Trends in Sudden Unexpected Deaths in an Australian Population: Impact of the COVID-19 Pandemic.

BACKGROUND AND AIM: SARS-CoV-2 infection is associated with increased cardiovascular (CV) morbidity and mortality, manifesting as increased adverse outcomes in the first 30 days, extending to 12 months. This study aimed to investigate trends in sudden unexpected deaths between 2018 and 2022, with a focus on CV deaths. METHOD: A retrospective analysis was performed on autopsy reports (n=9,330) obtained from New South Wales Coroners Court, Australia, specifically targeting cases of unexplained deaths that occurred between 2018 and 2022. Statistical analysis was conducted using chi-square tests and a post hoc analysis with Bonferroni correction, as well as analysis of variance with multiple comparisons. RESULTS: There were 349 (18.3%) CV deaths in 2018, 346 (18.0%) in 2019, 338 (17.5%) in 2020, 395 (21.9%) in 2021, and (23.4%) 413 in 2022 (p=0.0002). Among CV deaths, the number of deaths from sudden arrhythmic death syndrome were 25 (7.2%) in 2018, 26 (7.5%) in 2019, 18 (5.3%) in 2020, 52 (13.2%) in 2021, and 80 (19.4%) in 2022 (p=0.0001). Atherosclerosis was the most common cause of death among all CV categories; there were 196 (56.2%) atherosclerosis deaths in 2018, 207 (59.8%) in 2019, 192 (56.8%) in 2020, 221 (56.0%) in 2021, and 197 (47.7%) in 2022 (p=0.43). The average age of death from sudden arrhythmic death syndrome (42.8±19.1 years) across 2018-2022 was younger than atherosclerosis (56.2±12.4 years) and total groups (53.1±15.1 years) (p<0.001). Males comprised 76% of all CV deaths from 2018 to 2022 (p<0.0001). CONCLUSIONS: Compared with pre-pandemic data, a noteworthy increase in CV deaths was observed in occurrence with the escalation in COVID-19 cases in Australia. This may be attributed to direct or indirect factors, such as lifestyle modifications, disrupted access to routine cardiac care, or COVID-19 infection-triggered CV deaths.

Intracoronary thrombolysis in ST-elevation myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Despite restoration of epicardial blood flow in acute ST-elevation myocardial infarction (STEMI), inadequate microcirculatory perfusion is common and portends a poor prognosis. Intracoronary (IC) thrombolytic therapy can reduce microvascular thrombotic burden; however, contemporary studies have produced conflicting outcomes. OBJECTIVES: This meta-analysis aims to evaluate the efficacy and safety of adjunctive IC thrombolytic therapy at the time of primary percutaneous coronary intervention (PCI) among patients with STEMI. METHODS: Comprehensive literature search of six electronic databases identified relevant randomised controlled trials. The primary outcome was major adverse cardiac events (MACE). The pooled risk ratio (RR) and weighted mean difference (WMD) with a 95% CI were calculated. RESULTS: 12 studies with 1915 patients were included. IC thrombolysis was associated with a significantly lower incidence of MACE (RR=0.65, 95% CI 0.51 to 0.82, I2=0%, p<0.0004) and improved left ventricular ejection fraction (WMD=1.87; 95% CI 1.07 to 2.67; I2=25%; p<0.0001). Subgroup analysis demonstrated a significant reduction in MACE for trials using non-fibrin (RR=0.39, 95% CI 0.20 to 0.78, I2=0%, p=0.007) and moderately fibrin-specific thrombolytic agents (RR=0.62, 95% CI 0.47 to 0.83, I2=0%, p=0.001). No significant reduction was observed in studies using highly fibrin-specific thrombolytic agents (RR=1.10, 95% CI 0.62 to 1.96, I2=0%, p=0.75). Furthermore, there were no significant differences in mortality (RR=0.91; 95% CI 0.48 to 1.71; I2=0%; p=0.77) or bleeding events (major bleeding, RR=1.24; 95% CI 0.47 to 3.28; I2=0%; p=0.67; minor bleeding, RR=1.47; 95% CI 0.90 to 2.40; I2=0%; p=0.12). CONCLUSION: Adjunctive IC thrombolysis at the time of primary PCI in patients with STEMI improves clinical and myocardial perfusion parameters without an increased rate of bleeding. Further research is needed to optimise the selection of thrombolytic agents and treatment protocols.

Prevalence of Coronary Vasomotor Disorders in Patients With Angina and Nonobstructive Coronary Arteries: A Sydney Experience.

