Impaired Renal Function Research Articles

External validation of a stepwise 0/1/3h algorithm to triage patients with suspected myocardial infarction

Abstract Background In patients with suspected myocardial infarction (MI), application of 0/1h-algorithms is recommended by guidelines of the European Society of Cardiology. Depending on assay-specific changes of high-sensitivity troponin (hs-Tn), these algorithms allow for rule-in or rule-out of MI at presentation or after 1 hour (h). Yet, a relevant proportion of patients remain in the observe group at 1h in need for further diagnostic. Recently, specific cutoffs at 3h were suggested for hs-TnT, enabling an additional 3h triage option in conjunction with the 0/1h algorithm to further reduce the proportion of patients in the observe zone. Objective We aimed to externally validate the diagnostic performance of the 0/1/3h algorithm in patients with suspected MI. Methods We consecutively enrolled patients with symptoms suggestive of MI in the emergency department of a tertiary hospital in Germany. Patients with STEMI were excluded. Concentrations of hs-TnT were measured at presentation, after 1h and 3h. Final diagnoses were adjudicated by two cardiologists according to the 4th Universal Definition of MI. Applying the 0/1/3h algorithm, patients were triaged into rule-in, rule-out- and observe-group. We assessed the diagnostic performance parameters in the overall sample as well as for predefined subgroups including sex, age ≥65 vs. <65 years, glomerular filtration rate (GFR) ≥60ml/min/m² vs. <60ml/min/m², and symptom onset time <1h vs. 1-3h vs. >3h). Results In 2,514 patients (median age 64 years, 36.4% female), prevalence of NSTEMI was 14.4%. Application of the 0/1/3h algorithm ruled-out 1511 (60.1%) and ruled-in 587 (23.3%) patients. Only 416 (16.6%) remained in the observe group at 3h. Safety of rule-out was high with a sensitivity of 98.6% (95%CI 96.8%, 99.4%) and a corresponding negative predictive value of 99.7% (95%CI 99.2%, 99.9%). Rule-in performance was acceptable with a specificity of 89.3% (95%CI 87.9%, 90.5%) and positive predictive value (PPV) of 60.8% (95%CI 56.8, 64.7, Figure 1). Regarding subgroup analyses, sensitivity and NPV were marginally but statistically lower in patients with normal as compared with impaired renal function (p both <0.001). Further, specificity was substantially lower in older patients (84.8% vs. 93.3%, p<0.001), patients with GFR<60ml/min/m² (78.3% vs. 93.0%, p<0.001) as well as in male patients (88.1% vs. 91.2%, p=0.028) (Figure 2). A relevantly larger proportion of patients remained in the observe group after 3h in patients with impaired renal function (32.3% vs. 10.9%), as well as in patients aged ≥ 65 years (26.8% vs. 6.8%). Conclusion Application of the 0/1/3h algorithm in patients with suspected MI resulted in good diagnostic performance with excellent rule-out safety and moderate rule-in capacity. In patients with impaired renal function as well as elderly patients, specificity was significantly lower while observing a larger proportion of patients remaining in the observe zone at three hours.Figure 1:Diagnostic flowFigure 2:Forest Plots

Association between renal function impairment and body roundness index (BRI) in elderly hypertensive patients

Abstract Objective The purpose of this study was to explore the associations of renal function impairment and body roundness index (BRI) in elderly hypertensive patients. Methods This is a community-based observational and cross-sectional study.A total of 1482 elderly hypertensive patients from our center in 2021 were enrolled. Waist-to-hip ratio(WHR) , Body mass index(BMI) and BRI were calculated with validated formulas. According to tri quantile method of BRI level , the patients were divided into low , medium and high BRI groups. The incidence of renal function impairment in the three groups was compared to explore the associations of renal function impairment and BRI in elderly hypertensive patients. Result According to the estimated glomerular filtration rate (eGFR) level, the patients were divided into two groups: impaired renal function group and non impaired renal function group. 133 cases were included in the group with impaired renal function, and 1349 cases were included in the group without impaired renal function. The proportion of patients with impaired renal function was 8%, 497 were in the low BRI group, 491 in the medium BRI group, and 494 in the high BRI group. Comparing the incidence of renal function impairment in patients with different BRI levels, the results showed that the incidence of renal function impairment in patients with high BRI was higher than that in patients with low BRI (7.0%vs.11.5%,p=0.015). The results of binary logistic regression analysis showed that the risk of renal function impairment increased by 19% for each unit of BRI increase (95%CI 1.037-1.122,P=0.024). After adjusting for age, gender, blood lipid, smoking and drinking history, years of hypertension, diabetes, years of diabetes,and random blood glucose levels, the risk of renal function impairment in high BRI group was still significantly higher than low BRI group (OR=1.697,95%CI 1.031-2.794,P=0.038),shows that BRI is an independent risk factor for renal function impairment in elderly hypertension patients. The receiver operating characteristic curve (ROC) results show that the prediction ability of BRI in the whole population is better than that of BMI and waist circumference (WC), and the prediction ability of BRI in elderly female population is the best (AUC=0.569). Conclusion Increasing of BRI is correlated with the occurrence of renal function impairment in elderly hypertension patients, and has the best predictive value for renal function impairment in elderly women with hypertension.

