Comparison of the empirical linear ablation and low voltage area-guided ablation in addition to pulmonary vein isolation in patients with persistent atrial fibrillation: a propensity score-matched analysis.

BACKGROUND: The efficacy of pulmonary vein isolation (PVI) alone is not guaranteed for persistent atrial fibrillation (PeAF), and it is unclear which type of ablation approach should be applied in addition to PVI. This study aimed to compare outcomes and prognosis between empirical linear ablation and low-voltage area (LVA) ablation after PVI for PeAF. METHODS: We enrolled 128 patients with PeAF who were assigned to the linear ablation group (n = 64) and the LVA ablation group (n = 64) using a propensity score-matched model. After PVI and cardioversion, the patients underwent either empirical linear ablation or LVA ablation during sinus rhythm. All patients in the linear ablation group underwent both roof line and mitral valve isthmus (MVI) ablations. An electrical-guided ablation targeting LVA (< 0.5 mV) was performed in the LVA group. When there was no LVA in the LVA group, only PVI was applied. We compared the procedural outcomes and recurrence after ablation between the two groups. RESULTS: The baseline characteristics were well-balanced between the two groups. Fifty patients had LVA (22 and 28 patients in the linear and LVA groups). The roof and MVI lines were completed in 100% and 96.9% of the patients. During the mean follow-up of 279.5 ± 161.3 days, the LVA group had significantly lower recurrence than the linear group (15 patients [23%] vs. 29 patients [45%], p = 0.014). Thirty-five patients were prescribed antiarrhythmic drugs during the follow-up period (linear group, n = 17; LVA group, n = 18); amiodarone and bepridil were administered to most of the patients (15 and 17 patients, respectively). The difference in the prognosis was relevant among the patients with LVA, while this trend was not observed in those without LVA. The LVA ablation group demonstrated significantly lower radiofrequency energy and shorter procedural time compared to the linear ablation group. The recurrence of atrial flutter was more likely to occur in the linear group than in the LVA group (14 [22%] vs. 6 [9.4%], p = 0.052). CONCLUSION: The electrophysiological-guided LVA ablation is more effective than empirical linear ablation in PeAF patients with LVA. Unnecessary empirical linear ablation might have a risk of iatrogenic gap and atrial flutter recurrence.

Large interventricular membranous septal aneurysm renders the anatomy unsuitable for transcatheter aortic valve replacement.

An interventricular membranous septal aneurysm, though rare, can coexist with aortic valve stenosis. In this report, we present an unsuitable anatomy for transcatheter aortic valve replacement (TAVR) due to large interventricular membranous septal aneurysm. This case suggests that the feasibility of TAVR would depend on the location and size of the aneurysm and its relationship with the aortic root.

An Epilepsy-Associated Mutation of Salt-Inducible Kinase 1 Increases the Susceptibility to Epileptic Seizures and Interferes with Adrenocorticotropic Hormone Therapy for Infantile Spasms in Mice.

Six mutations in the salt-inducible kinase 1 (SIK1) have been identified in developmental and epileptic encephalopathy (DEE-30) patients, and two of the mutations are nonsense mutations that truncate the C-terminal region of SIK1. In a previous study, we generated SIK1 mutant (SIK1-MT) mice recapitulating the C-terminal truncated mutations using CRISPR/Cas9-mediated genome editing and found an increase in excitatory synaptic transmission and enhancement of neural excitability in neocortical neurons in SIK1-MT mice. NMDA was injected into SIK1-MT males to induce epileptic seizures in the mice. The severity of the NMDA-induced seizures was estimated by the latency and the number of tail flickering and hyperflexion. Activated brain regions were evaluated by immunohistochemistry against c-fos, Iba1, and GFAP. As another epilepsy model, pentylenetetrazol was injected into the adult SIK1 mutant mice. Seizure susceptibility induced by both NMDA and PTZ was enhanced in SIK1-MT mice. Brain regions including the thalamus and hypothalamus were strongly activated in NMDA-induced seizures. The epilepsy-associated mutation of SIK1 canceled the pharmacological effects of the ACTH treatment on NMDA-induced seizures. These results suggest that SIK1 may be involved in the neuropathological mechanisms of NMDA-induced spasms and the pharmacological mechanism of ACTH treatment.

Inhibition of DNA ligase IV enhances the CRISPR/Cas9-mediated knock-in efficiency in mouse brain neurons.

