Coronary Artery Disease Risk Prediction in Patients With Severe Aortic Stenosis: Development and Validation of the Aortic Stenosis-Coronary Artery Disease (AS-CAD) Score.

Patients at a low risk of coronary artery disease (CAD) could be triaged to noninvasive coronary computed tomography angiogram instead of invasive coronary angiography, reducing health care costs and patient morbidity. Therefore, we aimed to develop a CAD risk prediction score to identify those who underwent transcatheter aortic valve implantation (TAVI) at a low risk of CAD. We enrolled 1,782 patients who underwent TAVI and randomized the patients to the derivation or validation cohort 2:1. The aortic stenosis-CAD (AS-CAD) score was developed using logistic regression, followed by separation into low- (score 0 to 5), intermediate- (6 to 10), or high-risk (>11) categories. The AS-CAD was validated initially through the k-fold cross-validation, followed by a separately held validation cohort. The average age of the cohort was 82 ± 7 years, and 41% (730 of 1,782) were female; 35% (630) had CAD. The male sex, previous percutaneous coronary intervention, stroke, peripheral arterial disease, diabetes, smoking status, left ventricular ejection fraction <50%, and right ventricular systolic pressure >35 mm Hg were all associated with an increased risk of CAD and were included in the final AS-CAD model (all p <0.03). Within the validation cohort, the AS-CAD score stratified those into low, intermediate, and high risk of CAD (p <0.001). Discrimination was good within the internal validation cohort, with a c-statistic of 0.79 (95% confidence interval 0.74 to 0.84), with similar power obtained using k-fold cross-validation (c-statistic 0.74 [95% confidence interval 0.70 to 0.77]). In conclusion, The AS-CAD score robustly identified those at a low risk of CAD in patients with severe AS. The use of AS-CAD in practice could avoid potential complications of invasive coronary angiogram by triaging low-risk patients to noninvasive coronary assessment using existing computed tomography data.

Polymorphic Ventricular Tachycardia Storm After Coronary Artery Bypass Graft Surgery: A Form of 'Angry Purkinje Syndrome'.

BACKGROUND: Polymorphic ventricular tachycardia (PMVT) is a highly lethal arrhythmia which is commonly caused by acute myocardial ischaemia. PMVT mediated by short-coupled ventricular ectopy patients with ischaemic heart disease but in the absence of acute ischaemia may relate to transient peri-infarct Purkinje fibre irritability and has been termed 'Angry Purkinje Syndrome'. METHODS: We present a case series of three patients with PMVT storm 3-5 days following coronary artery bypass graft surgery (CABG). In all three cases, recurrent episodes of PMVT were initiated by monomorphic ventricular ectopy with a short coupling interval. Acute coronary ischaemia was excluded in all three patients with a coronary angiogram and graft study. Two out of three of the patients commenced oral quinidine sulphate with subsequent rapid suppression of arrhythmia. Implantable cardiac defibrillators were implanted in all three patients and revealed no recurrence of PMVT following hospital discharge. CONCLUSION: The Angry Purkinje Syndrome is a rare but important cause of ventricular tachycardia storm after CABG surgery and is mediated by short-coupled ventricular ectopy in the absence of acute myocardial ischaemia. This arrhythmia may be highly responsive to quinidine.

Long-Term Valve Durability in Patients Undergoing Transcatheter Aortic Valve Implantation.

