Mortality and healthcare resource utilisation after cardiac arrest in the United States - A 10-year nationwide analysis prior to the COVID-19 pandemic.

AIM: Understanding the public health burden of cardiac arrest (CA) is important to inform healthcare policies, particularly during healthcare crises such as the COVID-19 pandemic. This study aimed to analyse outcomes of in-hospital mortality and healthcare resource utilisation in adult patients with CA in the United States over the last decade prior to the COVID-19 pandemic. METHODS: The United States (US) National Inpatient Sample was utilised to identify hospitalised adult patients with CA between 2010 and 2019. Logistic and Poisson regression models were used to analyse outcomes by adjusting for 47 confounders. RESULTS: 248,754 adult patients with CA (without "Do Not Resuscitate"-orders) were included in this study, out of which 57.5% were male. In-hospital mortality was high with 51.2% but improved significantly from 58.3% in 2010 to 46.4% in 2019 (P < 0.001). Particularly, elderly patients, non-white patients and patients requiring complex therapy had a higher mortality rate. Although the average hospital LOS decreased by 11%, hospital expenses have increased by 13% between 2010 and 2019 (each P < 0.001), presumably due to more frequent use of mechanical circulatory support (MCS, e.g. ECMO from 2.6% to 8.7% or Impella® micro-axial flow pump from 1.8% to 14.2%). Strong disparities existed among patient age groups and ethnicities across the US. Of note, the number of young adults with CA and opioid-induced CA has almost doubled within the study period. CONCLUSION: Over the last ten years prior to the COVID-19 pandemic, CA-related survival has incrementally improved with shorter hospitalisations and increased medical expenses, while strong disparities existed among different age groups and ethnicities. National standards for CA surveillance should be considered to identify trends and differences in CA treatment to allow for standardised medical care.

Magnetocardiography for the detection of myocardial ischemia.

Ischemic heart disease (IHD) continues to be a significant global public health concern and ranks among the leading causes of mortality worldwide. However, the identification of myocardial ischemia in patients suspected of having coronary artery disease (CAD) remains a challenging issue. Functional or stress testing is widely recognized as the gold standard method for diagnosing myocardial ischemia, but it is hindered by low diagnostic accuracy and limitations such as radiation exposure. Magnetocardiography (MCG) is a non-contact, non-invasive method that records magnetic fields produced by the electrical activity of the heart. Unlike electrocardiography (EKG) and other functional or stress testing, MCG offers numerous advantages. It is highly sensitive and can detect early signs of myocardial ischemia that may be missed by other diagnostic tools. This review aims to provide an extensive overview of the available evidence that establishes the utility of MCG as a valuable diagnostic tool for identifying myocardial ischemia, accompanied by a discussion of potential future research directions in this domain.

Fibrotic plaques in heart transplanted patients and their association with insulin resistance syndrome and Lp(a).

BACKGROUND: Angiographic evidence of cardiac allograft vasculopathy (CAVangio) is a major limiting factor to survival after heart transplantation (HTx). Prevention of CAVangio is therefore most relevant. Whether modifiable risk factors could be targeted for the prevention of fibrotic plaques, that are common and related to CAVangio, is not clear. METHODS AND RESULTS: In a cohort of 74 consecutive HTx patients (median post-transplant interval 9.2 [4.1-15.5] years), we used the high resolution of optical coherence tomography (OCT) to quantify angulation parameters (maximal and mean arc) and plaque load (mean arc*relative plaque length) of fibrotic plaques. Mean arc was defined as the mean value of all angulation measurements per patient. We assessed the association between cardiovascular risk factors and OCT findings. Linear regression analysis showed a significant association of TG/HDL-c with mean fibrotic arc (12.7 [3.9-21.5], p = 0.006) and fibrotic plaque load (2298 [617-3979], p = 0.009) after adjustment for recipient age and sex. We used the median value of fibrotic plaque load to define high fibrotic plaque load. In binary logistic regression analysis, TG/HDL-c (odds ratio [OR] 1.81 with 95% CI [1.09-3.03], p = 0.02) and Lp(a) (OR 1.02 [1.00-1.05], p = 0.02) were associated with high fibrotic plaque load. Multivariable logistic regression analysis confirmed Lp(a) as significant predictor of high fibrotic plaque load (OR 1.03 [1.01-1.05], p = 0.02). CONCLUSION: TG/HDL-c ratio, a surrogate of insulin resistance syndrome, and Lp(a) were significantly associated with fibrotic plaque in HTx patients. Insulin resistance syndrome and Lp(a) might therefore represent additional targets for CAV prevention.

