Door-to-diuretic time and mortality in patients with acute heart failure: A systematic review and meta-analysis.

Early decongestion therapy with intravenous diuretics may be associated with improved outcomes in acute heart failure (AHF), however data is conflicting. This meta-analysis sought to evaluate the impact of door-to-IV diuretic (D2D) time on mortality in patients with AHF. Pooled estimates from observational studies comprising 28,124 patients, early IV diuresis (reference time 30-105 minutes) was associated with a 23% reduction in 30-day mortality in AHF (OR 0.77; 95% CI 0.64-0.93), despite no significant in-hospital death reduction (OR 0.84; 95% CI 0.57-1.24).

Management of the liver transplant candidate with high cardiac risk: Multidisciplinary best practices and recommendations.

In a setting characterized by a growing prevalence of patients with alcohol-associated and metabolic dysfunction-associated steatotic liver diseases, coupled with an aging patient demographic, the incidence of cardiac comorbidities in liver transplant candidates is on the rise. These comorbidities not only pose barriers to transplant eligibility but also impact the intraoperative course and affect posttransplant outcomes. As such, there is a significant need to optimize the clinical management of these cardiac comorbidities. However, there is a scarcity of evidence regarding the best practices for managing cardiac comorbidities such as coronary and valvular heart diseases, arrhythmia, and cardiomyopathy in this population, both before and during transplant surgery. These conditions necessitate a coordinated and multidisciplinary approach to care. In this manuscript, we conduct a comprehensive review of the most recent evidence pertaining to the preoperative and intraoperative management of these cardiac comorbidities in liver transplant candidates. Our aim is to provide recommendations that improve and standardize their clinical care.

Atherosclerosis on CT coronary angiography and the risk of long-term cardiovascular events after liver transplantation.

Computed tomography coronary angiography (CTCA) is increasingly utilized for preoperative risk stratification before liver transplantation (LT). We sought to assess the predictors of advanced atherosclerosis on CTCA using the recently developed Coronary Artery Disease-Reporting and Data System (CAD-RADS) score and its impact on the prediction of long-term major adverse cardiovascular events (MACE) following LT. We conducted a retrospective cohort study of consecutive patients who underwent CTCA for LT work-up between 2011 and 2018. Advanced atherosclerosis was defined as coronary artery calcium scores > 400 or CAD-RADS score ≥ 3 (≥50% coronary artery stenosis). MACE was defined as myocardial infarction, heart failure, stroke, or resuscitated cardiac arrest. Overall, 229 patients underwent CTCA (mean age 66 ± 5 y, 82% male). Of these, 157 (68.5%) proceeded with LT. The leading etiology of cirrhosis was hepatitis (47%), and 53% of patients had diabetes before transplant. On adjusted analysis, male sex (OR 4.6, 95% CI 1.5-13.8, p = 0.006), diabetes (OR 2.2, 95% CI 1.2-4.2, p = 0.01) and dyslipidemia (OR 3.1, 95% CI 1.3-6.9, p = 0.005) were predictors of advanced atherosclerosis on CTCA. Thirty-two patients (20%) experienced MACE. At a median follow-up of 4 years, CAD-RADS ≥ 3, but not coronary artery calcium scores, was associated with a heightened risk of MACE (HR 5.8, 95% CI 1.6-20.6, p = 0.006). Based on CTCA results, 71 patients (31%) commenced statin therapy which was associated with a lower risk of all-cause mortality (HR 0.48, 95% CI 0.24-0.97, p = 0.04). The standardized CAD-RADS classification on CTCA predicted the occurrence of cardiovascular outcomes following LT, with a potential to increase the utilization of preventive cardiovascular therapies.

Cardiovascular Disease in Patients With Breast Cancer Treated in the Modern Era.

