A randomised trial of selective intracoronary hypothermia during primary PCI.

BACKGROUND: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking. AIMS: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI. METHODS: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months. RESULTS: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53). CONCLUSIONS: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).

Spontaneous Coronary Artery Dissection and COVID-19: A Review of the Literature.

SARS-CoV-2 is responsible for the global coronavirus disease 2019 (COVID-19) pandemic. While the cardiovascular effects of COVID-19 have been thoroughly described, there are limited published studies in the literature establishing a connection between spontaneous coronary artery dissection (SCAD) and COVID-19. Cardiovascular manifestations include, among others, myocarditis, acute myocardial infraction, and thrombosis. In general, SCAD is an uncommon and underdiagnosed cause of acute myocardial infarction (AMI), particularly in younger women and in patients with underlying fibromuscular dysplasia (FMD). Many patients with SCAD often report significant emotional stress, especially in relation with job loss, during the week preceding their cardiac event. Moreover, the COVID-19 pandemic has led to societal stress and increased unemployment, factors that have been associated with cardiovascular morbidity. SCAD emerges as a rare manifestation of coronary artery disease, which a few recent case reports link to COVID-19. The aim of this article is to summarize the relevant data on the pathophysiology of COVID-19 and SCAD along with a review of the reported cases on acute coronary syndrome (ACS) following SARS-CoV2 infection and, thus, to provide insights about the relationship between COVID-19 and SCAD.

The Effect of Hydrostatic Pressure on Coronary Flow and Pressure-Based Indices of Coronary Stenosis Severity.

Background: To assess whether hydrostatic pressure gradients caused by coronary height differences in supine versus prone positioning during invasive physiological stenosis assessment affect resting and hyperaemic pressure-based indices or coronary flow. Methods: Twenty-three coronary stenoses were assessed in twenty-one patients with stable coronary artery disease. All patients had a stenosis of at least 50% visually defined on previous coronary angiography. Pd/Pa, iFR, FFR, and coronary flow velocity (APV) measured using a Doppler were recorded across the same stenosis, with the patient in the prone position, followed by repeat measurements in the standard supine position. Results: When comparing prone to supine measurements in the same stenosis, in the LAD, there was a significant change in mean Pd/Pa of 0.08 ± 0.04 (p = 0.0006), in the iFR of 0.06 ± 0.07 (p = 0.02), and in the FFR of 0.09 ± 0.07 (p = 0.003). In the Cx, there was a change in mean Pd/Pa of 0.05 ± 0.04 (p = 0.009), iFR of 0.07 ± 0.04 (p = 0.01), and FFR of 0.05 ± 0.03 (p = 0.006). In the RCA, there was a change in Pd/Pa of 0.05 ± 0.04 (p = 0.032), iFR of 0.04 ± 0.05 (p = 0.19), and FFR of 0.04+-0.03 (p = 0.004). Resting and hyperaemic coronary flow did not change significantly (resting delta APV = 1.6 cm/s, p = 0.31; hyperaemic delta APV = 0.9 cm/s, p = 0.85). Finally, 36% of iFR measurements and 26% of FFR measurements were re-classified across an ischaemic threshold when prone and supine measurements were compared across the same stenosis. Conclusions: Pd/Pa, iFR, and FFR were affected by hydrostatic pressure variations caused by coronary height differences in prone versus supine positioning. Coronary flow did not change signifying a purely pressure-based phenomenon.

Comparison of bolus versus continuous thermodilution derived indices of microvascular dysfunction in revascularized coronary syndromes.

