Impact of the COVID-19 pandemic on provision of interventional cardiology and cardiac surgery services in Australia: a review of Medicare claims data.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted healthcare service provision worldwide. There is limited information on changes in invasive cardiovascular services during the pandemic, particularly in Australia. AIM: We sought to assess temporal trends on the use of interventional cardiology and cardiac surgery services before and following the COVID-19 pandemic in Australia. METHODS: Medicare Benefits Schedule items data from the Australian Government Services Australia on outpatient and private hospital interventional cardiology procedures (coronary angiogram, percutaneous coronary intervention and transcatheter aortic valve implantation) and cardiac surgery procedures (coronary artery bypass grafting [CABG] and surgical valve replacement, repair and annuloplasty) were analysed from March 2019 to 2021. This was superimposed on monthly COVID-19 case data obtained from the Australian Department of Health and Aged Care epidemiology reports. RESULTS: A sustained reduction in CABG (-10.1%) and surgical valve intervention (-11.1%) was appreciated from March 2019-2020 to March 2020-2021, in the first year of the COVID-19 pandemic. During this period, an overall increase (+25.9%) in the use of transcatheter aortic valve implantation was observed. Following the initial period of mandated isolation in March-April 2020, a reduction in coronary angiography (-29.1%) and percutaneous coronary intervention (-19.5%) was observed in comparison to March-April 2019; however, this was largely attenuated over time. CONCLUSIONS: The COVID-19 pandemic has resulted in reductions in the use of interventional cardiology and cardiac surgery services, with cardiac surgery most affected. However, an increase in uptake of transcatheter aortic valve implantation has been observed during the pandemic. This may have implications for future planning and resource allocation in the aftermath of the pandemic.

Cardiovascular presentations during the COVID-19 pandemic: an interrupted time series analysis.

BACKGROUND: The broader implications of the Coronavirus disease 2019 pandemic on cardiovascular hospitalizations remain unclear. We aimed to assess trends in cardiovascular presentations during the Coronavirus disease 2019 pandemic. METHODS: This multicentre study examined cardiovascular presentations from March 2018 to February 2023. Patients with cardiovascular presentations were identified through administrative health records using ICD-10-AM diagnosis codes. Four key study periods were analysed: T0-pre-pandemic, T1-first lockdown, T2-easing of restrictions and T3-release of restrictions and widespread vaccination. Interrupted time series analysis was used to predict weekly cardiovascular presentations, with the mean difference between actual and predicted numbers assessed for significance. RESULTS: Overall, 116 518 patients were included across three major public hospitals in Australia. Cardiovascular presentations were significantly lower in T1 than predicted, with a mean decline of 13.1% (SD 16.2%; P = 0.004). There was a significant difference between the expected and actual number of most cardiovascular presentations in T2 and T3, apart from a significant reduction in cardiomyopathy and heart failure presentations during T3 (4.5% [SD 23.7%]; P = 0.007). CONCLUSIONS: Cardiovascular presentations were significantly lower during the initial lockdown phase of the COVID-19 pandemic; this attenuated with easing of social restrictions and widespread vaccination, except for persistent reduction in cardiomyopathy and heart failure presentations.

Phenotypic Characterisation of Obstructive Sleep Apnoea in Acute Coronary Syndrome.