Digoxin loading doses for atrial fibrillation in critically Ill patients

Abstract Introduction The use of digoxin, a cardiac glycoside, for inotropic effects and electrophysiologic actions date back as far as the 18th century. Loading doses (LD) of digoxin are recommended when used for rate control in the setting of atrial fibrillation or atrial flutter (AF/AFL), though the optimal serum drug concentration (SDC) remains unknown. Pharmacokinetic based formulas used to calculate a LD target a SDC of 0.8-1.2 ng/mL. Still, digoxin pharmacokinetics remain unpredictable and are influenced by age, weight, renal impairment, and critical illness. Purpose The purpose of this study was to assess the safety and efficacy of digoxin LD used in critically ill patients to rate control AF/AFL and to assess the SDC achieved after a LD. Methods We conducted an Institutional Review Board approved retrospective cohort study at New York University Langone Health between January 2013 and March 2018. Adult patients (18 years of age or older) were included if they received an intravenous digoxin LD for AF/AFL in any intensive care unit and had a digoxin SDC measured between 6 and 24 hours after the LD. Patients were excluded if they received the LD orally. The primary endpoint was the SDC achieved after the LD. Secondary safety endpoints were the incidence of supratherapeutic digoxin SDC (> 1.2 ng/mL). Secondary efficacy endpoints included the incidence of rate control success, defined as a heart rate (HR) less than 110 beats per minute (bpm) within 24 hours of the digoxin LD. Results A total of 92 patients were included in the final analysis. The cohort was 53% male with a median age of 72 years, median BMI of 27, a median creatinine clearance (CrCL) of 47 mL/min at the time of IV digoxin LD and 66% of the cohort had AF. The highest HR associated with the AF/AFL 24 hours prior to digoxin was 133 (121, 145) bpm. The median total LD of digoxin for the entire cohort was 11 mcg/kg (750 mcg). In those with impaired renal function (CrCl < 30 mL/min), the median LD of digoxin was 8.3 mcg/kg. For 61% of the cohort, the LD was distributed over 6-hour intervals. The median SDC after completion of the IV digoxin LD was 1.3 ng/mL (0.9, 1.7), with a range of 0.4-4.1 ng/mL. A SDC > 1.2 ng/mL was observed in 51% of the cohort. Secondary outcomes of rate control success occurred in 60% of the cohort. No patients experienced any digoxin associated dysrhythmias or required reversal. Conclusion We found a SDC of 1.3 ng/mL post a digoxin LD in critically ill patients with AF/AFL to be successful in achieving rate control in 60% of our cohort. Despite 51% of the cohort achieving a SDC > 1.2 ng/mL, digoxin related adverse events were uncommon. Our analysis support previous data suggesting dose adjustment of digoxin in patients with impaired renal function but suggest a higher SDC may be acceptable in the acute setting when used for rate control. Our sample size is limited, and future studies should confirm our findings in critically ill patients.

Is etiology of severe tricuspid regurgitation related to prognosis?

Abstract Objective Our aim was to assess the prognostic role of the etiology tricuspid valve disease in patients with severe tricuspid regurgitation (TR). Methods Multicenter, observational, and prospective registry in which all patients with severe TR have been consecutively collected within a 6-month period and followed up for one year. Results A total of 1247 patients with severe TR [mean age: 76.7±10.5 years, 876 women (70.2%)] were included: 810 (64.9%) met criteria for severe TR, 301 (24.1%) massive TR, and 136 (11%) torrential TR. The most frequent etiology was functional TR secondary to left-heart disease in 621 patients (49.9%) followed by "atriogenic" TR in 247 (19.8%). TR etiology distribution is described in Figure 1. Death due to refractory HF occurred in 9,2% of patients, hospitalization for HF in 20,8%, and 12,3% underwent TR interventions. In the univariate and multivariate analysis, age, impaired renal function, previous HF admission, and massive and torrential TR were associated with an increased risk of HF hospitalization and cardiovascular mortality. Global (p=0,476) and cardiovascular mortality (p=0,138) rates were similar when comparing different TR etiologies (Figure 2). Conclusion Severe TR is associated with high rates of CV mortality and new HF admission. These findings are and independent from TR etiology.

A new right-heart failure staging system in patients with severe tricuspid regurgitation. Prognostic implications

Abstract Objective Our aim was to describe a new right-heart failure (RHF) staging system in patients with severe tricuspid regurgitation (TR). Methods Multicenter, observational, and prospective registry in which all patients with severe TR have been consecutively collected within a 6-month period, classified according to their clinical condition and right ventricular status, and followed up for one year. Results A total of 1247 patients with severe TR [mean age: 76.7±10.5 years, 876 women (70.2%)] were included: 810 (64.9%) met criteria for severe TR, 301 (24.1%) massive TR, and 136 (11%) torrential TR. A new RHF staging was proposed depending on clinical condition, RV dilation and RV systolic dysfunction (Table). The largest group of patients had a normal right ventricle with signs/symptoms of RHF (41%). Death due to refractory HF occurred in 9,2% of patients, hospitalization for HF in 20,8%, and 12,3% underwent TR interventions. In the multivariate analysis the predictors of CV mortality were age, impaired renal function, previous HF admission, massive and torrential TR and Stages III and IV of the new right-heart failure staging system (figure). Conclusion The new RHF staging system accurately stratifies patients with severe TR into prognostic categories.