Background: The assessment of coronary microvascular dysfunction (CMD) using invasive methods is a field of growing interest, however the preferred method remains debated. Bolus and continuous thermodilution are commonly used methods, but weak agreement has been observed in patients with angina with non-obstructive coronary arteries (ANOCA). This study examined their agreement in revascularized acute coronary syndromes (ACS) and chronic coronary syndromes (CCS) patients. Objective: To compare bolus thermodilution and continuous thermodilution indices of CMD in revascularized ACS and CCS patients and assess their diagnostic agreement at pre-defined cut-off points. Methods: Patients from two centers underwent paired bolus and continuous thermodilution assessments after revascularization. CMD indices were compared between the two methods and their agreements at binary cut-off points were assessed. Results: Ninety-six patients and 116 vessels were included. The mean age was 64 ± 11 years, and 20 (21 %) were female. Overall, weak correlations were observed between the Index of Microcirculatory Resistance (IMR) and continuous thermodilution microvascular resistance (Rµ) (rho = 0.30p = 0.001). The median coronary flow reserve (CFR) from continuous thermodilution (CFRcont) and bolus thermodilution (CFRbolus) were 2.19 (1.76-2.67) and 2.55 (1.50-3.58), respectively (p < 0.001). Weak correlation and agreement were observed between CFRcont and CFRbolus (rho = 0.37, p < 0.001, ICC 0.228 [0.055-0.389]). When assessed at CFR cut-off values of 2.0 and 2.5, the methods disagreed in 41 (35 %) and 45 (39 %) of cases, respectively. Conclusions: There is a significant difference and weak agreement between bolus and continuous thermodilution-derived indices, which must be considered when diagnosing CMD in ACS and CCS patients.

Iliac artery stent dislodgement: a rare transcatheter aortic valve implantation complication.

An 82-year-old male patient with severe, symptomatic aortic stenosis was referred for transcatheter aortic valve implantation.

Assessing the Impact of Prolonged Averaging of Coronary Continuous Thermodilution Traces.

Continuous Thermodilution is a novel method of quantifying coronary flow (Q) in mL/min. To account for variability of Q within the cardiac cycle, the trace is smoothened with a 2 s moving average filter. This can sometimes be ineffective due to significant heart rate variability, ventricular extrasystoles, and deep inspiration, resulting in a fluctuating temperature trace and ambiguity in the location of the "steady state". This study aims to assess whether a longer moving average filter would smoothen any fluctuations within the continuous thermodilution traces resulting in improved interpretability and reproducibility on a test-retest basis. Patients with ANOCA underwent repeat continuous thermodilution measurements. Analysis of traces were performed at averages of 10, 15, and 20 s to determine the maximum acceptable average. The maximum acceptable average was subsequently applied as a moving average filter and the traces were re-analysed to assess the practical consequences of a longer moving average. Reproducibility was then assessed and compared to a 2 s moving average. Of the averages tested, only 10 s met the criteria for acceptance. When the data was reanalysed with a 10 s moving average filter, there was no significant improvement in reproducibility, however, it resulted in a 12% diagnostic mismatch. Applying a longer moving average filter to continuous thermodilution data does not improve reproducibility. Furthermore, it results in a loss of fidelity on the traces, and a 12% diagnostic mismatch. Overall, current practice should be maintained.

Efficacy and Safety of Thirty-Day Dual-Antiplatelet Therapy Following Complex Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

The optimal duration of DAPT after complex PCI remains under investigation. The purpose of this systematic review and meta-analysis was to explore the safety and efficacy of a one-month therapy period versus a longer duration of DAPT after complex PCI. We systematically screened three major databases, searching for randomized controlled trials or sub-analyses of them, which compared shortened DAPT (S-DAPT), namely, one month, and longer DAPT (L-DAPT), namely, more than three months. The primary endpoint was any Net Adverse Clinical Event (NACE), and the secondary was any MACE (Major Adverse Cardiac Event), its components (mortality, myocardial infarction, stroke, and stent thrombosis), and major bleeding events. Three studies were included in the analysis, with a total of 6275 patients. Shortening DAPT to 30 days after complex PCI did not increase the risk of NACEs (OR: 0.77, 95% CI: 0.52-1.14), MACEs, mortality, myocardial infractions, stroke, or stent thrombosis. Pooled major bleeding incidence was reduced, but this finding was not statistically significant. This systematic review and meta-analysis showed that one-month DAPT did not differ compared to a longer duration of DAPT after complex PCI in terms of safety and efficacy endpoints. Further studies are still required to confirm these findings.

