Project description:Heart failure (HF) is highly prevalent and a major cause of death in the United States. The effect of HF medications on survival has been predicted by validated models studied in populations predominantly of European descent. This study aimed to identify medications associated with survival in a racially diverse HF population. Patients with HF were recruited and followed from 2001 to 2015. Data were collected from electronic health records and the Social Security Death Index. The primary analysis tested the association between medication dose and all-cause mortality, with a secondary analysis assessing the composite outcome of death or cardiac-related hospitalization. Circulating concentration of the fibrotic marker procollagen type III N-terminal peptide (PIIINP) was also compared with medication doses in patients with concentrations available. The study population consisted of 337 patients, of which 25.2% died and 46% were hospitalized. Increased beta-blocker (BB) dose was significantly associated with survival in the base model [hazard ratio (HR) = 0.71, P = 0.017] and marginally associated in the comprehensive model (HR = 0.75, P = 0.068). BB dose was also associated with decreased risk of the composite end point in the base model (HR = 0.80, P = 0.029) and to a lesser extent in the comprehensive model (HR = 0.83, P = 0.085). Furthermore, increased BB dose was inversely associated with circulating PIIINP concentration (P = 0.041). In conclusion, our study highlights the importance of BB dose escalation for survival and decreased hospitalization in patients with HF, regardless of race or HF type. It also suggests that benefits observed with high-dose BBs could be mediated, at least in part, by decreased cardiac fibrosis.
Project description:Beta-blockers (metoprolol, bisoprolol, and carvedilol) are a cornerstone of heart failure (HF) treatment. However, it is well recognized that responses to a beta-blocker are variable among patients with HF. Numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to a beta-blocker, including left ventricular ejection fraction improvement, survival, and hospitalization due to HF exacerbation. This review summarizes the pharmacogenetic data for beta-blockers in patients with HF and discusses the potential implications of beta-blocker pharmacogenetics for HF patients.
Project description:AimsBeta-blockers are proven to improve survival among patients with heart failure with reduced ejection fraction. Their efficacy in patients with heart failure with reduced ejection fraction and pacemaker devices has not been demonstrated. Our aim was to test the hypothesis that beta-blocker therapy is associated with improved survival in patients with chronic heart failure and a pacemaker rhythm on electrocardiogram (ECG).Methods and resultsThis is a post hoc analysis from the GISSI-HF randomized clinical trial. We evaluated efficacy of beta-blockers by creating Cox proportional hazards models adjusting for pacemaker rhythm and heart rate, among other variables. Interactions between pacemaker rhythm, heart rate, and beta-blocker were also examined. Of the 6975 patients enrolled in the GISSI-HF trial, 813 (11.7%) had a pacemaker rhythm on baseline ECG. Of these 813 patients, 511 (62.9%) were receiving beta-blocker therapy. The effect of beta-blocker therapy on mortality was assessed using multivariable Cox proportional hazards adjusted for 27 co-variates. In the whole cohort, beta-blocker therapy was significantly associated with reduced mortality (hazard ratio 0.79 [0.72-0.87], P < 0.001), without interaction between beta-blockers, pacemaker rhythm and heart rate. Beta-blocker therapy was beneficial in the sub-group restricted to baseline pacemaker rhythm (hazard ratio 0.62 [0.49-0.79], P < 0.001).ConclusionsBeta-blocker therapy is associated with improved survival among patients with heart failure and a pacemaker rhythm on ECG. Further studies are necessary to analyse differences between atrial and ventricular pacemakers.
Project description:IntroductionOur objective was to assess whether clusters of centers with similar peritoneal dialysis (PD) catheter related practices were associated with differences in the risk of technique failure.MethodsPatients on incident PD in French centers contributing to the French Language PD Registry from 2012 to 2016 were included in a retrospective analysis of prospectively collected data. Centers with similar catheter cares practices were gathered in clusters in a hierarchical analysis. Clusters of centers associated with technique failure were evaluated using Cox and Fine and Gray models. A mixed effect Cox model was used to assess the influence of a center effect, as explained by the clusters.ResultsData from 2727 catheters placed in 64 centers in France were analyzed. Five clusters of centers were identified. After adjustment for patient-level characteristics, the fourth cluster was associated with a lower risk of technique failure (cause specific-HR 0.70, 95%CI 0.54-0.90. The variance of the center effect decreased by 5% after adjusting for patient characteristics and by 26% after adjusting for patient characteristics and clusters of centers in the mixed effect Cox model. Favorable outcomes were observed in clusters with a greater proportion of community hospitals, where catheters were placed via open surgery, first dressing done 6 to 15 days after catheter placement, and local prophylactic antibiotics was applied on exit-site.ConclusionSeveral patterns of PD catheter related practices have been identified in France, associated with differences in the risk of technique failure. Combinations of favorable practices are suggested in this study.