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.

Epidemiology and temporal trends of infective endocarditis between 2006 and 2018 at a tertiary referral center

Abstract Introduction Despite modern diagnostics, targeted antibiotic therapy and surgical treatment the mortality rate of infective endocarditis (IE) remains high. In developed countries both the risk factors and pathogens have changed. Objective and methods In our retrospective study we analyzed the clinical and microbiological characteristics, short- and long-term all-cause mortality, and temporal trends of consecutive patients admitted with IE between 2006 and 2018. Results We included 537 cases in our study, the mean age was 55.9 ± 16.5 years (72.2% male). 325 (60.5%) cases were native left-sided IE, 14 (3%) cases were right-sided IE, 130 (24%) cases were prosthetic valve IE, 62 (11.5%) cases were intracardiac device-related IE and 6 (1%) other cases. The most common microorganisms were Staphylococci (n=175; 33%), including 104 cases of methicillin-sensitive Staphylococcus aureus (MSSA), 27 cases of methicillin-resistant Staphylococcus aureus (MRSA) and 44 cases of coagulase-negative Staphylococci. Streptococcus species were identified in 141 cases (26%), Enterococcus species in 88 cases (16%) and 72 cases (13%) were classified as blood culture-negative IE. In-hospital all-cause mortality was 14%, mortality at six months was 27%, at one-year was 31%, and at five-year was 45%. The incidence of MSSA infections increased over time (p=0.024), while coagulase-negative Staphylococci (p<0.001), and Streptococci (p=0.047) infections decreased. None of the observed mortality rates showed significant change over the study period. Predictors of mortality were advanced age (HR 1.37; p<0.001), impaired renal function (HR: 1.03; p<0.001), reduced ejection fraction on admission (HR 1.38; p<0.001), stroke (HR 1.74; p=0.001), and MRSA infection compared to Streptococci (HR 2.56; p=0.002). Conclusion During the observed 13-year period Staphylococci were the most common pathogens, with an increasing incidence of MSSA infection in our tertiary center. The mortality rate of IE remained high and showed no improvement over time.

Rezafungin versus caspofungin for patients with candidaemia or invasive candidiasis in the intensive care unit: pooled analyses of the ReSTORE and STRIVE randomised trials

BackgroundRezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation.MethodsSTRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation. Data were pooled for patients in the ICU at randomisation who received intravenous rezafungin (400 mg loading dose then 200 mg once weekly) or caspofungin (70 mg loading dose then 50 mg once daily) for ≤ 4 weeks. Outcomes were Day 30 all-cause mortality (primary outcome), Day 5 and 14 mycological eradication, time to negative blood culture, mortality attributable to candidaemia/invasive candidiasis, safety, and pharmacokinetics.ResultsOf 294 patients in STRIVE/ReSTORE, 113 were in the ICU at randomisation (rezafungin n = 46; caspofungin n = 67). At baseline, ~ 30% of patients in each group had impaired renal function and/or an Acute Physiologic Assessment and Chronic Health Evaluation II score ≥ 20. One patient (in the caspofungin group) was neutropenic at baseline. Day 30 all-cause mortality was 34.8% for rezafungin versus 25.4% for caspofungin. Day 5 and 14 mycological eradication was 78.3% and 71.7% for rezafungin versus 59.7% and 65.7% for caspofungin, respectively. Median time to negative blood culture was 18 (interquartile range, 12.6–43.0) versus 38 (interquartile range, 15.9–211.3) h for rezafungin versus caspofungin (stratified log-rank P = 0.001; nominal, not adjusted for multiplicity). Candidaemia/IC-attributable deaths occurred in two rezafungin patients versus one caspofungin patient. Safety profiles were similar between groups. Overall, 17.4% (rezafungin) versus 29.9% (caspofungin) of patients discontinued due to treatment-emergent adverse events. Rezafungin exposure following the initial 400-mg dose was comparable between patients in the ICU at randomisation (n = 50) and non-ICU patients (n = 117).ConclusionsRezafungin was well tolerated and efficacious in critically ill, mainly non-neutropenic patients with candidaemia and/or IC. This analysis provides additional insights into the efficacy and safety of rezafungin in the ICU population.