AIMS: With improving cancer survivorship, cardiovascular disease (CVD) has become a leading cause of death in breast cancer (BC) survivors. At present, there is no prospectively validated, contemporary risk assessment tool specific to this patient cohort. Accordingly, we sought to investigate long-term cardiovascular outcomes in early-stage BC patients utilising a well characterised database at a quaternary referral centre. With the assembly of this cohort, we have derived a BC cardiovascular risk index titled the 'CRIB (Cardiovascular Risk Index in Breast Cancer)' to estimate the risk of a major adverse cardiovascular event (MACE) in women undergoing treatment for BC. METHODS: A retrospective cohort study was conducted examining all female patients aged ≥18 years of age who underwent treatment for early-stage BC at a cancer centre in Melbourne, Australia, between 2009 and 2019. The primary aim of this study was to assess causes and predictors of MACE. RESULTS: A total of 1,173 women with early-stage BC were included. During a median follow-up of 4.4 (1.8-6.7) years, 80 (6.8%) women experienced a MACE. These women were more likely to be older, with a high burden of cardiovascular risk factors and were more likely to have a history of established coronary artery disease (CAD) (p≤0.001 for all). A CRIB ≥3 (2 points: renal impairment, 1 point: age ≥65 years, body mass index [BMI]>27, diabetes, hypertension, history of smoking) demonstrated moderate discrimination (c-statistic 0.75) with appropriate calibration. A CRIB ≥3, which represented 23.9% of our cohort, was associated with a high risk of MACE (odds ratio [OR] 17.85, 95% confidence interval [CI] 6.36-50.05; p<0.001). A total of 138 (11.8%) women died during the study period. Mortality was significantly higher in patients who experienced a MACE (HR 2.72, 95%CI 1.75-4.23; p<0.001). CONCLUSION: Cardiovascular risk stratification at the time of BC diagnosis using the novel CRIB may help guide surveillance and the use of cardioprotective therapies as well as identify those who require long-term cardiac follow-up.

Long-term mortality in asymptomatic patients with stable ischemic heart disease undergoing percutaneous coronary intervention.

OBJECTIVES: Patients with stable ischemic heart disease (SIHD) may present with a variety of symptoms including typical angina, angina equivalents such as dyspnea or no symptoms. We sought to determine whether symptom status affects periprocedural safety and long-term mortality in patients undergoing PCI. METHODS: Prospectively enrolled consecutive patients undergoing PCI for SIHD at six hospitals in Australia between 2005 to 2018 as part of the Melbourne Interventional Group registry. Symptom status was recorded at the time of PCI and patients undergoing staged PCI were excluded. RESULTS: Overall, 11,730 patients with SIHD were followed up for a median period of 5 years (maximum 14.0 years, interquartile range 2.2-9.0 years) with 1,317 (11.2%) being asymptomatic. Asymptomatic patients were older, and more likely to be male, have triple-vessel disease, with multiple comorbidities including renal failure, diabetes and heart failure (all P < .01). These patients had significantly higher rates of periprocedural complications and major adverse cardiovascular events at 30-days. Long-term mortality was significantly higher in asymptomatic patients (27.2% vs 18.0%, P < .001). On cox regression for long-term mortality, after adjustment for more important clinical variables, asymptomatic status was an independent predictor (Hazard ratio (HR) 1.39 95% CI 1.16-1.66, P < .001). CONCLUSIONS: In a real-world cohort of patients undergoing revascularization for SIHD, absence of symptoms was associated with higher rates of periprocedural complications and, after adjustment for more important clinical variables, was an independent predictor of long-term mortality. As the primary goal of revascularization in SIHD remains angina relief, the appropriateness of PCI in the absence of symptoms warrants justification.

Invasive versus conservative management in patients aged ≥85 years presenting with non-ST-elevation myocardial infarction.

