Cardiovascular outcomes for people hospitalised with COVID-19 in Australia, and the effect of vaccination: an observational cohort study.

OBJECTIVES: To assess the frequency of clinical cardiovascular outcomes for people hospitalised with coronavirus disease 2019 (COVID-19), and the impact of vaccination. STUDY DESIGN: Observational cohort study. SETTING, PARTICIPANTS: All index admissions of adults with laboratory-confirmed COVID-19 to 21 hospitals participating in the Australian Cardiovascular COVID-19 Registry (AUS-COVID), 4 September 2020 - 11 July 2022. MAIN OUTCOME MEASURES: Frequency of elevated troponin levels, new arrhythmia, new or deteriorating heart failure or cardiomyopathy, new pericarditis or myocarditis, new permanent pacemaker or implantable cardioverter-defibrillator, and pulmonary embolism. SECONDARY OUTCOMES: impact of COVID-19 vaccination on likelihood of in-hospital death, intubation, troponin elevation, and clinical cardiovascular events. RESULTS: The mean age of the 1714 people admitted to hospital with COVID-19 was 60.1 years (standard deviation, 20.6 years); 926 were men (54.0%), 181 patients died during their index admissions (10.6%), 299 required intensive care (17.4%). Thirty-eight patients (2.6%) developed new atrial fibrillation or flutter, 27 (2.6%) had pulmonary embolisms, new heart failure or cardiomyopathy was identified in 13 (0.9%), and pre-existing cardiomyopathy or heart failure was exacerbated in 21 of 110 patients (19%). Troponin was elevated in 369 of the 986 patients for whom it was assessed (37.4%); in-hospital mortality was higher for people with elevated troponin levels (86, 23% v 23, 3.7%; P < 0.001). The COVID-19 vaccination status of 580 patients was known (no doses, 232; at least one dose, 348). The likelihood of in-hospital death (adjusted odds ratio [aOR], 0.38; 95% confidence interval [CI], 0.18-0.79) and intubation (aOR, 0.30; 95% CI, 0.15-0.61) were lower for people who had received at least one vaccine dose, but not the likelihood of troponin elevation (aOR, 1.44; 95% CI, 0.80-2.58) or clinical cardiovascular events (aOR, 1.56; 95% CI, 0.59-4.16). CONCLUSIONS: Although troponin levels were elevated in a considerable proportion of people hospitalised with COVID-19, clinical cardiovascular events were infrequent, and their likelihood was not influenced by vaccination. COVID-19 vaccination, however, was associated with reduced likelihood of in-hospital death and intubation. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12620000486921 (prospective).

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.

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.

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.

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.

Machine-learning based risk prediction of in-hospital outcomes following STEMI: the STEMI-ML score.

Background: Traditional prognostic models for ST-segment elevation myocardial infarction (STEMI) have limitations in statistical methods and usability. Objective: We aimed to develop a machine-learning (ML) based risk score to predict in-hospital mortality, intensive care unit (ICU) admission, and left ventricular ejection fraction less than 40% (LVEF < 40%) in STEMI patients. Methods: We reviewed 1,863 consecutive STEMI patients undergoing primary percutaneous coronary intervention (pPCI) or rescue PCI. Eight supervised ML methods [LASSO, ridge, elastic net (EN), decision tree, support vector machine, random forest, AdaBoost and gradient boosting] were trained and validated. A feature selection method was used to establish more informative and nonredundant variables, which were then considered in groups of 5/10/15/20/25/30(all). Final models were chosen to optimise area under the curve (AUC) score while ensuring interpretability. Results: Overall, 128 (6.9%) patients died in hospital, with 292 (15.7%) patients requiring ICU admission and 373 (20.0%) patients with LVEF < 40%. The best-performing model with 5 included variables, EN, achieved an AUC of 0.79 for in-hospital mortality, 0.78 for ICU admission, and 0.74 for LVEF < 40%. The included variables were age, pre-hospital cardiac arrest, robust collateral recruitment (Rentrop grade 2 or 3), family history of coronary disease, initial systolic blood pressure, initial heart rate, hypercholesterolemia, culprit vessel, smoking status and TIMI flow pre-PCI. We developed a user-friendly web application for real-world use, yielding risk scores as a percentage. Conclusions: The STEMI-ML score effectively predicts in-hospital outcomes in STEMI patients and may assist with risk stratification and individualising patient management.