Short versus conventional DAPT in patients undergoing PCI with ultra-thin DES by renal function: an analysis from the HOST-IDEA trial

Abstract Background Patients with impaired renal function are known to have an elevated risk of both ischemic and bleeding events following percutaneous coronary intervention (PCI). However, there is insufficient data available on the optimal duration of dual antiplatelet therapy (DAPT), especially with the latest generation of drug-eluting stent (DES)s. Objective We investigated to assess the efficacy and safety of abbreviated duration of DAPT in patients undergoing PCI with 3rd generation DESs based on their renal function. Methods In this prespecified subgroup analysis of the HOST-IDEA trial, a total of randomized 1997 patients with available baseline estimated glomerular filtration rate (eGFR) were categorized into three groups: high eGFR (>90 mL/min), intermediate eGFR (60 to 90 mL/min), and low eGFR (<60 mL/min). The primary outcome assessed during the 1-year follow-up period was net adverse clinical events (NACE). Ischemic and bleeding endpoints were also evaluated. Results Compared to intermediate or high eGFR groups, the low eGFR group resulted in significantly worse outcomes (P < 0.001). 3-6 month DAPT was associated with similar risk of NACE across all eGFR groups (High eGFR: HR: 0.91; 95% CI: 0.38-2.20; Intermediate eGFR: HR: 0.76; CI: 0.33-1.73; Low eGFR: HR: 0.99; CI: 0.51-1.92). There was also no significant difference in target lesion failure (HR: 0.95; CI: 0.32-2.83, HR: 0.77; CI: 0.29-2.06, and HR: 1.14; CI: 0.47-2.75) and major bleeding (HR: 0.84; CI: 0.19-3.74, HR: 0.59 CI: 0.14-2.48; and HR 0.83 CI: 0.34-2.05) among all stratified eGFR groups. This effect was also consistent in patients of end stage of renal disease (eGFR <15 mL/min). Conclusions In patients undergoing PCI with third generation DESs, short DAPT was comparable to conventional DAPT regardless of their baseline renal function.

Shortened versus standard duration of dual antiplatelet treatment after percutaneous coronary intervention in patients with and without chronic kidney disease: a systematic review and meta-analysis

Abstract Background Impaired renal function is an established risk factor for recurrent cardiac events. The severity of chronic kidney disease (CKD) is related with an increased risk for both ischemic and bleeding complications. As a result, the clinical implications of antithrombotic therapies may be different in patients with CKD as compared to those without. Recently, shortened duration of DAPT, namely one to three months, after percutaneous coronary intervention (PCI) has been proven as a safe and feasible strategy in various different clinical scenarios, like in high-bleeding risk patients, in acute coronary syndromes and complex PCI. However, it remains debatable whether DAPT should be shortened in patients with high ischemic and bleeding risk, such as those with CKD. Purpose The aim of our systematic review and meta-analysis is to explore the safety and efficacy of shortened therapy (1-3 months; S–DAPT) in patients without and without CKD undergoing PCI. Methods Three major databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) were screened for eligible randomized – controlled trials, or subgroup or post – hoc analyses of them. The studies should compare shortened (S–DAPT) with longer (>3 months) DAPT (L–DAPT) in patients undergoing PCI, and include data on CKD presence. The endpoints were Net Adverse Clinical Events (NACE) and Major Adverse Cardiac Events (MACE) and should be evaluated at 12 months. NACE and MACE were used as per trial defined. The effect of different DAPT regimens was assessed by calculating the risk ratio (RR) with 95% confidence interval (CI) using random-effects model (Mantel-Haenzel). Results A total of eight studies and 56,660 patients were included in our analysis; a notable proportion of patients (9.7%, N=5,466) suffered from CKD. Our analysis showed an overall benefit of S-DAPT in NACE (RR: 0.88, 95%CI: 0.81 – 0.95), which was consistent in patients with and without CKD (p-interaction=0.58). (Figure 1) No significant difference regarding MACE was observed between S-DAPT and L-DAPT (RR: 0.98, 95%CI: 0.90 – 1.06) in both patients with and without CKD (p-interaction=0.19). (Figure 2) Conclusions Our analysis showed an overall benefit of S-DAPT in NACE without any difference in MACE, with similar findings among patients with and without CKD. Thus, DAPT shortening could be a feasible and safe approach when it is required, even in patients with impaired renal function. Further randomized controlled trials focusing on patients with CKD are required for validating the previous results and exploring further benefits of abbreviated duration of DAPT.Net adverse clinical eventsMajor adverse cardiac events

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.

Circulating secretoneurin concentrations predict cardiovascular death in ambulatory patients with heart failure

