Protocol Variation in Functional Coronary Angiography Among Patients With Suspected Angina With Non-Obstructive Coronary Arteries: A Nationwide Snapshot of Current Practice Within Australia and New Zealand.

BACKGROUND: Functional coronary angiography (FCA) for endotype characterisation (vasospastic angina [VSA], coronary microvascular disease [CMD], or mixed) is recommended among patients with angina with non-obstructive coronary arteries. Whilst clear diagnostic criteria for VSA and CMD exist, there is no standardised FCA protocol. Variations in testing protocol may limit the widespread uptake of testing, generalisability of results, and expansion of collaborative research. At present, there are no data describing protocol variation across an entire geographic region. Therefore, we aimed to capture current practice variations in the approach to FCA to improve access and standardisation for diagnosis of coronary vasomotor disorders in Australia and New Zealand. METHOD: Between July 2022 and July 2023, we conducted a national survey across all centres in Australia and New Zealand with an active FCA program. The survey captured attitudes towards FCA and protocols used for diagnosis of coronary vasomotor disorders at 33 hospitals across Australia and New Zealand. RESULTS: Survey responses were received from 39 clinicians from 33 centres, with representation from centres within all Australian states and territories and both North and South Islands of New Zealand. A total of 21 centres were identified as having an active FCA program. In general, respondents agreed that comprehensive physiology testing helped inform clinical management. Barriers to program expansion included cost, additional catheter laboratory time, and the absence of an agreed-upon national protocol. Across the clinical sites, there were significant variations in testing protocol, including the technique used (Doppler vs thermodilution), order of testing (hyperaemia resistance indices first vs vasomotor function testing first), rate and dose of acetylcholine administration, routine use of temporary pacing wire, and routine single vs multivessel testing. Overall, testing was performed relatively infrequently, with very little follow-on FCA performed, despite nearly all respondents believing this would be clinically useful. CONCLUSIONS: This survey demonstrates, for the first time, variations in FCA protocol among testing centres across two entire countries. Furthermore, whilst FCA was deemed clinically important, testing was performed relatively infrequently with little or no follow-on testing. Development and adoption of a standardised national FCA protocol may help improve patient access to testing and facilitate further collaborative research within Australia and New Zealand.

Increased interdigitation zone visibility on optical coherence tomography following systemic fibroblast growth factor receptor 1-3 tyrosine kinase inhibitor anticancer therapy.

BACKGROUND: To describe ocular adverse events and retinal changes during fibroblast growth factor receptor (FGFR) inhibitor (AZD4547) anticancer therapy. METHODS: This is a sub-study examining ocular adverse effects from AZD4547 therapy (single-centre, open-label, single arm phase II clinical trial). Comprehensive ocular examinations were performed 3 weekly in 24 patients. Macular optical coherence tomography (OCT) scan (300 × 250 ) was obtained at each visit and OCT parameters [central 1 mm retinal thickness (CRT) and total macular volume in central 6 mm] extracted. OCT scans were subdivided into outer (ELM to RPE) and inner (ELM to ILM) layers to compare outer and inner retinal changes. RESULTS: In 24 patients, AZD4547 was associated with eyelash elongation (n = 5, 21%) and punctate corneal erosion (n = 2, 8%). One patient developed clinically significant posterior capsular opacification during the study. OCT data were available in 23 patients, retinal changes ranged from an asymptomatic increased visibility of the interdigitation zone (IDZ) (n = 10, 43%) to multilobular subretinal fluid pockets (n = 5, 22%), which was associated with mild visual acuity loss. In a subset of patients (n = 9) with pre-AZD4547 dosing OCT baseline, CRT increased by mean (SD) of 9 (4) µm in those with IDZ change only compared with 64 (38) µm in those with other retinal changes. Retinal changes tended to be bilateral, self-limiting and improved over time without medical intervention. CONCLUSIONS: The ocular signs and symptoms did not result in dose cessation. Posteriorly, FGFR inhibition leads to outer retinal changes ranging from increased visibility of IDZ to distinct, multiple fluid pockets.

