Enhancing pre-transplant cardiac assessment: Validation and utility of the CAD-LT score with CCTA in liver transplant candidates.

BACKGROUND: Coronary computed tomography angiography (CCTA) is increasingly being used in the preoperative workup for liver transplantation (LT). We sought to assess the utility of integrating CCTA with the novel CAD-LT (Coronary Artery Disease in Liver Transplantation) score and its impact on reducing the need for invasive coronary angiography prior to LT. METHODS: We conducted a retrospective cohort study of consecutive patients (age ≥ 18 years) who underwent CCTA for LT workup between 2011 and 2018 at the Victorian Liver Transplant Unit, Melbourne, Australia. CAD-LT scores, a traditional risk factor-based criteria, were calculated, and patients stratified as low-, intermediate- or high-risk. RESULTS: Overall, 229 patients underwent CCTA. The mean age was 66 ± 5 years (82% male) with a modest-to-high risk factor burden (diabetes, 53%; hypertension, 46%; current or former smoker, 62%). The mean CAD-LT score of our cohort was 12.4 ± 4.0. No patients were classified as low-risk, 49 patients (21.4%) were deemed intermediate-risk and 180 patients (78.6%) were deemed high-risk. A high CAD-LT score (≥ 9) showed high sensitivity (95.3% [95% CI 86-98%]) and modest specificity (27.8% [95% CI 21-35%]) for the detection of obstructive coronary artery disease on CCTA, with a negative predictive value of 94%. Following multidisciplinary discussions, only 41 patients (18%) of patients proceeded to ICA of which 27% received percutaneous coronary intervention. CONCLUSIONS: The use of CCTA in patients deemed intermediate- to high-risk by the CAD-LT score has the potential to reduce the need for invasive coronary angiography in patients undergoing LT workup.

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.

Natural History and Clinical Outcomes After ST-Segment Elevation Myocardial Infarction Without Stent Insertion.

After restoration of coronary perfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI), discrete severe stenotic coronary lesions are not always apparent. There remains ambiguity whether drug-eluting stent (DES) insertion or initial medical management is best practice. We sought to assess short-term clinical outcomes in patients presenting with STEMI without initial stent insertion. Patients who underwent percutaneous coronary intervention for STEMI between 2014 and 2020 were prospectively enrolled and assessed for inclusion. Patients presenting with in-stent restenosis or stent thrombosis, or who did not survive to hospital discharge were excluded. Of 13,871 patients presenting, 456 (3.3%) were treated without initial stenting. These patients were older than those treated with DES (66.1 ± 13.6 vs 62.3 ± 12.4 years, p <0.001), had higher rates of diabetes (23.5% vs 16.0%, p <0.001) and previous revascularization with either percutaneous coronary intervention (14.0% vs 7.3%, p <0.001) or coronary artery bypass graft (3.5% vs 1.8%, p = 0.008). Thirty-day mortality was elevated in patients treated without stenting compared to those receiving DES (4.2% vs 0.9%, p <0.001), as were rates of myocardial infarction (1.3% vs 0.5%, p = 0.026) and major adverse cardiac events (10.5% vs 2.4%, p <0.001). After propensity matching, a trend toward increased mortality remained (4.2% vs 2.0%, p = 0.055). In conclusion, a no-stenting initial strategy, compared with DES insertion, is associated with increased 30-day mortality in those presenting with STEMI without severe stenosis. These data suggest when appropriate, current-generation DES insertion should be undertaken.

Prediction of Perioperative Cardiovascular Events in Liver Transplantation.

