wire was placed inside the aneurysm. A measurement of ASP and aortic pressure (AP) was performed during the procedure. The systolic pressure index (SPI), diastolic pressure index (DPI), and pulse pressure index (PPI) were calculated as a quotient of the ASP and AP values. After the procedure, SPI and PPI were lower in the BEVAR group than in the MFM group. During a procedure, a drop in SPI and PPI was noted in patients undergoing BEVAR, while no changes were revealed in the MFM group. This indicates that BEVAR, but not MFM, is associated with a reduction in systolic and pulse pressure in the aneurysm sac in patients with TAAA.

The Impact of a Modified Anaesthetic Protocol on Animal Survival and the Characteristics of Ventricular Arrhythmias in the Course of Acute Myocardial Infarction in a Domestic Pig Model.

Introduction: Acute myocardial infarction (MI) is one of the most common causes of death in humans in highly developed countries. Among its most frequent complications affecting the patient's prognosis are cardiac arrhythmias: ventricular tachycardia (VT) and ventricular fibrillation (VF). Material and Methods: The study aimed to characterise arrhythmias in 19 pigs subjected to experimentally induced MI obtained by occlusion of the proximal left anterior descending (LAD) coronary artery using an angioplasty balloon. The anaesthetic protocol was modified to reduce mortality by including procedures stabilising haemodynamic disorders which develop during episodes of ischaemia and arrhythmia. During 30 min of experimentally induced ischaemia, the heart rhythm was recorded using a 12-lead ECG. The time, frequency, and type of arrhythmias were analysed. Results: Ventricular arrhythmias were found in 94.74% of the treated pigs. The most common were ventricular premature complexes, reported in 88.89% of pigs with arrhythmia. Ventricular tachycardia was recorded in 66.67% and ventricular fibrillation in 50% of pigs with arrhythmias. Conclusion: Myocardial infarction due to proximal LAD occlusion is characterised by a high incidence of ventricular arrhythmias, especially VT and VF. Because of the high survival rate, this MI porcine model may serve as a model for research on acute ischaemic ventricular arrhythmias in humans. Additionally, it reduces the total number of animals required for testing while yielding meaningful results, which is in line with the 3R principle.

Preliminary Assessment of Intra-Aneurysm Sac Pressure During Endovascular Aneurysm Repair as an Early Prognostic Factor of Aneurysm Enlargement.

Purpose: Numerous cases of abdominal aortic aneurysm (AAA) enlargement, and even rupture, despite endovascular aneurysm repair (EVAR), have been documented. This has been linked to increased aneurysm sac pressure (ASP). We decided to conduct further research with the aim to identify correlations between ASP during EVAR and subsequent aneurysm enlargement. Patients and Methods: This experimental prospective study included 30 patients undergoing EVAR of infrarenal AAAs. Invasive ASP measurements were done using a thin pressure wire. Aortic pressure (AP) was measured using a catheter placed over the wire. Systolic pressure index (SPI), diastolic pressure index (DPI), mean pressure index (MPI), and pulse pressure index (PPI) were calculated both for ASP and AP. The results of follow-up computed tomography angiography (CTA) at 3 months were compared with baseline CTA findings. Results: During EVAR, a significant reduction was observed for SPI (from 98% to 61%), DPI (from 100% to 87%), MPI (from 99% to 74%), and PPI (from 97% to 34%). There were no significant correlations of pressure indices with an aneurysm diameter, cross-sectional area, velocity, thrombus shape and size, number of patent lumbar arteries, length and diameter of aneurysm neck, diameter of the inferior mesenteric artery, as well as diameter and angle of common iliac arteries. On the other hand, aneurysm neck angulation was significantly inversely correlated with reduced PPI. After combining CTA findings with pressure measurements, we identified a positive correlation between PPI and aneurysm enlargement (ratio of the cross-sectional area at the widest spot at baseline and at 3 months after EVAR). Conclusion: The study showed that ASP can be successfully measured during EVAR and can facilitate the assessment of treatment efficacy. In particular, PPI can serve as a prognostic factor of aneurysm enlargement and can help identify high-risk patients who remain prior monitoring.