CRISPR/Cas9-mediated gene knock-in in in vivo neurons using in utero electroporation is a powerful technique, but the knock-in efficiency is generally low. We previously demonstrated that co-transfection with RAD51, a key molecule of the initial step of homology-directed repair (HDR), expression vector increased EGFP knock-in efficiency in the ß-actin site up to 2.5-fold in the pyramidal neurons in layer 2/3 of the somatosensory cortex of mouse brain. To further improve the efficiency, we examined the effect of inhibition of DNA ligase IV (LIG4) that is an essential molecule for non-homologous end joining (NHEJ). Co-transfection with small hairpin RNA for LIG4 (shlig4) expression vector increased the EGFP knock-in efficiency in the ß-actin site up to 3.6-fold compared to the condition without shlig4. RAD51 and shlig4 expression vector co-transfection further increased the knock-in efficiency up to 4.7-fold of the control condition. These results suggest that the inhibition of LIG4 is more effective than RAD51 overexpression, and it enhances the effect of RAD51 overexpression on HDR-mediated gene knock-in in vivo neurons.

Role of Splice Variants of Gtf2i, a Transcription Factor Localizing at Postsynaptic Sites, and Its Relation to Neuropsychiatric Diseases.

We previously reported that various mRNAs were associated with postsynaptic density (PSD) purified from rat forebrain. Among the thousands of PSD-associated mRNAs, we highlight the biology of the general transcription factor II-I (Gtf2i) mRNA, focusing on the significance of its versatile splicing for targeting its own mRNA into dendrites, regulation of translation, and the effects of Gtf2i expression level as well as its relationship with neuropsychiatric disorders.

Orexin-neuromodulated cerebellar circuit controls redistribution of arterial blood flows for defense behavior in rabbits.

We investigated a unique microzone of the cerebellum located in folium-p (fp) of rabbit flocculus. In fp, Purkinje cells were potently excited by stimulation of the hypothalamus or mesencephalic periaqueductal gray, which induced defense reactions. Using multiple neuroscience techniques, we determined that this excitation was mediated via beaded axons of orexinergic hypothalamic neurons passing collaterals through the mesencephalic periaqueductal gray. Axonal tracing studies using DiI and biotinylated dextran amine evidenced the projection of fp Purkinje cells to the ventrolateral corner of the ipsilateral parabrachial nucleus (PBN). Because, in defense reactions, arterial blood flow has been known to redistribute from visceral organs to active muscles, we hypothesized that, via PBN, fp adaptively controls arterial blood flow redistribution under orexin-mediated neuromodulation that could occur in defense behavior. This hypothesis was supported by our finding that climbing fiber signals to fp Purkinje cells were elicited by stimulation of the aortic nerve, a high arterial blood pressure, or a high potassium concentration in muscles, all implying errors in the control of arterial blood flow. We further examined the arterial blood flow redistribution elicited by electric foot shock stimuli in awake, behaving rabbits. We found that systemic administration of an orexin antagonist attenuated the redistribution and that lesioning of fp caused an imbalance in the redistribution between active muscles and visceral organs. Lesioning of fp also diminished foot shock-induced increases in the mean arterial blood pressure. These results collectively support the hypothesis that the fp microcomplex adaptively controls defense reactions under orexin-mediated neuromodulation.

Novel splice variants in the 5'UTR of Gtf2i expressed in the rat brain: alternative 5'UTRs and differential expression in the neuronal dendrites.

General transcription factor II-I (Gtf2i) is a transcription factor and one of the genes implicated in Willams-Beuren syndrome, an autism spectrum disorder. In this study, we investigated splice variants of the Gtf2i gene in both the 5'untranslated region (5'UTR) and the coding region. To search for novel 5'UTRs of Gtf2i, we utilized the cap analysis gene expression database of the mouse. We identified seven novel Gtf2i transcripts with alternatively spliced 5'UTRs in the rat brain. We also identified four novel splice variants in the coding sequence of Gtf2i. Furthermore, we identified a selective usage of certain types of 5'UTR by coding variants. In situ hybridization demonstrated a differential pattern of expression of Gtf2i mRNAs with alternatively spliced 5'UTRs among neuronal cells, and the localization of one of the variants in neuronal dendrites in the rat brain. Immunohistochemistry also demonstrated a distribution of Gtf2i-immunoreactivity in the dendrites. These results suggest multiple pathways of expression of Gtf2i gene in the brain. The expression patterns may be under the control of alternative promoters coupled to the alternative splicing in the coding region. Differential localization of mRNA to neuronal dendrites suggests spatiotemporal-specific translation at the post-synaptic sites that is involved in transfer of synaptic activity to expression of specific sets of genes in the nucleus. Gtf2i is a transcription factor and implicated in Willams-Beuren syndrome. We identified seven novel Gtf2i transcripts with alternatively spliced 5'UTRs in the rat brain. In situ hybridization demonstrated a differential expression of Gtf2i mRNAs with different 5'UTRs in somas and dendrites of neuronal cells. Differential localization of mRNA to neuronal dendrites suggests spatiotemporal-specific translation at the postsynaptic sites. The scheme shows genomic structure showing the positions of the potential transcription start tags (rDEC695, rDEC3D7, rDEC1D3, rDEC104, rDEC072 and rDEBE25). Newly identified exons (1.1-1.6) are shown with the white boxes. The distances from rDEC695-5'end are indicated in bp.

Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion and positron emission tomography/computed tomography of upper gastrointestinal cancers.

PURPOSE: Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) strongly contrasts cancerous tissue against background healthy tissues. Positron emission tomography/computed tomography (PET/CT) applies the uptake of 18-fluorodeoxyglucose in the diagnosis of cancer. Our aim was to compare DWIBS/T2 and PET/CT in patients with upper gastrointestinal cancers. METHODS: Patient records, including imaging results from July 2012 to March 2015, were analyzed retrospectively. Four men (age, 72.5 ± 5.3 years) and ten women (age, 71.6 ± 4.0 years) were enrolled in this study. The numbers of patients with esophageal cancer, gastric cancer, gastrointestinal stromal tumor, and duodenal cancer were one, eight, three, and two, respectively. RESULTS: Six out of eight patients with gastric cancer had positive results on both DWIBS/T2 and PET/CT. The diameter and depth of invasion of gastric cancer was larger in patients with positive DWIBS/T2 and PET/CT findings than those with negative findings. These results suggested that patients with gastric cancer with larger pixel numbers might tend to show positive results with DWIBS/T2. CONCLUSIONS: DWIBS/T2 and PET/CT have similar sensitivity for the diagnosis of upper gastrointestinal cancer. The diameter and depth of invasion affected the detectability of gastric cancer.

Factors affecting the detection of colorectal cancer and colon polyps on screening abdominal ultrasonography.

BACKGROUND/AIMS: The aim of this study was to identify factors affecting the detection of colorectal cancer (CRC) and colon polyps (CPs) using abdominal ultrasonography (US). METHODOLOGY: Patient records were analyzed retrospectively. Those diagnosed as having either CRC or CPs by colonoscopy performed after screening abdominal US were enrolled. The diagnostic criterion for CRC was an irregularly thickened wall or mass. CPs were diagnosed as spherical or ovoid hypoechoic lesions arising within the colonic lumen as seen on abdominal US. RESULTS: Sixteen patients had a total of 16 CRC lesions and 11 patients had a total of 17 CPs. All CRC lesions invaded deeper than the subserosa. Cancer cell invasion limited to the submucosa was noted in the two 1.5-cm CPs. Detection of these lesions was not associated with invasion to lymph or blood vessels. These results suggest that wall thickening might be the consequence of cancer cells invading below the subserosa, thereby resulting in the lesions becoming detectable on abdominal US. CONCLUSIONS: Detection of CRC and CPs on abdominal US was associated with lesion size and depth of invasion.

An association of elevated levels of alkaline phosphatase and gamma-glutamyl transpeptidase with acute cholangitis.

BACKGROUND/AIMS: The early diagnosis of acute cholangitis (AC) is critical for appropriate treatment. METHODOLOGY: Patient records from April 2008 to December 2012 were retrospectively analyzed. Data on white blood cell count and levels of C-reactive protein, total-bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase (gamma-GTP) were collected from AC patients on the day they underwent endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and treatment. Data were collected 3 months before ERCP to analyze the rate of change of these variables. Receiver operating characteristics curve analysis was performed. RESULTS: We enrolled 63 patients with AC and 65 patients with non-AC. The threshold values of ALP and gamma-GTP were 1.09 and 1.30, respectively. CONCLUSIONS: 450 (IU/L) and 100 (IU/L), respectively, were thresholds of ALP and gamma-GTP on the day of ERCP. 1.09 and 1.30, respectively, were thresholds of ALP and gamma-GTP rates of change for the diagnosis of AC.

Deep-Learning-Based Analysis Reveals a Social Behavior Deficit in Mice Exposed Prenatally to Nicotine.