BACKGROUND: Hepatorenal syndrome (HRS) is a serious complication of liver cirrhosis with poor survival in the absence of liver transplantation (LT). HRS represents a state of profound circulatory and cardiac dysfunction. Whether it increases risk of perioperative major adverse cardiovascular events (MACE) following LT remains unclear. METHODS: We performed a retrospective cohort study of 560 consecutive patients undergoing cardiac workup for LT of whom 319 proceeded to LT. All patients underwent standardized assessment including dobutamine stress echocardiography. HRS was defined according to International Club of Ascites criteria. RESULTS: Primary outcome of 30-day MACE occurred in 74 (23.2%) patients. A significantly higher proportion of patients with HRS experienced MACE (31 [41.9%] versus 54 [22.0%]; P = 0.001). After adjusting for age, model for end-stage liver disease score, cardiovascular risk index, history of coronary artery disease, and a positive stress test, HRS remained an independent predictor for MACE (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.13-5.78). Other independent predictors included poor functional status (OR, 3.38; 95% CI, 1.41-8.13), pulmonary hypertension (OR, 3.26; 95% CI, 1.17-5.56), and beta-blocker use (OR, 2.56; 95% CI, 1.10-6.48). Occurrence of perioperative MACE was associated with a trend toward poor age-adjusted survival over 3.6-year follow-up (hazard ratio, 2.0; 95% CI, 0.98-4.10; P = 0.057). CONCLUSIONS: HRS, beta-blocker use, pulmonary hypertension, and poor functional status were all associated with over a 2-fold higher risk of MACE following LT. Whether inclusion of these variables in routine preoperative assessment can facilitate cardiac risk stratification warrants further study.

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.

Inducible Left Ventricular Outflow Tract Obstruction in Patients Undergoing Liver Transplantation: Prevalence, Predictors, and Association With Cardiovascular Events.

BACKGROUND: Inducible left ventricular outflow tract obstruction (LVOTO) is often encountered in liver transplantation (LT) candidates during cardiac workup. While the impact of LVOTO on adverse cardiovascular hemodynamics is well reported, it is unclear whether it predisposes to perioperative cardiovascular complications. METHODS: Consecutive patients with end-stage liver disease undergoing dobutamine stress echocardiography (DSE) were evaluated at an LT center between 2010 and 2017. Perioperative major adverse cardiovascular events (MACEs) at 30 days and all-cause death were recorded from a prospectively maintained LT database. RESULTS: We evaluated 560 patients who underwent DSE during LT workup, with LVOTO identified in 24.3% (n = 136). Of these, 309 patients progressed to transplant. Patients with LVOTO demonstrated a lower peak systolic blood pressure (SBP) and an overall reduction in SBP on DSE. A total of 85 MACEs were recorded in 72 patients (23.3%) including 3 deaths, 19 cases of heart failure, 11 cardiac arrests, 8 acute coronary syndromes, and 44 arrhythmias. MACE occurred in 15/64 patients (23.4%) with LVOTO and 57/245 (23.3%) without (P = 0.92). There was an increased risk of perioperative cardiac arrest in patients with LVOTO (7.4% versus 2.4%, P = 0.04). Intraoperatively, patients with LVOTO required higher doses of vasopressors (P = 0.01) and received greater volumes of fluid (10.5 ± 8.1 versus 8.4 ± 6.4 L, P = 0.03). CONCLUSIONS: Patients with end-stage liver disease and LVOTO demonstrate a reduction in SBP during physiological stress that may translate to hemodynamic instability during LT. LVOTO was not associated with an increased rate of perioperative MACE or death.

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.

Epidemiology of infections and antimicrobial use in Greek Neonatal Units.

OBJECTIVE: To describe the epidemiology of neonatal infections and of antimicrobial use in Greek Neonatal Units (NNUs) in order to develop national, evidence-based guidelines on empiric antimicrobial use for neonatal sepsis in Greece. DESIGN: Retrospective analysis of prospectively collected infection surveillance data from 2012 to 2015, together with a Point Prevalence Survey (PPS) on antimicrobial use and the collection of data on local empiric antimicrobial policies. SETTING: 16 NNUs in Greece participating in the neonIN infection surveillance network PATIENTS: Newborns in participating NNUs who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of antibiotics. RESULTS: 459 episodes were recorded in 418 infants. The overall incidence of infection was 50/1000 NNU-admissions. The majority of episodes were late-onset sepsis (LOS) (413, 90%). Coagulase-negative Staphylococci (80%) were the most common Gram-positive organisms causing LOS and Klebsiella spp (39%) the most common Gram-negative. Nearly half (45%) of the Klebsiella spp were resistant to at least one aminoglycoside. The PPS revealed that 196 of 484 (40%) neonates were on antimicrobials. The survey revealed wide variation in empiric antimicrobial policies for LOS. CONCLUSIONS: This is the largest collection of data on the epidemiology of neonatal infections in Greece and on neonatal antimicrobial use. It provides the background for the development of national evidence-based guidelines. Continuous surveillance, the introduction of antimicrobial stewardship interventions and evidence-based guidelines are urgently required.