The Effect of Stent Artefact on Quantification of Plaque Features Using Optical Coherence Tomography (OCT): A Feasibility and Clinical Utility Study.

BACKGROUND: Optical coherence tomography (OCT) can detect detailed plaque features in native coronary arteries. Stent struts cause shadows that partially obscure the vessel wall, but plaque features can still be seen. We investigated the impact of stent artefact on plaque quantification and whether the plaque behind struts is associated with microvascular dysfunction. METHODS: Patients retrospectively recruited from two centres, underwent OCT pre- and post-stenting on the same vessel segment. Lipid (LA) and calcium (CA) were measured as arcs. Macrophages, microchannels and cholesterol crystals were counted. Subsequently, we determined whether stented plaque features were associated with reduced Thrombolysis in Myocardial Infarction (TIMI) flow grade in consecutive patients who underwent OCT post-stenting. RESULTS: In 52 patients the lipid arc was similar pre- vs post-stent: median (55º [13º-93º] vs. 40º [18º-87°]; difference 1º [-7º to 16º], p = NS). Pre- and post-stent lipid were strongly correlated (r = 0.92, p < 0.001). In a further 128 patients those with reduced (TIMI ≤ II) vs normal flow post percutaneous coronary intervention (PCI) showed more plaque behind struts: lipid (89º [50º-139º] vs 62º [29º-88°]; p < 0.001); and calcium (24º [6º-45º] vs 7° [0º-34º]; p = 0.031). Multivariate logistic regression analysis showed that abnormal TIMI flow post-stenting was associated with diabetes (Odds ratio [OR] 2.87, CI 1.01-8.19, p = 0.048), LA (OR 1.29, 95% CI 1.14-1.38, p < 0.001) and CA (OR 1.26, CI 1.07-1.40, p = 0.005). CONCLUSIONS: Plaque behind the struts can be accurately quantified using OCT. Furthermore, OCT plaque features in stented segments are associated with microvascular dysfunction post PCI.

Feasibility and efficacy of the 2.5 L and 3.8 L impella percutaneous left ventricular support device during high-risk, percutaneous coronary intervention in patients with severe aortic stenosis.

OBJECTIVE: Assessment of the feasibility and outcomes of the 2.5 L and 3.8 L Impella cardiac pump in patients with severe aortic stenosis (AS) and left ventricular impairment undergoing percutaneous revascularization (PCI) with or without balloon aortic valvuloplasty (BAV). METHODS: We reviewed the clinical and procedural findings from a consecutive series of unselected patients with severe AS who underwent PCI during Impella support. In addition, we describe novel "balloon-assist" techniques that allowed implantation of Impella into the left ventricle (LV) when initial unassisted attempts failed. RESULTS: Five patients with severe AS were identified (four males, age 78.2 years, aortic valve area (AVA) 0.6 cm(2) , left ventricular ejection fraction (LVEF) 24 ± 5%, mean Society of Thoracic Surgeons (STS) mortality 11% (range 3-17%)). The Impella catheter traversed the aortic valve (AV) unassisted in only one patient, with four cases requiring balloon-assist techniques. All patients underwent planned revascularisation; mean procedure time 177 min (range 135-252 min), mean number of stents 3.4 (range 1-8), with three patients requiring rotational atherectomy. All procedures were well tolerated, with absence of arrhythmia, hypotension, pulmonary edema, stroke, or myocardial infarction. One patient died 48 hr post-PCI of multi-organ failure. The four remaining patients were well at 30 days. CONCLUSION: Implantation of the 2.5 and 3.8 L Impella appears feasible in patients with severe AS and left ventricle (LV) impairment. A balloon-assist technique may be used to facilitate device implantation when initial unassisted attempts fail. Improved hemodynamic stability may enhance the tolerability of lengthy and complex procedures.

Use of left ventricular support devices during acute coronary syndrome and percutaneous coronary intervention.