Association between pre-existing cardiovascular disease, mortality and cardiovascular outcomes in hospitalised patients with COVID-19.

Background: Pre-existing cardiovascular disease and cardiovascular risk factors are common in patients with COVID-19 and there remain concerns for poorer in-hospital outcomes in this cohort. We aimed to analyse the relationship between pre-existing cardiovascular disease, mortality and cardiovascular outcomes in patients hospitalised with COVID-19 in a prospective, multicentre observational study. Method: This prospective, multicentre observational study included consecutive patients of age ≥18 in their index hospitalisation with laboratory-proven COVID-19 in Australia. Patients with suspected but not laboratory-proven COVID-19 and patients with no available past medical history were excluded. The primary exposure was pre-existing cardiovascular disease, defined as a composite of coronary artery disease, heart failure or cardiomyopathy, atrial fibrillation or flutter, severe valvular disease, peripheral arterial disease and stroke or transient ischaemic attack. The primary outcome was in-hospital mortality. Secondary outcomes were clinical cardiovascular complications (new onset atrial fibrillation or flutter, high-grade atrioventricular block, sustained ventricular tachycardia, new heart failure or cardiomyopathy, pericarditis, myocarditis or myopericarditis, pulmonary embolism and cardiac arrest) and myocardial injury. Results: 1,567 patients (mean age 60.7 (±20.5) years and 837 (53.4%) male) were included. Overall, 398 (25.4%) patients had pre-existing cardiovascular disease, 176 patients (11.2%) died, 75 (5.7%) had clinical cardiovascular complications and 345 (37.8%) had myocardial injury. Patients with pre-existing cardiovascular disease had significantly increased in-hospital mortality (aOR: 1.76 95% CI: 1.21-2.55, p = 0.003) and myocardial injury (aOR: 3.27, 95% CI: 2.23-4.79, p < 0.001). There was no significant association between pre-existing cardiovascular disease and in-hospital clinical cardiovascular complications (aOR: 1.10, 95% CI: 0.58-2.09, p = 0.766). On mediation analysis, the indirect effect and Sobel test were significant (p < 0.001), indicating that the relationship between pre-existing cardiovascular disease and in-hospital mortality was partially mediated by myocardial injury. Apart from age, other cardiovascular risk factors such as diabetes, hypercholesterolemia and hypertension had no significant impact on mortality, clinical cardiovascular complications or myocardial injury. Conclusions: Pre-existing cardiovascular disease is associated with significantly higher mortality in patients hospitalised with COVID-19. This relationship may be partly explained by increased risk of myocardial injury among patients with pre-existing cardiovascular disease which in turn is a marker associated with higher mortality.

Vessel-Specific Outcomes of Deferred Revascularization Following Negative Fractional Flow Reserve.