Cigarette smoking during pregnancy is known to be associated with the incidence of attention-deficit/hyperactive disorder (ADHD). Recent developments in deep learning algorithms enable us to assess the behavioral phenotypes of animal models without cognitive bias during manual analysis. In this study, we established prenatal nicotine exposure (PNE) mice and evaluated their behavioral phenotypes using DeepLabCut and SimBA. We optimized the training parameters of DeepLabCut for pose estimation and succeeded in labeling a single-mouse or two-mouse model with high fidelity during free-moving behavior. We applied the trained network to analyze the behavior of the mice and found that PNE mice exhibited impulsivity and a lessened working memory, which are characteristics of ADHD. PNE mice also showed elevated anxiety and deficits in social interaction, reminiscent of autism spectrum disorder (ASD). We further examined PNE mice by evaluating adult neurogenesis in the hippocampus, which is a pathological hallmark of ASD, and demonstrated that newborn neurons were decreased, specifically in the ventral part of the hippocampus, which is reported to be related to emotional and social behaviors. These results support the hypothesis that PNE is a risk factor for comorbidity with ADHD and ASD in mice.

The incidence and influencing factors of in-hospital frailty progression following transcatheter aortic valve implantation.

Objective Patients undergoing transcatheter aortic valve implantation (TAVI) are generally older and frailty is therefore an important clinical issue. The baseline degree of frailty is associated with the prognosis in patients undergoing TAVI; however, the incidence of in-hospital frailty progression and its influencing factors have not yet been elucidated. Methods This observational, single-center study retrospectively evaluated 281 patients who underwent TAVI. The degree of frailty at baseline and discharge was evaluated using the Clinical Frailty Scale (CFS). In-hospital frailty progression was defined as an increase of at least one level in the CFS score at discharge from baseline, and predictors of frailty progression were assessed. Results The median baseline CFS score was 4.0 (interquartile range: 3.0-4.0). In-hospital frailty progression was observed in 49 patients (17.4%). No significant differences were observed in age, sex, comorbidities, or surgical risk scores between patients with and without frailty progression. Patients with frailty progression experienced stroke more frequently during hospitalization than those without (12.2% vs. 1.3%, p = 0.001). A multivariable logistic analysis showed that in-hospital stroke was a significant predictor of frailty progression (odds ratio, 10.7; 95% confidence interval: 2.34-49.2, p = 0.002). Patients with frailty progression had a longer hospital stay than those without frailty progression [7.0 (4.0-17.0) vs. 4.0 (4.0-8.0) days, p = 0.001]. Conclusions In-hospital frailty progression was not uncommon in patients undergoing TAVI. Stroke incidence was a significant influencing factor in frailty progression, whereas baseline comorbidities and surgical risks were not.

Lipid signaling in cytosolic phospholipase A2alpha-cyclooxygenase-2 cascade mediates cerebellar long-term depression and motor learning.

In this study, we show the crucial roles of lipid signaling in long-term depression (LTD), that is, synaptic plasticity prevailing in cerebellar Purkinje cells. In mouse brain slices, we found that cPLA(2)alpha knockout blocked LTD induction, which was rescued by replenishing arachidonic acid (AA) or prostaglandin (PG) D(2) or E(2). Moreover, cyclooxygenase (COX)-2 inhibitors block LTD, which is rescued by supplementing PGD(2)/E(2). The blockade or rescue occurs when these reagents are applied within a time window of 5-15 min following the onset of LTD-inducing stimulation. Furthermore, PGD(2)/E(2) facilitates the chemical induction of LTD by a PKC activator but is unable to rescue the LTD blocked by a PKC inhibitor. We conclude that PGD(2)/E(2) mediates LTD jointly with PKC, and suggest possible pathways for their interaction. Finally, we demonstrate in awake mice that cPLA(2)alpha deficiency or COX-2 inhibition attenuates short-term adaptation of optokinetic eye movements, supporting the view that LTD underlies motor learning.

Screening ultrasonography is useful for the diagnosis of gastric and colorectal cancer.

