Acute Failure Research Articles

Kidney status and events preceding death in heart failure: A real world data study on 18,456 patients with heart failure

Abstract Background Despite advancements in heart failure (HF) management, kidney dysfunction remains a significant clinical challenge, and is associated with higher mortality rates and other adverse outcomes. However, there are few studies of kidney events preceding death in patients with HF in the real world. Methods Using registry-based data, the prevalence of kidney events preceding death in patients with HF over the period 2014-2018 in Denmark. All deaths in patients with a diagnosis of HF within the previous 10 years were included. Kidney events occurring during within 1 year of death compromised of: acute kidney injury, chronic renal replacement therapy, sustained eGFR<15 mL/min/1.73 m2, or renal transplantation. The prevalence of kidney events preceding death was calculated and different subgroups were compared. Results Among the 18,586 HF patients who died, a total of 3107 (16.7%) experienced kidney events during within 1 year of death. The prevalence of HF patients with kidney events before death was 15.5% for acute kidney injury, 5.8% for chronic renal replacement therapy, 7.4% for an eGFR<15 mL/min/1.73 m2, and 0.18% for renal transplantation (see Figure 1). Acute kidney injury episodes were frequently observed in the last month before death (7.5%) (Figure 2). Age-specific analysis revealed a higher proportion of deaths associated with kidney dysfunction in patients under the age of 65 years compared to those aged 80 years and above (24.3% vs 13.4%). Furthermore, male sex, death in-hospital, reduced pre-existing kidney function, a higher degree of frailty, and lower educational status were associated with higher frequency of death associated with kidney dysfunction. Conclusion In this real-world study, a significant proportion of deaths among HF patients were associated with kidney dysfunction, particularly with acute kidney injury. Further research and awareness of renal complications are necessary to improve outcomes in this population.

Adverse events following transcatheter aortic valve implantation (TAVI) in patients with amyloidosis: observations from a global federated network

Abstract Background A high proportion of patients with aortic stenosis are affected by cardiac amyloidosis, but there is a paucity of data describing the effect of amyloidosis on the clinical course of patients who underwent transcatheter aortic valve implantation (TAVI). Purpose To assess the one-year risk of adverse events following TAVI in patients with amyloidosis. Methods Retrospective study using data from a large multinational electronic health record network (TriNetX). Patients aged 18 years or older who underwent TAVI between 2005 and 2022 were included in the analysis. The patients were categorised in two groups based on the presence of amyloidosis (ICD-10-cm code E85). Primary outcome was the one-year risk of the composite of emergency department (ED) admission, acute heart failure (HF), stroke, conduction system disease, pacemaker (PM) implantation, acute kidney injury, and all-cause death. Secondary outcomes were the risks for each component of the composite outcome. We used Cox regression analysis to calculate hazard ratio (HR) and 95% confidence interval (CI) after propensity score matching (PSM) 1:1. Results We identified 477 TAVI recipients with a diagnosis of amyloidosis (age 78.6±8.1 years, 31.4% females) and 43,379 TAVI patients without a diagnosis of amyloidosis (78.1±8.8, 40.2% females). Before PSM, patients affected by amyloidosis were more likely to be Black or African American and had a higher prevalence of cardiovascular risk factors compared to TAVI patients without amyloidosis. After PSM, patients with a diagnosis of amyloidosis showed a higher one-year risk of composite outcome (HR 1.28, 95%CI 1.10-1.49) compared to those who underwent TAVI without amyloidosis. Regarding secondary outcomes, amyloidosis patients had a higher risk of ED admission (HR 1.41, 95%CI 1.13-1.75), acute HF (HR 1.56, 1.23-1.99), stroke (HR 1.55, 1.04-2.32), conduction system disease (HR 1.27, 1.04-1.55), PM implantation (HR 1.55, 1.06-2.28), but not acute kidney injury (HR 1.11, 0.84-1.48) and all-cause death (HR 0.98, 0.66-1.45). Conclusion Among patients undergoing TAVI, those affected by amyloidosis are at higher risk of adverse events in the first year after TAVI. More studies are needed to define the exact role of amyloid fibrils in structural valve deterioration and to elucidate whether subtypes of amyloidosis have a different impact on patients’ outcomes following TAVI.Risk of composite outcome following TAVI

Research Progress on Acute Kidney Injury in Patients with Cardiogenic Shock Undergoing Venoarterial Extracorporeal Membrane Oxygenation

Cardiogenic shock (CS) is a life-threatening syndrome characterized by peripheral hypoperfusion and organ dysfunction caused by primary heart disease. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a temporary mechanical circulatory support device for CS, used in cases of profound shock, biventricular failure, respiratory failure, and cardiac arrest that require urgent maximal support. While VA-ECMO provides effective tissue perfusion and ensures oxygen supply to organs, it is also associated with severe complications, among which acute kidney injury (AKI) is one of the most common and serious. To date, no comprehensive review has been conducted on the pathophysiology, influencing factors, and treatment of AKI associated with VA-ECMO. This paper aims to elaborate on the pathophysiological mechanisms, influencing factors, and treatment options for AKI in patients with CS undergoing VA-ECMO, providing clinical and nursing references.

