Impact of cardiovascular risk factors on vessel wall inflammation and calcified plaque burden differs across vascular beds: a PET-CT study

To evaluate the effect of age, gender and cardiovascular risk factors on vessel wall inflammation and the calcified plaque burden in different vascular beds as assessed by PET/CT. 315 patients (mean age: 57.8 years, 123 male and 192 female) who underwent whole body 18F-FDG PET/CT examinations were included in the study. Blood pool-corrected standardised uptake value (TBR) and the calcified plaque score (CPS, grade 0–4) were determined in the thoracic and abdominal aorta, both common carotid and both iliac arteries. The following cardiovascular risk factors were documented: Age ≥65 years (n = 114), male gender (n = 123), diabetes (n = 15), hyperlipidemia (n = 62), hypertension (n = 76), body mass index (BMI) ≥ 30 (n = 38), current smoker (n = 32). Effects of risk factors on TBR and CPS in different arterial beds were assessed using multivariate regression analysis. In the thoracic aorta TBR was independently associated with age ≥65 years and male gender, CPS was independently associated with age ≥65 years, male gender, hypertension and diabetes. In the abdominal aorta, TBR was independently associated with age ≥65 years and male gender, CPS with age ≥65 years, diabetes and smoking. Independent associations in the carotid arteries were found for age ≥65 years, male gender and BMI ≥ 30 in TBR and for age ≥65 and diabetes in CPS. In the iliac arteries, TBR was independently associated with age ≥65 and CPS with age ≥65, male gender, hypertension, diabetes and smoking. Findings of this PET/CT study demonstrate that the impact of cardiovascular risk factors on vessel wall inflammation and calcified plaque burden differs across vascular territories. Overall, CPS was more closely associated with cardiovascular risk factors compared to TBR.     

Multidetector-row computed tomography and magnetic resonance imaging of atherosclerotic lesions in human ex vivo coronary arteries

In the present study, we tested the ability of multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI) to identify and retrospectively characterize atherosclerotic lesions in human ex vivo coronary arteries. Thirteen ex vivo hearts were studied with MDCT and MRI. MDCT-images were obtained with an isotropic voxel size of 0.6mm(3). MR images were obtained with an in-plane resolution of 195 microm and 3mm slice thickness. All images were matched with histopathology sections. For both modalities, the sensitivity for the detection of any atherosclerotic lesion was evaluated, and a retrospective analysis of plaque morphology according to criteria defined by the American Heart Association (AHA) was performed. At histopathology, 28 atherosclerotic lesions were found. 21 and 23 of these lesions were identified by MDCT and MRI, respectively. Both modalities detected a small number of false-positive lesions. After retrospective matching with histopathology, MDCT as well as MRI were able to differentiate typical morpholocigal features for fatty, fibrous or calcified plaque components. Using the information presented in this study, in vivo coronary artery wall imaging using MDCT as well as MRI could be facilitated and supported for future investigations on this subject.     

Hydrogen peroxide contrast echocardiography

Several agents are used as echocardiographic contrast agents, but their unreliability discourages routine clinical use. Studies from the early 1960s suggest that dilute hydrogen peroxide (H₂O₂) is a safe intravascular agent. Its use was evaluated in contrast echocardiography. To obtain dense opacification reliably, H₂O₂ (3%) was passed through a sterile 0.2 μ Millipore filter and diluted with heparinized saline solution to make a 0.1 to 0.2% solution. A drop of blood was withdrawn from an indwelling peripheral venous needle into a syringe containing 0.5 to 2.0 ml of the dilute H₂O₂ and the contents injected. Studies in dogs, normal adults and 36 patients with noncyanotic congenital and acquired cardiac disorders produced dense opacification with no complications. In vitro mixture of H₂O₂ (0.3%) with leukocyte-poor blood or plasma produced only a few microbubbles, while addition to whole blood or buffy coat produced many, suggesting a role for leukocyte peroxidase. H₂O₂ contrast echocardiography is simple, inexpensive, and reliably provides dense, sustained opacification. This study and previous studies suggest that intravenous injection of 0.2% H₂O₂ can be done safely. Great caution should be exercised in patients with severe pulmonary hypertension or large right-to-left shunts because little clinical experience with H₂O₂ is available.     