Percutaneous Coronary Interventions Using a Ridaforolimus-Eluting Stent in Patients at High Bleeding Risk.

BACKGROUND: Patients treated with percutaneous coronary intervention are often considered to be at a high bleeding risk (HBR). Drug-eluting stents have been shown to be superior to bare-metal stents in patients with HBR, even when patients were given abbreviated periods of dual antiplatelet therapy (DAPT). Short DAPT has not been evaluated with the EluNIR ridaforolimus-eluting stent. The aim of this study was to evaluate the safety and efficacy of a shortened period of DAPT following implantation of the ridaforolimus-eluting stent in patients with HBR. METHODS AND RESULTS: This was a prospective, multicenter, binational, single-arm, open-label trial. Patients were defined as HBR according to the LEADERS-FREE (Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug-Coated Stent versus the Gazelle Bare-Metal Stent in Patients at High Bleeding Risk) trial criteria. After percutaneous coronary intervention, DAPT was given for 1 month to patients presenting with stable angina. In patients presenting with an acute coronary syndrome, DAPT was given for 1 to 3 months, at the investigator's discretion. The primary end point was a composite of cardiac death, myocardial infarction, or stent thrombosis up to 1 year (Academic Research Consortium definite and probable). Three hundred fifteen patients undergoing percutaneous coronary intervention were enrolled, and 56.4% presented with acute coronary syndrome; 33.7% were receiving oral anticoagulation. At 1 year, the primary end point occurred in 15 patients (4.9%), meeting the prespecified performance goal of 14.1% (P<0.0001). Stent thrombosis (Academic Research Consortium definite and probable) occurred in 2 patients (0.6%). Bleeding Academic Research Consortium type 3 and 5 bleeding occurred in 6 patients (1.9%). CONCLUSIONS: We observed favorable results in patients with HBR who underwent percutaneous coronary intervention with a ridaforolimus-eluting stent and received shortened DAPT, including a low rate of ischemic events and low rate of stent thrombosis. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03877848.

The Usefulness of Intracoronary Imaging in Patients with ST-Segment Elevation Myocardial Infarction.

Intracoronary imaging (ICI) modalities, namely intravascular ultrasound (IVUS) and optical coherence tomography (OCT), have shown to be able to reduce major adverse cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). Nevertheless, patients with ST-segment elevation myocardial infarction (STEMI) have been practically excluded from contemporary large randomized controlled trials. The available data are limited and derive mostly from observational studies. Nevertheless, contemporary studies are in favor of ICI utilization in patients who undergo primary PCI. Regarding technical aspects of PCI, ICI has been associated with the implantation of larger stent diameters, higher balloon inflations and lower residual in-stent stenosis post-PCI. OCT, although used significantly less often than IVUS, is a useful tool in the context of myocardial infarction without obstructive coronary artery disease since, due to its high spatial resolution, it can identify the underlying mechanism of STEMI, and, thus, guide therapy. Stent thrombosis (ST) is a rare, albeit a potential lethal, complication that is expressed clinically as STEMI in the vast majority of cases. Use of ICI is encouraged with current guidelines in order to discriminate the mechanism of ST among stent malapposition, underexpansion, uncovered stent struts, edge dissections, ruptured neoatherosclerotic lesions and coronary evaginations. Finally, ICI has been proposed as a tool to facilitate stent deferring during primary PCI based on culprit lesion characteristics.

The role of intravascular imaging in chronic total occlusion percutaneous coronary intervention.

Chronic total occlusions (CTOs) represent the most complex subset of coronary artery disease and therefore careful planning of CTO percutaneous coronary recanalization (PCI) strategy is of paramount importance aiming to achieve procedural success, and improve patient's safety and post CTO PCI outcomes. Intravascular imaging has an essential role in facilitating CTO PCΙ. First, intravascular ultrasound (IVUS), due to its higher penetration depth compared to optical coherence tomography (OCT), and the additional capacity of real-time imaging without need for contrast injection is considered the preferred imaging modality for CTO PCI. Secondly, IVUS can be used to resolve proximal cap ambiguity, facilitate wire re-entry when dissection and re-entry strategies are applied and most importantly to guide stent deployment and optimization post implantation. The role of OCT during CTO PCI is currently limited to stent sizing and optimization, however, due to its high spatial resolution, OCT is ideal for detecting stent edge dissections and strut malapposition. In this review, we describe the use of intravascular imaging for lesion crossing, plaque characterization and wire tracking, extra- or intra-plaque, and stent sizing and optimization during CTO PCI and summarize the findings of the major studies in this field.

