Prevalence and prognostic relevance of electrocardiographic abnormalities among patients with ANCA-associated vasculitis.

OBJECTIVES: Current guidelines provide limited evidence for cardiovascular screening in ANCA-associated vasculitis (AAV). This study aimed to investigate the prevalence of electrocardiogram (ECG) abnormalities and associations between no, minor or major ECG abnormalities with cardiovascular mortality in AAV patients compared with matched controls. METHOD: Using a risk-set matched cohort design, patients diagnosed with granulomatosis with polyangiitis or microscopic polyangiitis with digital ECGs were identified from Danish registers from 2000-2021. Patients were matched 1:3 to controls without AAV on age, sex, and year of ECG measurement. Associated hazards of cardiovascular mortality according to ECG abnormalities were assessed in Cox regression models adjusted for age, sex, and comorbidities, with subsequent computation of 5-year risk of cardiovascular mortality standardized to the age- and sex-distribution of the sample. RESULTS: A total of 1431 AAV patients were included (median age: 69 years, 52.3% male). Median follow-up was 4.8 years. AAV was associated with higher prevalence of left ventricular hypertrophy (17.5% vs 12.5%), ST-T deviations (10.1% vs 7.1%), atrial fibrillation (9.6% vs 7.5%), and QTc prolongation (5.9% vs 3.6%). Only AAV patients with major ECG abnormalities demonstrated significantly elevated risk of cardiovascular mortality [HR 1.99 (1.49-2.65)] compared with controls. This corresponded to a 5-year risk of cardiovascular mortality of 19.14% (16-22%) vs 9.41% (8-11%). CONCLUSION: Patients with AAV demonstrated a higher prevalence of major ECG abnormalities than controls. Notably, major ECG abnormalities were associated with a significantly increased risk of cardiovascular mortality. These results advocate for the inclusion of ECG assessment into routine clinical care for AAV patients.

Patiromer to Reduce Albuminuria Through Increased Renin Angiotensin Aldosterone System Inhibition in Patients With CKD-A Feasibility Trial.

Introduction: We tested the feasibility of adding a potassium binder to enable increased renin angiotensin aldosterone system inhibition (RAASi) and reduce albuminuria in patients with chronic kidney disease (CKD). In a controlled trial design, a potassium binder was introduced exclusively in patients developing hyperkalemia after intensified RAASi, thereby mirroring clinical decision-making. Methods: We planned to include 140 patients aged 18 to 80 years with estimated glomerular filtration rate (eGFR) 25 to 60 ml/min per 1.73 m2, albuminuria, and a history of hyperkalemia to an open-label, randomized trial comparing treatment with or without patiromer alongside maximally tolerated RAASi. Patients were randomized only if developing a documented P-potassium >5.5 mmol/l during run-in with intensified RAASi (losartan/spironolactone). The primary end point was change in urine albumin-creatinine ratio (UACR). Results: Screening among 800,000 individuals with available laboratory results yielded just 317 candidates meeting major selection criteria during 18⅔ months, with 75 ultimately included. Among them, only 23 developed P-potassium >5.5 mmol/l, qualifying for randomization. Consequently, only 20 participants completed the study, falling short of the planned 98, precluding a significant effect on the primary outcome. Inclusion and randomization challenges stemmed from a limited pool of eligible patients for intensified RAASi at risk of hyperkalemia, along with a lower than expected incidence of hyperkalemia during run-in. Conclusion: Despite extensive screening efforts, few eligible patients were identified, and fewer developed hyperkalemia during run-in. Hence, a trial design limited to CKD patients at high hyperkalemia risk and including a run-in phase appears unlikely to provide evidence for a potential renal benefit from additional use of potassium binders.

Increased risk of cardiovascular disease preceding diagnosis of incident ANCA-associated vasculitis: a Danish nationwide study.