BACKGROUND: Guidelines recommend early coronary angiography (CA) in patients with non-ST-elevation myocardial infarction (NSTEMI) irrespective of age. However, elderly patients are less likely to be treated according to these guidelines due to their perceived high risk and medical comorbidities. Whether an invasive strategy is associated with improved survival in patients aged ≥85 years remains uncertain due to their exclusion from randomised trials. AIMS: Patients were stratified based on whether they underwent invasive management with CA with a view to revascularisation versus conservative management. The primary outcome was long-term mortality. METHODS: Consecutive patients aged ≥85 years presenting to a tertiary centre with NSTEMI between 2008 and 2018 were included in this retrospective cohort study. RESULTS: Of 7591 patients with NSTEMI, 1052 patients aged ≥85 years were included. Ninety-nine (9.4%) patients underwent CA. Those undergoing CA were more likely to be younger, male, live independently, without mobility or cognitive issues (all P < 0.01). Overall, 495 (47%) patients died during a mean follow up of 1.3 ± 1 year. On Cox regression, after adjusting for age, pre-morbid functional status, cognition and cardiovascular risk factors, invasive management was the strongest predictor for survival (hazard ratio 0.47; 95% confidence interval 0.26-0.85; P = 0.01). Invasive management was associated with a trend to increased risk of in-hospital bleeding (6.1% vs 2.6%; P = 0.054) with no significant difference in stroke (2.0% vs 3.8%; P = 0.37). CONCLUSION: In patients aged ≥85 years who presented with NSTEMI, invasive management was associated with improved survival without significant differences in bleeding or stroke. A randomised controlled study assessing the efficacy and safety of invasive management in very elderly patients with NSTEMI is warranted.

Factor Xa Inhibition for the Treatment of Venous Thromboembolism Associated With Cancer: A Meta-Analysis of the Randomised Controlled Trials.

BACKGROUND: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients. Until recently, guidelines recommended the use of low-molecular weight heparin (LMWH) as standard of care for VTE in patients with cancer. Despite the proven efficacy of direct oral anticoagulants (DOACs) for treatment of VTE, there is equipoise supporting their use in cancer patients. METHODS: A systematic review of PubMed, Medline and EMBASE identified four randomised controlled trials (RCTs) in patients with cancer and VTE comparing a factor Xa inhibitor (FXaI) to LMWH. A meta-analysis was performed with a primary outcome of VTE recurrence and key secondary outcomes of major bleeding, clinically relevant non-major bleeding (CRNMB) and gastrointestinal (GI) bleeding. RESULTS: Four RCTs with 2,907 patients were included. 1,451 patients were randomised to FXaI and 1,456 to LMWH. VTE recurrence was lower in the FXaI group (RR 0.62, 95%CI 0.44-0.87; p=0.01; I2=24.90), with an absolute risk difference of -4% equating to a number needed to treat of 25 for prevention of recurrent VTE with FXaI. No significant difference in major bleeding was noted between groups (RR 1.33, 95%CI 0.84-2.11; p=0.23). Rates of GI bleeding (RR 1.87, 95%CI 1.06-3.29; p=0.03) and CRNMB (RR 1.57, 95%CI 1.11-2.23; p=0.01) were greater with FXaIs. CONCLUSION: In patients with cancer and VTE, the rate of VTE recurrence was significantly lower with FXaI than with LMWH without an increased risk of major bleeding. Our data supports the use of FXaIs as the standard of care for the treatment of VTE in this population.

Postoperative Atrial Fibrillation and Long-Term Risk of Stroke in Patients Undergoing Liver Transplantation.

BACKGROUND AND PURPOSE: Postoperative atrial fibrillation (POAF) is the commonest cardiovascular complication following liver transplantation (LT). This study sought to assess a possible association of POAF with subsequent thromboembolic events in patients undergoing LT. METHODS: A retrospective cohort study of consecutive adults undergoing LT between 2010 and 2018 was undertaken. Patients were classified as POAF if atrial fibrillation (AF) was documented within 30 days of LT without a prior history of AF. Cases of ischemic stroke or systemic embolism were adjudicated by a panel of 2 independent physicians. RESULTS: Among the 461 patients included, POAF occurred in 47 (10.2%) a median of 3 days following transplantation. Independent predictors of POAF included advancing age, postoperative sepsis and left atrial enlargement. Over a median follow-up of 4.9 (interquartile range, 2.9-7.2) years, 21 cases of stroke and systemic embolism occurred. Rates of thromboembolic events were significantly higher in patients with POAF (17.0% versus 3.1%; P<0.001). After adjustment, POAF remained a strong independent predictor of thromboembolic events (hazard ratio, 8.36 [95% CI, 2.34-29.79]). Increasing CHA2DS2VASc score was also an independent predictor of thromboembolic events (hazard ratio, 1.58 [95% CI, 1.02-2.46]). A model using POAF and a CHA2DS2VASc score ≥2 alone yielded a C statistic of 0.77, with appropriate calibration for the prediction of thromboembolic events. However, POAF was not an independent predictor of long-term mortality. CONCLUSIONS: POAF following LT is associated with an 8-fold increased risk of thromboembolic events and the use of the CHA2DS2VASc score may facilitate risk stratification of these patients. Prospective studies are warranted to assess whether the use of oral anticoagulants can reduce the risk of thromboembolism following LT.

