Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial.

BACKGROUND: The administration of intravenous fluid remains the cornerstone treatment for the prevention of contrast-induced acute kidney injury. However, no well-defined protocols exist to guide fluid administration in this treatment. We aimed to establish the efficacy of a new fluid protocol to prevent contrast-induced acute kidney injury. METHODS: In this randomised, parallel-group, comparator-controlled, single-blind phase 3 trial, we assessed the efficacy of a new fluid protocol based on the left ventricular end-diastolic pressure for the prevention of contrast-induced acute kidney injury in patients undergoing cardiac catheterisation. The primary outcome was the occurrence of contrast-induced acute kidney injury, which was defined as a greater than 25% or greater than 0·5 mg/dL increase in serum creatinine concentration. Between Oct 10, 2010, and July 17, 2012, 396 patients aged 18 years or older undergoing cardiac catheterisation with an estimated glomerular filtration rate of 60 mL/min per 1·73 m(2) or less and one or more of several risk factors (diabetes mellitus, history of congestive heart failure, hypertension, or age older than 75 years) were randomly allocated in a 1:1 ratio to left ventricular end-diastolic pressure-guided volume expansion (n=196) or the control group (n=200) who received a standard fluid administration protocol. Four computer-generated concealed randomisation schedules, each with permuted block sizes of 4, were used for randomisation, and participants were allocated to the next sequential randomisation number by sealed opaque envelopes. Patients and laboratory personnel were masked to treatment assignment, but the physicians who did the procedures were not masked. Both groups received intravenous 0·9% sodium chloride at 3 mL/kg for 1 h before cardiac catheterisation. Analyses were by intention to treat. Adverse events were assessed at 30 days and 6 months and all such events were classified by staff who were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT01218828. FINDINGS: Contrast-induced acute kidney injury occurred less frequently in patients in the left ventricular end-diastolic pressure-guided group (6·7% [12/178]) than in the control group (16·3% [28/172]; relative risk 0·41, 95% CI 0·22-0·79; p=0·005). Hydration treatment was terminated prematurely because of shortness of breath in three patients in each group. INTERPRETATION: Left ventricular end-diastolic pressure-guided fluid administration seems to be safe and effective in preventing contrast-induced acute kidney injury in patients undergoing cardiac catheterisation. FUNDING: Kaiser Permanente Southern California regional research committee grant.

Cardiogenic Shock and Respiratory Failure Complicating Takotsubo Syndrome.

OBJECTIVES: This study's purpose is to evaluate the incidence, predictors, and outcomes of patients presenting to the cardiac catheterization laboratory with takotsubo syndrome complicated by respiratory failure or shock. BACKGROUND: The presentation of takotsubo syndrome mimics acute myocardial infarction. It is often diagnosed in the cardiac catheterization laboratory when no coronary obstruction is found. A subset of these patients develops shock or respiratory failure. METHODS: This is a retrospective study of patients who underwent cardiac catheterization at the Kaiser Permanente Southern California health system with takotsubo syndrome between 2006 to 2016. Medical records were manually reviewed to identify patient characteristics, treatment, and clinical outcomes. RESULTS: Among 530 patients with takotsubo syndrome, 56 (10.6%) developed shock or respiratory failure and required mechanical or inotropic support. A higher proportion of these patients were men (14.3% vs 5.7%) and Black (10.7% vs 7.0%). In multivariate logistic regression analyses, factors associated with respiratory failure or shock were age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.94-0.99; P=.02), chronic obstructive pulmonary disease (OR, 1.9; 95% CI, 1.1-3.5; P=.02), chronic kidney disease (OR, 2.6; 95% CI, 1.3-5.3; P=.01), physical trigger (OR, 5.7; 95% CI, 3.0-10.8; P<.01), and ST elevation on the presenting electrocardiogram (OR, 2.5; 95% CI, 1.4-4.8; P=.04). Patients who required mechanical ventilation or inotropic support had significantly higher mortality (hazard ratio, 3.9; 95% CI, 2.1-7.1; P<.001). CONCLUSION: Shock or respiratory failure occur in 10.6% of patients presenting with takotsubo syndrome. Men and patients with baseline respiratory or renal disease were disproportionally affected. These patients have significantly worse clinical outcomes.

Characteristics and outcomes of pregnant women with cardiomyopathy stratified by etiologies: A population-based study.