Acute renal failure in patients with infective endocarditis

Abstract Background/Introduction Acute kidney failure (AKF) appears in a high percentage of patients with infective endocarditis (IE), becoming a complication related to the mortality of the disease and delayed recovery of patients. Purpose To investigate the factors that are related to the development of AKF in patients with IE. Methods Study of all cases of IE consecutively diagnosed in an university hospital between 2005 and 2021. A disease extension protocol was carried out using imaging tests and the levels of potentially nephrotoxic antibiotics were monitored. Furthermore, starting in 2010, a multidisciplinary committee (MC) was created to follow patients with EI. Factors potentially related to the development of AKF during hospital admission according to RIFLE criteria were analyzed using a binary logistic regression analysis. Results 305 cases were included, 96.7% of them meeting definitive IE criteria. The median age was 66 (54-74.5) years, 75.4% male. The most frequent microorganism was S. aureus (66; 21.6%), 172 (56.4%) underwent surgery and 107 patients (35.1%) died. 149 cases (45.3%) developed AKF, with no differences before (45.3%) and after the creation of the CM. The variables related in the multivariate analysis to the appearance of AKF were age (OR 1.01; 95% CI: 1.01-1.05; p= 0.006), baseline creatinine (OR= 1.53; 95% CI = 1.22-1.68; p<0.001). ), peripheral embolism (OR=1.86; 95% CI = 1.07-3.22; p= 0.027), the development of heart failure (OR=1.98; 95% CI = 1.12-3.22; p= 0.017) and left ventricular systolic dysfunction (OR= 4.02; 95% CI = 1.09-14.85; p= 0.037). None of the other variables analyzed, including the type of microorganism and the use of nephrotoxic antibiotics, were related to the development of AKF. Conclusions In a hospital center with a protocol for the study and treatment of infective endocarditis, the development of AKF is related to age, baseline creatinine, peripheral embolism, and the development of heart failure.

Proenkephalin improves risk prediction in acute coronary syndromes: derivation and external validation of the KID-ACS risk score

Abstract Background Early assessment of renal and mortality risk in patients with acute coronary syndromes (ACS) is essential to guide treatment decisions according to international guidelines. Circulating proenkephalin (PENK) is a stable opioid metabolite with fast response to changes in kidney function. Purpose This study examined the predictive value of PENK for acute kidney injury (AKI) and mortality in patients presenting with acute coronary syndromes (ACS). Methods Plasma PENK levels were measured using a validated sandwich immunoassay in a prospective multicentre ACS cohort from Switzerland (n = 4 787) and in validation cohorts from the UK (n = 1 141) and Czechia (n = 920). A biomarker-enhanced risk score for simultaneous prediction of both in-hospital acute kidney injury (AKI) and 30-day death (KID-ACS score) with model coefficients adjusted to the outcome was derived and externally validated. In the development of the in-hospital AKI model, patients from one participating study centre were reserved for external validation (Swiss validation cohort). Results Circulating PENK ranked among the top predictors of renal outcomes and mortality in patients with ACS. Accounting for established risk factors and risk models, circulating PENK levels at presentation were independently associated with in-hospital AKI (per log2 increase: adjusted odds ratio [OR] 1.56, 95% CI 1.14 – 2.12, P = 0.005) and with 30-day mortality (per log2 increase: adjusted OR 2.69, 95% CI 1.89 – 3.84, P < 0.001). Dynamic changes in PENK levels within the first 12-24 hours after presentation were strongly and independently associated with in-hospital AKI (increase vs. decrease: adjusted OR 2.83, 95% CI 1.98 – 4.05, P < 0.001). The simple 6-item KID-ACS risk score for in-hospital AKI and 30-day mortality integrates PENK levels at presentation and showed an AUC of 0.72 (95% CI 0.68 – 0.76) for in-hospital AKI, and of 0.91 (95% CI 0.87 – 0.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS had similarly high performance for in-hospital AKI (Swiss validation cohort: AUC 0.73, 95% CI 0.70 – 0.77; Czech validation cohort: 0.74, 95% CI 0.68 – 0.80) and 30-day mortality (UK validation cohort: AUC of 0.87, 95% CI 0.82 – 0.91; Czech validation cohort: 0.91, 95% CI 0.87 – 0.94). The simple 6-item KID-ACS score was non-inferior to established risk models and significantly outperformed the CA-AKI risk score in predicting in-hospital AKI (Zurich cohort: delta AUC 0.11, 95% CI 0.07 – 0.15, P = 0.001) and the GRACE 2.0 in predicting 30-day mortality (UK cohort: delta AUC 0.05, 95% CI 0.01 – 0.09, P = 0.027). Conclusions Circulating PENK was identified as independent predictor of in-hospital AKI and 30-day mortality in patients with ACS. The simple 6-item KID-ACS risk score integrates circulating PENK levels and provides a novel tool for simultaneous assessment of renal and mortality risk in patients presenting with ACS.Independent Predictive Value PENKPerformance and validation of KID-ACS

Association of cardiac amyloidosis with periprocedural complications in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: a systematic review and meta-analysis