BACKGROUND: Recent neutral randomised clinical trials have created clinical equipoise for treating obstructive sleep apnoea (OSA) for managing cardiovascular risk. The importance of defining the links between OSA and cardiovascular disease is needed with the aim of advancing the robustness of future clinical trials. We aimed to define the clinical correlates and characterise surrogate cardiovascular markers in patients with acute coronary syndrome (ACS) and OSA. METHOD: Overall, 66 patients diagnosed with ACS were studied. Patients underwent an unattended polysomnogram after hospital discharge (median [interquartile range] 62 [37-132] days). The Epworth Sleepiness Scale, Berlin, and STOP-BANG questionnaires were administered. Surrogate measures of vascular structure and function, and cardiovascular autonomic function were conducted. Pulse wave amplitude drop was derived from the pulse oximetry signals of the overnight polysomnogram. RESULTS: OSA (apnoea-hypopnea index [AHI] ≥5) was diagnosed in 94% of patients. Moderate-to-severe OSA (AHI≥15) was observed in 68% of patients. Daytime sleepiness (Epworth Sleepiness Scale ≥10) was reported in 17% of patients. OSA screening questionnaires were inadequate to identify moderate-to-severe OSA, with an area under the receiver operating characteristic curve of approximately 0.64. Arterial stiffness (carotid-femoral pulse wave velocity, 6.1 [5.2-6.8] vs 7.4 [6.6-8.6] m/s, p=0.002) and carotid intima-media thickness (0.8 [0.7-1.0] vs 0.9 [0.8-1.0] mm, p=0.027) was elevated in patients with moderate-to-severe OSA. After adjusting for age, sex and body mass index, these relationships were not statistically significant. No relationships were observed in other surrogate cardiovascular markers. CONCLUSIONS: A high prevalence of OSA in a mostly non-sleepy population with ACS was identified, highlighting a gross underdiagnosis of OSA among cardiovascular patients. The limitations of OSA screening questionnaires highlight the need for new models of OSA screening as part of cardiovascular risk management. A range of inconsistent abnormalities were observed in measures of vascular structure and function, and these appear to be largely explained by confounding factors. Further research is required to elucidate biomarkers for the presence and impact of OSA in ACS patients.

Impact of coronary disease patterns, anatomical factors, micro-vascular disease and non-coronary cardiac factors on invasive coronary physiology.

Invasive coronary physiology has been applied by interventional cardiologists to guide the management of coronary artery disease (CAD), with well-defined thresholds applied to determine whether CAD should be managed with optimal medical therapy (OMT) alone or OMT and percutaneous coronary intervention (PCI). There are multiple modalities in clinical use, including hyperaemic and non-hyperaemic indices. Despite endorsement in the major guidelines, there are various factors which impact and confound the readings of invasive coronary physiology, both within the coronary tree and beyond. This review article aims to summarise the mechanisms by which these factors impact invasive coronary physiology, and distinguish factors that contribute to ischaemia from confounding factors. The potential for mis-classification of ischaemic status is highlighted. Lastly, the authors identify targets for future research to improve the precision of physiology-guided management of CAD.

Outcomes of deferred revascularisation following negative fractional flow reserve in diabetic and non-diabetic patients: a meta-analysis.

BACKGROUND: Fractional Flow Reserve (FFR) is a widely applied invasive physiological assessment, endorsed by major guidelines to aid in the decision to perform or defer revascularisation. While a threshold of > 0.8 has been applied universally, clinical outcomes may be affected by numerous factors, including the presence of diabetes. This meta-analysis aims to investigate the outcomes of diabetic versus non-diabetic patients in whom revascularisation was deferred based on negative FFR. METHODS: We performed a meta-analysis investigating the outcomes of diabetic and non-diabetic patients in whom revascularisation was deferred based on negative FFR. A search was performed on MEDLINE, PubMed and EMBASE, and peer-reviewed studies that reported MACE for diabetic and non-diabetic patients with deferred revascularisation based on FFR > 0.8 were included. The primary end point was MACE. RESULTS: The meta-analysis included 7 studies in which 4275 patients had revascularisation deferred based on FFR > 0.8 (1250 diabetic). Follow up occurred over a mean of 3.2 years. Diabetes was associated with a higher odds of MACE (OR = 1.66, 95% CI 1.35-2.04, p = < 0.001), unplanned revascularisation (OR = 1.48, 95% CI 1.06-2.06, p = 0.02), all-cause mortality (OR = 1.74, 95% CI 1.20-2.52, p = 0.004) and cardiovascular mortality (OR = 2.08, 95% CI 1.07-4.05, p = 0.03). CONCLUSIONS: For patients with stable coronary syndromes and deferred revascularisation based on FFR > 0.8, the presence of diabetes portends an increased long-term risk of MACE compared to non-diabetic patients. Trail registration URL:  https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42022367312.

Immediate recruitment of dormant coronary collaterals can provide more than half of normal resting perfusion during coronary occlusion in patients with coronary artery disease.