Right ventricular pacing is an independent predictor for ventricular tachycardia/ventricular fibrillation occurrence and heart failure events in patients with an implantable cardioverter-defibrillator

Aims: There is increasing evidence that right ventricular (RV) pacingmay have detrimental effects by increasing morbidity and mortalityfor heart failure in implantable cardioverter–defibrillator(ICD) patients. In this study we prospectively tested the hypothesisthat cumulative RV pacing increases ventricular tachycardia/ventricularfibrillation (VT/VF) occurrence (primary endpoint) and hospitalizationand mortality for heart failure (secondary endpoint) in a predominantlysecondary prophylactic ICD patient population. Methods and results: Two hundred and fifty patients were divided into two groupsaccording to the median of cumulative RV pacing (2 vs. >2%)and prospectively followed-up for occurrence of primary andsecondary endpoints for 18 ± 4 months. Established predictorsfor VT/VF occurrence and heart failure events such as age, leftventricular ejection fraction (EF), QRS duration, history ofatrial fibrillation, and NT-proBNP were collected at enrolment.Multivariate Cox regression analysis revealed that cumulativeRV pacing > 2% and EF < 40% were independent predictorsfor VT/VF occurrence and heart failure events. Kaplan–Meieranalysis showed that patients with >2% cumulative RV pacingmore frequently suffered from VT/VF occurrence and heart failurehospitalization. Conclusion: Cumulative RV pacing > 2% and EF < 40% are independentpredictors for VT/VF occurrence and mortality and hospitalizationfor heart failure in predominantly secondary prophylactic ICDpatients. Our data show that algorithms capable of reducingcumulative RV pacing should be used more frequently in clinicalpractice.     

Time on previous renal replacement therapy is associated with worse outcomes of COVID-19 in a regional cohort of kidney transplant and dialysis patients

Chronic renal replacement therapy by either a kidney transplant (KTX) or hemodialysis (HD) predisposes patients to an increased risk for adverse outcomes of COVID-19. However, details on this interaction remain incomplete. To provide further characterization, we undertook a retrospective observational cohort analysis of the majority of the hemodialysis and renal transplant population affected by the first regional outbreak of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) in Germany. In a region of 250,000 inhabitants we identified a total of 21 cases with SARS-CoV-2 among 100 KTX and 260 HD patients, that is, 7 KTX with COVID-19, 14 HD with COVID-19, and 3 HD with asymptomatic carrier status. As a first observation, KTX recipients exhibited trends for a higher mortality (43 vs 18%) and a higher proportion of acute respiratory distress syndrome (ARDS) (57 vs 27%) when compared to their HD counterparts. As a novel finding, development of ARDS was significantly associated with the time spent on previous renal replacement therapy (RRT), defined as the composite of dialysis time and time on the transplant (non-ARDS 4.3 vs ARDS 10.6 years, P = .016). Multivariate logistic regression analysis showed an OR of 1.7 per year of RRT. The association remained robust when analysis was confined to KTX patients (5.1 vs 13.2 years, P = .002) or when correlating the time spent on a renal transplant alone (P = .038). Similarly, longer RRT correlated with death vs survival (P = .0002). In conclusion our data suggest renal replacement vintage as a novel risk factor for COVID-19-associated ARDS and death. The findings should be validated by larger cohorts.     

Oxygenation Status in Chronic Leg Ulcer After Topical Hemoglobin Application May Act as a Surrogate Marker to Find the Best Treatment Strategy and to Avoid Ineffective Conservative Long-term Therapy

Purpose

Chronic leg ulcers can be a challenge to treat and long-term therapy a significant cost factor in western public health budgets. Objective wound assessment assays enabling selection of appropriate wound therapy regimes would be desirable. Oxygenation status in ulcer tissue has obtained increased attention as a relevant factor in wound healing. To increase oxygenation in wounds, a topical hemoglobin spray was developed. Although favorable results have been noted, the link between clinical efficacy and the mode of action has not been demonstrated. The aims were to determine if changes in tissue oxygenation can be measured after topical application of hemoglobin on chronic wounds and to evaluate the findings in terms of therapy strategies.

Procedures

Photoacoustic imaging was used to measure the local oxygen saturation (StO₂) in leg ulcers before and after hemoglobin spray treatment. Sclerosis of the leg ulcers was histopathologically graded and the change in wound size was documented in a follow-up examination.

Results

Measuring 49 patients, an increase in StO₂ after topical hemoglobin application from on average 66.1 to 71 % (p = 0.017) after 20 min was observed. Depending on the increase in StO₂ (>10 % or <10 %) patients were stratified into a Responder and a Non-Responder group. Wound size significantly decreased in the Responder Group (p = 0.001), while no significant difference in the Non-Responder group (p = 0.950) was noted.