Invasive Detection of Coronary Microvascular Dysfunction: How It Began, and Where We Are Now.

The landscape of interventional cardiology is ever evolving. Contemporary practice has shifted from a stenosis-centred approach to the total characterisation of both the epicardial and microcirculatory vessels. Microcirculatory dysfunction plays an important role in the pathophysiology of acute and chronic coronary syndromes, and characterisation of the microcirculation has important clinical consequences. Accordingly, the invasive diagnosis of microcirculatory dysfunction is becoming a key feature of the interventional cardiologist's toolkit. This review focuses on the methodology underpinning the invasive diagnosis of microvascular dysfunction and highlights the indices that have arisen from these methodologies.

Ultrasound-Guided Femoral Vascular Access for Percutaneous Coronary and Structural Interventions.

Radial access has largely substituted femoral access for coronary interventions. Nevertheless, the femoral artery remains indispensable for gaining access to structural and complex percutaneous coronary interventions such as transcatheter aortic valve implantation and chronic total occlusion interventions, respectively. Ultrasound-guided femoral puncture is a broadly available, inexpensive, and relatively easy-to-learn technique. According to the existing evidence, ultrasound guidance for gaining femoral access has improved the effectiveness and safety of the technique. In the present paper, we sought to review the current literature in order to provide the reader with up-to-date data regarding the benefits of ultrasound-guided femoral access compared with the conventional technique as well as describing the state-of-the-art technique for gaining femoral access under ultrasound guidance.

Agreement of wall shear stress distribution between two core laboratories using three-dimensional quantitative coronary angiography.

Wall shear stress (WSS) estimated in models reconstructed from intravascular imaging and 3-dimensional-quantitative coronary angiography (3D-QCA) data provides important prognostic information and enables identification of high-risk lesions. However, these analyses are time-consuming and require expertise, limiting WSS adoption in clinical practice. Recently, a novel software has been developed for real-time computation of time-averaged WSS (TAWSS) and multidirectional WSS distribution. This study aims to examine its inter-corelab reproducibility. Sixty lesions (20 coronary bifurcations) with a borderline negative fractional flow reserve were processed using the CAAS Workstation WSS prototype to estimate WSS and multi-directional WSS values. Analysis was performed by two corelabs and their estimations for the WSS in 3 mm segments across each reconstructed vessel was extracted and compared. In total 700 segments (256 located in bifurcated vessels) were included in the analysis. A high intra-class correlation was noted for all the 3D-QCA and TAWSS metrics between the estimations of the two corelabs irrespective of the presence (range: 0.90-0.92) or absence (range: 0.89-0.90) of a coronary bifurcation, while the ICC was good-moderate for the multidirectional WSS (range: 0.72-0.86). Lesion level analysis demonstrated a high agreement of the two corelabls for detecting lesions exposed to an unfavourable haemodynamic environment (WSS > 8.24 Pa, κ = 0.77) that had a high-risk morphology (area stenosis > 61.3%, κ = 0.71) and were prone to progress and cause events. The CAAS Workstation WSS enables reproducible 3D-QCA reconstruction and computation of WSS metrics. Further research is needed to explore its value in detecting high-risk lesions.

The challenges of a randomised placebo-controlled trial of CTO PCI vs. placebo with optimal medical therapy: The ORBITA-CTO pilot study design and protocol.