Variations in myocardial supply area and hydrostatic pressure gradients result in greater likelihood of positive fractional flow reserve (FFR) in the left anterior descending (LAD) compared with the circumflex (Cx) and right coronary artery (RCA). However, the same FFR threshold for deferral of revascularization is applied to all arteries, without evidence that this results in equivalent outcomes. We assessed vessel-specific outcomes of deferred revascularization for the 3 major coronary arteries based on FFR > 0.8. In this retrospective study, data were obtained on consecutive patients who underwent indicated FFR assessment across 2 tertiary institutions. Patients with deferred revascularization were followed for 36 months for the primary end point of vessel-specific target lesion failure (TLF). Of 1,916 major coronary arteries (1,579 patients), the odds ratio of positive FFR was highest in the LAD (odds ratio 3.36, p <0.001). In total, 867 vessels (733 patients) with FFR > 0.8 had complete 3-year medical record follow-ups. The TLF rate for deferred vessels was 10.21%, 11.52%, and 10.96% for the LAD, Cx, and RCA respectively. In a multivariate analysis, there was no significant difference in the odds of TLF for the 0.84 (0.53 to 1.33, p = 0.459), 1.17 (0.68 to 2.01, p = 0.582), and 1.11 (0.62 to 2.00, p = 0.715) in the LAD, Cx, and RCA, respectively. In a multivariate analysis, diabetes mellitus was the only baseline characteristic significantly associated at risk of TLF (1.43 [1.01 to 2.02], p = 0.043). In conclusion, despite greater likelihood of positive FFR in the LAD, the FFR threshold for deferred revascularization resulted in equivalent outcomes in all 3 major coronary arteries, and patients with diabetes mellitus may represent a group that requires aggressive surveillance and risk factor modification after deferred revascularization.

Prospective observational study on the accuracy of predictors of high-grade atrioventricular conduction block after transcatheter aortic valve implantation (CONDUCT-TAVI): study protocol, background and significance.

INTRODUCTION: Aortic stenosis is the most common cardiac valve pathology worldwide and has a mortality rate of over 50% at 5 years if left untreated. Transcatheter aortic valve implantation (TAVI) is a minimally invasive and highly effective alternative treatment option to open-heart surgery. High-grade atrioventricular conduction block (HGAVB) is one of the most common complications after TAVI and requires a permanent pacemaker. Due to this, patients are typically monitored for 48 hours post TAVI, however up to 40% of HGAVB may delayed, and occur after discharge. Delayed HGAVB can cause syncope or sudden unexplained cardiac death in a vulnerable population, and no accurate methods currently exist to identify patients at risk. METHODS AND ANALYSIS: The prospective observational study on the accuracy of predictors of high-grade atrioventricular conduction block after transcatheter aortic valve implantation (CONDUCT-TAVI) trial is an Australian-led, multicentre, prospective observational study, aiming to improve the prediction of HGAVB, after TAVI. The primary objective of the trial is to assess whether published and novel invasive electrophysiology predictors performed immediately before and after TAVI can help predict HGAVB after TAVI. The secondary objective aims to further evaluate the accuracy of previously published predictors of HGAVB after TAVI, including CT measurements, 12-lead ECG, valve characteristics, percentage oversizing and implantation depth. Follow-up will be for 2 years, and detailed continuous heart rhythm monitoring will be obtained by inserting an implantable loop recorder in all participants. ETHICS AND DISSEMINATION: Ethics approval has been obtained for the two participating centres. Results of the study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12621001700820.

Association of hypertension with mortality in patients hospitalised with COVID-19.

OBJECTIVE: To assess whether hypertension is an independent risk factor for mortality among patients hospitalised with COVID-19, and to evaluate the impact of ACE inhibitor and angiotensin receptor blocker (ARB) use on mortality in patients with a background of hypertension. METHOD: This observational cohort study included all index hospitalisations with laboratory-proven COVID-19 aged ≥18 years across 21 Australian hospitals. Patients with suspected, but not laboratory-proven COVID-19, were excluded. Registry data were analysed for in-hospital mortality in patients with comorbidities including hypertension, and baseline treatment with ACE inhibitors or ARBs. RESULTS: 546 consecutive patients (62.9±19.8 years old, 51.8% male) hospitalised with COVID-19 were enrolled. In the multivariable model, significant predictors of mortality were age (adjusted OR (aOR) 1.09, 95% CI 1.07 to 1.12, p<0.001), heart failure or cardiomyopathy (aOR 2.71, 95% CI 1.13 to 6.53, p=0.026), chronic kidney disease (aOR 2.33, 95% CI 1.02 to 5.32, p=0.044) and chronic obstructive pulmonary disease (aOR 2.27, 95% CI 1.06 to 4.85, p=0.035). Hypertension was the most prevalent comorbidity (49.5%) but was not independently associated with increased mortality (aOR 0.92, 95% CI 0.48 to 1.77, p=0.81). Among patients with hypertension, ACE inhibitor (aOR 1.37, 95% CI 0.61 to 3.08, p=0.61) and ARB (aOR 0.64, 95% CI 0.27 to 1.49, p=0.30) use was not associated with mortality. CONCLUSIONS: In patients hospitalised with COVID-19, pre-existing hypertension was the most prevalent comorbidity but was not independently associated with mortality. Similarly, the baseline use of ACE inhibitors or ARBs had no independent association with in-hospital mortality.

