https://onlinelibrary.wiley.com/doi/pdf/10.1111/ajt.13529

Late Failing Heart Allografts: Pathology of Cardiac Allograft Vasculopathy and Association With Antibody‐Mediated Rejection

New therapies for human cytomegalovirus infections.

Ischemic heart disease is one of the leading causes of morbidity and death worldwide. Consequently, myocardial infarctions are often encountered in clinical and forensic autopsies, and diagnosis can be challenging, especially in the absence of an acute coronary occlusion. Precise histopathological identification and timing of myocardial infarction in humans often remains uncertain while it can be of crucial importance, especially in a forensic setting when third person involvement or medical responsibilities are in question. A proper post-mortem diagnosis requires not only up-to-date knowledge of the ischemic coronary and myocardial pathology, but also a correct interpretation of such findings in relation to the clinical scenario of the deceased. For these reasons, it is important for pathologists to be familiar with the different clinically defined types of myocardial infarction and to discriminate myocardial infarction from other forms of myocardial injury. This article reviews present knowledge and post-mortem diagnostic methods, including post-mortem imaging, to reveal the different types of myocardial injury and the clinical-pathological correlations with currently defined types of myocardial infarction.

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Diagnosis of myocardial infarction at autopsy: AECVP reappraisal in the light of the current clinical classification

Background Optical coherence tomography (OCT) is a novel intravascular imaging modality with excellent spatial resolution. This study explored the utility of OCT in cardiac transplantation for the detection and characterization of early changes associated with coronary allograft vasculopathy (CAV). Methods Fifteen consecutive patients, 1 to 4 years after transplant with no angiographic evidence of CAV, underwent successful OCT imaging using the Fourier-domain OCT system (C7-XR, St. Jude Medical, St. Paul, MN) in the left anterior descending artery. Analysis included measurements of the lumen, intima, and media layers, and characterization of atherosclerotic plaques. Patients were stratified by intima-to-media (I/M) ratio and classified as normal (≤1) or abnormal (>1). Results Patients were a mean of 2.8 years after transplant, 58 years old, and 92% were men. OCT imaging revealed 8 of 15 patients had intimal hyperplasia with an I/M ratio >1. Comparing those with I/M ratio of ≤1 and >1, the median (interquartile range) intimal thickness was greater (75 [70–101] vs 206 [97–269]μm, p = 0.03), whereas the media thickness was no different (72 [70–103] vs 94 [73–113]μm, p = 0.53). In addition, 7 of 15 patients had lipid-rich or calcified atherosclerotic plaques. Conclusions OCT provides high-resolution quantitative imaging of the coronary arteries and its use allows for detailed assessment of the coronary artery wall and early morphologic changes that occur after cardiac transplantation. The clinical predictive value of these OCT-derived measurements remains to be determined.

Optical coherence tomography for characterization of cardiac allograft vasculopathy after heart transplantation (OCTCAV study)

Objectives The aims of this study were to characterize cardiac allograft vasculopathy (CAV) phenotypes using optical coherence tomography (OCT) and to evaluate the prognostic significance of OCT-determined CAV severity. Background Intravascular OCT enables in vivo characterization of CAV microstructure after heart transplantation. Methods Sixty-two patients undergoing heart transplantation were enrolled at routine angiography from September 2013 through October 2015 and prospectively followed until censoring on May 27, 2016. Optical coherence tomographic acquisitions aimed for the longest possible pull-backs, including proximal segments of all 3 major vessels. Plaques and bright spots were analyzed by delineating circumferential borders and measuring the angulation of total circumference. Layers were contoured for absolute and relative estimates. Nonfatal CAV progression (NFCP) during follow-up was registered. NFCP included occluded vessels or severe (≥70%) new angiographic coronary stenosis or percutaneous coronary intervention. Results A total of 172 vessels were categorized as follows: no CAV, n = 111; mild to moderate CAV ( Conclusions OCT enables the detection of CAV-associated plaque compositions and allows early detection and differentiation of vessel wall disease not visible on angiography. LFP was the most prevalent plaque component, was strongly associated with NFCP, and may be associated with stepwise CAV progression caused by organizing mural thrombi. (The GRAFT Study: Evaluation of Graft Function, Rejection and Cardiac Allograft Vasculopathy in First Heart Transplant Recipients; NCT02077764)

Layered Fibrotic Plaques Are the Predominant Component in Cardiac Allograft Vasculopathy: Systematic Findings and Risk Stratification by OCT.