Abstract Introduction Cardiac amyloidosis (CA) has been frequently observed in patients with aortic stenosis (AS). While transcatheter aortic valve replacement (TAVR) may be an option, the association of CA with risk of periprocedural complications has not been well evaluated. Purpose This study aimed to evaluate the association of CA with periprocedural complications after TAVR in patients with severe AS. Methods A literature search was performed for studies evaluating patients with severe AS undergoing AVR, comparing periprocedural safety endpoints for patients with and without CA. The primary endpoints were vascular complications and bradyarrhythmias post-TAVR requiring permanent pacemaker (PPM) implantation. Secondary endpoints included periprocedural acute kidney injury (AKI), cerebrovascular accidents (CVA), and major bleeding events. Endpoints were defined using the Valve Academic Research Consortium-2 criteria. The search was not restricted to time or publication status. Results 6 studies with 1,138 patients with severe AS (150 with CA, 988 without CA) met inclusion criteria. Mean age was 82 years, 52.4% were men, all except 1 study assessed only patients with ATTR CA. Echocardiographic mean aortic valve parameters included valve area of 0.718 cm2, mean gradient of 40.8, and peak velocity of 4.13 m/s. The mean left ventricular ejection fraction was 55.2%. The presence of CA was not associated with an increased risk of periprocedural vascular complications (OR 0.69, 95% CI 0.25-1.88; p=0.47). While a trend toward higher risk of periprocedural PPM implantation was observed in patients with CA, this finding did not reach statistical significance (OR 1.51; 95% CI 0.77-2.94; p=0.23). The presence of CA was not associated with increased risk of periprocedural AKI, CVA, or major bleeding (OR 1.3, 95% CI 0.32-5.3; p=0.72, OR 0.65, 95% CI 0.17-2.41; p=0.52; OR 0.55, 95% CI 0.16-1.87; p=0.34). Conclusion In the context of patients with severe AS undergoing TAVR, the presence of cardiac amyloidosis did not increase the risk of periprocedural complications, including vascular complications, AKI, CVA, or major bleeding. Although a trend toward a higher risk of bradyarrhythmias requiring PPM implantation was noted in patients with CA, further studies are warranted to confirm this observation. Overall, these findings contribute valuable insight into the safety profile of TAVR in the patients with CA.Figure 1Figure 2

Mortality rates in patients undergoing urgent versus elective transcatheter aortic valve replacement: a systematic review and meta-analysis

Abstract Background Patients with severe aortic stenosis (AoS) often present with acute heart failure and compensation, leading frequently to cardiogenic shock. Transcatheter Aortic Valve Replacement (TAVR) has been recently performed as a bailout treatment in such patients. The aim of our meta-analysis is to compare urgent TAVR to elective procedures. Methods We systematically screened three databases searching for studies comparing urgent versus elective TAVR. Primary endpoint is the 30-days mortality. Secondary endpoints included in-hospital mortality, device success, periprocedural vascular complications, 30-day stroke, 30-day acute kidney injury (AKI), permanent pacemaker implantation (PPM), moderate or severe paravalvular leakage and 30-day bleedings. Results Seventeen studies were included, with a total of 84,495 patients. Urgent TAVR was associated with an increased risk for 30-days mortality (RR: 2.53, 95% CI: 1.81 – 3.54), in-hospital mortality (RR: 2.67, 95% CI: 1.94 – 3.68), periprocedural vascular complications (RR: 1.91, 95% CI: 1.28 – 2.85) and AKI (RR: 2.83, 95% CI: 1.93 – 4.14), compared to elective procedure. No differences were observed in the rest secondary endpoints. Conclusions Urgent TAVR was associated with higher in-hospital and 30-day mortality, possibly driven by the increased incidence of AKI and vascular complications in urgent TAVR. The results highlight the importance of early TAVR in stable AoS patients.

Time course of plasma urea and urinary urea excretion in patients with a prolonged ICU stay

Whereas urinary creatinine excretion (UCE) is an established marker of muscle mass, both in critically ill and non-critically ill patients, analysis of urinary urea excretion (UUE) may allow estimation of proteolysis that is associated with critical illness. We evaluated the time courses of plasma urea and creatinine as well UUE and UCE in critically ill patients with a prolonged ICU stay. Our goal was to evaluate changes in plasma urea and creatinine in conjunction with their urinary excretion, to get a better understanding of urea handling in ICU patients. From 2002 to 2021, plasma urea and creatinine, UUE and UCE were determined in routinely obtained 24 h urine samples between ICU admission and day 30, in adult patients with an ICU-stay ≥ 28d. Urea-to-creatinine ratios in plasma and urine were calculated. Patients with stage 3 acute kidney injury (AKI) were excluded. Analyses were performed separately for females and males and for patients with and without acute renal failure to account for respectively differences in muscle mass and impaired renal function. Of 47,120 patients, who were admitted to the ICU between 2002 and 2021, 638 patients met the inclusion criteria. During the first 10 days mean ± SD plasma urea increased from 9.7 ± 6.0 mmol/L at ICU admission to 12.4 ± 7.9 mmol/L (P < 0.001) on day 11 and decreased afterwards with a rate of 0.1 mmol/l/d. UUE peaked at 590 ± 317 mmol/day on day 13 whereas UCE peaked already on day 4. Males had higher plasma urea, plasma creatinine, UUE and UCE than females. Plasma and urinary urea-to-creatinine ratio (UCR) stabilized after day 7, with a gradual increase in plasma UCR and urinary UCR between day 7 and day 30. Similar courses, although less pronounced, were seen in patients without AKI. The course of urea in critically ill patients is characterized by an initial rise of both plasma urea and urinary urea excretion, presumably due to increased catabolism of endogenous and exogenous protein in the first week of ICU admission. Subsequently, UUE and UCE declined steadily in a rate that was comparable to the known loss of muscle mass during ICU admission of approximately 1%/day.