BACKGROUND: Dormant coronary collaterals are highly prevalent and clinically beneficial in cases of coronary occlusion. However, the magnitude of myocardial perfusion provided by immediate coronary collateral recruitment during acute occlusion is unknown. We aimed to quantify collateral myocardial perfusion during balloon occlusion in patients with coronary artery disease (CAD). METHODS: Patients without angiographically visible collaterals undergoing elective percutaneous transluminal coronary angioplasty (PTCA) to a single epicardial vessel underwent two scans with 99mTc-sestamibi myocardial perfusion single-photon emission computed tomography (SPECT). All subjects underwent at least three minutes of angiographically verified complete balloon occlusion, at which time an intravenous injection of the radiotracer was administered, followed by SPECT imaging. A second radiotracer injection followed by SPECT imaging was performed 24 h after PTCA. RESULTS: The study included 22 patients (median [interquartile range] age 68 [54-72] years. The perfusion defect extent was 19 [11-38] % of the LV, and the collateral perfusion at rest was 64 [58-67]% of normal. CONCLUSION: This is the first study to describe the magnitude of short-term changes in coronary microvascular collateral perfusion in patients with CAD. On average, despite coronary occlusion and an absence of angiographically visible collateral vessels, collaterals provided more than half of the normal perfusion.

Safety and Feasibility of Rotational Atherectomy in Severe Aortic Stenosis.

OBJECTIVES: We aimed to evaluate the safety and feasibility of rotational atherectomy (RA) in patients with severe aortic stenosis (AS). BACKGROUND: Heavily calcified coronary lesions are commonly encountered in elderly patients with severe AS who are being considered for transcatheter aortic valve implantation. The use of RA in these patients is controversial as they may be at a higher risk of complications. METHODS: We retrospectively enrolled patients with severe AS who underwent RA across two hospitals from March 2010 to September 2019. Patients with severe AS prior to or within 8 weeks of RA were included. RESULTS: Twenty-seven (27) consecutive patients (83±5.2 yrs 63% male) with severe AS (peak velocity 4.1±0.5 m/s, mean gradient 40.0±10.2 mmHg) were enrolled and 31 lesions were treated with RA across 30 separate procedures. Three (3) (11.1%) patients had left ventricular ejection fraction ≤30%. Nine (9) (30%) procedures involved percutaneous coronary intervention of multiple arteries, with most lesions in the right coronary artery (51.6%) and left anterior descending artery (32.3%). Three (3) (9.7%) lesions were in the left main stem. RA-facilitated stenting was successful in all lesions. There were no episodes of coronary perforation or slow-flow/no-reflow. There was one episode of coronary dissection in an artery that did not undergo RA, which was successfully treated with a drug-eluting stent. There were no deaths within 30 days and three deaths (11.1%) within 1 year. CONCLUSIONS: Rotational atherectomy in patients with severe AS is feasible and has a low rate of procedural complications.

Internet search volume for chest pain during the COVID-19 pandemic.

During the COVID-19 pandemic there has been a reduction in hospital admissions for acute myocardial infarction. This manuscript presents the analysis of Google Trends meta-data and shows a marked spike in search volume for chest pain that is strongly correlated with COVID-19 case numbers in the United States. This raises a concern that fear of contracting COVID-19 may be leading patients to self-triage using internet searches.

Prognostic impact of collaterals in patients with a coronary chronic total occlusion: A meta-analysis of over 3,000 patients.

OBJECTIVES: To assess the prognostic implications of the degree of coronary collaterals on outcomes in patients with a CTO. BACKGROUND: Coronary chronic total occlusions (CTO) are identified frequently in patients undergoing coronary angiography and have been associated with poorer prognosis. Whether the degree of coronary collaterals, the hallmark of CTOs impacts prognosis, is unknown. METHODS: A search of EMBASE, MEDLINE, and Cochrane Library was conducted to identify studies reporting on coronary collaterals and risk of all-cause mortality, acute myocardial infarction (AMI) and successful percutaneous coronary intervention (PCI). Patients with Rentrop grade 0 or 1 collaterals were defined as poor collaterals, while Rentrop grade 2 or 3 were defined as robust collaterals. RESULTS: Twelve studies with a total of 3,369 were included. Patients with robust collaterals did not have lower rates of AMI (OR: 0.89, 95%CI: 0.39-2.04) or lower rates of all-cause mortality (OR: 0.81, 95% CI: 0.42-1.58), however were more likely to have successful PCI (OR: 4.04, 95%CI: 1.10-14.85). CONCLUSION: The presence of robust collaterals is not associated with lower rates of AMI or mortality, but does increase the likelihood of successful CTO PCI. These results have importance implications with respect to the indications for CTO PCI as well as selecting appropriate patients to undergo the procedure.