Conclusion

Our findings suggest that the likelihood of wound healing under conservative therapy can be predicted by measuring changes in StO₂ after topical hemoglobin application. This assay may reduce treatment time and costs by avoiding ineffective conservative long-term therapy.

Trial Registration

German Clinical Trials Register: DRKS00005993

     

Flu and Finances: Influenza Outbreaks and Loan Defaults in US Cities, 2004–2012

Objectives. We examined the association between influenza outbreaks in 83 metropolitan areas and credit card and mortgage defaults, as measured in quarterly zip code–level credit data over the period of 2004 to 2012.Methods. We used ordinary least squares, fixed effects, and 2-stage least squares instrumental variables regression strategies to examine the relationship between influenza-related Google searches and 30-, 60-, and 90-day credit card and mortgage delinquency rates.Results. We found that a proxy for influenza outbreaks is associated with a small but statistically significant increase in credit card and mortgage default rates, net of other factors. These effects are largest for 90-day defaults, suggesting that influenza outbreaks have a disproportionate impact on vulnerable borrowers who are already behind on their payments.Conclusions. Overall, it appears there is a relationship between exogenous health shocks (such as influenza) and credit default. The results suggest that consumer finances could benefit from policies that aim to reduce the financial shocks of illness, particularly for vulnerable borrowers.Seasonal influenza is a viral airborne disease that generally spreads each fall and winter, causing an estimated 1.5 million people to get sick and 200 000 to be hospitalized in a typical year in the United States.1,2 Symptoms can range from mild and hardly distinguishable from a common cold to severe and life-threatening. Influenza accounts for at least 500 000 deaths in the United States in the past 3 decades.3For employed individuals, influenza can make attending work difficult, because of either personal illness or caring for sick household members. This generates significant costs to employers and employees. Estimates from 2007 suggest that annual influenza outbreaks lead to $16.3 billion in lost productivity and wages, and $10.4 billion in medical costs,4 although these costs vary considerably across place.5Although there is a robust literature on the economic costs of influenza, we know little about how such unexpected health shocks are associated with other aspects of the economy, such as loan defaults. We built on existing knowledge of the economic costs of influenza by examining how influenza outbreaks influence credit card and mortgage default rates in US cities.In the wake of the Great Recession, loan defaults have increased, with negative financial consequences for families.6 For loans due on a monthly basis, such as mortgages and credit cards, past-due balances and late fees accumulate each month. Three missed payments (90-day delinquent) is a signal of a loan at high risk for failure and in most states triggers legal collections processes.7In the microeconomic literature, illness is seen as a shock—an unexpected event—that can affect household income and expenses. If the shock results in a disruption to income, households will respond with shifts in consumption and expenditure patterns.8 We contend that influenza, as a health shock, has the potential to trigger loan default by constraining a family’s budget because of personal illness or caretaking burdens. Influenza may also trigger inattention to household financial management and a lack of planning for future bill payments.9–11 This may be especially problematic for borrowers who are already behind on their payments, whom we define as vulnerable borrowers. For these borrowers, who also tend to be economically vulnerable and disadvantaged in other ways,12,13 an influenza outbreak could increase the likelihood of further missed payments. A recent study supports this notion, and shows that economically vulnerable households are more likely to borrow and borrow more in the event of a health shock than less vulnerable households.14 However, this study did not examine credit default.A growing literature examines the complex and potentially multidirectional relationship between health and default.15–19 Most research examines whether defaults influence health,15,19,20 and less examines how health may have an impact on default risk.21 However, a key problem inherent in this literature is that health status is endogenous, and it is difficult if not impossible to disentangle processes of causation, selection, and reverse causation with survey data.Our interest in influenza provides us with a unique opportunity to improve causal estimates of health shocks on default. Influenza occurs to varying degrees in every city and year in the United States, and the intensity of the outbreak is an ostensibly exogenous health shock for communities. Thus, influenza outbreaks provide a natural experiment in which we use variation in influenza severity across time and place to identify the effects of a particular health shock on default. Specifically, we ask whether influenza outbreaks in US metropolitan statistical areas (MSAs) are associated with defaults from the first quarter (March) of 2004 (Q1 2004) to the second quarter (June) of 2012 (Q2 2012).We make 3 contributions with this study. First, we extended the literature on the economic costs of influenza. Second, we contributed to the literature on health shocks and default by providing a stronger test of the potential causal impacts of health shocks on loan default. Third, we considered whether effects vary across types of default, including 30-, 60-, and 90-day defaults. We predicted that influenza may have the greatest effect on borrowers who are already in default, such that the association between influenza and default should be stronger for borrowers who are farther behind.