Single arterial access versus standard access in TAVI: results from a large multicenter registry

Abstract Background The transfemoral approach has become the gold standard primary access for transcatheter aortic valve implantation (TAVI) due to low complication rates. An additional secondary access (ScA) is used for angiographic guidance of the procedure. Recently, small, single-center studies demonstrated feasibility of single-access for transfemoral TAVI without a secondary access. However, comparative and large-scale data are missing. Purpose We assessed vascular and bleeding complications of ScA and Single access (SA) approaches in a large multicenter registry to evaluate both strategies. Methods The PULSE registry (Plug or sUture based vascuLar cloSurE after TAVI) retrospectively evaluated data of 10,120 patients who underwent transfemoral TAVI at 10 high-volume German heart centers from 2016 to 2021. In 9,457 patients who qualified for analysis ScA (80.7% femoral, 19.3% radial) were performed in 8709 (92%) and SA in 748 (8%). Outcomes were evaluated in accordance with the Valve Academic Research Consortium (VARC-3) definitions. Results Median age was 81.9[IQR 78.2, 85.1] years and 48.9% of patients were female (median logistic EuroSCORE II: 3.3% [IQR 2.1, 5.6]). Peripheral artery disease was comparable between groups (13.5 vs. 14.0%, p=0.73). While overall major access-related vascular complications did not differ significantly (6.1% vs. 4.8%, p=0.20), there was a higher incidence of minor complications for ScA compared to SA (9.0% vs. 2.8%, p&amp;lt;0.001). Secondary access complications amounted to 2.7% in the ScA group and were mainly characterized as bleeding (1.2%) and pseudoaneurysms (1.2%) mostly treated conservatively (1.2%), yet in some cases surgical repair was needed (0.8%). No significant difference was observed regarding type III/IV bleeding (4.1% vs. 4.3%, p=0.91), stroke rate (2.4% vs. 3.6%, p=0.05), stage III/IV acute kidney injury (2.4% vs. 2.4%, p=1.00) or all-cause 30-day mortality (5.8% and 5.7%, p=0.99) for ScA compared to SA groups. Conclusion In patients treated with transfemoral TAVI, a single access approach was associated with lower rates of minor access-related vascular complications without compromising overall outcomes, suggesting potential benefits of a minimally-invasive TAVI approach with the omission of additional vascular access.

Outcome of early versus late CRRT in critically ill patients with acute kidney injury

AKI is a common but serious complication in acutely unwell patients and results in high morbidity and mortality. This review considers the issue of the effects of early versus late initiation of CRRT on patient outcomes. Early CRRT may be defined as inception shortly after the diagnosis of AKI has been established, especially in the case of signs related to fluid overload or severe electrolyte disturbances. Early CRRT would offer potential benefits like an improved survival rate, complications avoided as regards pulmonary edema and cardiac failure, better nutritional support, and a reduced need for more intensive renal replacement support later. On the other hand, late CRRT is performed in clinical practice when more severe AKI manifestations have occurred, which are usually associated with higher mortality and complications due to fluid overload and metabolic disturbances. Key studies referred to report worse outcomes for late initiation, considering higher multi-organ failure and prolongation of the length of stay in the ICU. Most observational studies report better outcomes with early CRRT, while randomized controlled trials exhibit variable results, with some finding no clinically significant difference in mortality between the timing of early and delayed initiation.

Vericiguat in heart failure patients: analyzing safety, tolerability, and quality of life via meta-analysis of randomized controlled trials

Abstract Background Heart failure (HF) poses a significant burden on global healthcare systems, necessitating effective therapeutic interventions. Vericiguat, a novel agent targeting soluble guanylate cyclase, has emerged as a potential treatment for HF. Purpose To understand its impact on patient outcomes, including safety, tolerability, and quality of life (QoL). Methods A comprehensive meta-analysis was conducted, encompassing four randomized controlled trials (RCTs) identified through Cochrane CENTRAL, Ovid Medline R, Pubmed, and Web of Science databases up to December 1, 2023. The primary efficacy outcome, Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (OSS), and the primary safety outcome, drug-related serious adverse events (AEs), were analyzed. Pooled mean differences (MD) and risk ratios (RR) were calculated using inverse variance common-effect model. Results The meta-analysis encompassed 5947 patients across the four RCTs. Our findings indicated that vericiguat did not demonstrate a significant beneficial effect on KCCQ-OSS (MD -0.13, 95% CI -1.32 to 1.05), suggesting no substantial impact on overall QoL, despite a statistically significant improvement in the KCCQ-Physical Limitation Score (PLS) (MD 3.74, 95% CI 0.24 to 7.24) compared to placebo. Notably, vericiguat exhibited a favorable safety and tolerability profile, with comparable risk for AEs leading to death (RR 1.32, 95%CI, 0.58 to 3.03), withdrawal due to AEs (RR 1.08, 95% CI 0.88 to 1.32) or serious AEs (RR 1,18, 95%CI, 0,50; 2,80), renal and urinary disorders (RR 0.99, 95% CI 0.88 to 1.11), symptomatic hypotension (RR 1.17, 95% CI 0.98 to 1.40), and acute kidney injury (RR 1.04, 95% CI 0.83 to 1.31) compared to placebo. Conclusion Vericiguat demonstrates promising safety and tolerability profiles in patients with HF. While our analysis reveals significant improvement in KCCQ-PLS, indicating enhanced physical limitation scores, the lack of statistically significant impact on overall QoL raises questions about its comprehensive efficacy. These findings underscore the need for further research to elucidate the holistic impact of vericiguat on patient-reported outcomes in heart failure management.Forest plot of quality of life outcomesForest plot of safety outcomes

Cardio-renal syndromes in patients admitted with ST-elevation myocardial infarctions: Incidence and impact on renal and overall outcome