BACKGROUND: Patients with angina and non-obstructive coronary arteries (ANOCA) frequently have coronary vasomotor disorders (CVaD), characterised by transient pathological vasoconstriction and/or impaired microvascular vasodilatation. Functional coronary angiography is the gold standard for diagnosing CVaD. Despite recommendations, testing is only available at a limited number of Australian and New Zealand centres. This study aimed to determine the prevalence of CVaDs in an Australian ANOCA population and identify predictive factors associated with specific endotypes. METHOD: Functional coronary angiography was performed in patients with suspected ANOCA. Vasoreactivity testing was performed using intracoronary acetylcholine provocation. A pressure-temperature sensor guidewire was used for coronary physiology assessment. Comprehensive clinical data on patient characteristics, cardiac risk factors, and symptom profiles was collected before testing. RESULTS: This prospective observational study at Royal Prince Alfred and Concord Repatriation General Hospital included 110 patients (58±13 years with 63.6% women), with 81.8% (90/110) having a CVaD. Regarding specific ANOCA endotypes, microvascular angina (MVA) occurred in 31.8% (35/110) of cases, vasospastic angina (VSA) in 25.5% (28/110) and a mixed presentation of MVA and VSA in 24.5% (27/110) of patients. Patients with CVaD were found to be older (59±11 vs 51±15, p=0.024), overweight (61.1% vs 15.0%, p<0.001) and had a worse quality of life (EuroQol 5 Dimensions-5 Levels; 0.61 vs 0.67, p=0.043). MVA was associated with being overweight (odds ratio [OR] 4.2 [95% confidence interval [CI] 1.9-9.3]; p=0.015) and ischaemia on stress testing (OR 2.4 [95% CI 1.1-4.3]; p=0.028), while VSA was associated with smoking (OR 9.1 [95% CI 2.21-39.3]; p=0.007). CONCLUSIONS: Coronary vasomotor disorders are highly prevalent among ANOCA patients. This study highlights the importance of increasing national awareness and the use of functional coronary angiography to evaluate and manage this unique cohort.

Multivessel Coronary Function Testing Increases Diagnostic Yield in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA). METHODS: Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 µg) and right (20 to 80µg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels. RESULTS: This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486). CONCLUSIONS: Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.

Validation of oscillometric ratio and maximum gradient methods for non-invasive blood pressure measurement with intra-arterial blood pressure measurements as reference.

Most non-invasive blood pressure (BP) measurements are carried out using instruments which implement either the Ratio or the Maximum Gradient oscillometric method, mostly during cuff deflation, but more rarely during cuff inflation. Yet, there is little published literature on the relative advantages and accuracy of these two methods. In this study of 40 lightly sedated individuals aged 64.1 ± 9.6 years, we evaluate and compare the performance of the oscillometric ratio (K) and gradient (Grad) methods for the non-invasive estimation of mean pressure, SBP and DBP with reference to invasive intra-arterial values. There was no significant difference between intra-arterial estimates of mean pressure made via Korotkoff sounds (MP-OWE) or the gradient method (MP-Grad). However, 17.7% of MP-OWE and 15% of MP-Grad were in error by more than 10 mmHg. SBP-K and SBP-Grad underestimated SBP by 14 and 18 mmHg, whilst accurately estimating DBP with mean errors of 0.4 ±â€Š5.0 and 1.7 ±â€Š6.1 mmHg, respectively. Relative to the reference standard SBP-K, SBP-Grad and DBP-Grad were estimated with a mean error of -4.5 ±â€Š6.6 and 1.4 ±â€Š5.6 mmHg, respectively, noting that using the full range of recommended ratios introduces errors of 12 and 7 mmHg in SBP and DBP, respectively. We also show that it is possible to find ratios which minimize the root mean square error (RMSE) and the mean error for any particular individual cohort. We developed linear models for estimating SBP and SBP-K from a range of demographic and non-invasive OWE variables with resulting mean errors of 0.15 ±â€Š5.6 and 0.3 ±â€Š5.7 mmHg, acceptable according to the Universal standard.

Evaluation of the oscillometric method for noninvasive blood pressure measurement during cuff deflation and cuff inflation with reference to intra-arterial blood pressure.