Project description:BackgroundMatrix metalloproteinase-7 (MMP7) is markedly expressed in patients with chronic kidney disease; its expression in dialysate and role in patients undergoing peritoneal dialysis (PD) have not been well established.MethodsParticipants undergoing PD from June 1st, 2015, to June 30th, 2020, were involved and were followed up every 3 months for the first year and every 6 months thereafter until death, PD withdrawal, or the end of the study. Data at each follow-up point were collected and analyzed for the association with congestive heart failure (CHF), PD withdrawal, and combined endpoint.ResultsA total of 283 participants were included in this study. During a median follow-up of 21 months, 20 (7%) participants died, 93 (33%) withdrew from PD, and 105 (37%) developed CHF. A significantly increased level of serum and dialysate MMP7 was observed at baseline. Dialysate MMP7 presented a good linearity with serum MMP7. Baseline serum and dialysate MMP7 levels were associated with CHF in multivariable Cox proportional hazards regression models. After categorization, participants with high baseline MMP7 levels had a higher incidence of CHF (42%), and the hazard ratios (95% confidence intervals) were 1.595 (1.023-2.488). Interestingly, participants with higher serum MMP7 levels were trended to use dialysate with higher glucose concentration. However, the ultrafiltration volumes were not significantly increased. Higher MMP7 levels were also positively associated with PD withdrawal and combined endpoint.ConclusionsThe expression of MMP7 in serum and dialysate was markedly increased and was tightly associated with the risk of CHF in PD patients. This finding suggests that the measurement of MMP7 may inform strategies for managing CHF at an earlier stage.
Project description:Rationale & objectiveIt is a common practice to start patients in urgent need of dialysis on hemodialysis via a central venous catheter. Because central venous catheter use is associated with increased risk of infections, hospitalizations, and mortality, urgent start peritoneal dialysis (PD) increasingly represents a viable alternative. This study aimed to examine clinical outcomes, complications, mortality, and modality retention in patients who initiated urgent start PD.Study designRetrospective cohort study.Setting and participantsEighty-four adult members of a large integrated health care system who initiated urgent start PD between January 1, 2011, and December 31, 2014.ExposureUrgent start PD.OutcomesRetention rates at 30, 90, and 365 days; time to the development of noninfectious and infectious complications, modality failure, and all-cause mortality.Analytical approachCumulative incidence of all-cause mortality was estimated using the Kaplan-Meier method. Retention rates for PD were computed using binomial proportions.ResultsOccurrence of major complications was less than 5%. Catheter malfunction occurred in 6% of cases; of those, catheter patency could be established in 80%. Infectious complications occurred in 20% of patients who initiated PD and included peritonitis and exit site infections. At 365 days after initiation, the cumulative incidence of all-cause mortality was 9.7% (95% CI, 4.7%-19.4%). PD retention rates were 98.8%, 91.3%, and 80.0% at 30 days, 90 days, and 1 year, respectively.LimitationsRetrospective cohort design, a well-matched comparable group of urgent start hemodialysis patients could not be identified, small number of patients in a single integrated health care system, uncertain or limited generalizability of findings to other health care systems.ConclusionsAt 1 year after initiation, patients who initiated urgent start PD had high survival and modality retention rates. In unplanned initiation of dialysis, urgent start PD is a viable and sustainable option and should be considered in selected patients to optimize care.
Project description:BackgroundSodium disarrays are common in peritoneal dialysis (PD) patients, and may be associated with adverse outcomes in this population. However, few studies of limited sample size have examined the association of serum sodium with mortality in PD patients, with inconsistent results. We hypothesized that both hypo- and hypernatremia are associated with higher death risk in a nationally representative cohort of US PD patients.MethodsWe sought to examine the association of serum sodium over time and mortality among 4687 adult incident PD patients from a large US dialysis organization who underwent one or more serum sodium measurements within the first 3 months of dialysis over January 2007 to December 2011. We examined the association of time-dependent and baseline sodium with all-cause mortality as a proxy of short- and long-term sodium-mortality associations, respectively. Hazard ratios were estimated using Cox models with three adjustment levels: minimally adjusted, case-mix adjusted, and case-mix + laboratory adjusted.ResultsIn time-dependent analyses, sodium levels <140 mEq/L were associated with incrementally higher death risk in case-mix models (ref: 140 to <142 mEq/L); following laboratory covariate adjustment, associations between lower sodium and higher mortality remained significant for levels <136 mEq/L. In analyses using baseline values, sodium levels <140 mEq/L were associated with higher mortality risk across all models (ref: 140 to <142 mEq/L).ConclusionsIn PD patients, lower time-dependent and baseline sodium levels were independently associated with higher death risk. Further studies are needed to determine whether correction of dysnatremia improves longevity in this population.