Abstract Background The importance of cardiorenal syndromes (CRS) in patients with heart failure has been shown in many studies. However, there is little data on the impact of a combination of heart failure and renal disease in patients with acute myocardial infarctions. Aim of the present study was to investigate, how often a combination of heart failure (HF) and kidney disease (KD) could be detected in patients with ST-elevation myocardial infarctions and to estimate its impact on outcome. Methods All patients from a German heart center, admitted with STEMI between 2006 and 2022 were analysed. CRS was defined as a combination of heart failure (HF: left ventricular ejection fraction (LV-EF&amp;lt;40%), HF) and kidney disease (KD: GFR at admission &amp;lt;60 ml/min). Patients were assigned in a 2x2 model: HF-/KD-, HF-/KD+, HF+/KD-, HF+/KD+. Outcome analysis was adjusted by confounders in a multivariate Cox-regression-model. Acute kidney injury (AKI) was calculated by AKIN-criteria (KDIGO) Results Of a total of 8276 STEMI-patients included in the study 5696(69%) had a preserved LV-EF and no KD (HF-/KD-), 1354 (16%) a preserved LV-EF and KD (HF-/KD+), 743 (9%) a reduced LV-EF and no KD (HF+/KD-) and 483 (6%) both a reduced LV-EF and KD (HF+/KD+, CRS-Group). In the CRS-group patients were on average older (74.2±12 yrs. vs. 60.8±13 yrs., p&amp;lt;0.01), more likely to be female (36.9% vs. 23.1% in the control group, p&amp;lt;0.01) and more likely to be diabetics (31.0% vs. 16.8% in the control group, p&amp;lt;0.01). CRS was associated with higher rates of cardiogenic shock (41.5% vs. 8.7% in the control group) and higher rates of subsequent AKI with a 18x higher risk to develop AKIN-3 with or without the need for renal replacement therapy (RRT), (table, upper part). In patients with CRS in 11% of patients a temporal RRT was necessary vs. 0.5% in controls. Furthermore, in CRS-patients in-hospital and 1 year-mortality-rates were markedly higher (table, lower part). When adjusting outcomes for confounders (age, gender, CS, diabetes, anterior STEMI, 3 VD) the detrimental effect of CRS on outcome remained: AKIN-3/RRT: OR 16.5, 95% CI 7.5-30.0, p&amp;lt;0.01, In-hospital-mortality: OR 14.2, 95% CI 7.8-21, p&amp;lt;0.01, 1-year-mortality: HR 10.5, 95% CI 7.5-14.1, p&amp;lt;0.01. Conclusions In this analysis of registry data, cardiorenal disease could be detected in 6% of STEMI-patients, with higher rates in women and in diabetics. Patients with cardiorenal disease showed a more than 18-fold higher risk of suffering severe renal failure during the index event and a 24-fold higher risk of in-hospital death. Patients with either heart failure or renal disease were situated between the CRS and control group with regard to outcome. These results underline the additive effects of cardiac and renal disease.Table:Event rates by HF and KD group

Early- and mid-term outcomes following redo aortic surgeries: a retrospective cohort study

BackgroundRedo aortic surgeries are complex procedures known to be associated with increased morbidity and mortality compared to patients who undergo de novo aortic procedures. We aimed to report the survival and outcomes following redo aortic surgeries in our centre. We performed a retrospective cohort study of 77 patients who underwent redo aortic surgery between January 1st, 2018, and August 30th, 2023. The primary outcome of interest was operative mortality. Other secondary outcomes of interest included overall mortality, survival rates, and other peri-operative major adverse events. Survival analysis was performed and Cox- proportional hazard regression models were fitted to explore the relationship between exposure variables and outcomes of interest in the total cohort of patients.ResultsThe mean age of the total cohort was 64.22 ± 12.22 years with majority being males (n = 57, 69.3%). The most common indication for redo surgery was aortic aneurysm (n = 41, 53.2%) and majority of the patients had a first redo aortic surgery (n = 69, 89.6%). The rate of freedom from in-hospital mortality was 63.1% (95% confidence interval (CI) 35.4–100%). Overall survival rate during the 5-year study period was 73.1% (95% CI 62.6–85.4%) in the whole cohort. The factors found to be predictive of overall mortality were priority of surgery hazard ratio (HR) 3.48 (95% CI 1.20–10.05, p = 0.02), time to re-operation HR 0.89 (95% CI 0.81–0.99, p = 0.025), pre-operative chronic kidney disease HR 3.16 (95% CI 1.18–8.43, p = 0.022), need for mechanical circulatory support HR 12.7 (95% CI 4.23–38.12, P < 0.001), post-operative renal dysfunction requiring hemofiltration HR 4.03 (95% CI 1.50–10.79, p = 0.006), and post-op re-exploration HR 47.82 (95% CI 13.9–164.4, p < 0.001).ConclusionsOur study shows that short-term and mid-term outcomes following redo aortic surgery are favourable. The factors found to be associated with overall mortality include post-op re-exploration, renal dysfunction, use of post-op mechanical circulatory support, priority of surgery, and time to re-operation.Graphical Summary of outcomes following redo aortic surgery over a 5-year period (2018–2013). CI, confidence interval; HR, hazard ratio; CKD, chronic kidney disease, AKI, acute kidney injury, MCS, mechanical circulatory support.