BACKGROUND/AIMS: To clarify the usefulness of screening ultrasonography (US) to diagnose gastric and colorectal cancer, patient records were analyzed retrospectively. METHODOLOGY: Ultrasonography was performed for patients with abdominal symptoms. They were then subjected to computed tomography (CT) when diagnosed with gastric cancer, colorectal cancer, or bowel obstruction. Patient records were analyzed retrospectively after final diagnosis of gastric cancer or colorectal cancer by endoscopy, surgery or necropsy. RESULTS: Twelve patients were diagnosed with colorectal cancer and six with gastric cancer. The detailed structure of colorectal cancer was visible as wall thickening with US, while cancer was often illustrated as a mass by CT. Loss of stratification was clear with US in 11 patients. US demonstrated wall thickening in 10 patients and a mass in 1 patient, while CT demonstrated wall thickening in 3 patients and a mass in 8 patients. The structure of colorectal cancer was more obvious when using US than when using CT. One patient demonstrated focal wall thickening with US, but this was not detected by CT. CONCLUSIONS: US is useful for diagnosis of gastric cancer and colorectal cancer. US produces more detailed findings in colorectal cancer than CT.

Structural Analysis Implicates CASK-Liprin-α2 Interaction in Cerebellar Granular Cell Death in MICPCH Syndrome.

Microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome is a neurodevelopmental disorder caused by the deficiency of the X-chromosomal gene CASK. However, the molecular mechanisms by which CASK deficiency causes cerebellar hypoplasia in this syndrome remain elusive. In this study, we used CASK knockout (KO) mice as models for MICPCH syndrome and investigated the effect of CASK mutants. Female CASK heterozygote KO mice replicate the progressive cerebellar hypoplasia observed in MICPCH syndrome. CASK KO cultured cerebellar granule (CG) cells show progressive cell death that can be rescued by co-infection with lentivirus expressing wild-type CASK. Rescue experiments with CASK deletion mutants identify that the CaMK, PDZ, and SH3, but not L27 and guanylate kinase domains of CASK are required for the survival of CG cells. We identify missense mutations in the CaMK domain of CASK derived from human patients that fail to rescue the cell death of cultured CASK KO CG cells. Machine learning-based structural analysis using AlphaFold 2.2 predicts that these mutations disrupt the structure of the binding interface with Liprin-α2. These results suggest that the interaction with Liprin-α2 via the CaMK domain of CASK may be involved in the pathophysiology of cerebellar hypoplasia in MICPCH syndrome.

Impact of proteinuria on long-term prognosis in patients with coronary artery disease.

BACKGROUND: This study aimed to investigate the association between proteinuria and long-term prognosis in patients with coronary artery disease. METHODS: This was a single-center observational study. A total of 1351 patients were identified who underwent percutaneous coronary intervention, and whose urine data were available. Patients were divided into two groups according to the presence (n = 245) or absence (n = 1106) of proteinuria. All-cause and cardiovascular deaths were primarily evaluated. RESULTS: The prevalence rates of hypertension and diabetes were significantly higher, and the baseline estimated glomerular filtration rate (eGFR) was lower in patients with proteinuria than in those without proteinuria. During the median follow-up of 4.1 years (interquartile range, 1.7-6.8 years), the occurrences of all-cause and cardiovascular deaths were significantly higher in patients with proteinuria. Multivariable Cox regression analysis indicated that the presence of proteinuria was a significant predictor of cardiovascular death as well as age, BMI, reduced eGFR, and left ventricular ejection fraction. When stratified into four groups based on eGFR category (eGFR <60 or ≥60 ml/min/1.73 m2) and absence or presence of proteinuria, the incidence rates of all-cause and cardiovascular deaths were highest in patients with proteinuria and eGFR less than 60 ml/min/1.73 m2. Furthermore, the incidence rates of all-cause and cardiovascular deaths were significantly higher in patients with proteinuria among both diabetic and nondiabetic patients. CONCLUSION: Proteinuria is associated with the long-term prognosis, and all-cause and cardiovascular deaths in patients with coronary artery disease, regardless of eGFR and the presence or absence of diabetes mellitus.

Impact of Handgrip Strength on Clinical Outcomes after Percutaneous Coronary Intervention.