Angiotensin-Converting Enzyme 2 Activity Is Associated With Embolic Stroke of Undetermined Source.

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Relationship between QT interval prolongation and structural abnormalities in cirrhotic cardiomyopathy: A change in the current paradigm.

It is postulated that cardiac structural abnormalities observed in cirrhotic cardiomyopathy (CCM) contribute to the electrophysiologic abnormality of QT interval (QTc) prolongation. We sought to evaluate whether QTc prolongation is associated with intrinsic abnormalities in cardiac structure and function that characterize CCM. Consecutive patients undergoing liver transplant work-up between 2010 and 2018 were included. Measures of cardiac function on stress testing including cardiac reserve and chronotropic incompetence were collected prospectively and a corrected QTc ≥ 440 ms was considered prolonged. Overall, 439 patients were included and 65.1% had a prolonged QTc. There were no differences in markers of left ventricular and atrial remodeling, or resting systolic and diastolic function across QTc groups. The proportion of patients that met the criteria for a low cardiac reserve (39.2 vs 36.6%, p = .66) or chronotropic incompetence (18.1 vs 21.3%, p = .52) was not different in those with a QTc ≥ 440 vs <440 ms. Further, there was no association between QTc prolongation and CCM by either the 2005 World College of Gastroenterology or modified 2020 Cirrhotic Cardiomyopathy Consortium criteria. QT interval prolongation was not associated with structural or functional cardiac abnormalities that characterize CCM. These findings suggest that CCM and QT interval prolongation in cirrhosis may be two separate entities with distinct pathophysiological origins.

Effect of QT interval prolongation on cardiac arrest following liver transplantation and derivation of a risk index.

Liver transplantation (LT) has a 4-fold higher risk of periprocedural cardiac arrest and ventricular arrhythmias (CA/VAs) compared with other noncardiac surgeries. Prolongation of the corrected QT interval (QTc) is common in patients with liver cirrhosis. Whether it is associated with an increased risk of CA/VAs following LT is unclear. Rates of 30-day CA/VAs post-LT were assessed in consecutive adults undergoing LT between 2010 and 2017. Pretransplant QTc was measured by a cardiologist blinded to clinical outcomes. Among 408 patients included, CA/VAs occurred in 26 patients (6.4%). QTc was significantly longer in CA/VA patients (475 ± 34 vs 450 ± 34 ms, P < .001). Optimal QTc cut-off for prediction of CA/VAs was ≥480 ms. After adjustment, QTc ≥480 ms remained the strongest predictor for the occurrence of CA/VAs (odds ratio [OR] 5.2, 95% confidence interval [CI] 2.2-12.6). A point-based cardiac arrest risk index (CARI) was derived with the bootstrap method for yielding optimism-corrected coefficients (2 points: QTc ≥480, 1 point: Model for End-Stage Liver Disease [MELD] ≥30, 1 point: age ≥65, and 1 point: male). CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study.

Cardiac Risk Stratification in Liver Transplantation: Results of a Tiered Assessment Protocol Based on Traditional Cardiovascular Risk Factors.

