Contrast-Induced Nephropathy and Long-Term Adverse Events: Cause and Effect?

Background and objectives: The relationship of contrast-induced nephropathy (CIN) to long-term adverse events (AEs) is controversial. Although an association with AEs has been previously reported, it is unclear whether CIN is causally related to these AEs.Design, setting, participants, & measurements: We obtained long-term (≥1 yr) follow-up on 294 patients who participated in a randomized, double-blind comparison of two prevention strategies for CIN (iopamidol versus iodixanol). A difference in the incidence of AEs between patients who had developed CIN and those who had not was performed using a χ² test and Poisson regression analysis. A similar statistical approach was used for the differences in AEs between those who received iopamidol or iodixanol. Multiple definitions of CIN were used to strengthen and validate the results and conclusions.Results: The rate of long-term AEs was higher in individuals with CIN (all definitions of CIN). After adjustment for baseline comorbidities and risk factors, the adjusted incidence rate ratio for AEs was twice as high in those with CIN. Randomization to iopamidol reduced both the incidence of CIN and AEs.Conclusions: The parallel decrease in the incidence of CIN and AEs in one arm of this randomized trial supports a causal role for CIN.Contrast-induced nephropathy (CIN), a form of acute kidney injury (AKI), has received increasing attention in the past few years as a result of new knowledge regarding its pathogenesis, the proliferation of innovative approaches to its prevention, and recognition that CIN is associated with long-term adverse events (AEs) (1–5). The increased incidence of AEs after CIN is derived primarily from retrospective analyses of large databases (2,4,5) or observational studies (3) of patients who have undergone coronary angiography and/or percutaneous coronary intervention. A cause-and-effect relationship cannot be determined from such data. Patients with an increased burden of cardiovascular risk factors before contrast medium exposure may be more likely to develop CIN and independent of the occurrence of CIN have more long-term AEs. Alternatively, the occurrence of CIN may in some as-yet-undefined manner alter the future likelihood of AEs (i.e., CIN is on a pathophysiologic pathway that leads to AEs).Randomized, prospective trial designs provide an opportunity to explore causal relationships. If CIN is causally related to long-term AEs, then a strategy that prevents CIN should reduce long-term AEs, as long as the strategy itself does not alter any other risk factors for those AEs. In a randomized trial of two different treatments, the assumption is that the baseline risk factors for long-term AEs will be equally distributed between the two treatments being tested. Differences in the incidence of CIN between treatments, if paralleled by differences in long-term AEs, would suggest that CIN is on a pathophysiologic pathway that leads to those AEs.The Cardiac Angiography in Renally Impaired Patients (CARE) Study was a large, multicenter, prospective, double-blind, randomized clinical trial of patients who had moderate to severe chronic kidney disease and were undergoing cardiac angiography (6). The primary end point was the incidence of CIN. Patients were randomly assigned to two different treatments represented by two different contrast media: The low-osmolar, nonionic monomer iopamidol (Isovue; Bracco Diagnostics Inc., Princeton, NJ) and the iso-osmolar, nonionic dimer iodixanol (Visipaque; GE Healthcare, Princeton, NJ). Neither contrast medium has any known effect on the baseline risk factors that might contribute to long-term AEs. In this report, follow-up data were collected on 294 of the original participants of the CARE trial approximately 12 mo after entry into the trial. To explore whether a causal link exists between CIN and long-term AEs, we studied the differences in the incidence of CIN and long-term AEs between the two treatments (contrast media). Since the results of the CARE study were published, new definitions of AKI and thus CIN have been suggested (7). These new definitions increase the incidence of CIN and thus enhance the statistical power to detect associations with long-term outcomes.     

Clinical,Angiographic, and Procedural Correlates of Very Late Absorb Scaffold Thrombosis: Multistudy Registry Results

Objectives

The aim of this study was to identify independent correlates of very late scaffold thrombosis (VLST) from an analysis of consecutively treated patients from 15 multicenter studies.

Clinical Cardiovascular Adverse Events Reported Post-COVID-19 Vaccination: Are They a Real Risk?

Given the urgent need to control the spread of the novel COVID-19 virus, 13 vaccines have been approved for emergency use before completing all 3 phases of the clinical trials. Thereby a careful monitor of the adverse effects postvaccination is essential. We searched through PubMed and other reporting systems like VAERS for the reported cardiovascular adverse events post-COVID-19 vaccination. Through our review, we determined that the incidence of all the reported cardiovascular events is very rare. Additionally, the vaccine was initially given to the elderly and high-risk populations in which cardiovascular events such as myocardial infarction and arrhythmias are already more prevalent, while other cardiovascular events such as myocarditis or vaccine-induced thrombotic thrombocytopenia were more common in younger populations. Moreover, a direct causal relationship, if any, between vaccination and adverse events is yet to be fully elucidated. Thus, at this time point, the benefits of vaccination far outweigh the risk.     