Abstract Background Secretoneurin (SN) is a novel biomarker, which predicts cardiovascular (CV)-related mortality in patients with acute dyspnea and sepsis. Higher SN concentrations have also been found associated with all-cause death in outpatients with heart failure (HF), but whether SN primarily reflects cardiovascular (CV)-related mortality in HF outpatients is not known. Objectives To evaluate the relation between SN concentrations and CV- &amp; non-CV death in ambulatory patients with HF. Methods We studied 184 consecutive patients who attended our HF clinic for routine follow up and had stored blood samples available for SN analysis. SN concentrations were measured with a CE-marked SN ELISA assay. We assessed the associations between SN concentrations and CV &amp; non-CV death. Mortality was ascertained using medical records, autopsy reports and death certificates, and CV deaths included sudden cardiac deaths or mortality due to myocardial infarction, HF or stroke. We assessed association with CV &amp; non-CV death by Kaplan-Meier curves and by Cox proportional hazard regression analysis. Results Median age was 76 years (range: 38-94 years) and two thirds were male. Sixty-three percent had HF with reduced ejection fraction, 22% had NYHA III/IV symptoms and median NT-proBNP was 1079 (interquartile range: 462-2347) ng/L. Median SN level was 60 (range: 21-134) pmol/L. In multivariable linear regression analysis, impaired renal function and lower body-mass index were significantly associated with increasing (log)SN concentration. During median follow up of 540 days, there were 18 CV deaths, including 15 HF deaths, and 7 non-CV deaths. A higher SN concentration was associated with higher risk of CV death, while we did not find statistically significant association between SN concentrations and non-CV deaths (Figure). Patients with SN concentration in the top tertile had 15-fold increased risk of CV death compared to patients with SN concentration in the lowest tertile. In multivariable Cox regression analysis that adjusted for age, NYHA functional class, frailty status, increasing SN concentrations were independently associated with CV death: hazard ratio per logSN (95% CI): 3.01 (1.02-8.90), p=0.04. Conclusion In ambulatory patients with HF, circulating SN concentrations were predictive of CV death. Higher SN concentrations in ambulatory HF patients seemed to be linked to impaired renal function and lower body-mass index. Figure: Kaplan Meier curves illustrating the relation between SN tertiles and (A) CV mortality (B) Non-CV mortality.

Increased frailty is associated with risk of hospital-acquired infections and death during heart failure hospital admissions

Abstract Background Frailty is common in patients admitted with acute decompensation of heart failure (ADHF) and it is unclear how the frailty syndrome affects heart failure (HF) patients during their acute hospital admission. Understanding the interplay between frailty, impaired renal function, hospital-acquired infections (HAI), and death may be useful in optimising patient care and prognosis. Purpose The aim of this analysis was to explore the relationship between admission frailty levels and the incidence of HAI, acute kidney injury (AKI), and mortality in acute HF hospital admissions. Methods This is a retrospective analysis of data submitted from a single centre to the National HF audit between January and June 2023. Additional frailty and baseline renal function data was retrospectively collected from electronic patient health records. Patients were categorised into three groups according to their Rockwood Clinical Frailty Scale (CSF) (1): no/mild frailty (CFS 1-3), moderate frailty (CFS 4-6) and severe frailty (CFS 7-9). AKI was defined based on baseline and admission creatinine, as per KDIGO guidelines (2). Chi-squared and t-tests were used to compare baseline characteristics between frailty groups. Chi-squared tests were used to compare frailty groups in terms of: HAI, AKI, mortality. Results Between 1st January and 22nd June 2023, there were 344 acute HF hospital admissions in our centre. Most patients had moderate frailty on admission (n=256, 74.4%). Frail patients were significantly older, had a lower admission mean haemoglobin and more were female, compared to non-frail patients (Figure 1A). Patients who were more frail were more likely to experience HAI during their admission; p=0.035 (figure 1B). Furthermore, patients with HAI had a greater risk of mortality, at a median follow-up of 171 (IQR 100.25) days after admission, compared to those without HAI (p&amp;gt;0.001). 41.9% of acute HF admissions were associated with an AKI, and although numerically more frail patients had an AKI, this did not achieve statistical significance (p=0.084). Patients who were more frail were more likely to die, both during hospital admission and at 3 months following discharge; p&amp;lt;0.001 (Figure 1B). Furthermore, this trend persisted after follow-up; p&amp;lt;0.001 (Figure 2). Conclusions Patients with moderate or severe frailty are at greater risk of adverse events (HAI, death) during an acute HF hospital admission, than patients with no or mild frailty. It is imperative to consider the frailty status of all patients with ADHF, to be aware of the frailty-associated risks, and act proactively with targeted interventions (screen for infections, daily bloods, early conversations with patients and their families about treatment escalation plans and patient priorities) to improve outcomes and enhance the quality of care for this vulnerable patient population. Further research is warranted to explore potential interventions to address frailty-related risks in HF management.

Long-term clinical implications of routine follow-up coronary angiography of asymptomatic patients with long-duration diabetes mellitus after percutaneous coronary intervention in drug-eluting stent e

Abstract Background Diabetes mellitus (DM) is a major risk factor for coronary artery disease (CAD), significantly contributing to mortality in affected patients. There are concerns about the adequacy of clinical follow-up for post-percutaneous coronary intervention (PCI) surveillance, especially in uncontrolled DM, due to potential asymptomatic CAD. This study assesses whether routine follow-up coronary angiography (FUCAG) offers a surveillance advantage over clinical follow-up in uncontrolled DM post-PCI. Methods From 2014 to 2020, a study was conducted on patients with DM who underwent PCI at our university medical. Poorly controlled DM was defined as a mean HbA1c of 9 or higher during the index PCI and follow-up period. Out of a total of 2,864 individuals, after excluding 538 individuals with a follow-up period of less than 4 years and 232 individuals who experienced an event within a year, a total of 2,094 was enrolled. Follow-up coronary angiography (FUCAG) was defined as angiography performed between 6- and 18-months post-index PCI for lesion evaluation. To adjust for any differences in baseline characteristics between the groups, propensity score matching (PSM) was implemented. The primary outcome was defined as Major Adverse Cardiac Events (MACE), comprising all-cause death, myocardial infarction, and target-lesion revascularization. Results PSM was conducted to correct the difference in baseline characteristics between the two groups. In the Kaplan-Meier analysis, there was no difference between FUCAG and clinical follow-up for MACE (Log-rank: P=0.770). Cox proportional regression analysis revealed a hazard ratio (HR) of 0.77 with a 95% confidence interval (CI) of 0.70-1.63, indicating no statistically significant difference. Conclusions Even in poorly controlled DM patients, there was no apparent clinical benefit of FUCAG compared to clinical follow-up. Particularly considering concerns such as renal function deterioration in DM patients, post-PCI surveillance through clinical follow-up may be advantageous.