Epidemiology of UK neonatal infections: the neonIN infection surveillance network.

OBJECTIVE: To describe the epidemiology of neonatal infection over the past decade in UK neonatal units. DESIGN: Retrospective analysis of prospectively collected infection surveillance network data from 2005 to 2014. SETTING: 30 neonatal units in the UK. PATIENTS: Newborns on participating neonatal units who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of appropriate antibiotics. RESULTS: 2171 episodes of neonatal infection in 1922 infants were recorded. The incidence of infection was 6.1/1000 live births and 48.8/1000 neonatal admissions (2.9 and 23.5 respectively if coagulase-negative staphylococci (CoNS) cultures excluded). The incidence of infection showed a statistically significant reduction over time with reductions in the rates of both early-onset sepsis (EOS) and late-onset sepsis (LOS).The majority of episodes (76%) represented LOS (diagnosed > 48 hours after birth), and infection was more common in premature (<37 weeks gestation) and low birth weight (<2500 g) neonates (84% and 81%, respectively). Commonly identified pathogens included group B streptococci (43%) and Escherichia coli (18%) for EOS, while E. coli (15%), Staphylococcus aureus (14%) and CoNS were prominent causes of LOS. CONCLUSIONS: This paper describes the epidemiology of neonatal infection in the UK over the past decade. These data enable benchmarking of practice and inform areas of future research and guideline development. The results support the hypothesis that the introduction of infection prevention care bundles and antibiotic stewardship programmes in the UK has reduced the burden of LOS.

Antimicrobial resistance in UK neonatal units: neonIN infection surveillance network.

OBJECTIVE: To define the susceptibilities of the common causative pathogens of neonatal sepsis in the UK. DESIGN: Retrospective analysis of the prospectively collected neonIN infection surveillance network data between 2005 and 2014. SETTING: 30 neonatal units in the UK. PATIENTS: Newborns admitted to participating neonatal units who return a positive blood, cerebrospinal fluid or urine culture and are treated with at least 5 days of appropriate antibiotics. RESULTS: 1568 isolates with recorded antimicrobial data were collected including 328 early-onset sepsis (EOS) isolates and 1240 late-onset sepsis (LOS) isolates. The majority of EOS pathogens (>92%) were susceptible to the four empirical commonly used antimicrobial combinations (eg, 93% for benzylpenicillin/gentamicin), while LOS pathogens demonstrated higher levels of resistance (eg, 89% for flucloxacillin/gentamicin). Among infants<1500 g and <32 weeks gestation, an amoxicillin/gentamicin combination demonstrated a trend towards improved coverage of EOS isolates than benzylpenicillin/gentamicin (93% vs 86%, p=0.211). CONCLUSIONS: This analysis provides insights into the patterns of antimicrobial resistance among UK neonatal pathogens. These data will inform areas of future research and can be used to update national evidence-based guidelines on antimicrobial usage.

The current and future roles of neonatal infection surveillance programmes in combating antimicrobial resistance.

Neonatal sepsis is an important cause of morbidity and mortality, particularly in premature or low birth weight babies. Hospital-acquired blood stream infections represent a significant and largely preventable cause of disease in this population. Neonatal units have been identified as a common site for the development and transmission of antimicrobial-resistant pathogens, a significant issue in modern medicine. Neonatal surveillance programmes collect prospective data on infection rates and may be used to optimise therapy, benchmark practice and develop quality improvement programmes. Despite this, the number of networks is relatively few and these are largely concentrated in resource-rich nations. Furthermore, surveillance definitions may vary between programmes impairing our ability to draw comparisons between them. Better harmonisation is required between networks to ensure that they achieve their potential as a valuable tool for benchmarking of hospital-acquired infection rates between units.