Project description:Technique failure is a frequent complication of peritoneal dialysis (PD), but the association between causes of death-censored technique failure and mortality remains unclear. Using Australian and New Zealand Dialysis and Transplant (ANZDATA) registry data, we examined the associations between technique failure causes and mortality in all incident PD patients who experienced technique failure between 1989-2014. Of 4663 patients, 2415 experienced technique failure attributed to infection, 883 to inadequate dialysis, 836 to mechanical failure and 529 to social reasons. Compared to infection, the adjusted hazard ratios (HR) for all-cause mortality in the first 2 years were 0.83 (95%CI 0.70-0.98) for inadequate dialysis, 0.78 (95%CI 0.66-0.93) for mechanical failure and 1.46 (95%CI 1.24-1.72) for social reasons. The estimates from the competing risk models were similar. There was an interaction between age and causes of technique failure (pinteraction < 0.001), such that the greatest premature mortality was observed in patients aged >60 years post social-related technique failure. There was no association between causes of technique failure and mortality beyond 2 years. In conclusion, infection and social-related technique failure are associated with premature mortality within 2 years post technique failure. Future studies examining the associations may help to improve outcomes in these patients.
Project description:Background It remains unclear whether beta-blocker use at hospital admission is associated with better in-hospital outcomes in patients with acute decompensated heart failure. Methods and Results We evaluated the factors independently associated with beta-blocker use at admission, and the effect of beta-blocker use at admission on in-hospital mortality in 3817 patients with acute decompensated heart failure enrolled in the Kyoto Congestive Heart Failure registry. There were 1512 patients (39.7%) receiving, and 2305 patients (60.3%) not receiving beta-blockers at admission for the index acute decompensated heart failure hospitalization. Factors independently associated with beta-blocker use at admission were previous heart failure hospitalization, history of myocardial infarction, atrial fibrillation, cardiomyopathy, and estimated glomerular filtration rate <30 mL/min per 1.73 m2. Factors independently associated with no beta-blocker use were asthma, chronic obstructive pulmonary disease, lower body mass index, dementia, older age, and left ventricular ejection fraction <40%. Patients on beta-blockers had significantly lower in-hospital mortality rates (4.4% versus 7.6%, P<0.001). Even after adjusting for confounders, beta-blocker use at admission remained significantly associated with lower in-hospital mortality risk (odds ratio, 0.41; 95% CI, 0.27-0.60, P<0.001). Furthermore, beta-blocker use at admission was significantly associated with both lower cardiovascular mortality risk and lower noncardiovascular mortality risk. The association of beta-blocker use with lower in-hospital mortality risk was relatively more prominent in patients receiving high dose beta-blockers. The magnitude of the effect of beta-blocker use was greater in patients with previous heart failure hospitalization than in patients without (P for interaction 0.04). Conclusions Beta-blocker use at admission was associated with lower in-hospital mortality in patients with acute decompensated heart failure. Registration URL: https://www.upload.umin.ac.jp/; Unique identifier: UMIN000015238.
Project description:Patients with end-stage renal disease (ESRD) are at a higher mortality risk compared with the general population. Previous studies have described a relationship between mortality and patients with ESRD, but the data on standardized mortality ratio (SMR) corresponding to different causes of death in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) are limited. This study was designed as a nationwide population-based retrospective cohort study. Incident dialysis patients between January 2000 and December 2015 in Taiwan were included. Using data acquired from the Taiwan Death Registry, SMR values were calculated and compared with the overall survival. The results showed there were a total of 128,966 patients enrolled, including 117,376 incident HD patients and 11,590 incident PD patients. It was found that 75,297 patients (58.4%) died during the period of 2000-2017. The overall SMR was 5.21. The neoplasms SMR was 2.11; the endocrine, nutritional, metabolic, and immunity disorders SMR was 13.53; the circulatory system SMR was 4.31; the respiratory system SMR was 2.59; the digestive system SMR was 6.1; and the genitourinary system SMR was 27.22. Therefore, more attention should be paid to these diseases in clinical care.