Population pharmacokinetic and pharmacodynamic model of evogliptin: Severe uremia increases the bioavailability ofevogliptin.

Uremia, a condition characterized by the retention of uremic toxins due to impaired renal function, may affect drug metabolism mediated by CYP3A4 enzymes. Evogliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor diabetic drug that is primarily metabolized by CYP3A4. This study aimed to construct a population pharmacokinetic (PK) and pharmacodynamic (PD) model for evogliptin in patients with varying degrees of renal disease, including end-stage renal disease on hemodialysis. A total of 688 evogliptin concentration and 598 DPP-4 activity data were available from 46 subjects. PK and PD data analyses were performed using a nonlinear mixed-effects model. The PK of evogliptin was optimally described by a two-compartment model with first-order absorption. The significant covariates in the final model included blood amylase and triglyceride on F1 (relative bioavailability). The simulation findings, together with previously reported PK data, provided evidence of a significant inhibition of the first-pass effect of evogliptin in patients with renal impairment. A direct link sigmoidal Emax model was developed to describe the relationship between evogliptin concentration and DPP-4 inhibition. The PD model predicted significant inhibition of DPP-4 at maximum effect (Emax: 88.9%) and a low EC50 value (1.08 μg/L), indicating the high potency and efficacy of evogliptin. The developed PK/PD model accurately predicted exposure and the resulting DPP-4 activity of evogliptin in renal impairment. The findings of this study suggest that renal impairment and associated biochemical changes may impact the bioavailability of CYP3A4-metabolized drugs.

Biomarkers for monitoring patients with cardiac amyloidosis during transthyretin-stabilizer therapy

Abstract Introduction Cardiac amyloidosis is characterized by deposition of amyloid fibrils in the heart, leading to structural abnormalities and functional impairments resulting in heart failure. Amyloid transthyretin amyloidosis cardiomyopathy (ATTR-CM) is the most common form with increasing incidence due to growing awareness and improved diagnosis. The ATTR stabilizer tafamidis serves as the first specific therapy approved for ATTR-CM, and many promising substances are in late-stage clinical trials. With growing numbers of patients receiving stabilizer therapy, valid tools for monitoring treatment response and detecting disease progression are currently lacking. Here, we aim to assess systemic and cardiac biomarkers in patients receiving stabilizer therapy. Method All individuals diagnosed with ATTR-CM at our university hospital, were systematically assessed for eligibility in this study. We enrolled patients who were undergoing therapy with tafamidis. Biomarkers including Hemoglobin (Hb), Creatinine, estimated glomerular filtration rate (eGFR), International Normalized Ratio (INR), C-reactive protein (CRP), Troponin and NT-proBNP were examined at baseline and during 6 and 12 months follow-up. Wilcoxon signed rank test was used for statistical analysis. The study was approved by the local ethics committee (23-11500-BO). Results 194 patients were included in the analysis with median age of 80 (76-83) years (86,6% male). Results showed an impaired renal function at baseline (all mean ± SD) with creatinine 1.24 ± 0.46 mg/dl and eGFR 58.64 ± 18.24 ml/min/kg with statistically significant increase after 6 months in creatinine (1.31 ± 0.51 mg/dl, p&amp;lt;0.001) and eGFR (55.06 ± 17.65 ml/min/kg, p&amp;lt;0.001) and after 12 months (creatinine 1.35 ± 0.54 mg/dl, p&amp;lt;0.001, eGFR 53.27 ± 17.68 ml/min/kg, p&amp;lt;0.001). Hb showed a significant increase after 6 (13.61 ± 1.78 g/dl, p&amp;lt;0.001) and 12 months (13.6 ± 1.79 g/dl, p&amp;lt;0.001), compared to baseline (13.41 ± 1.71 g/dl, p&amp;lt;0.001). Comparison of baseline values for CRP (0.08 ± 1.18 mg/dl), Troponin (86.33 ± 190.6 ng/l), NT-pro BNP (4703 ± 4385 pg/ml) and INR (1.25 ± 0.46) after 6 (CRP p=0.28, Troponin p=0.7, NT-pro BNP p=0.97, INR p=0.91) and 12 months (CRP p=0.12, Troponin p=0.59, NT-pro BNP p=0.78, INR p=0.28) showed no significant changes. Conclusion Although troponin and BNP are routinely used and recommended as biomarker for monitoring patients with ATTR-CM, the diagnostic value may be insufficient to assess therapy response. Results emphasize the need to identify new biomarkers to adequately reflect the specific aspects of ATTR-CM disease progression. This study reveals significant alterations in creatinine and eGFR due to a worsening of kidney function, but an increase of Hb, suggesting a potential indicator for treatment response. Future research should explore innovative approaches like proteomic analysis as promising approach for both diagnostic and prognostic biomarkers.