In an effort to improve outcomes in percutaneous coronary intervention (PCI), percutaneous ventricular assist devices (PVADs) have been investigated in (1) high-risk PCI, (2) acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) and (3) in AMI without CS. PCI has become an increasing complex due to an ageing population with complex disease and the frequent presence of impaired LV function. Patients undergoing high-risk PCI in these circumstances are prone to acute cardiovascular collapse. Additionally, mortality in AMI complicated by CS remains high. Lastly, LV support during AMI may reduce infarct size and therefore preserve LV function. At present, four commercially available devices exist: intra-aortic balloon pump counterpulsation (IABP), Impella, TandemHeart and extracorporeal membrane oxygenation (ECMO). These devices are employed in an effort to increase cardiac output, mean arterial pressure (MAP) and coronary perfusion and to reduce pulmonary capillary wedge pressure (PCWP). The mechanism of action differs with each device, and there are advantages and disadvantages. In this update, we discuss recent data describing the use of PVADs to support patients with AMI with or without cardiogenic shock and during high-risk PCI. We focus on the unique features of each device, highlighting strengths, weaknesses and frequently encountered complications, which may be important when tailoring the most appropriate PVAD therapy to an individual patient's need.

Automated cardiopulmonary resuscitation: a case study.

Rates of survival after cardiac arrest are low and correlate with the quality of cardiopulmonary resuscitation (CPR). Devices that deliver automated CPR (A-CPR) can provide sustained and effective chest compressions, which are especially useful during patient transfer and while simultaneous invasive procedures are being performed. The use of such devices can also release members of resuscitation teams for other work. This article presents a case study involving a man with acute myocardial infarction complicated by cardiogenic shock and pulmonary oedema. It describes how ED nursing and medical teams worked together to deliver A-CPR, discusses the use of A-CPR devices in a tertiary cardiac centre, and highlights the advantages of using such devices.

A Case of Aborted Sudden Cardiac Death Due to Coronary Artery Spasm.

Coronary artery spasm remains an important yet rarely recognized cause of myocardial ischemia, which may manifest as vasospastic angina, ventricular arrhythmia, or sudden cardiac death. Here we present a case of ST-segment elevation myocardial infarction complicated by cardiac arrest secondary to coronary artery spasm, diagnosed with invasive coronary function testing.

Single high-sensitivity troponin levels to assess patients with potential acute coronary syndromes.

OBJECTIVE: We tested the hypothesis that patients with a potential acute coronary syndrome (ACS) and very low levels of high-sensitivity cardiac troponin I can be efficiently and safely discharged from the emergency department after a single troponin measurement. METHODS: This prospective cohort study recruited 2255 consecutive patients aged ≥18 years presenting to the Emergency Department, Royal Perth Hospital, Western Australia, with chest pain without high-risk features but requiring the exclusion of ACS. Patients were managed using a guideline-recommended pathway or our novel Single Troponin Accelerated Triage (STAT) pathway. The primary outcome was the percentage of patients discharged in <3 hours. Secondary outcomes included the duration of observation and death or acute myocardial infarction in the next 30 days. RESULTS: The study enrolled 1131 patients to the standard cohort and 1124 to the STAT cohort. Thirty-eight per cent of the standard cohort were discharged directly from emergency department compared with 63% of the STAT cohort (p<0.001). The median duration of observation was 4.3 (IQR 3.3-7.1) hours in the standard cohort and 3.6 (2.6-5.4) hours in the STAT cohort (p<0.001), with 21% and 38% discharged in <3 hours, respectively (p<0.001). No patients discharged directly from the emergency department died or suffered an acute myocardial infarction within 30 days in either cohort. CONCLUSIONS: Among low-risk patients with a potential ACS, a pathway which incorporates early discharge based on a single very low level of high-sensitivity cardiac troponin increases the proportion of patients discharged directly from the emergency department, reduces length of stay and is safe. TRIAL REGISTRATION NUMBER: ACTRN12618000797279.

Coronary 18F-sodium fluoride PET detects high-risk plaque features on optical coherence tomography and CT-angiography in patients with acute coronary syndrome.