Persistent reduction in global longitudinal strain in the longer term after radiation therapy in patients with breast cancer.

BACKGROUND: More than 80% of breast cancer patients receive radiotherapy (RT). However, RT can lead to cardiotoxicity, which usually develops insidiously over years, making diagnosis difficult. It is also unknown whether early identification of at-risk patients might improve long-term outcome. We have previously described subclinical alterations, detected by two-dimensional speckle tracking strain echocardiography, in left ventricular (LV) function immediately following RT in breast cancer. HYPOTHESIS: Subclinical myocardial alterations in LV function consequent to RT cardiotoxicity, observed early, persist at 12 months. METHODS: 40 chemotherapy naive women with left-sided breast cancer, treated with surgery and adjuvant breast RT, were prospectively recruited from two tertiary hospitals. Transthoracic echocardiography was performed at baseline (pre-RT), 6 weeks post-RT, and 12 months post-RT. RESULTS: An increase in LV end diastolic and end systolic volumes was seen from baseline, consistent with persistent LV remodelling; however, due to the increase in both systolic and diastolic volumes over time, no change in LV ejection fraction (EF) was observed. Global longitudinal strain (GLS) and S' velocity remained significantly lower at 12 months post-RT. GLS dropped by >10% in 16 patients and by >20% in 4 patients compared to baseline. CONCLUSIONS: Subclinical cardiac dysfunction using strain analysis, evident early, persists one year after RT, despite unchanged conventional indices such as LVEF. Persistent GLS reduction may be of particular importance in breast cancer patients receiving concomitant chemotherapy. Longer term prospective studies are required to determine if reductions in strain post-RT are associated with future adverse cardiovascular events.

Evaluation of traditional and novel echocardiographic methods of cardiac diastolic dysfunction post radiotherapy in breast cancer.

BACKGROUND: To investigate alterations in left ventricular (LV) diastolic function using traditional and novel echocardiographic parameters, following radiation therapy (RT) in breast cancer patients in the acute setting. METHODS: 40 chemotherapy-naïve women with left-sided breast cancer undergoing RT were prospectively recruited. A comprehensive transthoracic echocardiogram (TTE) was performed at baseline, during RT and 6weeks post-RT. Traditional echocardiographic diastolic parameters and diastolic strain rate were measured and analysed. The relationship between alterations in diastolic parameters, changes in global longitudinal systolic strain (GLS) and radiation dose were investigated. RESULTS: Traditional diastolic parameters remained largely unchanged; however diastolic strain parameters, E-Sr and A-Sr were significantly reduced 6weeks post-RT [Longitudinal E-Sr (s-1) 1.47+/-0.32 vs 1.29+/-0.27*; Longitudinal A-Sr (s-1) 1.19+/-0.31 vs 1.03+/-0.24*; *p<0.05 vs baseline]. When patients were divided by a reduction ≥10% versus <10% in GLS post-RT, a greater reduction in both traditional diastolic and diastolic strain parameters was observed in the group with >10% reduction in systolic function as evaluated by GLS. When patients were divided by mean v30 dose, a greater % change in E-Sr was noted in those receiving more than mean V30 dose. CONCLUSION: Diastolic dysfunction was only evident acutely, post-RT with the use of newer methods like strain analysis. A significant reduction in diastolic function was seen in the patient subgroup with ≥10% reduction in systolic function, enhancing the notion of diastolic function as a potential indicator for systolic dysfunction. Future longitudinal studies are required to determine the specific prognostic value of these observations.