Coronary artery disease (CAD) confers increased perioperative risk in patients undergoing liver transplantation (LT). Although routine screening for CAD is recommended, there are limited data on the effectiveness of screening strategies. We evaluated the safety and efficacy of a 3-tiered cardiac risk-assessment protocol that stratifies patients based on age and traditional cardiac risk factors. We peformed a single-center, prospective, observational study of consecutive adult patients undergoing LT assessment (2010-2017). Patients were stratified into low-risk (LR), intermediate-risk (IR), or high-risk (HR) cardiac groups and received standardized investigations with selective use of transthoracic echocardiography (TTE), dobutamine stress echocardiography (DSE), computed tomography coronary angiography (CTCA), and coronary angiography (CA). Primary outcomes were cardiac events (CEs) and cardiovascular death up to 30 days after LT. Overall, 569 patients were included, with 76 patients identified as LR, 256 as IR, and 237 as HR. Cardiac risk factors included diabetes mellitus (26.0%), smoking history (47.3%), hypertension (17.8%), hypercholesterolemia (7.2%), family (17.0%) or prior history of heart disease (6.0%), and obesity (27.6%). Of the patients, 42.0% had ≥2 risk factors. Overall compliance with the protocol was 90.3%. Abnormal findings on TTE, DSE, and CTCA were documented in 3, 23, and 44 patients, respectively, and 12 patients were not listed for transplantation following cardiac assessment (1 LR, 2 IR, and 9 HR). Moderate or severe CAD was identified in 25.4% of HR patients on CTCA following a normal DSE. CEs were recorded in 7 patients (1.2%), with 2 cardiovascular deaths (0.4%). Cardiac risk stratification based on traditional cardiac risk factors with the selective use of DSE, CTCA, and CA is a safe and feasible approach that results in a low perioperative cardiac event rate.

Transcatheter aortic valve replacement in patients with a history of cancer: Periprocedural and long-term outcomes.

BACKGROUND: A history of cancer is incorporated into the surgical risk assessment of patients undergoing surgical aortic valve replacement through the Society for Thoracic Surgeons score. However, the prognostic significance of cancer in patients treated with transcatheter aortic valve replacement (TAVR) is unclear. As the cancer survivorship population increases, it is imperative to establish the efficacy and safety of TAVR in patients with severe symptomatic aortic stenosis (AS) and a history of malignancy. OBJECTIVES: The primary goal of this study was to assess the periprocedural outcomes and long-term mortality in patients with a history of cancer undergoing TAVR. METHODS: A systematic review of PubMed, MEDLINE, and EMBASE was conducted to identify studies reporting outcomes in patients with a history of malignancy undergoing TAVR. A meta-analysis was performed using a random-effects model with a primary outcome of all-cause mortality and cardiac mortality at the longest follow-up. On secondary analyses, procedural safety was assessed. RESULTS: A total of 13 observational studies with 10,916 patients were identified in the systematic review. Seven studies including 6,323 patients were included in the quantitative analysis. Short-term mortality (relative risk [RR] 0.61, 95%CI 0.36-1.01; p = .06) and long-term all-cause mortality (RR 1.24, 95%CI 0.95-1.63; p = .11) were not significantly different when comparing patients with and without a history of cancer. No significant difference in the rate of periprocedural complications including stroke, bleeding, acute kidney injury, and pacemaker implantation was noted. CONCLUSION: In patients with severe AS undergoing TAVR, a history of cancer was not associated with adverse short or long-term survival. Based on these findings, TAVR should be considered in all patients with severe symptomatic AS, irrespective of their history of malignancy.

SMARTphone Based Cardiovascular Risk Reduction in BREAST Cancer Patients (SMART-BREAST): A Randomised Controlled Trial Protocol.