There is little quantitative clinical data available to support blood pressure measurement accuracy during cuff inflation. In this study of 35 male and 5 female lightly anaesthetized subjects aged 64.1 ±â€Š9.6 years, we evaluate and compare the performance of both the oscillometric ratio and gradient methods during cuff deflation and cuff inflation with reference to intra-arterial measurements. We show that the oscillometric waveform envelopes (OWE), which are key to both methods, exhibit significant variability in both shape and smoothness leading to at least 15% error in the determination of mean pressure (MP). We confirm the observation from our previous studies that K1 Korotkoff sounds underestimate systolic blood pressure (SBP) and note that this underestimation is increased during cuff inflation. The estimation of diastolic blood pressure (DBP) is generally accurate for both the ratio and the gradient method, with the latter showing a significant increase during inflation. Since the gradient method estimates SBP and DBP from points of maximum gradient on each OWE recorded, it may offer significant benefits over the ratio method. However, we have shown that the ratio method can be optimized for any data set to achieve either a minimum mean error (ME) of close to 0 mmHg or minimum root mean square error (RMSE) with standard deviation (SD) of <5.0 mmHg. We conclude that whilst cuff inflation may offer some advantages, these are neither significant nor substantial, leaving as the only benefit, the potential for more rapid measurement and less patient discomfort.

Comparison of cuff inflation and cuff deflation brachial sphygmomanometry with intra-arterial blood pressure as reference.

Conventional sphygmomanometry with cuff deflation is used to calibrate all noninvasive BP (NIBP) instruments and the International Standard makes no mention of calibrating methods specifically for NIBP instruments, which estimate systolic and diastolic pressure during cuff inflation rather than cuff deflation. There is however increasing interest in inflation-based NIBP (iNIBP) instruments on the basis of shorter measurement time, reduction in maximal inflation pressure and improvement in patient comfort and outcomes. However, we have previously demonstrated that SBP estimates based on the occurrence of the first K1 Korotkoff sounds during cuff deflation can underestimate intra-arterial SBP (IA-SBP) by an average of 14 ±â€Š10 mmHg. In this study, we compare the dynamics of intra-arterial blood pressure (IABP) measurements with sequential measurement of Korotkoff sounds during both cuff inflation and cuff deflation in the same individual. In 40 individuals aged 64.1 ±â€Š9.6 years (range 36-86 years), the overall dynamic responses below the cuff were similar, but the underestimation error was significantly larger during inflation than deflation, increasing from 14 ±â€Š10 to 19 ±â€Š12 mmHg ( P  < 0.0001). No statistical models were found which could compensate for this error as were found for cuff deflation. The statistically significant BP differences between inflation and deflation protocols reported in this study suggest different behaviour of the arterial and venous vasculature between arterial opening and closing which warrant further investigation, particularly for iNIBP devices reporting estimates during cuff inflation. In addition, measuring Korotkoff sounds during cuff inflation represents significant technical difficulties because of increasing pump motor noise.

Accurate detection of Korotkoff sounds reveals large discrepancy between intra-arterial systolic pressure and simultaneous noninvasive measurement of blood pressure with brachial cuff sphygmomanometry.

Cardiovascular disease is the number 1 cause of death globally, with elevated blood pressure (BP) being the single largest risk factor. Hence, BP is an important physiological parameter used as an indicator of cardiovascular health. Noninvasive cuff-based automated monitoring is now the dominant method for BP measurement and irrespective of whether the oscillometric or the auscultatory method is used, all are calibrated according to the Universal Standard (ISO 81060-2:2019), which requires two trained operators to listen to Korotkoff K1 sounds for SBP and K4/K5 sounds for DBP. Hence, Korotkoff sounds are fundamental to the calibration of all NIBP devices. In this study of 40 lightly sedated patients, aged 64.1 ±â€Š9.6 years, we compare SBP and DBP recorded directly by intra-arterial fluid filled catheters to values recorded from the onset (SBP-K) and cessation (DBP-K) of Korotkoff sounds. We demonstrate that whilst DBP-K measurements are in good agreement, with a mean difference of -0.3 ±â€Š5.2 mmHg, SBP-K underestimates true intra-arterial SBP (IA-SBP) by an average of 14 ±â€Š9.6 mmHg. The underestimation arises from delays in the re-opening of the brachial artery following deflation of the brachial cuff to below SBP. The reasons for this delay are not known but appear related to the difference between SBP and the pressure under the cuff as blood first begins to flow, as the cuff deflates. Linear models are presented that can correct the underestimation in SBP resulting in estimates with a mean difference of 0.2 ±â€Š7.1 mmHg with respect to intra-arterial SBP.

Insights into the invasive diagnostic challenges of coronary artery vasospasm - A systematic review.