CMR characterisation of patients with heart failure and left bundle branch block

Abstract Introduction Cardiac magnetic resonance (CMR) is recommended internationally for tissue characterisation, volumetric assessment and assessment of prior myocardial infarction (1). Patients with left bundle branch block (LBBB) form a significant sub-group of individuals, however, there is limited data available to accurate determine whether LBBB is associated with any CMR-definable phenotypes. Aim We aimed to identify the distinctive cardiac magnetic resonance (CMR) features of patients with left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF) of presumed non-ischaemic aetiology. Methods Participants from the MATCH (MyocArdial Tissue CHaracteristics in patients with heart failure according to glycaemic status) registry were prospectively enrolled. Exclusion criteria included: LVEF &amp;gt;40% at initial evaluation, established diagnosis of coronary artery disease, known presence of structural heart disease, suspected myocarditis, congenital heart disease and significantly impaired renal function. Following identification of HF, guideline-directed medical therapy was initiated based on the decision of the treating physician. LV recovery was defined as achieving ≥10% absolute improvement to a level of 40% or greater of LVEF from baseline evaluation upon the date of CMR quantification. Electrocardiograms were analysed to establish the presence or absence of LBBB. Results A total of 391 patients were recruited including 115 (29.4%) presenting with LBBB. Compared to controls, LBBB patients exhibited larger left ventricles and smaller right ventricles, but no differences were observed with respect to LVEF (35.8±12 vs. 38± 12 %, p=0.105) or right ventricular ejection fraction (RVEF). The prevalence of ischaemic scar (18.3% vs 21%, p=0.54), non-ischaemic fibrosis (25.2% vs 32.6%, p=0.15) and inducible ischaemia (6.1% vs. 7.6%, p=0.6) was comparable in patients with LBBB and those without. The overall rate of LV recovery was not significantly different between LBBB and non-LBBB patients (27.8% vs. 33%, p=0.32) from their baseline evaluation to the time of CMR assessment (70 [42 - 128] days). In the multivariate logistic regression, reduced LVEF remained an independent predictor of LV non-recovery in patients with LBBB, even after adjusting for gender and QRS duration (OR 0.93, 95%CI 0.87 – 0.99, p=0.03). In contrast, this association was not observed among patients without LBBB, whereas ischaemic scar was the primary predictor of LV non-recovery (OR 4.31, 95%CI 1.85 – 10.04, p=0.0007). Conclusion In this study patients presenting with a combination of HFrEF and LBBB had a larger LV cavity and smaller RV cavity than those without LBBB. However, there were no differences in the prevalence of ischaemic scar, non-ischaemic scar of inducible ischaemia according to the presence of absence of LBBB. Rates of LV recovery were similar between LBBB and non-LBBB patients.Clinical CMR ParametersSegmental Distributions

Evaluation of concordance and association with clinical outcomes across eGFR values calculated with eight different formulas in a large cohort of european patients with atrial fibrillation

Abstract Background In randomized clinical trials of Direct Oral Anticoagulants (DOACs), the assessment of renal function impairment glomerular filtration rate (eGFR) in patients with Atrial Fibrillation (AF) has predominantly utilized the Cockroft-Gault (CG) formula for estimating Creatinine clearance (CrCl). However, in clinical practice, several other formulas for estimating glomerular filtration rate (eGFR) are employed. Limited data exist regarding the evaluation and comparison of eGFR/CrCl in AF patients. Objectives This study aimed to assess the concordance in the categorisation of renal function in in 6 classes taking into account eight different formulas for eGFR/CrCl (CG, CKD-EPI, CG/body surface area [BSA], BIS1, LMK, EKFC, FAS, MDRD) and their associations with a composite outcome (Major Adverse Cardiovascular Events [MACE] and all-cause death) in AF patients. Methods A contemporary European AF patient registry was utilized, and eGFR/CrCl were calculated using CG, CKD-EPI, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. eGFR was categorized according to KDIGO classes, with CKD patients defined as having eGFR/CrCl &amp;lt;60 ml/min/m2. Concordance was estimated using weighted Cohen’s kappa. Associations were evaluated through adjusted Cox regression analyses for the composite outcome, and results were plotted as spline curves. Results: A total of 8516 patients were included in the analysis (Median [IQR] age: 70 [63-77] years; 3518 women, 41.3%). Among the formulas, EKFC exhibited the highest median values of eGFR and the lowest prevalence of CKD patients, while BIS1 had the lowest median eGFR values, and the FAS formula led to the highest prevalence of CKD patients [Figure 1]. In the concordance analysis, CKD-EPI demonstrated the highest concordance with all other formulas, even if Cohen’s kappa for measuring the degree of concordance ranged from 0.61 to 0.88 [Figure 1]. In adjusted Cox regression analyses, all formulas were associated with an increased risk for the composite outcome, progressively as eGFR decreased. When plotted as spline curves, the associations with the composite outcome visually showed a similar behaviour of risks across eGFR values in all formulas compared to the CG spline [Figure 2]. Conclusions Among AF patients, the CKD-EPI formula exhibited variable, but substantially good concordance with CG, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. All calculated eGFR values showed a strong association with the composite outcomes, similarly to the CG formula, with higher risk when renal function decreased.FIGURE 1FIGURE 2