INTRODUCTION: Breast cancer survivors are at greater risk for cardiovascular-related mortality compared to women without breast cancer. Accordingly, attention to reducing the risk of cardiovascular disease must be a priority in the long-term management of these patients. With the exponential rise in cancer survivors, there is a need for innovative cardio-oncology programs. This paper describes the study design of a randomised controlled trial assessing the effectiveness of a smartphone-based cardiovascular risk reduction program in improving physical activity and cardiovascular health in patients undergoing treatment for breast cancer. METHODS AND ANALYSIS: The aim of this study is to assess the efficacy and usability of a smartphone-based model of care for exercise promotion, cardiovascular risk reduction and community engagement in women undergoing treatment for breast cancer. This will be achieved by testing our personalised smartphone application "BreastMate", as an adjunct to standard care in a single-blinded, parallel, randomised controlled trial. The primary outcome of the trial is change in exercise capacity, as measured by the 6-minute walk test distance at 12 months compared to baseline. Secondary endpoints include improvements in cardiovascular risk factor status and quality of life, received dose intensity of chemotherapy and major adverse cardiovascular events. ETHICS: Multicentre ethical approval has been granted by the Austin Hospital (HREC/47081/Austin/2018). DISSEMINATION OF RESULTS: The analysed results will be published in a peer reviewed journal on completion of the clinical trial. REGISTRATION DETAILS: SMART-BREAST has been prospectively registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR12620000007932).

Impaired Cardiac Reserve on Dobutamine Stress Echocardiography Predicts the Development of Hepatorenal Syndrome.

OBJECTIVES: Cardiac dysfunction has been implicated in the genesis of hepatorenal syndrome (HRS). It is unclear whether a low cardiac output (CO) or attenuated contractile response to hemodynamic stress can predict its occurrence. We studied cardiovascular hemodynamics in cirrhosis and assessed whether a diminished cardiac reserve with stress testing predicted the development of HRS on follow-up. METHODS: Consecutive patients undergoing liver transplant workup with dobutamine stress echocardiography (DSE) were included. CO was measured at baseline and during low-dose dobutamine infusion at 10 µg/kg/min. HRS was diagnosed using guideline-based criteria. RESULTS: A total of 560 patients underwent DSE, of whom 488 were included after preliminary assessment. There were 64 (13.1%) patients with established HRS. The HRS cohort had a higher baseline CO (8.0 ± 2 vs 6.9 ± 2 L/min; P < 0.001) and demonstrated a blunted response to low-dose dobutamine (ΔCO 29 ± 22% vs 44 ± 32%, P < 0.001) driven primarily by inotropic incompetence. Optimal cutpoint for ΔCO in patients with HRS was determined to be <25% and was used to define a low cardiac reserve. Among the 424 patients without HRS initially, 94 (22.1%) developed HRS over a mean follow-up of 1.5 years. Higher proportion with a low cardiac reserve developed HRS (52 [55.0%] vs 56 [16.9%]; hazard ratio 4.5; 95% confidence interval 3.0-6.7; P < 0.001). In a Cox multivariable model, low cardiac reserve remained the strongest predictor for the development of HRS (hazard ratio 3.9; 95% confidence interval 2.2-7.0; P < 0.001). DISCUSSION: Patients with HRS demonstrated a higher resting CO and an attenuated cardiac reserve on stress testing. On longitudinal follow-up, low cardiac reserve was an independent predictor for the development of HRS. Assessment of cardiac reserve with DSE may provide a novel noninvasive risk marker for developing HRS in patients with advanced liver disease.HRS is a life-threatening complication of liver disease. We studied whether an inability to increase cardiac contraction in response to stress can assist in the prediction of HRS. We demonstrate that patients with liver disease who exhibit cardiac dysfunction during stress testing had a 4-fold increased risk of developing HRS. This may improve our ability for early diagnosis and treatment of patients at a higher risk of developing HRS.

Ischaemic heart disease and Cancer: competing malignant conditions.