Abnormally high plasma concentrations of M-4, the active metabolite of edoxaban, at the onset of acute kidney injury in a patient receiving rifampin and clarithromycin: a case report

BackgroundEdoxaban, the only factor Xa inhibitor with active metabolites, is metabolized by carboxylesterase-1 to its main active metabolite, M-4, which is a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) and is excreted in bile and urine. Because the area under the plasma concentration–time curve ratio of M-4 to parent compound is typically less than 10% in healthy subjects, M-4 is generally considered to exhibit negligible antithrombotic activity in patients treated with edoxaban. However, we identified a case in which drug interactions and kidney impairment led to a substantive increase in plasma M-4 concentrations.Case presentationThis case report involved a 68-year-old man with pancreatic cancer who was orally administered edoxaban tablets for prevention of thrombus formation in non-valvular atrial fibrillation, in addition to rifampin and clarithromycin (CAM) for treatment of mycobacterium avium complex lung disease. These medications were temporarily discontinued for a pancreaticoduodenectomy but were resumed 8 days post-surgery (POD8). On POD9, the patient developed acute kidney injury, and the trough concentrations of edoxaban and M-4 were 131.1 ng/mL and 115.8 ng/mL, respectively (M-4 ratio: 88.3%). On POD11, the M-4 trough concentration and M-4 ratio increased to 216.2 ng/mL and 186.2%, respectively. The plasma concentration of coproporphyrin-I, an endogenous biomarker of OATP1B1 activity, increased during this period.ConclusionsThis case suggests that in patients with impaired renal function taking edoxaban, co-administration of carboxylesterase-1 inducers such as rifampin and/or OATP1B1 inhibitors such as rifampin or clarithromycin may increase plasma concentrations of M-4 to clinically non-negligible levels.

Procedural and clinical outcomes according to ultrasound-guided access in TAVI: a propensity-matched comparative sub-analysis from the PULSE registry

Abstract Background Access-related vascular and bleeding complications during transcatheter aortic valve implantation (TAVI) are associated with significant morbidity and mortality. Ultrasound-guided (USG) puncture may reduce the incidence of these events, particularly in large-bore arterial access. However, large-scale data on this approach are limited and it has not yet fully been implemented into standard clinical practice during TAVI. Purpose We compared access-related vascular and bleeding complications in USG versus fluoroscopy-guided (FG) access from a large multicenter TAVI registry. Methods The PULSE registry (Plug or sUture based vascuLar cloSurE after TAVI) retrospectively evaluated data of 9,295 patients who underwent transfemoral TAVI at 10 high-volume German heart centers from 2016 to 2021. USG and FG access were performed in 1,992 (21.4%) and 7,303 (78.6%) patients, respectively. A propensity score was used to match 1,023 FG with 1,023 USG access patients in a 1:1 fashion. The primary endpoint was a composite of minor and major vascular complications at the TAVI-access site or bleeding type II-IV. Outcomes were evaluated in accordance with the Valve Academic Research Consortium (VARC-3) definitions. Results Mean age was 81.9±6.25 years and 48.0% of patients were female. Comorbidities and clinical variables were well-balanced in matched groups. The overall risk profile was comparable in USG vs. FG (mean EuroSCORE II: 3.4 [2.1, 6.4] vs. 3.6 [2.2, 5.7], p=0.54). The primary end point occurred in 12.0% in the USG and 17.7% in the FG group, p&amp;lt;0.001. While major large bore access-related vascular complications did not differ significantly (3.5% vs. 4.2%, p=0.49), there was a trend towards lower minor complications for USG compared to FG (5.9% vs. 7.8%, p=0.096). Large bore access-related bleeding occurred in 5.5% versus 7.8% (p=0.04) of patients. Endovascular balloon inflation was required in 0.6% and 3.3% (p&amp;lt;0.001) of all large-bore access vascular complications. Stroke (1.7% vs. 1.5%, p=0.86) and stage III/IV acute kidney injury (3.0% vs. 2.2%, p=0.42) were similar in both groups. Conclusion In patients treated with transfemoral TAVI, ultrasound-guidance for gaining access was associated with lower rates of access-related vascular complications or type II-IV bleeding. Endovascular treatment was required more frequently in case of a fluoroscopy-guided approach. These findings challenge the fact that most TAVI procedures were performed with fluoroscopy-guidance.

Intracranial haemorrhage following treatment for pulmonary embolism: analysis of the german nationwide inpatient sample

Abstract Background Intracranial haemorrhage (ICH) can be a life-threatening complication of pulmonary embolism (PE) and its treatment during the acute phase. Purpose To characterize patients hospitalized with PE and ICH by identifying risk factors across different treatment groups, and to detect temporal trends in a large nationwide sample. Methods The German nationwide inpatient sample was screened for patients admitted with PE during the period 2005-2020. All hospitalizations were stratified based on the occurrence of ICH and accordingly, risk factors for ICH were investigated (source: Research data center [RDC] of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations). Results Overall, 816,653 hospitalizations were included in the present study; among them, 2516 (0.3%) experienced an ICH event and 84,810 (10.4%) died in-hospital. The annual number of hospitalizations of patients admitted due to PE increased steadily from 38,749 in 2005 to 54,966 in 2020, whereas the incidence of ICH remained, despite annual fluctuations, largely stable over time, both in the entire study population and in the subgroup of patients with severe PE as defined by clinical and haemodynamic parameters (n=270,980 [33.2%]). ICH was overall more frequent after the seventh decade of life but, interestingly, no correlation with age was found amongst patients with severe PE (Figure 1). ICH in hospitalized PE patients was associated with an aggravated comorbidity burden mirrored by a higher Charlson Comorbidity Index (5.0 [interquartile range 4.0-7.0] vs. 4.0 [2.0-5.0], P&amp;lt;0.001). This was mainly driven by the higher prevalence of heart failure (27.3% vs. 19.4%, P&amp;lt;0.001) and acute or chronic kidney disease (27.6% vs. 18.1%, P&amp;lt;0.001) in patients with ICH. In addition, severe PE (OR 3.09 [95% CI 2.84-3.35], P&amp;lt;0.001), acute kidney injury (OR 3.60 [3.09-4.18], P&amp;lt;0.001), and particularly ischaemic stroke (OR 14.64 [12.61-17.00], P&amp;lt;0.001) were identified as independent predictors of ICH by multivariable logistic regressions. Overall, 27% of the ICH cases were related to systemic thrombolysis. In PE patients treated with systemic thrombolysis, age ≥70 years as well as female sex were independent predictors of ICH. Finally, ICH was independently associated with a substantial increase in case-fatality in patients hospitalized with PE (univariate OR: 5.38 [4.97-5.84], P&amp;lt;0.001; multivariable OR: 6.16 [5.64-6.72], P&amp;lt;0.001). Conclusions In this healthcare dataset of the German nationwide inpatient sample, the overall incidence of ICH remained low at 0.3% over the 15-year study period. Severe PE, age, comorbidity burden, kidney disease, heart failure and ischaemic stroke were independent risk factors for ICH.