BACKGROUND AND AIMS: 18F-Sodium Fluoride Positron Emission Tomography (18F-NaF PET) non-invasively detects micro-calcification activity, the earliest stage of atherosclerotic arterial calcification. We studied the association between coronary 18F-NaF uptake and high-risk plaque features on intra-coronary optical coherence tomography (OCT) and CT-angiography (CTCA) and the potential application to patient-level risk stratification. METHODS: Sixty-two prospectively recruited patients with acute coronary syndrome (ACS) underwent multi-vessel OCT, 18F-NaF PET and CTCA. The maximum tissue to background ratio (TBRmax = standardised uptake value (SUV)max/SUVbloodpool) was measured in each coronary segment on 18F-NaF PET scans. High-risk plaque features on OCT and CTCA were compared in matched coronary segments. The number of patients testing positive (>2SD above the normal range) for micro-calcification activity was determined. RESULTS: In 62 patients (age, mean ± standard deviation (SD) = 61 ± 9 years, 85% male) the coronary segments with elevated 18F-NaF uptake had higher lipid arc (LA) (median [25th-75th centile]: 74° [35°-117°] versus 48° [15°-83°], p=0.021), higher prevalence of macrophages [n(%): 37 (62%) versus 89 (39%), p=0.008] and lower plaque free wall (PFW) (50° [7°-110°] versus 94° [34°-180°], p=0.027) on OCT, and a higher total plaque burden (p=0.011) and higher dense calcified plaque burden (p= 0.001) on CTCA, when compared with 18F-NaF negative segments. Patients grouped by increasing number of coronary lesions positive for microcalcification activity (0,1, ≥2) showed decreasing plaque free wall, increasing calcification and increasing macrophages on OCT (respectively p=0.008, p < 0.001 and p=0.028). CONCLUSIONS: 18F-NaF uptake is associated with high-risk plaque features on OCT and CTCA in a per-segment and per-patient analysis in subjects hospitalized for ACS.

A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma.

OBJECTIVES: Currently, there is no optimal salvage therapy for patients with malignant pleural mesothelioma (MPM) who relapse after treatment with first-line chemotherapy. In line with the strong preclinical rationale for targeting fibroblast growth factor receptor (FGFR) signalling in malignant mesothelioma, we conducted a phase II study assessing the efficacy of AZD4547, an oral tyrosine multi-kinase FGFR 1-3 inhibitor, as a second or third-line treatment. MATERIALS AND METHODS: We conducted a single-center, open-label, single-arm phase II study of AZD4547 in eligible patients with confirmed, measurable MPM and radiological progression after first or second-line systemic chemotherapy. Patients received continuous, twice-daily oral AZD4547 on a 3-weekly cycle. The primary end point was 6-month progression free survival (PFS6). Response was assessed with CT scan every 6 weeks according to the modified RECIST criteria for mesothelioma (mRECIST) and toxicities were also assessed. The study used a Simon's two-stage design: 26 patients would be recruited to the first stage and more than 7 (27 %) of 26 patients were required to achieve PFS6 to continue to stage two, for a potential total cohort of 55 patients. RESULTS: 3 of 24 patients (12 %) were progression-free at 6 months. Hence, the study fulfilled stopping criteria regardless of further recruitment and warranted discontinuation. The most common toxicities (across all grades) were hyperphosphatemia, xerostomia, mucositis, retinopathy, dysgeusia, and fatigue. Maximum toxicities were grade 2 or below for all patients across all cycles. There was no association between tumour BAP1 protein loss and clinical outcomes. CONCLUSIONS: The FGFR 1-3 inhibitor AZD4547 did not demonstrate efficacy in patients with MPM who had progressed after first line treatment with platinum-based chemotherapy.

Achieving routine sub 30 minute door-to-balloon times in a high volume 24/7 primary angioplasty center with autonomous ambulance diagnosis and immediate catheter laboratory access.