OBJECTIVE: To examine if patients with ANCA-associated vasculitis (AAV) have an increased risk of cardiovascular disease in the months prior to diagnosis of AAV. METHODS: Using a nested case-control framework, patients with Granulomatosis with polyangiitis and Microscopic polyangiitis were identified through Danish Nationwide Registries from 1996-2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV-diagnosis) as their corresponding case. Conditional logistic regression was used to compute adjusted Hazard Ratios (HRs) for major adverse cardiovascular events (MACE), ischemic heart disease, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischemic stroke, pericarditis, and ventricular arrhythmias/ICD-implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before index date. RESULTS: A total of 2371 patients with AAV (median age: 63yrs, 53.7% male) were matched with 7113 controls. The prevalence of any cardiovascular outcome and MACE within 12 months preceding index date were 10.3% and 2.4% for AAV, compared to 3.8% (HR 3.05[2.48-3.75]) and 1.3% (HR 1.98[1.39-2.82]) of controls. The risk of cardiovascular outcomes was similarly increased in temporal proximity to the diagnosis, with the highest HR at 1 month prior to index date: Any cardiovascular outcome (HR 10.73[7.05-16.32]) and MACE (HR 5.78[2.67-12.52]). In individual analysis, a significantly higher rate was observed for all outcomes (excluding VA/ICD/CA). CONCLUSIONS: AAV disease is associated with an increased risk of cardiovascular disease in the months preceding diagnosis, which underlines the importance of early clinical vigilance toward cardiovascular disease.

Long-term cardiovascular outcomes and temporal trends in patients diagnosed with ANCA-associated vasculitis: a Danish nationwide registry study.

OBJECTIVES: To examine long-term cardiovascular outcomes and temporal trends among patients with ANCA-associated vasculitis (AAV) using Danish nationwide registries. METHODS: Using a cohort design, we examined patients with granulomatosis with polyangiitis (ICD-10: DM31.3) and microscopic polyangiitis (ICD-10: DM3.17) in Denmark from 1996-2018. Hazard ratios (HRs) of cardiovascular outcomes were compared between patients with AAV and age and gender-matched controls. Counterfactual G-estimation of HRs was performed to estimate 5-year absolute risks. Temporal trends were obtained by grouping cohorts into evenly distributed tertiles according to inclusion year. RESULTS: A total of 2306 patients with AAV (median age: 62.9yrs, 52.6% male) were matched with 6918 controls. Median follow-up was 9.5yrs. Patients with AAV had a higher rate of ischaemic heart disease [HR 1.86 (1.62-2.15)], myocardial infarction [HR 1.62 (1.26-2.09)], coronary angiogram [HR 1.64 (1.37-1.96)], percutaneous coronary intervention [HR 1.56 (1.17-2.07)] and ventricular arrhythmias/implantable-cardioverter-defibrillator (ICD)-implantations [HR 2.04 (1.16-3.57)]. Similarly, an increased rate of heart failure [HR 2.12 (1.77-2.54)], deep vein thrombosis [HR 3.13 (2.43-4.05)], pulmonary embolism [HR 4.04 (3.07-5.32)], atrial fibrillation [HR 2.08 (1.82-2.39)], ischaemic stroke [HR 1.58 (1.31-1.90)] and in-hospital cardiac arrest [HR 2.27 (1.49-3.48)] was observed. The 5-year risk of all outcomes were significantly higher (excluding ventricular arrhythmia/ICD-implantations). For temporal trends among patients with AAV, a decreased 3-year risk of cardiovascular mortality was observed over time. CONCLUSIONS: Patients with AAV are at increased risk of heart failure, atrial-/ventricular arrhythmias, venous thrombotic events, ischaemic stroke and myocardial infarction. Furthermore, patients with AAV were more frequently examined with coronary procedures and underwent more coronary revascularizations. No temporal changes in ischaemic cardiovascular outcomes were observed, albeit the cardiovascular mortality has decreased over time.

The prevalence of sarcopenia is markedly increased in patients with intestinal failure and associates with several risk factors.