AIM: The relationship between handgrip strength (HGS) and clinical outcomes after percutaneous coronary intervention (PCI) has not yet been thoroughly investigated. METHODS: This was a single-center, observational study. A total of 469 patients who underwent PCI and whose periprocedural HGS was measured were included. Patients were divided into two groups: the low HGS group (men, ＜28 kg; women, ＜18 kg) and the high HGS group (men, ≥ 28 kg; women, ≥ 18 kg). The primary outcome was the composite endpoint of all-cause death, myocardial infarction (MI), and heart failure readmission. RESULTS: There were 151 patients in the low HGS group and 318 patients in the high HGS group. The age of patients in the low HGS group was significantly higher (median [interquartile range]: 78 [71-82] vs. 70 [61-75] years, p＜0.001), while the body mass index and serum albumin level were significantly lower (body mass index: 22.5 [20.2-24.3] vs. 24.3 [22.3-26.6] kg/m2, p＜0.001; serum albumin: 3.6 [3.1-3.9] vs. 4.0 [3.7-4.3] g/dL, p＜0.001) than those in the high HGS group. During the median follow-up period of 778 days, the low HGS group had a higher incidence of composite endpoint than the high HGS group (p＜0.001). The low HGS group had a higher risk of all-cause, cardiac, and non-cardiac death (p＜0.001). Multivariable Cox proportional hazards analysis showed that low handgrip strength was an independent predictor for the composite endpoint (hazard ratio 1.80, 95% confidence interval 1.04-3.12, p=0.04). CONCLUSIONS: Low HGS was independently associated with adverse outcomes after PCI.

Impact of Albuminuria on the Prognosis After Transcatheter Aortic Valve Implantation.

The impact of preoperative albuminuria on the prognosis after transcatheter aortic valve implantation (TAVI) has not been studied. A total of 228 patients who underwent TAVI for severe aortic stenosis (AS) and for whom preoperative urinary data was available were retrospectively investigated. Patients were divided into two groups according to the urinary albumin-to-creatinine ratio (ACR): high (ACR≥ 30 mg/g) and low (ACR<30 mg/g). The urinary total protein-to-creatinine ratio (PCR) and dipstick proteinuria were also evaluated. The primary outcome was the composite outcome of all-cause death and readmission for heart failure. In total, 117 patients had a high ACR and 111 patients had a low ACR. During the median follow-up period of 467 days, patients with a high ACR had a higher incidence of the primary outcome than those with a low ACR (p<0.001). Patients with a high PCR or positive dipstick proteinuria were also at a higher risk for the primary outcome (p<0.001 and p=0.008, respectively). Multivariable Cox proportional hazards analysis showed a high ACR was independently associated with a primary outcome (hazard ratio, 4.98; 95% confidence interval, 1.84-13.49; p=0.002). In conclusion, preoperative albuminuria is an independent predictor of cardiac events in patients with severe AS undergoing TAVI.

Transcatheter Aortic Valve Replacement for Bicuspid Aortic Stenosis With a Severely Calcified Raphe Using An Under-Sized SAPIEN 3 Valve: Sizing by the Circle Method and Deployment by the Pressure-Regulated Method.

Transcatheter aortic valve replacement (TAVR) for bicuspid aortic valve stenosis is challenging, and the absence of established methods for sizing the bicuspid aortic valve (BAV) complicates TAVR. We report a case of successful TAVR for bicuspid aortic stenosis with a severely calcified raphe. We used an undersized SAPIEN 3 valve, with three safety measures based on assessment of structural characteristics, sizing by the circle method, and deployment of the valve by the pressure-regulated method.

Impact of C-Reactive Protein on Long-Term Cardiac Events in Stable Coronary Artery Disease Patients with Chronic Kidney Disease.

AIM: Chronic inflammation is associated with atherosclerosis development. Chronic kidney disease (CKD) is an independent risk factor for cardiovascular events and is associated with chronic inflammation. We aimed to investigate the influence of C-reactive protein (CRP), an important marker of inflammation, on the clinical outcomes of patients with CKD and stable coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). METHODS: Among patients with stable CAD and CKD who underwent PCI, 516 patients whose CRP levels were available before the PCI procedure were identified. The patients were divided into two groups according to the CRP levels: those with CRP ≥ 2.0 mg/L (high-CRP group) and those with CRP ＜2.0 mg/L (low-CRP group). The primary endpoint of this study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and unplanned revascularization. RESULTS: Overall, the mean age of the patients was 72.5±9.7 years, and 20.7% were female. The median CRP level was 1.43 mg/L (0.6-4.9 mg/L). The median follow-up period was 3.6 years. The occurrence of MACE was significantly higher in the high-CRP group than in the low-CRP group (log-rank p＜0.001). Notably, the incidence rate of cardiac death was significantly higher in the high-CRP group (log-rank p＜0.001). According to the multivariable analysis, CRP level ≥ 2.0 mg/L was found to be a significant predictor of MACE (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.04-2.28, p=0.003), as well as estimated glomerular filtration rate (HR: 0.98, 95% CI: 0.97-0.99, p＜0.01). CONCLUSION: High-CRP levels adversely affect long-term cardiac events in patients with stable CAD and CKD.