The indications and utility of adjunctive imaging modalities for chronic total occlusion (CTO) intervention.

Coronary chronic total occlusions (CTO) are common in patients undergoing coronary angiography, yet the optimal management strategy remains uncertain, with conflicting results from randomized trials. Appropriate patient selection and careful periprocedural planning are imperative for successful patient management. We review the role of adjunctive imaging modalities including myocardial perfusion imaging (MPI), cardiac magnetic resonance imaging (CMR), echocardiography and computed tomography coronary angiography (CTCA) in myocardial ischemic quantification, myocardial viability assessment, as well as procedural planning for CTO revascularization. An appreciation of the value, indications and limitations of these modalities prior to planned intervention are essential for optimal management.

Prognostic implications of the rapid recruitment of coronary collaterals during ST elevation myocardial infarction (STEMI): a meta-analysis of over 14,000 patients.

Acute coronary collateralisation of an infarct-related arterial (IRA) territory may be identified during angiography for ST elevation myocardial infarction (STEMI). Whether the presence or absence of these collaterals affects outcomes remains uncertain. A search of EMBASE, MEDLINE and Cochrane Library, using the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines was conducted to identify studies which reported on the association between coronary collaterals and in-hospital and longer term mortality, left ventricular ejection fraction (LVEF), risk of repeat acute myocardial infarction (AMI) and repeat revascularisation. Patients with Rentrop grade 0 or 1 were defined as poor collaterals whilst those with Rentrop grade two or three were defined as those with robust collaterals. Studies were eligible if they included patients ≥ 18 years of age who had immediate coronary angiography for STEMI. Included studies were observational which recorded the degree of collateral blood flow to the IRA. Two investigators reviewed all citations using a predefined protocol with final consensus for all studies, the data from which was then independently entered to ensure fidelity of results. Inverse variance random effects model for the meta-analysis along with risk of bias assessment was performed. 20 studies with a total of 14,608 patients were identified and included in the analysis. Patients with robust collaterals had lower mortality (OR 0.55, 95% CI 0.48-0.64), both in-hospital (OR 0.47, 95% CI 0.35-0.63) and longer term (OR 0.58, 95% CI 0.46-0.75). Patients with robust collaterals also had a higher mean LVEF (SMD 0.23, 95% CI 0.10-0.37). There was no difference in the rates of AMI or repeat revascularisation between patients with robust or poor collaterals. The presence of robust collaterals during STEMI is associated with reduced in-hospital and longer term mortality and improved left ventricular function. These findings have implications for prognostication and identifying patients who require close monitoring following STEMI.

Both surgical and percutaneous revascularization improve prognosis in patients with a coronary chronic total occlusion (CTO) irrespective of collateral robustness.

The impact of surgical or percutaneous coronary revascularization on prognosis in patients with a chronic total occlusion (CTO) remains uncertain. Particularly, whether revascularization of those with robust coronary collaterals improves prognosis is unknown. The objective of this study was to determine the predictors and prognostic impact of revascularization of a CTO, and to determine the clinical impact of robust coronary collaterals. Patients with a CTO diagnosed on coronary angiography between Jul 2010 and Dec 2019 were included in this study. Management strategy of the CTO was defined as percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical management. The degree of collateral robustness was determined by the Rentrop grading classification. Demographic, angiographic and clinical outcomes were recorded. A total of 954 patients were included in the study, of which 186 (19.5%) patients underwent CTO PCI, 296 (31.0%) patients underwent CABG and 472 (49.5%) patients underwent medical management of the CTO. 166 patients (17.4%) had Rentrop grade zero or one collaterals, 577 (60.5%) patients had Rentrop grade two and 211 (22.1%) had Rentrop grade three collaterals. The independent predictors of medical management of the CTO were older age, greater stenosis in the donor vessel, an emergent indication for angiography, a non-LAD CTO and female sex. The degree of collateral robustness was not associated with long-term mortality, while patients who were revascularized either through CABG or PCI had a significantly lower mortality compared to medical management alone (p < 0.0001). In patients with a CTO, the presence of robust collaterals is not associated with prognosis, while both surgical and percutaneous revascularization is associated with improved prognosis. Further research into the optimal revascularization strategy for a CTO is required.

