The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known. We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from randomization. This was a predetermined secondary end point of a randomized clinical trial designed to assess progression of coronary artery calcium (CAC) scores in the two treatment arms. Thirty-four deaths occurred during the follow-up period: 23 in subjects randomized to calcium-containing phosphate binders and 11 in subjects randomized to sevelamer. Baseline CAC score was a significant predictor of mortality after adjustment for age, race, gender, and diabetes with increased mortality proportional to baseline score (P=0.002). Mortality was borderline significantly lower in subjects randomized to sevelamer (5.3/100 patient years, confidence interval (CI) (2.2-8.5) compared to those randomized to calcium-containing binders (10.6/100 patient years, CI 6.3-14.9) (P=0.05). The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment (P=0.016, hazard ratio 3.1, CI 1.23-7.61). In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality. Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders.

IMPORTANCE Myocardial injury, detected by elevated plasma troponin levels, has been associated with mortality in patients hospitalized with coronavirus disease 2019 . However, the initial data were reported from single-center or 2-center studies in Chinese populations. Compared with these patients, European and US patients are older, with more comorbidities and higher mortality rates.OBJECTIVE To evaluate the prevalence and prognostic value of myocardial injury, detected by elevated plasma troponin levels, in a large population of White Italian patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This is a multicenter, cross-sectional study enrolling consecutive patients with laboratory-confirmed COVID-19 who were hospitalized in 13 Italian cardiology units from March 1 to April 9, 2020. Patients admitted for acute coronary syndrome were excluded. Elevated troponin levels were defined as values greater than the 99th percentile of normal values. MAIN OUTCOMES AND MEASURESClinical characteristics and outcomes stratified as elevated or normal cardiac troponin levels at admission, defined as troponin T or troponin I at a level greater than the 99th percentile of normal values.RESULTS A total of 614 patients with COVID-19 were included in this study (mean age [SD], 67 [13] years; 70.8% male), of whom 148 patients (24.1%) died during the hospitalization. Elevated troponin levels were found in 278 patients (45.3%). These patients were older (mean [SD] age, 64.0 [13.6] years vs 71.3 [12.0] years; P < .001) and had higher prevalence of hypertension (168 patients [50.5%] vs 182 patients [65.9%]; P < .001), heart failure (24 [7.2%]; 63 [22.8%]; P < .001), coronary artery disease (50 [15.0%] vs 87 [31.5%]; P < .001), and atrial fibrillation (33 [9.9%] vs 67 [24.3%]; P < .001). Elevated troponin levels were associated with an increased in-hospital mortality (37% vs 13%; HR, 1.71 [95% CI, 1.13-2.59]; P = .01 via multivariable Cox regression analysis), and this was independent from concomitant cardiac disease. Elevated troponin levels were also associated with a higher risk of in-hospital complications: heart failure (44 patients [19.2%] vs 7 patients [2.9%]; P < .001), sepsis (31 [11.7%] vs 21 [6.4%]; P = .03), acute kidney failure (41 [20.8%] vs 13 [6.2%]; P < .001), multiorgan failure (21 [10.9%] vs 6 [2.9%]; P = .003), pulmonary embolism (27 [9.9%] vs 17 [5.2%]; P = .04), delirium (13 [6.8%] vs 3 [1.5%]; P = .02), and major bleeding (16 [7.0%] vs 4 [1.6%]; P = .008). CONCLUSIONS AND RELEVANCEIn this multicenter, cross-sectional study of Italian patients with COVID-19, elevated troponin was an independent variable associated with in-hospital mortality and a greater risk of cardiovascular and noncardiovascular complications during a hospitalization for COVID-19.

SummaryBackground and Objectives Dietary phosphorous overload and excessive calcium intake from calcium-containing phosphate binders promote coronary artery calcification (CAC) that may contribute to high mortality of dialysis patients. CAC has been found in patients in early stages of nondialysis-dependent CKD. In this population, no study has evaluated the potential role of phosphorus binders on mortality. This study aimed to evaluate all-cause mortality as the primary end point in nondialysis-dependent CKD patients randomized to different phosphate binders; secondary end points were dialysis inception and the composite end point of all-cause mortality and dialysis inception.Design, Setting, Participants, & Measurements This is a randomized, multicenter, nonblinded pilot study. Consecutive outpatients (n=212; stage 3-4 CKD) were randomized to either sevelamer (n=107) or calcium carbonate (n=105). Phosphorus concentration was maintained between 2.7 and 4.6 mg/dl for patients with stage 3-4 CKD and between 3.5 and 5.5 mg/dl for patients with stage 5 CKD. The CAC score was assessed by computed tomography at study entry and after 6, 12, 18, and 24 months. All-cause mortality, dialysis inception, and the composite end point were recorded for up to 36 months.Results In patients randomized to sevelamer, all-cause mortality and the composite end point were lower; a nonsignificant trend was noted for dialysis inception.Conclusions Sevelamer provided benefits in all-cause mortality and in the composite end point of death or dialysis inception but not advantages in dialysis inception. Larger studies are needed to confirm these results.