AIMS: To evaluate the long-term incidence of structural valve deterioration (SVD) in patients who underwent transcatheter aortic valve implantation (TAVI). METHOD AND RESULTS: Between 2008 and 2018, 693 underwent TAVI at two centres. Four hundred and twenty-one (421) patients (mean age 83.6±6.0 yrs) survived for ≥2 years post TAVI and had at least two consecutive transthoracic echocardiographies (TTEs) with the latest TTE no less than 2 years after TAVI, and were therefore included in the analysis for SVD. Median follow-up was 4.7 (3.6-6.0) years and median echocardiography follow-up 3 (3.0-4.0) years. All-cause mortality was 30.9% (130) with a median time to death of 4.1 (3.0-5.6) years. The cumulative incidence of SVD increased from 1.7% (95% CI, 0.4-2.9) at 3 years to 3.5% (95% CI, 1.5-5.8) at 5 years and 4.7% (95% CI, 1.6-7.9) at 10 years. The overall median time to SVD was 3 (2-4) years. Twelve (12) patients demonstrated SVD stage 2, and 1 patient stage 3. No SVD required re-intervention. All other patients showed no significant changes in valve parameters over time. CONCLUSIONS: Structural valve deterioration is an uncommon event, occurring in 5% over a total follow-up of 10 years. Most patients show stable valve parameters. However, the analysis is limited by the loss of follow-up (owing to patient mortality), which renders extrapolation of the data to a younger patient population difficult.

Relation of Preprocedure Platelet-to-Lymphocyte Ratio and Major Adverse Cardiovascular Events Following Transcatheter Aortic Valve Implantation for Aortic Stenosis.

The platelet-to-lymphocyte ratio (PLR) is a novel inflammatory biomarker that has prognostic value in patients presenting with acute coronary syndrome. Transcatheter aortic valve implantation (TAVI) treats the inflammatory disease of aortic stenosis. However, the utility of preprocedure PLR in predicting major adverse cardiovascular events (MACE) after TAVI is not clear. Our study population included 470 patients who underwent TAVI at The Alfred Hospital in Melbourne, Australia from August 2008, to January 2019. Patients were divided into 4 groups based on PLR quartiles. The incidence of 30-day MACE (a composite of stroke, myocardial infarction, and death) was then compared. Outcomes were reported according to the Valve Academic Research Consortium-2 criteria. Of 470 patients, median age 84 years, 54% men, and median Society of Thoracic Surgeons score of 3.5%, 14 (3%) suffered a MACE within 30 days. Rates of MACE were low in all 4 groups (1.7%, 2.5%, 2.6%, 5.1%, respectively) with no statistically significant difference in the different PLR groups (p = 0.46). This nonsignificant association was supported by univariate logistic regression analysis of PLR as a continuous variable (odds ratio 1.01, p = 0.55). Using multivariable logistic regression analysis accounting for age, gender, self-expanding valve, and procedural risk, a higher PLR did not correlate with MACE (odds ratio 1.01, p = 0.60). In this study of a large cohort of TAVI patients, elevated preprocedure PLR was not independently associated with MACE after TAVI. This is a novel finding in comparison with previous studies.

Periprocedural Myocardial Injury and Coronary Artery Disease in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND/PURPOSE: PPMI and CAD are common in patients undergoing TAVR. Despite several studies evaluating their interaction as well as the influence these factors play on outcomes, there remains no consensus. We sought to evaluate the impact of peri-procedural myocardial injury (PPMI) and incidental coronary artery disease (iCAD) on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS/MATERIALS: We analyzed prospective data from 400 patients undergoing TAVI for severe aortic stenosis between 2008 and 2018 to determine rates of PPMI (troponin 15× the upper limit of normal) and iCAD (≥50% stenosis) and their impact on long-term mortality. RESULTS: Mean age was 83 ± 6 years; 45% were female. PPMI was observed in 65% (254/400). On multivariable logistic regression analysis, higher left ventricular ejection fraction (LVEF) (OR 1.04, 95%CI 1.01-1.06, p = 0.002), and first generation valves (OR 3.00, 95%CI 1.75-5.15, p < 0.001) were independently associated with PPMI, while oral anticoagulation was inversely associated (OR 0.48, 95%CI 0.28-0.82, p = 0.007). PPMI was not associated with 30-day, 1-year or long-term mortality. After excluding previous bypass grafting, iCAD was observed in 40% (129/324). In patients with iCAD, PCI was associated with reduced long-term mortality compared to medical management in adjusted analysis (OR 0.37, 95%CI 0.16-0.88, p = 0.03). CONCLUSIONS: PPMI and iCAD in patients undergoing TAVR are common. PPMI is associated with older generation valves and higher LVEF rather than traditional cardiovascular risk factors. In our study, PPMI was not associated with long-term mortality. However, in patients with iCAD, PCI was associated with reduced long-term mortality compared to medical management.