Background Cardiac allograft vasculopathy (CAV) is a major limitation to the long-term success of cardiac transplantation. Although there are published descriptions of the lesions, there have been no studies delineating the pathology of CAV in a large series of patients who underwent retransplantation for CAV. Methods We reviewed archival records and microscopic sections of surgically explanted hearts from 64 patients who underwent cardiac retransplantation: 54 adults (18 to 70 years old) and 10 children (3 to 15 years old). Vascular lesions were categorized as showing intimal fibromuscular hyperplasia, atherosclerosis and/or inflammation. The degree of luminal narrowing was estimated from gross descriptions and microscopic sections. Results In total, 75% of hearts had evidence of acute cellular rejection, mostly mild. Intramyocardial arteries showed primarily intimal fibromuscular hyperplasia and inflammation with no atheromas present. Large and branch epicardial coronary arteries were narrowed in at least one artery of all hearts. Lesions in the epicardial coronary arteries were composed of intimal fibromuscular hyperplasia, atherosclerosis and/or inflammation affecting one or more vascular layers (intima, media and adventitia). Severe CAV with >75% luminal narrowing was seen in the LAD in 17% of hearts, the LCx in 17% and the RCA in 22% of hearts. Two hearts had severe narrowing of the left main coronary artery. Nineteen arteries had luminal thrombi. All hearts had narrowing of smaller epicardial branch coronary arteries that was often severe. Atheromas were present in arteries of adults and children; thus, not all atheromas could be considered pre-existing prior to transplantation. Both arteries and veins showed intimal hyperplasia and inflammation. Conclusions CAV is a pathologically multifaceted disorder that affects large and small epicardial coronary arteries of adults and children, with different types of lesions: intimal fibromuscular hyperplasia; atherosclerosis; and/or inflammation (vasculitis). Therapies to address this disease must take into account the protean nature of the vascular lesions.

Diverse morphologic manifestations of cardiac allograft vasculopathy: a pathologic study of 64 allograft hearts.

OBJECTIVE
To observe the effect of electroacupuncture (EA) at different acupoint combination on intestinal inflammatory response, intestinal flora structure and metabolic function in obese rats.


METHODS
Ninety male Wistar rats aged 8 weeks were collected. Ten rats were randomly collected from 15 rats fed with regular forage in a normal group and the rest 75 rats were fed with high-fat forage to induce obesity models. Forty rats were modeled successfully and randomized into a model group, a lower-limb EA group, an abdomen EA group and a biaoben acupoints group, 10 rats in each one. "Zusanli" (ST 36) and "Fenglong" (ST 40) were selected in the lower-limb EA group, "Zhongwan "(CV 12), "Tianshu "(ST 25) and "Guanyuan" (CV 4) were selected in the abdomen EA group. The acupoint prescriptions in the above two groups were combined in the biaoben acupoints group. EA was delivered in all of the intervention groups, with continuous wave, 2 Hz in frequency and 1 mA in current intensity. The intervention was administered three times weekly (on Monday, Wednesday and Friday), for consecutive 8 weeks. Before intervention and on the last day of the 8th week of intervention, the body weight and 24 h food intake were observed. After intervention, using Western blot method, the proteins expressions of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were detected in the tissue of the small intestine; 16S rRNA sequencing technology was adopted to detect the distribution structure and metabolic function of intestinal flora.


RESULTS
Compared with the normal group, the body weight, the food intake and the proteins expressions of IL-6 and TNF-α in small intestine were all increased in the model group (P<0.01). The above indexes of each EA intervention group were all decreased (P<0.01) when compared with the model group. The proteins expressions of IL-6 and TNF-α in the small intestine tissue of rats in biaoben acupoints group were lower than those in the other two EA intervention groups (P<0.01). Compared with the normal group, the ratio of Firmicutes/Bacteroidetes was elevated (P<0.01), while the abundance of Lactobacillus, Muribaculaceae and Bifidobacteria decreased in the model group (P<0.01). When compared with the model group, the ratio of Firmicutes/Bacteroidetes in each EA intervention group was reduced (P<0.01) and the abundance of Lactobacillus, Bifidobacteria and Bacteroidetes increased (P<0.01). Compared with the other two EA intervention groups, the abundance of Lactobacillus and Muribaculaceae was increased (P<0.01), while the abundance of Collinsella and Ruminococcus Gauvreauii reduced (P<0.01) in the biaoben acupoints group. In the model group, the abundance of clusters of orthologous groups of proteins (COG) function of intestinal flora in the transportation and metabolism of carbohydrate, amino acid and lipid, as well as in the signal transduction mechanisms were reduced when compared with the normal group (P<0.01). In comparison with the model group, the abundance of the above COG function was increased in each EA intervention group (P<0.01, P<0.05).


CONCLUSION
Electroacupuncture at biaoben acupoint combination may attenuate intestinal inflammatory response and effectively improve the structure and function of intestinal flora. The effect is superior to the intervention at the acupoints on the lower limbs and those on the abdomen, better regulating the abundance of specific intestinal flora.

Wei-hui Lu

Papers

Diverse morphologic manifestations of cardiac allograft vasculopathy: a pathologic study of 64 allograft hearts.

[Effect of electroacupuncture at different acupoint combination on intestinal inflammatory response and intestinal flora in obese rats].