Predictors of discordance in estimating the presence of chronic kidney disease among patients with atrial fibrillation and impact on prescription of anticoagulants and cardiovascular outcomes

Abstract Background In patients with atrial fibrillation (AF), the prevalence, predictors and clinical implications of a potential discordance in estimating the presence/absence of chronic kidney disease (CKD) according to Cockroft-Gault (CG) and CKD-EPI formulas remain unclear. Objective To examine patients characterized by discordance in evaluation of renal function, specifically with regard to the threshold for defining the presence of CKD according to an estimated glomerular filtration rate (eGFR) &amp;lt; 60 ml/min, in a large cohort of European AF patients, and to assess the association with prescriptions of oral anticoagulants (OAC) and the risks of adverse outcomes. Methods Data related to AF patients enrolled in a large European observational prospective registry with an average follow up of 645.2 days were analysed. We evaluated renal function for assessing the presence of CKD according to CG and CKD-EPI formulas and we categorized the population in four groups: eGFR ≥ 60 ml/min according both to CG and CKD-EPI (Concordant ≥ 60); &amp;lt; 60 ml/min according to both formulas (Concordant &amp;lt;60); CG &amp;lt;60 ml/min and CKD-EPI ≥60 ml/min (Discordant-CKD-EPI), CG ≥ 60 ml/min and CKD-EPI &amp;lt;60 ml/min (Discordant-CG). Logistic regression analyses were used to assess factors associated with a Discordant assessment of CKD and its association with OAC therapy. Cox regression analysis was used to determine association between categories and the risk of adverse outcome. The primary endpoint was a composite of all-cause death and major adverse cardiovascular events (MACEs). Results 8.786 patients with AF (mean age 68.70, SD 11.58 years; 40.9% female) were included in the analysis. 1360 (15.5%) of them had Discordant CKD assessment: 577 (6.6%) with Discordant-CKD-EPI and 783 (8.9%) with Discordant-CG. Increasing age, female sex and coronary artery disease (CAD) were associated with Discordant-CKD-EPI, while BMI and heart failure (HF) showed an inverse association (Figure 1). Conversely, BMI and HF were factors significantly associated with Discordant-CG. Discordant-CKD-EPI patients showed lower odds of being prescribed with OAC therapy (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.54-0.95) with no significant differences regarding the type of OAC therapy (warfarin or direct oral anticoagulants). At Cox regression analysis, patients with Discordant-CKD-EPI showed a higher risk of composite endpoint events (Figure 2) and both Discordant-CKD-EPI and Discordant-CG patients were associated with a higher risk of all-cause death. Conclusions Age, BMI, female sex and comorbidities associated with AF (CAD and HF) significantly influenced the probability of having a discordant assessment of the presence of CKD, according to estimation of renal function impairment using CG or CKD-EPI formulas, respectively. A discordant assessment of CKD influenced the probability of being prescribed with OAC and was associated with a higher risk of adverse outcomes.Figure 1Figure2

Clinical Profile And Aetiology of Acute Kidney Injury Developing In Patients Hospitalized Due To Non-Renal Cause With Pre-Existing Normal Renal Function

Background: Acute kidney injury (AKI) is a common complication in patients hospitalized for non-kidney disease and having normal renal function. Early detection of development of deteriorating renal function and assessment of its cause can help to manage the cases effectively and can prevent further kidney damage or progression to end stage renal failure. Methods: This observational study was done on 50 patients selected from the departments of Medicine and Nephrology of Dhaka Medical College (DMCH) and BSMMU, from June 2012 to November 2012. Patients were included in the study who developed clinical features and biochemical findings of acute kidney injury, while being admitted with various non-renal diseases and had previous normal renal function. Results: In this study the cause of deterioration of renal function was Sepsis in 44.0% of the patients, 42.0% had fluid loss, 6.0% had used nephrotoxic drugs, 4.0% had hepatitis, 2.0% patients each had pancreatitis and insect bite respectively. 40% of the patients were above 40 years of age, 54% were male. Vomiting was present in 42% of the patients and diarrhoea in 20% of the patients. 26% patients had DM and 22% had hypertension. Conclusion: Sepsis and hypovolemia were the common causes of developing acute kidney injury in the hospital. In-hospital mortality was 18.0% and 22.0% patients developed CKD after three months follow-up. J Dhaka Med Coll. 2023; 32(1) : 85-91