Assessment of sex- and age-dependency of risk factors for intimal hyperplasia in heart transplant patients using the high resolution of optical coherence tomography.

BACKGROUND: Intimal hyperplasia in cardiac allograft vasculopathy (CAVIH) is limiting survival in pediatric and adult patients after heart transplantation (HTx). Analysis of risk factors for CAVIH using the high resolution of intracoronary optical coherence tomography (OCT) is scarce, particularly in children, and recommendations for CAV prevention are largely based on data obtained in adults. Whether the predictive value of risk factors is age- or sex-dependent is unknown. METHODS AND RESULTS: We used OCT to test the age- and sex-dependency of established risk factors regarding pathological CAVIH in a cohort of 102 pediatric and adult HTx patients (35% <18 years, 69% male). Modifiable parameters such as lipid values, and the diagnoses of dyslipidemia and diabetes showed age- and sex-dependent differences. Regarding CAVIH, receiver-operating characteristic analysis showed that LDL-c was relevant only in female patients (area under the curve [AUC] 0.79, p = 0.007), and total cholesterol in female (AUC 0.81; p = 0.004) and pediatric patients (AUC 0.73, p < 0.05). The association of dyslipidemia with CAVIH was stronger in adult (odds ratio [OR] 6.33) than in pediatric patients (OR 5.00) and in women (OR 6.00) than in men (OR 4.57). Diabetes was associated with CAVIH only in women (OR 11.25). CONCLUSION: In our cohort, modifiable risk factors, particularly total cholesterol and dyslipidemia, had a different impact depending on age and sex. Targeting risk factors in selected patients might improve individual CAVIH prevention.

Analysis of Fibrotic Plaques in Angiographic Manifest Cardiac Allograft Vasculopathy in Long-term Heart Transplanted Patients Using Optical Coherence Tomography.

BACKGROUND: The development and progression of cardiac allograft vasculopathy documented by coronary angiography (CAVangio) after heart transplantation (HTx) has prognostic relevance. Yet there are limited data regarding the role of concomitant intracoronary imaging in the presence CAVangio. In particular, atherosclerotic plaques might represent a potential target for prevention, but their impact on stenosis is understudied. METHODS: We used high-resolution intracoronary optical coherence tomography (OCT) to quantify and compare findings of intimal hyperplasia (IH) and plaque morphologies in HTx patients (fibrotic plaque, lipid plaque, and calcified plaque). OCT findings were related to the presence of CAVangio as well as to the severity of stenosis. RESULTS: We included 65 consecutive patients into analysis (66% with CAVangio, posttransplant interval 9.9 ± 7.6 y). Fibrotic, lipid, and calcified plaques were present in 41 (63.1%), 39 (60%), and 18 (27.7%) patients, respectively. In addition to IH, the presence of fibrotic, lipid, and calcified plaques was found to be associated with CAVangio. The prevalence of lipid plaque and quantitative measurements of fibrotic plaque increased with stenosis severity (lipid plaque, P < 0.001, maximal and mean fibrotic arc, P = 0.05 and P = 0.001, respectively). Receiver operating characteristic analysis showed that area under the curve of the fibrotic plaque parameter mean fibrotic arc (0.87, 95% confidence interval [0.76-0.99]; P = 0.002) was superior to area under the curve of intima parameters regarding CAVangio. The effect of mean fibrotic arc (r = 0.52, P < 0.001) was relevant regarding stenosis severity. CONCLUSIONS: After a longer posttransplant interval, CAV findings in OCT included a combination of IH and atherosclerotic plaques. In addition to IH, the presence of fibrotic, lipid, and calcified plaques is associated with CAVangio. Further studies are warranted to evaluate if the in vivo screening for plaque progress, particularly of fibrotic plaque, could improve individual secondary prevention and outcome in HTx patients.

Cardiac allograft vasculopathy: Differences of absolute and relative intimal hyperplasia in children versus adults in optical coherence tomography.