Valve unit instead of intensive care unit admission after transcatheter edge-to-edge tricuspid valve repair

Abstract Background Standardization of periprocedural pathways reduces the length of hospital stay and thus healthcare costs and increases patient safety. Post-procedure admission to the intensive care unit (ICU) after transcatheter edge-to-edge tricuspid valve repair (T-TEER) has been the standard of care. Due to the COVID-19 pandemic related decline in high-care hospital beds, our center established primary admission to a dedicated general cardiologic care ward, the valve unit (VU). Aim To assess benefits and risks of admission to the VU instead of ICU after T-TEER. Methods This retrospective observational study included 270 consecutive patients who underwent T-TEER between March 2017 and June 2023 at our university hospital. Patients were admitted to the ICU post-procedure up to April 9th 2020 as standard (ICU-group, n = 53). Subsequent patients were planned for admission to a dedicated VU (VU-group, n = 217). We compared the groups and assessed length of hospital stay and in-hospital complications. In the VU-group, we examined unplanned transfer to the ICU (cross-over) and its predictors. Results Monitoring at the VU included continuous telemetric ECG-recording, oxygen saturation assessment, periodical blood pressure measurements and 24-hours physician presence. In contrast to the ICU, only non-invasive blood pressure measurements, less frequent laboratory controls and less intense fluid monitoring took place. The postinterventional hospital stay of patients with planned VU admission was significantly shorter compared to patients with planned ICU admission (median 4 (interquartile range (IQR) 3 - 5) vs. 4 (IQR 4 - 5) days, p = 0.030). Remarkably, overall complication rates were low and cardiogenic shock, infections, bleeding, vascular complications, delirium and acute kidney injury requiring dialysis were similar in both groups. 37 patients that were planned for VU had to cross over to unplanned ICU admission (17.1 %). Patients that had crossed over to unplanned ICU treatment had significantly higher risk for acute kidney injury (20.0 vs. 10.0%, p = 0.039) and in-hospital mortality (5.6 vs. 0%, p = 0.045). Higher systolic pulmonary artery pressure (sPAP) (OR 1.048, 95 %-CI 1.015 – 1.082, p = 0.003), NYHA functional class &amp;gt;= III (OR 9.176, 95 % CI 1.141 – 74.396, p = 0.037), and pre-interventional tricuspid regurgitation (TR) grade V (OR 2.941, 95 % CI 1.089 – 7.970, p = 0.033) were found to independently predict cross-over to unplanned ICU treatment. Conclusion Postinterventional admission to the VU instead of ICU after T-TEER shortens postprocedural hospital stay. A small proportion of had an unplanned transfer to ICU, which was accompanied by slightly higher complication rates. This cross-over affects patients with more advanced disease indicated by high pulmonary pressures, NYHA class and TR grade. Thus, admission to a valve unit is favorable for most patients after T-TEER, but those with advanced disease should be monitored more closely.

Baseline characteristics and outcomes of patients admitted to intensive cardiovascular care unit

Abstract Background Intensive Cardiovascular Care Unit (ICCU) is a crucial element of care for critically ill patients suffering from cardiovascular disease. Therefore, we aimed to provide data on the characteristics and outcomes of patients admitted to ICCU. Methods Data was obtained from One Intensive Cardiovascular Care Unit (One ICCU) Registry, a collaborative multicentre research network of ICCU. A total of 10 centres participated in this registry, eight centres were ICCU level III and the remaining were ICCU level II. Each participating centre collected data of patients admitted to ICCU from August 2021 until August 2023. Data recorded were demographics, past medical history, diagnosis, treatment, complications, outcome, and 30-day follow up. Only first ICCU admission data from each patient was analysed to prevent outcome-related bias from readmission data. Results 12,950 patients were included in the analysis of which 9308 (71.9%) were male and the median age was 59 (51-66) years. Most common diagnosis on admission was acute coronary syndromes (69.8%) followed by acute heart failure (34.6%) and arrhythmias (25.8%). Cardiovascular complication most frequently during ICCU stay was cardiogenic shock (18.9%) while for non-cardiovascular complication was acute kidney injury (17.4%). Cardiac arrest (61.2%), respiratory failure (43%), and sepsis (38%) were among the highest case fatality rates for ICCU complications. Overall mortality was found to be approximately 11.4%, 14.3%, and 15.2% for intra ICCU, in-hospital and 30-day mortality, respectively. Non-cardiovascular variables which were independently associated with 30-day mortality were pre-existing asthma (OR 2.12, CI 1.315 – 3.411, p=0.002) and chronic kidney disease (OR 1.67, CI 1.308 – 2.139, p&amp;lt;0.001), initial diagnosis of respiratory failure (OR 4.01, CI 3.373 – 4.773, p&amp;lt;0.001), haemorrhagic stroke(OR 3.46, CI 1.396 – 8.574, p=0.007), ischaemic stroke (OR 3.12, CI 2.248 – 4.345, p&amp;lt;0.001), sepsis (OR 2.00, CI 1.715 – 2.334, p&amp;lt;0.001), urinary tract infection (OR 1.60, CI 1.228 – 2.226, p=0.001) and pneumonia (OR 1.29, CI 1.120 – 1.482, p&amp;lt;0.001), as well as complications during ICCU stay which consisted of haemorrhagic stroke (OR 3.91, CI 1.062 – 14.414, p=0.040), respiratory failure (OR 2.91, CI 2.081 – 4.070, p&amp;lt;0.001), sepsis (OR 2.17, CI 1.686 – 2.790, p&amp;lt;0.001), ischaemic stroke (OR 1.84, CI 1.074 – 3.139, p=0.026), and urinary tract infection (OR 1.39, CI 1.039 – 1.851, p=0.026). Conclusion Patients admitted to our ICCU were relatively younger and the cause for ICCU admission was still predominated by acute coronary syndrome. Despite that, non-cardiovascular condition also warrants clinicians attention due to its significant role as predictors of mortality. Non-cardiac complications that arise during ICCU care also emphasize the importance of collaboration with specialists in other disciplines to improve patient’s outcomes.Diagnosis (A) and Case Fatality (B)Mortality Predictors at 30 days