BACKGROUND: In primary angioplasty (primary percutaneous coronary intervention [PPCI]) for acute myocardial infarction, institutional logistical delays can increase door-to-balloon times, resulting in increased mortality. METHODS: We moved from a thrombolysis (TL) service to 24/7 PPCI for direct access and interhospital transfer in April 2004. Using autonomous ambulance diagnosis with open access to the myocardial infarction center catheter laboratory, we compared reperfusion times and clinical outcomes for the final 2 years of TL with the first 3 years of PPCI. RESULTS: Comparison was made between TL (2002-2004, n = 185) and PPCI (2004-2007, n = 704); all times are medians in minutes (interquartile range): for TL, symptom to needle 153 (85-225), call to needle 58 (49-73), first professional contact (FPC) to needle 47 (39-63), door to needle 18 (12-30) (mortality: 7.6% at 30 days, 9.2% at 1 year); for interhospital transfer PPCI (n = 227), symptom to balloon 226 (175-350), call to balloon 135 (117-188), FPC to balloon 121 (102-166), first door-to-balloon 100 (80-142) (mortality: 7.0% at 30 days, 12.3% at 1 year); for direct-access PPCI (n = 477), symptom to balloon 142 (101-238), call to balloon 79 (70-93), FPC to balloon 69 (59-82), door to balloon 20 (16-29) (mortality: 4.6% at 30 days, 8.6% at 1 year). There was no difference between direct-access PPCI and TL times for symptom to needle/balloon. Direct-access PPCI was significantly quicker for the group than in-hospital thrombolysis for door to needle/balloon times due to the lack of any long wait patients (P < .001). CONCLUSIONS: Interhospital transfer remains slow even with rapid institutional door-to-balloon times. With autonomous ambulance diagnosis and open access direct to the catheter laboratory, a median door-to-balloon time of <30 minutes day and night was achieved, and >95% of patients were reperfused within 1 hour.

Percutaneous Mechanical Ventricular Support in Acute Cardiac Care: A UK Quaternary Centre Experience Using 2.5L, 3.8L and 5.0L Impella Catheters.

AIMS: The Impella is a percutaneous ventricular assist device. The majority of published data describes the 2.5L and 5.0L devices, and little data is available for the newer 3.8L device. We examined the indications and outcomes from our single-centre "real-world" registry at The Queen Elizabeth Hospital, Birmingham, UK, using all three pump sizes. METHODS AND RESULTS: Records from all patients who underwent attempted Impella-assisted procedures at our centre were examined retrospectively. Impella implantation was attempted in 49 patients (mean age 72 ± 13 years; 80% male) and was successful in 48 (98%). 45 patients underwent high-risk percutaneous coronary intervention (PCI), one patient underwent balloon aortic valvuloplasty and 3 patients had Impella as a bridge to cardiac transplantation. The 2.5L and 3.8L devices were used in 36 (75%) and 11 (23%) patients, respectively, while one patient (2%) had the 5L device. Vascular complications occurred in only one patient (2%) and stroke and peri-procedural myocardial infarction occurred in one patient (2%), while in-hospital mortality was 20% (10/49). CONCLUSIONS: In this large real-world registry, we have demonstrated the safety and feasibility of the Impella device for a wide range of indications. This includes the first series of the 3.8L device which provides superior support with no increase in vascular complications.

Delayed left main stem obstruction following successful TAVI with an Edwards SAPIEN XT valve: successful resuscitation and percutaneous coronary intervention using a non-invasive automated chest compression device (AutoPulse).

Acute coronary artery obstruction at the time of device implantation is a recognized, albeit rare, complication of TAVI and is most frequently managed by emergency percutaneous intervention. This complication usually manifests with circulatory collapse due to compromising left ventricular ischemia and is most often observed immediately following valve deployment in the catheter laboratory or in theater. Immediate circulatory support is often necessary. We describe the first report of delayed left main stem obstruction 3.5 hours after successful deployment of a 26 mm Edwards SAPIEN XT valve via transfemoral implantation, with sudden development of circulatory collapse on the ward. Circulatory support was rapidly and effectively instituted with an automated non-invasive cardiac massage device, AutoPulse, that delivers continuous chest compressions. Successful emergency percutaneous intervention was then undertaken to the left main stem to displace a calcified nodule during automated external cardiac massage with the AutoPulse.