BACKGROUND: Heart failure is an uncommon diagnosis among pregnant women with limited data on this condition. We sought to describe the characteristics and outcomes of pregnant women with heart failure stratified by etiologies of cardiomyopathy. METHODS: This is a retrospective population-based cohort study across medical centers in Southern California in the United States. Pregnant women with heart failure were identified using ICD-9 codes and adjudicated by manual review of the medical records. Obstetric complications, fetal birthweight, and maternal mortality outcomes were evaluated. RESULTS: Between 2003 and 2014, there were 488 pregnancies (0.1% of all pregnancies) complicated by heart failure, of which 333 (68.2%) were due to peripartum cardiomyopathy (PPCM) and 155 (31.8%) were due to other etiologies (non-PPCM). Compared to patients with non-PPCM, patients with PPCM were more likely to be Black Americans (26.7% vs 15.5%) or Asian Americans (16.8% vs 7.1%). A high proportion of PPCM patients had preeclampsia (11.1% vs 5.2%, p = 0.04). Infants born to mothers with non-PPCM were more likely to be small for gestational age (SGA) (SGA <3% 4.1% vs 9.7%, p < 0.001; SGA <10% 20% vs 8.8%, p = 0.001). No significant difference in maternal mortality was observed between PPCM and non-PPCM patients. CONCLUSIONS: PPCM is the most common etiology of HF during pregnancy. Infants born to mothers with PPCM were likely to be small for gestational age.

Effect of Warfarin on Ischemic Stroke, Bleeding, and Mortality in Patients with Atrial Fibrillation Receiving Peritoneal Dialysis.

BACKGROUND: There is limited information on the risks and benefits of anticoagulation in patients with atrial fibrillation receiving peritoneal dialysis. OBJECTIVE: The aim was to determine the risk of mortality, ischemic stroke, and bleeding associated with warfarin use in patients with atrial fibrillation receiving peritoneal dialysis. PATIENTS AND METHODS: This is a retrospective observational study of a multi-ethnic cohort of patients with atrial fibrillation receiving peritoneal dialysis in the United States. Using a dialysis registry, we identified 476 patients with atrial fibrillation receiving peritoneal dialysis. Among these patients, 115 (24%) were treated with warfarin. Cox proportional hazard models were used to compare risks of mortality, ischemic stroke and bleeding between the groups. RESULTS: Compared to untreated patients, patients receiving warfarin were older (67.3 ± 10.8 vs 62.9 ± 13.3 years) and more likely to be white (42% vs 31%). Prevalence of comorbidities including hypertension, hyperlipidemia, diabetes, heart failure, and prior ischemic stroke were similar between the two groups. All cause mortality rates were 19.9 per 100 person-years in the warfarin group and 21.0 per 100 person-years in the untreated group. There was no difference between groups in the risk of mortality [hazard ratio (HR) 0.8, 95% confidence interval (CI) 0.53-1.2, p = 0.28], ischemic stroke (HR 2.3, 95% CI 0.94-5.4, p = 0.07), hemorrhagic stroke (HR 2.0, 95% CI 0.32-12.8, p = 0.46), gastrointestinal bleeding (HR 0.92, 95% CI 0.39-2.2, p = 0.86), or any bleeding (HR 1.2, 95% 0.60-2.3, p = 0.65). Even in the subgroup of patients with > 70% time in therapeutic range, no association was seen between warfarin treatment and mortality. CONCLUSION: There is no significant association between warfarin treatment with risks of mortality, ischemic stroke or bleeding in patients with atrial fibrillation receiving peritoneal dialysis.

Warfarin use and the risk of mortality, stroke, and bleeding in hemodialysis patients with atrial fibrillation.

BACKGROUND: The optimal management of stroke prophylaxis in hemodialysis patients with atrial fibrillation is controversial. OBJECTIVE: The purpose of this study was to determine the risk of mortality, stroke, and bleeding associated with the use of warfarin in hemodialysis patients with atrial fibrillation. METHODS: This was a retrospective, population-based study of hemodialysis patients with atrial fibrillation between January 1, 2006, and September 30, 2015. Association of warfarin use with mortality, stroke, and bleeding was determined by propensity score-matched, Cox proportional hazard models. RESULTS: Among the 4286 patients with atrial fibrillation on hemodialysis, 989 (23%) were prescribed warfarin. Propensity score matching was used to identify 888 matched pairs with similar baseline characteristics. Warfarin use was associated with lower risk of all-cause death (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.69-0.84) and lower risk of ischemic stroke (HR 0.68, 95% CI 0.52-0.91). Warfarin use was not associated with a higher risk of hemorrhagic stroke (HR 1.2, 95% CI 0.6-2.2) or gastrointestinal bleeding (HR 0.97, 95% CI 0.77-1.2). The treatment effect was largest in the group with the best international normalized ratio control as measured by time in therapeutic range. Subgroup analyses showed warfarin use was associated with survival benefit in most subgroups. The 2 subgroups that did not benefit were patients with a history of hemorrhagic stroke and patients with concurrent aspirin use. CONCLUSION: Warfarin use is associated with lower all-cause mortality and ischemic stroke, without significantly increasing the risk of bleeding in hemodialysis patients with atrial fibrillation.