Influence of Obstructive Sleep Apnoea Severity on Coronary Collateral Recruitment During Coronary Occlusion.

PURPOSE: Obstructive sleep apnoea (OSA) which results in hypoxia may affect the ability to recruit coronary collaterals. The aim of this study was to determine whether the severity of OSA affects collateral recruitment in patients with total coronary occlusions. METHODS: Patients with total coronary artery occlusion were reviewed. Records from the sleep investigation laboratory were reviewed to identify those patients who had undergone diagnostic polysomnography. Robust coronary collaterals were those with Rentrop grade 2 or 3 collaterals. RESULTS: Sixty-four patients with a total coronary occlusion had polysomnography performed, of whom 60 patients had OSA. Thirty-two patients (53.3%) had poor collaterals, whilst 28 (46.7%) had robust collaterals. Twenty-four (40%) patients had mild OSA, 10 (16.7%) had moderate OSA and 26 (43.3%) had severe OSA. Patients with robust collaterals were more likely to be males (96.4% vs 74.3%, p < 0.05) and have a history of hypercholesterolaemia (88.9% vs 51.6%, p < 0.01). Patients with robust collaterals had a lower apnoea-hypopnoea index (13.6 vs 45.5, p < 0.05), a higher MinSaO2 (85.4% vs 79.8%, p < 0.05), less time SaO2 < 90% (0 min vs 30.4 min, p < 0.05) and lower oxygen desaturation index (6.9 vs 26.8, p < 0.05). Those with moderate OSA had a higher mean Rentrop grade (1.6 ± 0.3) than those with mild OSA (1.5 ± 1.1) and severe OSA (0.6 ± 0.2). CONCLUSION: The presence of more severe OSA is associated with poorer coronary collateral recruitment in patients with total coronary artery occlusion. The effect of treatment of OSA on subsequent ability to recruit collaterals and other cardioprotective mechanisms requires further research.

Influence of Obstructive Sleep Apnoea on Outcomes in Patients With ST Elevation Myocardial Infarction (STEMI): the Role of the Coronary Collateral Circulation.

BACKGROUND: Obstructive sleep apnoea (OSA) occurs frequently in patients with coronary artery disease, with associated intermittent hypoxia a possible stimulus for coronary collateral recruitment through ischaemic preconditioning. We sought to determine whether OSA affects recruitment of coronary collaterals and prognosis of patients presenting with ST elevation myocardial infarction (STEMI). METHODS: Patients with a STEMI undergoing percutaneous coronary intervention (PCI) from July 2010 to December 2019 were reviewed. Electronic medical records were accessed to determine documented patient history of OSA. Patients with robust collaterals were defined as Rentrop Grade 2 or 3. RESULTS: 1,863 patients were included, of which 143 (7.7%) patients had documented evidence of OSA in their health record. Patients with OSA had a higher body mass index (BMI) (30.2 kg/m2 vs 27 kg/m2, p<0.0001), greater rate of hypertension (61.1% vs 45.1%, p<0.0001), hypercholesterolaemia (47.4% vs 38.4%, p<0.05) and diabetes mellitus (22.6% vs 15.9%, p<0.05). Patients with OSA were more likely to have robust coronary collaterals (OR: 2.2 [95% CI: 1.5-3.2]) and a lower rate of left ventricular (LV) impairment (50.7% vs 63.1%, p<0.01), a higher LV ejection fraction (50.3% vs 46.7%, p<0.0001) and a lower peak troponin-I level (26,452 ng/L vs 39,469 ng/L, p<0.01). There were no differences in rates of in-hospital or longer term mortality, in patients with OSA compared to those without. CONCLUSIONS: Patients with documented OSA presenting with STEMI appear to have more robust coronary collaterals observed on angiography which likely mediates lower myocardial necrosis. Broader implications of this finding on treatment require further investigation.