Adverse Safety Events in Chronic Kidney Disease: The Frequency of “Multiple Hits”

Background and objectives: Chronic kidney disease (CKD) lacks standardized patient safety indicators (PSIs); however, undetected safety events are likely to contribute to adverse outcomes in this disease. This study sought to determine the proportion of CKD patients who experience multiple potentially hazardous events from varied causes and to identify risk factors for the occurrence of “multiple hits.”Design, setting, participants, & measurements: A sample of patients with CKD (n = 70,154) in the Veterans Health Administration (VHA) were retrospectively examined for the occurrence of one or more safety events from a set of indicators defined a priori, including Agency for Healthcare Research and Quality (AHRQ) PSIs, hypoglycemia, hyperkalemia, and dosing for selected medications not accounting for CKD.Results: Approximately half of the cohort participants experienced one or two adverse safety events, whereas 7% had three or four (multiple) distinct events. Individuals with three or four of the predesignated safety events were more likely to be diabetic, non-Caucasian, have an estimated GFR (eGFR) < 30 ml/min/1.73 m², and be ≤65 yr of age. A “Safety Risk Index” was developed using these characteristics, and those subjects that had all four traits were 25 times as likely to have three or four adverse safety events versus those with none of the characteristics.Conclusions: Patients with CKD are at a high risk for safety events pertinent to this disease and a substantial number are subject to multiple events from a diverse set of safety indicators, which could have important consequences in disease outcomes.Chronic kidney disease (CKD) is increasing in prevalence in the United States (1), and patients with CKD are susceptible to adverse outcomes that may be linked to the delivery of care (2). The array of such potentially harmful events—often called safety events—in CKD includes those typically described for the general population as well as several others specific to this disease state. The Agency for Healthcare Research and Quality (AHRQ)-defined set of patient safety indicators (PSIs) has been shown to be an effective tool for monitoring and tracking safety events in the general hospitalized population (3,4). Broadening the set of potential safety measures to include events pertinent to inpatient and ambulatory care in CKD is likely to increase the detection of harmful safety events in this disease.We hypothesize that a broader set of safety measures in CKD will increase the probability of detecting potentially harmful safety events, and that there is an increased likelihood of multiple distinct events in any given individual with the disease. We defined a set of distinct safety indicators (AHRQ-defined PSIs, hypoglycemia, hyperkalemia, and select medications with inappropriate dosing) to be measured in a large sample of persons with CKD. The objective was to determine the proportion of the study population who experienced one or more of these predesignated safety events and to identify the risk factors for those individuals who suffered from multiple distinct safety events.     

Reduction of Adverse Events With Phosphodiesterase 5 Inhibitors Post LVAD Implantation: Is It Time for a Randomized Trial?

The improved survival of patients with advanced heart failure after left ventricular assist device (LVAD) implantation together with the scarcity of donor hearts has significantly increased the population of LVAD-supported patients. However, despite the improvement in LVAD technology and the advent of third-generation continuous flow LVADs, complications such as those related to hemocompatibility and stroke rates remain ongoing clinical challenges. Thus, improvement in LVAD technology should be coupled with innovative medical management to further reduce adverse events. We have previously shown a strong association between post LVAD implant phosphodiesterase-5 inhibitors (PDE-5i) use and fewer thrombotic events, as well as improved survival in 2 observational studies. We caution, nevertheless, the use of PDE-5i based on these observations and encourage clinicians to support enrollment in a randomized control trial. A randomized control trial will determine the efficacy and safety of PDE-5i use after implantation in patients with a centrifugal flow LVAD.     

Abnormal Coronary Anatomy in Patients with Transposition of the Great Arteries and Atrial Switch: A Predictor of Serious Cardiac Adverse Events?