Vascular calcification is associated with an adverse prognosis in end-stage renal disease. It can be accurately quantitated with computed tomography but simple in-office techniques may provide equally useful information. Accordingly we compared the results obtained with simple non-invasive techniques with those obtained using electron beam tomography (EBT) for coronary artery calcium scoring (CACS) in 140 prevalent hemodialysis patients. All patients underwent EBT imaging, a lateral X-ray of the lumbar abdominal aorta, an echocardiogram, and measurement of pulse pressure (PP). Calcification of the abdominal aorta was semiquantitatively estimated with a score (Xr-score) of 0-24 divided into tertiles, echocardiograms were graded as 0-2 for absence or presence of calcification of the mitral and aortic valve and PP was divided in quartiles. The CACS was elevated (mean 910+/-1657, median 220). The sensitivity and specificity for CACS > or = 100 was 53 and 70%, for calcification of either valve and 67 and 91%, respectively, for Xr-score > or = 7. The area under the curve for CACS > or = 100 associated with valve calcification and Xr-score was 0.62 and 0.78, respectively. The likelihood ratio (95% confidence interval) of CACS > or = 100 was 1.79 (1.09, 2.96) for calcification of either valve and 7.50 (2.89, 19.5) for participants with an Xr-score > or = 7. In contrast, no association was present between PP and CACS. In conclusion, simple measures of cardiovascular calcification showed a very good correlation with more sophisticated measurements obtained with EBT. These methodologies may prove very useful for in-office imaging to guide further therapeutic choices in hemodialysis patients.

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Bergamo province was badly hit by the coronavirus disease 2019 (COVID-19) epidemic. We organised a public-funded, multidisciplinary follow-up programme for COVID-19 patients discharged from the emergency department or from the inpatient wards of ‘Papa Giovanni XXIII’ Hospital, the largest public hospital in the area. As of 31 July, the first 767 patients had completed the first post-discharge multidisciplinary assessment. Patients entered our programme at a median time of 81 days after discharge. Among them, 51.4% still complained of symptoms, most commonly fatigue and exertional dyspnoea, and 30.5% were still experiencing post-traumatic psychological consequences. Impaired lung diffusion was found in 19%. Seventeen per cent had D-dimer values two times above the threshold for diagnosis of pulmonary embolism (two unexpected and clinically silent pulmonary thrombosis were discovered by investigating striking D-dimer elevation). Survivors of COVID-19 exhibit a complex array of symptoms, whose common underlying pathology, if any, has still to be elucidated: a multidisciplinary approach is fundamental, to address the different problems and to look for effective solutions.

The recent Kidney Disease: Improving Quality Outcomes (KDIGO) recommendations called for an investigation of the relationship between various radiological methods to assess cardiovascular calcification and measures of arterial stiffness. Accordingly, in 131 adult maintenance hemodialysis patients, we investigated the association of aortic pulse wave velocity (PWV) with calcification of cardiac valves on echocardiography, coronary artery, and thoracic aorta calcium on computed tomography and a calcification score of the abdominal aorta obtained on a plain abdominal X-ray. All tests were performed within a week. Mean PWV increased as the severity of coronary artery, thoracic, and abdominal aorta calcium scores increased (each P<0.05). No trend was present for number of valves with calcification. After multivariable adjustment, abdominal aorta X-ray calcium scores remained associated with PWV (P=0.004), whereas the association of PWV with thoracic aorta and coronary artery calcium scores became marginal (P=0.308 and P=0.083, respectively). No association was found between number of calcified valves and PWV. This study demonstrates a strong association between abdominal aorta calcification on plain X-ray and PWV and a borderline association with thoracic aorta and coronary artery calcification. Sudden death and congestive heart failure, two frequent causes of death in hemodialysis, are likely caused by increased arterial stiffness that can be closely predicted by the presence of aortic calcification on plain X-rays.

Aims To assess the prognostic value of a history of heart failure (HF) in patients with coronavirus disease 2019 (COVID‐19). Methods and results We enrolled 692 consecutive patients admitted for COVID‐19 in 13 Italian cardiology centres between 1 March and 9 April 2020. Mean age was 67.4 ± 13.2 years, 69.5% of patients were males, 90 (13.0%) had a history of HF, median hospitalization length was 14 days (interquartile range 9–24). In‐hospital death occurred in 37 of 90 patients (41.1%) with HF history vs. 126 of those with no HF history (20.9%). The increased risk of death associated with HF history remained significant after adjustment for clinical variables related to COVID‐19 and HF severity, including comorbidities, oxygen saturation, lymphocyte count and plasma troponin [adjusted hazard ratio (HR) for death: 2.25; 95% confidence interval (CI) 1.26–4.02; P = 0.006 at multivariable Cox regression model including 404 patients]. Patients with a history of HF also had more in‐hospital complications including acute HF (33.3% vs. 5.1%, P < 0.001), acute renal failure (28.1% vs. 12.9%, P < 0.001), multiorgan failure (15.9% vs. 5.8%, P = 0.004) and sepsis (18.4% vs. 8.9%, P = 0.006). Other independent predictors of outcome were age, sex, oxygen saturation and oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen ratio (PaO2/FiO2). In‐hospital treatment with corticosteroids and heparin had beneficial effects (adjusted HR for death: 0.46; 95% CI 0.29–0.74; P = 0.001; n = 404 for corticosteroids, and adjusted HR 0.41; 95% CI 0.25–0.67; P < 0.001; n = 364 for heparin). Conclusions Hospitalized patients with COVID‐19 and a history of HF have an extremely poor outcome with higher mortality and in‐hospital complications. HF history is an independent predictor of increased in‐hospital mortality.