Thromboelastography to Assess Coagulopathy in Traumatic Brain Injury Patients Undergoing Therapeutic Hypothermia.

Therapeutic hypothermia has been a treatment option for patients with severe traumatic brain injury (TBI) for many years. There has, however, been uncertainty whether hypothermia in this context also increased clinical bleeding risk, perhaps due to platelet dysfunction. Standard coagulation tests do not allow accurate assessment of in vivo coagulation. We studied specific coagulation abnormalities in patients undergoing therapeutic hypothermia for severe TBI using bedside thromboelastography (TEG).We studied 20 patients with severe blunt TBI from a single tertiary ICU who were enrolled in the prophylactic hypothermia to lessen traumatic brain injury (POLAR) trial. Ten patients had been randomized to hypothermia, and 10 were controls receiving normothermic standard care. TEG was undertaken during and after therapeutic hypothermia, and at the same time points in controls. Coagulation profiles were then compared between the hypothermic and control patients, and also between hypothermia and later normothermia in the study patients. Patients were primarily young (mean age 34 years) and male (85%). Measures of injury severity, including Glasgow coma score and injury severity scale, were not different between groups. Using TEG, the median alpha angle was reduced in hypothermic patients compared with controls (69.2° vs. 72.0°, p = 0.02), although both were within the normal range. LY30 was also reduced (0.0% vs. 0.5%, p < 0.01). Both differences persisted when hypothermic patients were compared with themselves during later normothermia. Therapeutic hypothermia during severe TBI causes a small decrease in the rate of clot formation. However, this decrease is within the normal range, and is unlikely to be clinically significant.

Long-Term Outcomes Stratified by Body Mass Index in Patients Undergoing Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) is emerging as the default strategy for older patients with severe, symptomatic, and trileaflet aortic stenosis. Increased body-mass index (BMI) is associated with a protective effect in patients undergoing percutaneous coronary intervention. We assessed whether elevated BMI was associated with a similar association in TAVI. We evaluated prospectively collected data from 634 patients who underwent TAVI at 2 centers from August 2008 to April 2019. Patients were stratified as normal weight (BMI 18.5 to 24.9 kg/m2, n = 214), overweight (25 to 29.9 kg/m2, n = 234), and obese (>30 kg/m2, n = 185). Outcomes were reported according to VARC-2 criteria. Mortality was assessed using Cox proportional hazards regression analysis (median follow-up 2 years). Kaplan-Meier analysis was used to estimate cumulative mortality. Baseline differences were seen in age (85 vs 84 vs 82, p <0.001), STS-PROM score (4.3 vs 3.4 vs 3.6, p <0.001), sex (50% vs 36% vs 55% female, p <0.001), clinical frailty score (p = 0.02), diabetes (21% vs 29% vs 40%, p <0.001), and presence of chronic obstructive pulmonary disease (COPD) (13% vs 13% vs 23%, p = 0.009). On multivariable analysis there was no mortality difference between normal and obese patients (hazard ratio [HR] 0.70, confidence interval [CI] 0.46 to 1.1 p = 0.11), however overweight patients had significantly lower mortality (HR 0.56 CI 0.38 to 0.85, p = 0.006). Variables independently associated with increased mortality were increasing age, male sex, COPD, previous balloon valvuloplasty, and higher STS-PROM. In conclusion, overweight patients have lower long-term mortality when compared with normal weight and obese patients undergoing TAVI.