Sudden cardiac death and heart failure are well known long-term complications after atrial switch for D-transposition of the great arteries (D-TGA). Right systemic ventricular dysfunction is common and myocardial ischemia has been implicated as a putative mechanism for sudden death, with coronary anomalies prevalent in 30% of cases. We sought to assess an association between adverse events and coronary anomalies in patients with D-TGA and atrial switch surgery. An observational study was conducted in 3 tertiary centers (Montreal Heart Institute, Canada, Nationwide Children’s hospital, Chicago, USA and Hopital cardiologique Louis Pradel de Lyon, France). Adults with D-TGA and atrial switch surgery qualified for inclusion if they had a major adverse cardiovascular event (MACE), i.e., ventricular arrhythmia, sudden cardiac death, heart failure, cardiac transplantation, or cardiovascular death. The prevalence of coronary anomalies was compared to historical controls. Forty-five patients were included. Twenty-one (46.7%) patients experienced a ventricular arrhythmia and 35 (77.8%) suffered from symptomatic heart failure and/or severe right ventricular dysfunction. Twelve patients (26.7%) had congenitally abnormal coronary arteries. There was no difference in the prevalence of coronary anomalies between the cohort with a MACE and a pooled population of 647 historical controls with D-TGA (28.7%, p = 0.89). In conclusion, the prevalence of congenital coronary anomalies is not higher in patients with D-TGA and atrial switch surgery who had adverse cardiovascular events. It could be hypothesized that ischemic complications in this patient population are more likely to be related to a supply-demand mismatch of the distal microvasculature rather than proximal coronary anomalies.     

Characteristics and Outcomes of Patients with Inflammatory Cardiomyopathies Receiving Mechanical Circulatory Support: An STS–INTERMACS Registry Analysis

BackgroundDurable mechanical circulatory support (MCS) therapy improves survival in patients with advanced heart failure. Knowledge regarding the outcomes experienced by patients with inflammatory cardiomyopathy (CM) who receive durable MCS therapy is limited.Methods and ResultsWe compared patients with inflammatory CM with patients with idiopathic dilated CM enrolled in the STS–INTERMACS registry. Among 19,012 patients, 329 (1.7%) had inflammatory CM and 5978 had idiopathic dilated CM (31.4%). The patients with inflammatory CM were younger, more likely to be White, and women. These patients experienced more preoperative arrhythmias and higher use of temporary MCS. Patients with inflammatory CM had a higher rate of early adverse events (<3 months after device implant), including bleeding, arrhythmias, non–device-related infections, neurologic dysfunction, and respiratory failure. The rate of late adverse events (≥3 months) was similar in the 2 groups. Patients with inflammatory CM had a similar 1-year (80% vs 84%) and 2-year (72% vs 76%, P = .15) survival. Myocardial recovery resulting in device explant was more common among patients with inflammatory CM (5.5% vs 2.3%, P < .001).ConclusionsPatients with inflammatory CM who received durable MCS appear to have a similar survival compared with patients with idiopathic dilated CM despite a higher early adverse event burden. Our findings support the use of durable MCS in an inflammatory CM population.     

Improving Healthcare Systems’ Disclosures of Large-Scale Adverse Events: A Department of Veterans Affairs Leadership,Policymaker, Research and Stakeholder Partnership

BACKGROUND

The Department of Veterans Affairs (VA) mandates disclosure of large-scale adverse events to patients, even if risk of harm is not clearly present. Concerns about past disclosures warranted further examination of the impact of this policy.

OBJECTIVE

Through a collaborative partnership between VA leaders, policymakers, researchers and stakeholders, the objective was to empirically identify critical aspects of disclosure processes as a first step towards improving future disclosures.

DESIGN

Semi-structured interviews were conducted with participants at nine VA facilities where recent disclosures took place.

PARTICIPANTS

Ninety-seven stakeholders participated in the interviews: 38 employees, 28 leaders (from facilities, regions and national offices), 27 Veteran patients and family members, and four congressional staff members.

APPROACH

Facility and regional leaders were interviewed by telephone, followed by a two-day site visit where employees, patients and family members were interviewed face-to-face. National leaders and congressional staff also completed telephone interviews. Interviews were analyzed using rapid qualitative assessment processes. Themes were mapped to the stages of the Crisis and Emergency Risk Communication model: pre-crisis, initial event, maintenance, resolution and evaluation.

KEY RESULTS

Many areas for improvement during disclosure were identified, such as preparing facilities better (pre-crisis), creating rapid communications, modifying disclosure language, addressing perceptions of harm, reducing complexity, and seeking assistance from others (initial event), managing communication with other stakeholders (maintenance), minimizing effects on staff and improving trust (resolution), and addressing facilities’ needs (evaluation).

CONCLUSIONS

Through the partnership, five recommendations to improve disclosures during each stage of communication have been widely disseminated throughout the VA using non-academic strategies. Some improvements have been made; other recommendations will be addressed through implementation of a large-scale adverse event disclosure toolkit. These toolkit strategies will enable leaders to provide timely and transparent information to patients and families, while reducing the burden on employees and the healthcare system during these events.