BACKGROUND & AIMS: Intestinal insufficiency and intestinal failure are conditions associated with malabsorption of micro- and macronutrients. Consequently, malnutrition and ensuing alterations in body composition are common in this context and patients may have an increased risk of progressive loss of skeletal muscle mass and function (i.e. sarcopenia). We investigated the prevalence of sarcopenia in patients with intestinal insufficiency and intestinal failure and identified associated risk factors. METHODS: This was a cross-sectional study including 113 clinically stable outpatients with intestinal insufficiency or intestinal failure. Body composition was assessed using bioelectrical impedance analysis and muscle function (strength or performance) using a handheld dynamometer and a timed up-and-go test. Sarcopenia was classified using the European Working Group on Sarcopenia in Older People criteria. Several parameters, including smoking, alcohol, and concurrent morbidities, were analyzed for association with sarcopenia. RESULTS: The prevalence of sarcopenia was 53.1% (95% CI; 43.8 to 62.2) in the combined patient group. In patients with intestinal failure the prevalence of sarcopenia was 72.7% (95% CI; 59.3 to 83.0) compared to 34.5% (95% CI; 23.3 to 47.8) in those with intestinal insufficiency (OR 5.07 [95% CI; 2.27 to 11.31]; p < 0.001). Excessive alcohol consumption (OR 7.69 [95% CI; 1.50 to 39.34]; p = 0.014), intestinal failure (OR 4.16 [95% CI; 1.69 to 10.28]; p = 0.002), and inflammatory activity (OR 3.83 [95% CI; 1.06 to 12.84]; p = 0.041), were identified as independent risk factors of sarcopenia. A trend was observed for hypermetabolism in multivariate analysis (OR 7.55 [95% CI; 0.79 to 72.03]; p = 0.079). CONCLUSIONS: Patients with intestinal insufficiency and intestinal failure are at immense risk of developing sarcopenia. Associated risk factors are excessive alcohol consumption, intestinal failure, and inflammatory activity.

Osteoporosis in patients with intestinal insufficiency and intestinal failure: Prevalence and clinical risk factors.

BACKGROUND & AIMS: Intestinal insufficiency and intestinal failure are associated with malabsorption of micro- and macronutrients that may negatively influence bone metabolism and increase the risk for developing osteoporosis. However, information regarding prevalence and contribution of individual risk factors is scarce. We investigated the prevalence of osteoporosis in patients with intestinal insufficiency and intestinal failure and identified associated risk factors. METHODS: This was a retrospective cross-sectional study including 167 clinically stable outpatients with intestinal insufficiency or intestinal failure. Bone mineral density (BMD) was measured by dual X-ray absorptiometry and the prevalence of osteoporosis was compared to a gender and age matched population. Several clinical and demographic parameters, including body mass index (BMI), vitamin-D, smoking habits and medications, were analyzed for association with BMD. RESULTS: The prevalence of osteoporosis was 56.9% in the combined patient group compared to 24.1% in the control group (OR 4.2 [95% CI, 2.3 to 7.7]; p < 0.001). BMD in the hip was independently associated with BMI (0.13 [95% CI, 0.09 to 0.18]; p < 0.001) and vitamin-D levels (-0.41 [95% CI, -0.76 to -0.06]; p = 0.03). Similar associations were seen for BMD in the spine (0.15 [95% CI, 0.08 - 0.22]; p < 0.001) and (-0.60 [95% CI, -0.76 to -0.06]; p = 0.02), respectively. Trends for low BMD were observed in smokers, and in patients using glucocorticoids, opioids, and proton pump inhibitors. CONCLUSIONS: Patients with intestinal insufficiency and intestinal failure are at immense risk of developing osteoporosis. Low BMI and vitamin-D deficiency were identified as independent risk factors.

Can We Rely on Predicted Basal Metabolic Rate in Patients With Intestinal Failure on Home Parenteral Nutrition?

BACKGROUND AND AIMS: Intestinal failure (IF) is a serious and common complication of short bowel syndrome with patients depending on parenteral nutrition (PN) support. Effective nutrition management requires an accurate estimation of the patient's basal metabolic rate (BMR) to avoid underfeeding or overfeeding. However, indirect calorimetry, considered the gold standard for BMR assessment, is a time- and resource-consuming procedure. Consequently, several equations for prediction of BMR have been developed in different settings, but their accuracy in patients with IF are yet to be investigated. We evaluated the accuracy of predicted BMR in clinically stable patients with IF dependent on home parenteral nutrition (HPN). METHODS: In total, 103 patients with IF were included. We used indirect calorimetry for assessment of BMR and calculated predicted BMR using different equations based on anthropometric and/or bioelectrical impedance parameters. The accuracy of predicted BMR was evaluated using Bland-Altman analysis with measured BMR as the gold standard. RESULTS: The average measured BMR was 1272 ± 245 kcal/d. The most accurate estimations of BMR were obtained using the Harris-Benedict equation (mean bias, 14 kcal/d [ P = .28]; limits of agreement [LoA], -238 to 266 kcal/d) and the Johnstone equation (mean bias, -16 kcal/d [ P = .24]; LoA, -285 to 253 kcal/d). For both equations, 67% of patients had a predicted BMR from 90%-110% All other equations demonstrated a statistically and clinically significant difference between measured and predicted BMR. CONCLUSIONS: The Harris-Benedict and Johnstone equations reliably predict BMR in two-thirds of clinically stable patients with IF on HPN.