Cardiac Complications in Patients Hospitalised With COVID-19 in Australia.

OBJECTIVES: Describe the incidence of cardiac complications in patients admitted to hospital with COVID-19 in Australia. DESIGN: Observational cohort study. SETTING: Twenty-one (21) Australian hospitals. PARTICIPANTS: Consecutive patients aged ≥18 years admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MAIN OUTCOME MEASURES: Incidence of cardiac complications. RESULTS: Six-hundred-and-forty-four (644) hospitalised patients (62.5±20.1 yo, 51.1% male) with COVID-19 were enrolled in the study. Overall in-hospital mortality was 14.3%. Twenty (20) (3.6%) patients developed new atrial fibrillation or flutter during admission and 9 (1.6%) patients were diagnosed with new heart failure or cardiomyopathy. Three (3) (0.5%) patients developed high grade atrioventricular (AV) block. Two (2) (0.3%) patients were clinically diagnosed with pericarditis or myopericarditis. Among the 295 (45.8%) patients with at least one troponin measurement, 99 (33.6%) had a peak troponin above the upper limit of normal (ULN). In-hospital mortality was higher in patients with raised troponin (32.3% vs 6.1%, p<0.001). New onset atrial fibrillation or flutter (6.4% vs 1.0%, p=0.001) and troponin elevation above the ULN (50.3% vs 16.4%, p<0.001) were more common in patients 65 years and older. There was no significant difference in the rate of cardiac complications between males and females. CONCLUSIONS: Among patients with COVID-19 requiring hospitalisation in Australia, troponin elevation was common but clinical cardiac sequelae were uncommon. The incidence of atrial arrhythmias and troponin elevation was greatest in patients 65 years and older.

Recruitment and maturation of the coronary collateral circulation: Current understanding and perspectives in arteriogenesis.

The coronary collateral circulation is a rich anastomotic network of primitive vessels which have the ability to augment in size and function through the process of arteriogenesis. In this review, we evaluate the current understandings of the molecular and cellular mechanisms by which this process occurs, specifically focussing on elevated fluid shear stress (FSS), inflammation, the redox state and gene expression along with the integrative, parallel and simultaneous process by which this occurs. The initiating step of arteriogenesis occurs following occlusion of an epicardial coronary artery, with an increase in FSS detected by mechanoreceptors within the endothelium. This must occur within a 'redox window' where an equilibrium of oxidative and reductive factors are present. These factors initially result in an inflammatory milieu, mediated by neutrophils as well as lymphocytes, with resultant activation of a number of downstream molecular pathways resulting in increased expression of proteins involved in monocyte attraction and adherence; namely vascular cell adhesion molecule 1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1) and transforming growth factor beta (TGF-ß). Once monocytes and other inflammatory cells adhere to the endothelium they enter the extracellular matrix and differentiate into macrophages in an effort to create a favourable environment for vessel growth and development. Activated macrophages secrete inflammatory cytokines such as tumour necrosis factor-α (TNF-α), growth factors such as fibroblast growth factor-2 (FGF-2) and matrix metalloproteinases. Finally, vascular smooth muscle cells proliferate and switch to a contractile phenotype, resulting in an increased diameter and functionality of the collateral vessel, thereby allowing improved perfusion of the distal myocardium subtended by the occluded vessel. This simultaneously reduces FSS within the collateral vessel, inhibiting further vessel growth.

Spontaneous coronary collateral recruitment in patients with recurrent ST elevation myocardial infarction (STEMI).