Transcatheter versus surgical aortic valve replacement in patients younger than 65 years: analysis from the national inpatient sample database

Abstract Background Data on the relative utilization and outcomes of transcatheter aortic valve replacement (TAVR) versus surgical AVR (SAVR) in patients &amp;lt;65 years are limited. Purpose To compare the relative utilization and outcomes of TAVR versus SAVR in patients &amp;lt;65 years in the United States. Methods We queried the National Inpatient Sample (2016-2020) to identify patients &amp;lt;65 years hospitalized for isolated AVR. In-hospital outcomes of TAVR versus SAVR were compared using multivariable regression and propensity-matching analyses. Results Of 74,155 patients aged &amp;lt;65 years hospitalized for isolated AVR, 17,300 (23.3%) underwent isolated TAVR, and 56,855 (76.7%) underwent isolated SAVR. From 2016-2020, the use of TAVR increased, while the use of SAVR decreased in patients &amp;lt;65 years (both ptrend&amp;lt;0.01). Factors independently associated with TAVR selection in patients &amp;lt;65 years included female sex, congestive heart failure, pulmonary disease, renal failure, liver disease, cancer, and prior revascularization. Factors independently associated with SAVR selection included bicuspid aortic valve. After adjustment for baseline characteristics, TAVR was associated with lower odds of in-hospital mortality (adjusted odds ratio [aOR] 0.61, 95% confidence interval [CI] 0.38-0.97), stroke (aOR 0.58, 95% CI 0.38-0.90), acute kidney injury (aOR 0.41, 95% CI 0.34-0.49), and major bleeding (aOR 0.62, 95% CI 0.38-0.96), and higher vascular complications compared with SAVR (aOR 2.39, 95% CI 1.75-3.24). Length of stay was shorter and nonhome discharges were lower with TAVR (all p&amp;lt;0.01). Similar findings were observed in the propensity-matched cohort. Conclusions This nationwide observational analysis showed that TAVR is a feasible treatment option for patients &amp;lt;65 years with lower in-hospital mortality and resource utilization compared with SAVR.Central Illustration

The real-world safety of ticagrelor among older adults (above 75 years): a pharmacovigilance study from the FDA data

Abstract Introduction Potent P2Y12 inhibitors are recommended in conjunction with Aspirin for the treatment of acute coronary syndrome. Since Prasugrel is relatively contraindicated in patients older than 75 years, Ticagrelor remains the primary potent P2Y12 inhibitor option for this age group. However, its safety profile among older adults has not been adequately examined. Purpose To examine Ticagrelor safety profile among older adults (≥75 years) patients Methods We conducted a retrospective pharmacovigilance study utilizing the FDA Adverse Event Reporting System (FAERS) database. We employed disproportionality analysis comparing Ticagrelor to Clopidogrel. We evaluated the reporting of predefined adverse events (dyspnea, bradyarrhythmia, complete AV block [CAVB], intracranial hemorrhage, gastrointestinal hemorrhage, acute kidney injury [AKI], and gout) in adults (&amp;lt;75 years) and older adults (≥75 years). For each group, we calculated reporting odds ratio (ROR) and its 95% confidence interval and compared them by calculating P for interaction. Results The FAERS database encompassed 6,476 adverse event reports for Ticagrelor; 4,795 (74%) adults and 1,681 (26%) older adults. Among older adults and compared to Clopidogrel, Ticagrelor was not associated with an increased reporting for dyspnea (ROR 3.3 [2.7-3.9] vs. 3.9 [3.5-4.5]), bradyarrhythmia (ROR 4.1 [2.5 – 6.7] vs 5.4 [3.9 – 7.6]) intracranial hemorrhage (ROR 1.1 [0.7-1.7] vs. 1.1[0.8-1.5]), CAVB (ROR 11.5 [3.1–42.4] vs. ROR 27.8 [6.7-116.3]), and gout (ROR 3.8 [0.5-27] vs. 3.9 [2-7.5]). AKI was reported more frequently among older adults (ROR 2.3 [1.5-3.6] vs. 0.6 [0.4-0.9]). Ticagrelor was not associated with an increased reporting of GI hemorrhage. Conclusion According to the FAERS, Ticagrelor is generally safe for use in older adults (≥75 years) with no significant increase in the reporting of major adverse events compared to adults (&amp;lt;75 years), except for a higher reporting of AKI.