Comparison of complications associated with peripherally inserted central catheters and Hickman™ catheters in patients with intestinal failure receiving home parenteral nutrition. Six-year follow up study.

BACKGROUND & AIM: Patients with intestinal failure (IF) are dependent on parenteral nutrition delivered through central access such as Hickman™ catheters. The peripherally inserted central catheter (PICC) is becoming increasingly popular for the purpose. The aim of the present study was to compare complication rates between the two types of catheters. PATIENTS AND METHODS: Over a six-year period (2008-2014), we included 136 patients with IF receiving home parenteral nutrition (HPN). These patients had a total of 295 catheters (169 Hickman™ catheters and 126 PICCs). Data were collected by reviewing their medical records. Incidences are given per 1000 catheter days. Data are given as means ± standard deviation (SD) and compared using independent student's t-tests, Mann-Whitney-Wilcoxon, and X(2)-tests. A survival analysis for time to the first infection was conducted using Cox regression. RESULTS: The total number of catheter days was 54,912 days for Hickman™ catheters (mean dwell time 325 ± 402) and 15,974 days for PICCs (mean dwell time 127 ± 121), respectively. The incidence of catheter-related blood stream infection (CRBSI) per 1000 catheter days was significantly lower for Hickman™ catheters compared to PICCs (0.56 vs. 1.63, p < 0.05). The mean time to first CRBSI was significantly shorter for PICCs compared to Hickman™ catheters (84 ± 94 days vs. 297 ± 387 days, p < 0.05), which was confirmed with a cox analysis corrected for age and gender. A total of 75 catheters were removed due to CRBSI, 49 Hickman™ catheters and 26 PICCs respectively. In addition, PICCs were more often removed due to local infection/phlebitis and mechanical causes (p < 0.001). CONCLUSION: We found a higher risk and shorter time to first CRBSI in PICCs compared to Hickman catheters supporting that PICCs should mainly be chosen for planned HPN up to 3-6 months. We therefore conclude that the choice of catheter must still be determined on an individual basis.

Environmental Risk Factors for Developing Catheter-Related Bloodstream Infection in Home Parenteral Nutrition Patients: A 6-Year Follow-up Study.

BACKGROUND: Tunneled, cuffed, central venous catheters, including Hickman catheters and peripherally inserted central venous catheters (PICCs), are the most commonly used venous access for home parenteral nutrition (HPN) therapy. Catheter-related bloodstream infection is the most prevalent and severe complication. This study investigated whether environmental risk factors, including smoking, catheter management by a home care nurse, colectomy with stoma, number of infusion days per week, and C-reactive protein at catheter insertion day, influenced the time to first catheter-related bloodstream infection (CRBSI). MATERIALS AND METHODS: In this 6-year (2008-2014) observational cohort study, adult patients with intestinal failure receiving HPN through either Hickman catheters or PICCs were included. Data were obtained by reviewing medical records, and the environmental risk factors were analyzed with the Cox proportional hazards model. RESULTS: A total of 295 catheters (Hickman catheters: n = 169 and PICCs: n = 126) inserted into 136 patients were registered. Using the PICCs, 1 additional infusion day per week showed to significantly decrease the time to first CRBSI by a factor of 2.47. Hickman catheters managed by a home care nurse had a significantly increased mean (SD) incidence of CRBSI of 1.45 (0.68) per 1000 catheter days. Hickman catheters not managed by a home care nurse had a mean (SD) incidence of 0.56 (0.24). CONCLUSION: Using the PICC, 1 additional infusion day per week decreased the time to first CRBSI, while having the Hickman catheter managed by a home care nurse increased the mean CRBSI incidence. No other risk factors were found.