Coronary provocation testing is an essential diagnostic procedure when evaluating vasospastic angina. Invasive methods using acetylcholine or ergonovine are considered the current gold standard. Despite efforts from global cardiovascular institutions, current protocols vary in dosage, administration time, and procedural approach. In addition, concerns over the specificity of findings and potential complications have limited routine uptake of this procedure in clinical practice. This systematic review evaluates current diagnostic protocols, focusing on invasive provocation testing. We included studies using intracoronary provocation testing with acetylcholine or ergonovine for the assessment of coronary artery vasospasm that detailed specific elements of the procedure (dosage, administration time, etc.) and included ≥50 patients. A total of 28 articles met strict inclusion criteria. Our review highlights the heterogeneity between current diagnostic protocols for invasive provocation testing. We believe standardization of a diagnostic protocol will encourage both current and future cardiologists to incorporate such procedures in the evaluation of variant angina.

Coronary microvascular dysfunction: A review of recent progress and clinical implications.

The coronary microcirculation plays a cardinal role in regulating coronary blood flow to meet the changing metabolic demands of the myocardium. Coronary microvascular dysfunction (CMD) refers to structural and functional remodeling of the coronary microcirculation. CMD plays a role in the pathogenesis of obstructive and non-obstructive coronary syndromes as well as myocardial diseases, including heart failure with preserved ejection fraction (HFpEF). Despite recent diagnostic advancements, CMD is often under-appreciated in clinical practice, and may allow for the development of novel therapeutic targets. This review explores the diagnosis and pathogenic role of CMD across a range of cardiovascular diseases, its prognostic significance, and the current therapeutic landscape.

Coronary Vasospastic Angina: A Review of the Pathogenesis, Diagnosis, and Management.

Vasospastic angina (VSA) is an under-appreciated cause of chest pain. It is characterised by transient vasoconstriction of the coronary arteries and plays a significant role in the pathogenesis of stable angina and acute coronary syndromes. Complex mechanistic pathways characterised by endothelial dysfunction and smooth muscle hypercontractility lead to a broad spectrum of clinical manifestations ranging from recurrent angina to fatal arrhythmias. Invasive provocation testing using intracoronary acetylcholine or ergonovine is considered the current gold standard for diagnosis, but there is a wide variation in protocols amongst different institutions. Conventional pharmacological therapy relies on calcium channel blockers and nitrates; however, refractory VSA has limited options. This review evaluates the pathophysiology, diagnostic challenges, and management strategies for VSA. We believe global efforts to standardise diagnostic and therapeutic guidelines will improve the outcomes for affected patients.

Emerging Concepts of Vascular Cell Clonal Expansion in Atherosclerosis.

Clonal expansion is a process that can drive pathogenesis in human diseases, with atherosclerosis being a prominent example. Despite advances in understanding the etiology of atherosclerosis, clonality studies of vascular cells remain in an early stage. Recently, several paradigm-shifting preclinical studies have identified clonal expansion of progenitor cells in the vasculature in response to atherosclerosis. This review provides an overview of cell clonality in atherosclerotic progression, focusing particularly on smooth muscle cells and macrophages. We discuss key findings from the latest research that give insight into the mechanisms by which clonal expansion of vascular cells contributes to disease pathology. The further probing of these mechanisms will provide innovative directions for future progress in the understanding and therapy of atherosclerosis and its associated cardiovascular diseases.

In Hospital Outcomes for High-Risk Percutaneous Coronary Intervention (PCI) in Patients Referred From a Rural Centre to Metropolitan Sites.