The spontaneous recruitment of acute coronary collaterals in the setting of an ST elevation myocardial infarction (STEMI) is seen frequently in those patients undergoing primary percutaneous coronary intervention (pPCI) and is associated with improved clinical outcomes. However, it is unknown whether in patients who present with a recurrent STEMI, the degree of collateral recruitment remains the same as in the index procedure. We reviewed all patients presenting to our tertiary centre with a STEMI undergoing primary or rescue percutaneous coronary intervention (PCI) from July 2010 until December 2018. We identified patients who presented with a recurrent STEMI following their index procedure. We defined patients with poor collateral recruitment as Rentrop grade 0 or 1, whilst patients with robust collateral recruitment as Rentrop grade 2 or 3. Of the 1795 patients who were identified, there were 27 cases in 25 patients who presented with a repeat STEMI following their index procedure. The median time between cases was 12.8 days (IQR 2.3-589.5 days). Compared to the index case, there was no statistically significant difference in the degree of collateral recruitment in recurrent presentations (Z = - 0.378, p = 0.70). In those patients presenting more than 6 months following the index procedure, the median time between cases was 654.5 days (IQR 479.5-1151.9). There was no difference in the degree of collateral recruitment in recurrent presentations (Z = 0.000, p = 1.0). Cases which had poorer collateral recruitment in recurrent presentations were less likely to be current smokers (0% vs 50%, p < 0.001) and less likely to have diabetes (0% vs 27.3%, p < 0.05) The recruitment of spontaneous coronary collaterals remains constant in recurrent STEMI presentations suggesting an innate biological process rather than merely a manifestation of alteration of haemodynamic blood flow. Further investigations to identify these processes is required.

Remote Ischemic Preconditioning induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway.

: Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in remote ischemic preconditioning (RIPC)-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by a 30-min transient blockade of the left coronary artery to simulate ischemia reperfusion (I/R) injury. Hindlimb muscle and the heart were excised 24 h post reperfusion. RIPC prior to I/R upregulated autophagy in the rat heart at 24 h post reperfusion. In vitro, autophagy inhibition or stimulation prior to RIPC, respectively, either ameliorated or stimulated the cardioprotective effect, measured as improved cell viability to mimic the preconditioning effect. Recombinant interleukin-6 (IL-6) treatment prior to I/R increased in vitro autophagy in a dose-dependent manner, activating the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway without affecting the other kinase pathways, such as p38 mitogen-activated protein kinases (MAPK), and glycogen synthase kinase 3 Beta (GSK-3ß) pathways. Prior to I/R, in vitro inhibition of the JAK-STAT pathway reduced autophagy upregulation despite recombinant IL-6 pre-treatment. Autophagy is an essential component of RIPC-induced cardioprotection that may upregulate autophagy through an IL-6/JAK-STAT-dependent mechanism, thus identifying a potentially new therapeutic option for the treatment of ischemic heart disease.

Predictors and Prognostic Implications of Well-Matured Coronary Collateral Circulation in Patients with a Chronic Total Occlusion (CTO).

The predictors and prognostic implications of well-matured collaterals in those with a chronic total occlusion (CTO) are unknown. We sought to identify the determinants of collateral maturation and to determine its effects on procedural outcomes and prognosis.Patients presenting for CTO percutaneous coronary intervention (PCI) between April 2010 and July 2019 were included. Patients with a previous coronary artery bypass (CABG) to the CTO and those with only bridging collaterals were excluded. The degree of collateral maturation was determined by the Rentrop grading classification. Demographic, biochemical, and anatomical factors and procedural and longer-term outcomes were identified.A total of 212 patients were included in the study. Patients with well-matured collaterals were more likely to be females (29.7% versus 15.2% versus 0%, P < 0.005 for Rentrop grade 3, 2, and 0 or 1, respectively), less likely to have chronic kidney disease (CKD) (8.8% versus 4.5% versus 19.2%, P < 0.05) and less likely to have had a prior CABG (15.6% versus 18.7% versus 19.2%). Patients with well-matured collaterals had lower neutrophil-to-leukocyte ratio (NLR) (2.8 versus 4.0 versus 5.7, P < 0.0001). Patients with well-matured collaterals were more likely to have procedural success (90.5% versus 62.5% versus 34.6%, P < 0.0001). The degree of collateral maturation was not associated with longer-term mortality.Improved collateral maturation was associated with female sex and lower rates of CKD and CABG and a lower NLR. Those with well-matured collaterals had a significantly higher rate of procedural success but not improved prognosis.