Atrial Fibrillation and Atrial Flutter in Pregnant Women-A Population-Based Study.

BACKGROUND: The goal of this study was to determine the prevalence of atrial fibrillation and atrial flutter (AF) in pregnant women and to examine the impact of AF on maternal and fetal outcomes. METHODS AND RESULTS: Between January 1, 2003 and December 31, 2013, there were 264 730 qualifying pregnancies (in 210 356 women) in the Kaiser Permanente Southern California hospitals, among whom AF was noted in 157 pregnancies (129 women; 61.3 per 100 000 women, or 59.3 per 100 000 pregnancies). Prevalence of AF (per 100 000 women) in white, black, Asian, and Hispanic women was 111.6, 101.7, 45.0, and 34.3, respectively. Older age was associated with higher odds of having AF. Compared to women <25 years of age, the odds ratio (OR) of AF was 4.1 in women age 30 to 34 years, 4.9 in women age 35 to 39 years, and 5.2 in women age ≥40. Odds of AF episodes were higher during the third trimester compared to the first trimester (OR, 3.2; 95% CI: 1.5-7.7). Among AF patients, adverse maternal cardiac events were rare-2 women developed heart failure and there were no strokes or systemic embolic events and no maternal death. There were 156 live births (99.4% of all pregnancies). Compared to women without AF, fetal birth weights were similar, but rate for neonates' admission to the neonatal intensive care unit was higher (10.8% vs 5.1%; P=0.003). CONCLUSIONS: AF is rare in pregnant women. Certain factors such as increased maternal age and white race increase the odds of having AF. Major maternal and fetal complications are infrequent, albeit a source of concern.

Discontinuation of long-term clopidogrel therapy is associated with death and myocardial infarction after saphenous vein graft percutaneous coronary intervention.

OBJECTIVES: This study sought to examine the pattern of death and myocardial infarction (MI) after clopidogrel cessation in patients undergoing percutaneous coronary intervention (PCI) of the saphenous vein graft (SVG). BACKGROUND: The timing and incidence of adverse events by different durations of clopidogrel therapy after SVG PCI remain unknown. METHODS: This is a cohort study of patients undergoing SVG PCI between 2000 and 2009, followed for all-cause mortality or MI after stopping clopidogrel. Incidence rates were calculated across different time periods after clopidogrel cessation. Adjusted incidence rate ratios (IRR) were calculated with multivariable regression (piecewise exponential and Poisson). RESULTS: There were 603 patients who underwent SVG PCI, of which 411 were event-free at the time of clopidogrel cessation. The incidence rate (95% confidence interval: [CI])/1,000 person-days of death or MI after stopping clopidogrel in the time intervals of 0 to 90 days, 91 to 365 days, and 1 to 2 years were 1.26 (95% CI: 0.93 to 1.70), 0.41 (95% CI: 0.30 to 0.56), and 0.41 (95% CI: 0.30 to 0.55), respectively. In multivariable analyses, the overall IRR (95% CI) for death or MI in the 0- to 90-day interval after stopping clopidogrel compared with the 91- to 365-day interval was 2.58 (95% CI: 1.64 to 4.07). Similar results were observed over a broad range of clopidogrel treatment durations (<6 months, 6 months to 1 year, 1 to 2 years, or >2 years). The results were also consistent across subgroups, including sex, stent type, stent diameter, PCI period, and diabetes status. When death alone was evaluated, there remained a significant increase in the event rate in the 0- to 90-day interval compared with the 91- to 365-day interval (IRR: 2.33; 95% CI: 1.32 to 4.11). CONCLUSIONS: A clustering of events was observed in the initial 0 to 90 days after clopidogrel cessation in all treatment durations of clopidogrel investigated after SVG PCI. These results might have important implications in high-risk cohorts undergoing PCI. Additional studies are needed to elucidate the mechanisms underlying the early clustering of events after clopidogrel cessation.