Background: Percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) has been performed for the improvement of symptoms and quality of life in patients with stable angina. The ORBITA study demonstrated the role of the placebo effect in contemporary PCI in non-CTO chronic coronary syndromes. However, the benefit of CTO PCI beyond that of a placebo has not been demonstrated. Aims: The ORBITA-CTO pilot study will be a double-blind, placebo-controlled study of CTO PCI randomising patients who have: (1) been accepted by a CTO operator for PCI; (2) experienced symptoms due to a CTO; (3) evidence of ischaemia; (4) evidence of viability within the CTO territory; and (5) a J-CTO score ≤3. Methods: Patients will undergo medication optimisation that will ensure they are on at least a minimum amount of anti-anginals and complete questionnaires. Patients will record their symptoms on an app daily throughout the study. Patients will undergo randomisation procedures, including an overnight stay, and be discharged the following day. All anti-anginals will be stopped after randomisation and re-initiated on a patient-led basis during the 6-month follow-up period. At follow-up, patients will undergo repeat questionnaires and unblinding, with a further 2-week unblinded follow-up. Results: The co-primary outcomes are feasibility (blinding) in this cohort and angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include changes in quality-of-life measures, Seattle Angina Questionnaire (SAQ), peak VO2, and anaerobic threshold on the cardiopulmonary exercise test. Conclusion: The feasibility of a placebo-controlled CTO PCI study will lead to future studies assessing efficacy. The impact of CTO PCI on angina measured using a novel daily symptom app may provide improved fidelity in assessing symptoms in patients with CTO's.

Early Recognition and Risk Stratification in Cardiogenic Shock: Well Begun Is Half Done.

Cardiogenic shock is a complex syndrome manifesting with distinct phenotypes depending on the severity of the primary cardiac insult and the underlying status. As long as therapeutic interventions fail to divert its unopposed rapid evolution, poor outcomes will continue challenging health care systems. Thus, early recognition in the emergency setting is a priority, in order to avoid delays in appropriate management and to ensure immediate initial stabilization. Since advanced therapeutic strategies and specialized shock centers may provide beneficial support, it seems that directing patients towards the recently described shock network may improve survival rates. A multidisciplinary approach strategy commands the interconnections between the strategic role of the ED in affiliation with cardiac shock centers. This review outlines critical features of early recognition and initial therapeutic management, as well as the utility of diagnostic tools and risk stratification models regarding the facilitation of patient trajectories through the shock network. Further, it proposes the implementation of precise criteria for shock team activation and the establishment of definite exclusion criteria for streaming the right patient to the right place at the right time.

Changes in absolute flow, myocardial resistance and FFR after chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Randomised studies of percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) have shown inconsistent outcomes, suggesting incomplete understanding of this cohort and their coronary physiology. To address this shortcoming, we designed a prospective observational study to measure the recovery of absolute coronary blood flow following successful CTO PCI Aims: We sought to identify patient and procedural characteristics associated with a favourable physiological outcome after CTO PCI. METHODS: Consecutive patients with a CTO subtending viable myocardium underwent PCI utilising contemporary techniques and the hybrid algorithm. Immediately after PCI, and at 3-month follow-up, physiological measurements were performed utilising continuous thermodilution. RESULTS: A total of 81 patients were included with a mean age of 63.6±8.9 years, and 66 (81.5%) were male. Physiological measurements of absolute coronary blood flow in the CTO vessel increased by 30% (p<0.001) and microvascular resistance reduced by 16% (p<0.001) from immediately post-CTO PCI to follow-up assessment. Fractional flow reserve increased by 0.02 (p=0.015) in the same period. Prior coronary artery bypass graft (CABG) and a higher estimated glomerular filtration rate (eGFR) were associated with a larger change in absolute flow. An extraplaque strategy was associated with a smaller change in absolute flow. CONCLUSIONS: Post-CTO PCI, there is a continued augmentation in absolute coronary blood flow and reduction in microvascular resistance from baseline to follow-up at 3 months. Prior CABG and a higher baseline eGFR were predictors of a larger change in absolute coronary flow, whilst an extraplaque final wire path strategy predicted a smaller change. Lastly, the patient characteristics and comorbidities had a larger influence than procedural factors on the observed change in absolute flow.