Impact of Gender on Transcatheter Aortic Valve Implantation Outcomes.

Previous studies indicate that women who underwentwho underwent transcatheter aortic valve implantation (TAVI) have poorer 30-day outcomes compared with men. However, the effect of gender as a prognostic factor for long-term outcomes following TAVI remains unclear. Between 2008 and 2018, all patients (n = 683) who underwent TAVI in 2 centres in Melbourne, Australia were prospectively included in a registry. The primary end-point was long-term mortality. The secondary end points were Valve Academic Research Consortium-2 (VARC-2) in-hospital complications and mortality at 30-days and 1-year. Of 683 patients, 328 (48%) were women. Women had a higher mean STS-PROM score (5.2 ± 3.1 vs 4.6 ± 3.5, p < 0.001) but less co-morbidities than men. Women had a significantly higher in-hospital bleeding rates (3.3% vs 1.0%, Odds Ratio 4.21, 95% confidence interval [CI] 1.16 to15.25, p = 0.027) and higher 30-day mortality (2.4% vs 0.3%, hazard ratio [HR] 8.75, 95% CI 1.09 to 69.6, p = 0.040) than men. Other VARC-2 outcomes were similar between genders. Overall mortality rate was 36% (246) over a median follow up of 2.7 (interquartile rang [IQR] 1.7 to 4.2) years. Median time to death was 5.3 (95% CI 4.7 to 5.7) years. One-year mortality was similar between genders (8.3% vs 7.8%), as was long-term mortality (HR = 0.91, 95% CI 0.71 to 1.17, p = 0.38). On multivariable analysis, female gender was an independent predictor for 1-year mortality (HR = 2.33, 95% CI 1.11 to 4.92, p = 0.026), but not long-term mortality (HR = 0.78, 95% CI 0.54 to 1.14, p = 0.20). In the women only cohort, STS-PROM was the only independent predictor of long-term mortality (HR 1.88, 95% CI 1.42 to 2.48, p < 0.001). In conclusion, women had higher rates of peri-procedural major bleeding and 30-day mortality following TAVI. However, long-term outcomes were similar between genders.

Comparison of Early Outcomes in Patients at Estimated Low, Intermediate and High Risk Undergoing Transcatheter Aortic Valve Implantation: A Multicentre Australian Experience.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been shown to be a safe and effective alternative to surgical aortic valve replacement (SAVR) in high- and intermediate-risk patients with severe aortic stenosis. TAVI for patients at lower risk of periprocedural mortality has not been extensively investigated. We aimed to describe outcomes in low-, intermediate- and high-risk patients undergoing TAVI in a multicentre Australian study. METHODS: We evaluated data from 601 patients who underwent TAVI at two hospitals in Melbourne, from August 2008 to February 2018. Patients were stratified according to low risk (STS <4%), intermediate risk (Society for Thoracic Surgeons [STS] 4.0-7.9%) and high risk (STS >8%). Outcomes were reported according to Valve Academic Research Consortium-2 (VARC-2) criteria. RESULTS: Mean age was 84±5 years and 49% were female. Two hundred and eighty-five (285) (47%) patients were low-risk, 243 (40%) were intermediate risk and 73 (12%) were high risk. Thirty-day (30-) mortality was low in all three groups (1.1%, 1.7% and 1.4%, respectively, p=0.8). Similarly, patients had a low risk of disabling stroke (0.4%, 1.3%, 0%, p=0.8). Rates of post-procedural permanent pacemaker were also similar (21%, 27%, 26%, p=0.5). At least moderate aortic regurgitation occurred in 9% of patients at discharge with no significant differences between groups. CONCLUSIONS: In this large Australian multicentre cohort of TAVI patients, 30-day mortality, and post-procedural outcomes were excellent and similar across the patient-risk spectrum. Our study offers further support for the safety of TAVI in low-risk populations and demonstrates the limitations of the STS score.