     

Appropriate therapy for fistulizing and fibrostenotic Crohn's disease: Results of a multidisciplinary expert panel — EPACT II

IntroductionMany therapeutic decisions in the management of fistulizing and fibrostenotic Crohn's disease (CD) have to be taken without the benefit of strong scientific evidence. For this reason, explicit appropriateness criteria for CD fistula and stenosis treatment were developed by a multidisciplinary European expert panel in 2004 with the aim of making them easily available on the Internet and thus allowing individual case scenario evaluation; these criteria were updated in 2007.MethodsTwelve international experts convened in Geneva, Switzerland in December 2007. Explicit clinical scenarios, corresponding to real daily practice, were rated on a 9-point scale based on evidence from the published literature and panelists' own expertise. Median ratings were stratified into three categories: appropriate (7–9), uncertain (4–6) and inappropriate (1–3).ResultsOverall, panelists rated 60 indications pertaining to fistulas. Antibiotics, azathioprine/6-mercaptopurine and conservative surgery are the mainstay of therapy for simple and complex fistulas. In the event of previous failure of azathioprine/6-mercaptopurine therapy, methotrexate and infliximab were considered appropriate for complex fistulas. The panel also rated 72 indications related to the management of fibrostenotic CD. The experts considered balloon dilation, if the stricture was endoscopically accessible, stricturoplasty and bowel resection to be appropriate for small bowel fibrostenotic Crohn's disease, and balloon dilation and bowel resection appropriate for fibrostenotic colonic disease. In the presence of an ileocolonic or ileorectal anastomotic stricture of < 7 cm, endoscopic balloon dilation, and bowel resection were considered appropriate.ConclusionAntibiotics, azathioprine/6-mercaptopurine, and conservative surgery are the mainstay of therapy for fistulizing Crohn's disease. Infliximab is a therapeutic option in patients without prior response to immunosuppressant therapy. In fibrostenotic Crohn's disease, endoscopic balloon dilation, if feasible, or surgical therapy should be considered. These expert recommendations are available online (www.epact.ch). Prospective evaluation is now needed to test the validity of these appropriateness criteria in clinical practice.     

Internal Procidentia of the Rectum — Treatment and Results

Thirty-nine patients, 34 women and 5 men, with internal procidentia have been studied regarding symptomatology and results of treatment. Nineteen women have been operated upon. The most common indication for operation was anal incontinence. Twenty patients have been treated conservatively with bulk laxatives. In the operated group, 11 were symptom-free, 5 had recurrences, 2 had unchanged symptoms and one patient was worse because of rectovaginal fistula. The 5 recurrences were operated upon according to the techniques of Graham and Moschcowitz (4, 5). One of the conservatively treated patients developed a rectal prolapse in the followup period.     

Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial

Background

Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE.

Risk of Cardiovascular Events and Death—Does Insurance Matter?

BACKGROUND Many Americans lack health insurance. Despite good evidence that lack of insurance compromises access to care, few prospective studies examine its relationship to health outcomes. OBJECTIVE To determine the relationship between insurance and cardiovascular outcomes and the relationship between insurance and selected process measures. DESIGN AND PARTICIPANTS We used data from 15,792 participants in the Atherosclerosis Risk in Communities Study, a prospective cohort study. Participants were enrolled in 1987–1989 and returned for follow-up visits every 3 years, for a total of 4 visits. MAIN OUTCOME MEASURES We estimated the hazard of myocardial infarction, stroke, and death associated with insurance status using Cox proportional hazard modeling. We used generalized estimating equations to examine the association between insurance status and risk of (1) reporting no routine physical examinations, (2) being unaware of a personal cardiovascular risk condition, and (3) inadequate control of cardiovascular risk conditions. RESULTS Persons without insurance had higher rates of stroke (adjusted hazard ratio, 95% CI 1.22–2.22) and death (adjusted hazard ratio 1.26, 95% CI 1.03–1.53), but not myocardial infarction, than those who were insured. The uninsured were less likely to report routine physical examinations (adjusted risk ratio 1.13, 95% CI 1.08–1.18); more likely to be unaware of hypertension (adjusted risk ratio 1.12, 95% CI 1.00–1.25) and hyperlipidemia (adjusted risk ratio 1.11, 95% CI 1.03–1.19); and more likely to have poor blood pressure control (adjusted risk ratio 1.23, 95% CI 1.08–1.39). CONCLUSIONS Lack of health insurance is associated with increased rates of stroke and death and with less awareness and control of cardiovascular risk conditions. Health insurance may improve cardiovascular risk factor awareness, control and outcomes.