BACKGROUND: The growing population of cancer survivors and their high frequency of cardiovascular disease have resulted in a dramatic increase in cancer patients requiring cardiovascular intervention. However, there is a lack of evidence to guide optimal management in this complex population who have historically been excluded from cardiovascular trials. DISCUSSION: We review the recently published meta-analysis by Roule et al. The findings of this analysis demonstrate that patients with cancer presenting with acute coronary syndrome (ACS) have increased rates of in-hospital cardiovascular mortality, bleeding and one-year cardiovascular mortality. All-cause mortality measured in-hospital and at one-year were also significantly greater in cancer patients as was all-cause mortality in cancer patients that undergo percutaneous coronary intervention (PCI). In contrast to the short-term outcomes, rates of long-term cardiovascular mortality did not differ significantly between groups. Patient-specific assessment of risk, accounting for disease characteristics and treatment, and close communication with oncology providers is vital in defining optimal treatment strategies in this population.

Renin-angiotensin system inhibition and risk of infection and mortality in COVID-19: a systematic review and meta-analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, enters human cells by binding of its viral protein to the aminopeptidase angiotensin-converting enzyme 2 (ACE2). This has led to speculation whether treatment with renin-angiotensin system (RAS) inhibitors was associated with an increased likelihood of a positive test for COVID-19 and risk of mortality. AIMS: We performed a systematic review and meta-analysis to investigate whether RAS inhibitors increased the likelihood of a positive test or death/severe illness in patients with COVID-19. METHODS: A systematic search of MEDLINE, PubMed and EMBASE was conducted for studies stratified by the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Pooled analysis was performed using a random-effects model. RESULTS: Seven trials of 73 122 patients were included. Overall, 16 624 (22.7%) patients had a positive COVID-19 test and 7892 (10.8%) were on a RAS inhibitor. RAS inhibitors were not associated with higher likelihood of a positive COVID-19 test result (odds ratio (OR) 0.97 (95% CI 0.97-1.05, P = 0.48) with low heterogeneity. This was comparable when stratifying by use of each medication class. The use of RAS inhibitors was also not associated with mortality or severe illness (OR 0.89, 95% CI 0.73-1.07, P = 0.21) with moderate heterogeneity. CONCLUSION: Use of ACEI or ARB was not associated with a heightened susceptibility for a positive diagnosis of COVID-19. Furthermore, they were not associated with increased illness severity or mortality due to COVID-19. Randomised controlled trials are needed to address definitively the potential benefits or harms of RAS inhibitors in patients with COVID-19.

Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has revolutionised the treatment of severe aortic stenosis (AS), though its safety and efficacy in low-risk patients remains to be established. METHODS: A systematic review of PubMed, Medline and EMBASE identified four randomised controlled trials (RCTs) in patients at low surgical risk comparing TAVR to surgical aortic valve replacement (SAVR). A meta-analysis was performed with a primary outcome of a composite of all-cause mortality and stroke at longest available follow-up. RESULTS: A total of four RCTs with 2,836 patients was included in the final analysis. 1,363 patients were randomised to SAVR and 1,473 to TAVR. The composite of all-cause mortality and stroke was significantly lower in patients undergoing TAVR compared with SAVR (OR 0.59, 95%CI 0.37-0.95, p=0.03) with low heterogeneity (I2=31%). The difference in the primary composite outcome was driven by a difference in mortality (OR 0.66, 95%CI 0.44-0.98, p=0.04; I2=0%) without significant differences in stroke (OR 0.75 95%CI 0.45-1.26, p=0.28; I2=37%). Weighted absolute risk difference (ARD) of the primary composite outcome also favoured TAVR (ARD -2.0% 95%CI -3.3 to -0.7%, p=0.002) with a number needed to treat (NNT) of 50 to prevent one death or stroke. Patients undergoing TAVR had a significantly higher risk of permanent pacemaker implantation (OR 3.9, 95%CI 1.8-8.4, p<0.001, I2=84%) and moderate or severe paravalvular leak (OR 5.0, 95%CI 1.6-15.7, p=0.01; I2=19%). CONCLUSIONS: In patients with severe AS at low surgical risk, the rate of the composite of death and stroke was significantly lower with TAVR than with SAVR. Longer term follow-up with a focus on the impact of permanent pacemaker (PPM) implantation, paravalvular leak (PVL) and structural valve deterioration is essential before the use of TAVR can be generalised to the broader population of patients with AS.