BACKGROUND: Cardiac Society of Australia and New Zealand (CSANZ) guidelines recommend elective high-risk percutaneous coronary intervention (PCI) is not performed in sites greater than 1 hour from cardiac surgery. METHODS: In hospital outcomes for all patients from Orange Health Service (OHS) from January 2017 to January 2020 who were transferred electively to tertiary centres in Sydney for high risk PCI were examined. RESULTS: One hundred and fourteen (114) patients were identified, with 1,259 PCIs performed at OHS over the same period without transfer. The mean age of these 114 patients was 71 years, with 74.6% male. Receiving hospitals were Royal Prince Alfred Hospital, Sydney, NSW (66.7%), Concord Repatriation General Hospital, Concord, NSW (19.3%) and Strathfield Private Hospital, Strathfield, NSW (14%). The definition of high risk and indication for transfer included at least one of: moderate or greater calcification of the target lesion or proximal segment (34%), single or multiple target lesions that in aggregate jeopardised over 50% of remaining viable myocardium (27%), degenerated saphenous vein grafts (14.8%), chronic total occlusions (7.0%) and severe left ventricular (LV) impairment (3.9%). American Heart Society/American College of Cardiology (AHA/ACC) lesion types were A (1%), B1 (4.2%), B2 (40.2%), and C (54.6%). PCI was performed via the femoral route in 96.2%. The mean procedure duration was 72 minutes, mean combined fluoroscopy time was 19 minutes and mean radiation dose as defined by Reference Air Kerma was 1,630 mGy. Complications occurred in 13 patients and were: acute vessel dissection requiring stenting (4), perforation (2), acute vessel closure (4), puncture site related (1), and life-threatening arrhythmia (2). There were no cases of emergent coronary artery bypass graft (CABG) or death. CONCLUSION: This contemporary cohort of high-risk patients transferred electively from a regional PCI centre to a tertiary cardiac unit underwent lengthy PCI procedures, with high radiation doses, and a modest rate of peri-procedural complications, but had otherwise excellent procedural and clinical outcomes.

Adult Congenital Heart Disease Survivors at Age 50 Years: Medical and Psychosocial Status.

BACKGROUND: Although advances in congenital heart disease (CHD) management have allowed survival of children with even highly complex CHD lesions well into adult life, the burden of disease (medical, psychological and social) has not been well characterised, for those living to middle age and beyond. METHODS: We assessed 121 consecutive patients from our adult CHD centre, who survived to age 50 years and who had had moderate or complex CHD lesions. Pre-specified groups included those with repaired tetralogy of Fallot (TOF) (n=56), coarctation of the aorta (CoA) (n=34), systemic right ventricle (RV) (n=9), Fontan surgery for "single ventricle" hearts (n=5), those with repaired Ebstein's Anomaly (n=9) and other complex CHD (n=8). RESULTS: The overall burden of disease was very substantial. Of the TOF patients, almost half (46%) had required at least one open-heart reoperation and 41% had had a pacemaker or implantable defibrillator; 20% had had a radiofrequency ablation and 32% were on anti-arrhythmic therapy. Over 40% had ≥1 admission for heart failure and 9% had had endocarditis. Only 64% were still employed. Of the CoA survivors, 50% had had a second operation (aortic valve and/or descending aortic surgery), 88% were on medications for hypertension and 62% were still employed. In the more complex groups, approximately half had been diagnosed with depression/anxiety and cerebrovascular event, heart failure and/or significant arrhythmias were common. CONCLUSIONS: Despite considerable advances, adults with CHD who survive to age 50 years have experienced high levels of physical and mental health complications.

The dangers to children from coconut tree trauma, in KiraKira, Solomon Islands: a retrospective clinical audit.

BACKGROUND: Kirakira is small community of 3,000 people and is the capital of Makira-Ulawa province in Solomon Islands. Kirakira is an impoverished community with a small 30 bed hospital with limited resources. This audit was conducted by final year students from Bond University as part of a selective clinical placement. METHODS: The audit included admissions to the hospital from 2011 to 2014. Trauma-related admissions were identified and classified according to the patient's age, sex, description of injury, mechanism of injury and whether they were transferred to the National Referral Hospital (NRH) in Honiara for further treatment. Injuries due to Coconut tree trauma were classified as being due to falls from the tree, or trauma from either falling branches or falling coconut fruit. RESULTS: There were 3455 admissions and 23(0.7 %) non-neonatal deaths over the 3 year period. 126(3.6 %) admissions were referred on to the NRH for further treatment. 277 (8.02 %) admissions were trauma-related with 57(21 %) of these referred on to the NRH. 142 (55 %) of the trauma admissions involved children. Coconut Tree trauma was the commonest cause of a traumatic admission to hospital. There were 49 Coconut Tree trauma admissions including 35 from falls, 12 from falling branches and two from falling coconuts. 80 % of Coconut tree trauma involved Males and the median age of those injured was 13. Primary School age children aged 6-14 years were most at risk for Coconut Tree Trauma. 15(31 %) of the Coconut tree trauma admissions were referred to NRH for further treatment. CONCLUSIONS: Coconut Tree Trauma is common in Kirakira and is an important preventable cause of serious injury that particularly affects primary school aged boys in Kirakira, Solomon Islands. A public education campaign that focuses on this at risk age group warning of the dangers of climbing Coconut trees should be considered.