BACKGROUND: Intracoronary imaging enables an early detection of intimal changes. To what extend the development of absolute and relative intimal hyperplasia in intracoronary imaging differs depending on age and post-transplant time is not known. METHODS: Aim of our retrospective study was to compare findings between 24 pediatric (cohort P) and 21 adult HTx patients (cohort A) using optical coherence tomography (OCT) at corresponding post-transplant intervals (≤5 years: P1 (n = 11) and A1 (n = 10); >5 and ≤ 10 years: P2 (n = 13) and A2 (n = 11),. Coronary intima thickness (IT), media thickness (MT) and intima to media ratio (I/M) were assessed per quadrant. Maximal IT >0.3 mm was considered absolute, I/M > 1 relative intimal hyperplasia. RESULTS: Compared to A1, I/M was significantly higher in P1 (maximal I/M: P1: 5.41 [2.81-13.39] vs. A1: 2.30 [1.55-3.62], p = 0.005), whereas absolute IT values were comparable. In contrast, I/M was comparable between P2 and A2, but absolute IT were significantly higher in A2 (maximal IT: P2: 0.16 mm [0.11-0.25] vs. A2: 0.40 mm [0.30-0.71], p < 0.001). A2 presented with higher absolute IT (maximal: A1: 0.16 mm [0.12-0.44] vs. A2: 0.40 mm [0.30-0.71], p = 0.02) and I/M (maximal I/M A1: 2.30 [1.55-3.62] vs. A2: 3.79 [3.01-5.62], p = 0.04). CONCLUSION: Our results suggest an age- and time-dependent difference in the prevalence of absolute and relative intimal hyperplasia in OCT, with an early peak in children and a progressive increase in adults.

ßIII-tubulin: a novel mediator of chemoresistance and metastases in pancreatic cancer.

Pancreatic cancer is a leading cause of cancer-related deaths in Western societies. This poor prognosis is due to chemotherapeutic drug resistance and metastatic spread. Evidence suggests that microtubule proteins namely, ß-tubulins are dysregulated in tumor cells and are involved in regulating chemosensitivity. However, the role of ß-tubulins in pancreatic cancer are unknown. We measured the expression of different ß-tubulin isotypes in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Next, we used RNAi to silence ßIII-tubulin expression in pancreatic cancer cells, and measured cell growth in the absence and presence of chemotherapeutic drugs. Finally, we assessed the role of ßIII-tubulin in regulating tumor growth and metastases using an orthotopic pancreatic cancer mouse model. We found that ßIII-tubulin is highly expressed in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Further, we demonstrated that silencing ßIII-tubulin expression reduced pancreatic cancer cell growth and tumorigenic potential in the absence and presence of chemotherapeutic drugs. Finally, we demonstrated that suppression of ßIII-tubulin reduced tumor growth and metastases in vivo. Our novel data demonstrate that ßIII-tubulin is a key player in promoting pancreatic cancer growth and survival, and silencing its expression may be a potential therapeutic strategy to increase the long-term survival of pancreatic cancer patients.

The severity of neural invasion is associated with shortened survival in colon cancer.

PURPOSE: Neural invasion (NI) is a histopathologic feature of colon cancer that receives little consideration. Therefore, we conducted a morphologic and functional characterization of NI in colon cancer. EXPERIMENTAL DESIGN: NI was investigated in 673 patients with colon cancer. Localization and severity of NI was determined and related to patient's prognosis and survival. The neuro-affinity of colon cancer cells (HT29, HCT-116, SW620, and DLD-1) was compared with pancreatic cancer (T3M4 and SU86.86) and rectal cancer cells (CMT-93) in the in vitro three-dimensional (3D)-neural-migration assay and analyzed via live-cell imaging. Immunoreactivity of the neuroplasticity marker GAP-43, and the neurotrophic-chemoattractant factors Artemin and nerve growth factor (NGF), was quantified in colon cancer and pancreatic cancer nerves. Dorsal root ganglia of newborn rats were exposed to supernatants of colon cancer, rectal cancer, and pancreatic cancer cells and neurite density was determined. RESULTS: NI was detected in 210 of 673 patients (31.2%). Although increasing NI severity scores were associated with a significantly poorer survival, presence of NI was not an independent prognostic factor in colon cancer. In the 3D migration assay, colon cancer and rectal cancer cells showed much less neurite-targeted migration when compared with pancreatic cancer cells. Supernatants of pancreatic cancer and rectal cancer cells induced a much higher neurite density than those of colon cancer cells. Accordingly, NGF, Artemin, and GAP-43 were much more pronounced in nerves in pancreatic cancer than in colon cancer. CONCLUSION: NI is not an independent prognostic factor in colon cancer. The lack of a considerable biologic affinity between colon cancer cells and neurons, the low expression profile of colonic nerves for chemoattractant molecules, and the absence of a major neuroplasticity in colon cancer may explain the low prevalence and impact of NI in colon cancer.