Ranolazine in chronic total occlusion percutaneous coronary intervention.

Ranolazine is an anti-anginal medication given to patients with chronic angina and persistent symptoms despite medical therapy. We examined 11 491 chronic total occlusion (CTO) percutaneous coronary interventions (PCI) that were performed at 41 US and non-US centers between 2012 and 2023 in the PROGRESS-CTO Registry. Patients on ranolazine at baseline had more comorbidities, more complex lesions, lower procedural and technical success (based on univariable but not multivariable analysis), and higher incidence of major adverse cardiac events (MACE) (on both univariable and multivariable analysis).

Validation of the BCIS CHIP Score in chronic total occlusion percutaneous coronary intervention.

BACKGROUND: The complex high-risk indicated percutaneous coronary intervention (CHIP) score is a tool developed using the British Cardiovascular Intervention Society (BCIS) database to define CHIP cases and predict in-hospital major adverse cardiac or cerebrovascular events (MACCE). AIM: To assess the validity of the CHIP score in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We evaluated the performance of the CHIP score on 8341 CTO PCIs from the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) performed at 44 centers between 2012 and 2023. RESULTS: In our cohort, 7.8% (n = 647) of patients had a CHIP score of 0, 50.2% (n = 4192) had a CHIP score of 1-2, 26.2% (n = 2187) had a CHIP score of 3-4, 11.7% (n = 972) had a CHIP score of 5-6, 3.3% (n = 276) had a CHIP score of 7-8, and 0.8% (n = 67) had a CHIP score of 9+. The incidence of MACCE for a CHIP score of 0 was 0.6%, reaching as high as 8.7% for a CHIP score of 9+, confirming that a higher CHIP score is associated with a higher risk of MACCE. The estimated increase in the risk of MACCE per one score unit increase was 100% (95% confidence interval [CI]: 65%-141%). The AUC of the CHIP score model for predicting MACCE in our cohort was 0.63 (95% CI: 0.58-0.67). There was a positive correlation between the CHIP score and the PROGRESS-CTO MACE score (Spearman's correlation: 0.37; 95% CI: 0.35-0.39; p < 0.001). CONCLUSIONS: The CHIP score has modest predictive capacity for MACCE in CTO PCI.

Activated clotting time and outcomes of chronic total occlusion percutaneous coronary intervention: insights from the PROGRESS-CTO Registry.

BACKGROUND: The optimal range of activated clotting time (ACT) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the association between ACT and in-hospital ischemic and bleeding outcomes in patients who underwent CTO PCI in the Prospective Global Registry for the Study of CTO Intervention. RESULTS: ACT values were available for 4377 patients who underwent CTO PCI between 2012 and 2023 at 29 centers. The mean ACT distribution was less than 250 seconds (19%), 250 to 349 seconds (50%), and greater than or equal to 350 seconds (31%). The incidence of ischemic events, bleeding events, and net adverse cardiovascular events (NACE) was 0.8%, 3.0%, and 3.8%, respectively. In multiple logistic regression analysis, increasing nadir ACT was associated with decreasing ischemic events (adjusted odds ratio [aOR] per 50-second increments: 0.69 [95% confidence interval (CI), 0.50-0.94; P=.017]; and increasing peak ACT was associated with increasing bleeding events (aOR per 50-second increments: 1.17 [95% CI ,1.01-1.36; P=.032]). A U-shaped association was seen between mean ACT and NACE, where restricted cubic spline analysis demonstrated that patients with a low ( less than 200 seconds) or high ( greater than 400 seconds) ACT had increasing NACE risk compared with an ACT of 200 to 400 seconds (aOR 2.06, 95% CI 1.18-3.62; P=.012). CONCLUSIONS: Among patients who underwent CTO PCI, mean ACT had a U-shaped relationship with NACE, where patients with a low ( less than 200 seconds) ACT (driven by ischemic events) or high ( greater than 400 seconds) ACT (driven by bleeding) had higher NACE compared with an ACT of 200 to 400 seconds.

Quality of life assessment in the first episode of acute coronary syndrome.

Background: Assessment of health-related quality of life (HRQoL) is an important measure of a patient's recovery after an illness. However, HRQoL among acute coronary syndrome (ACS) survivors has not been extensively studied following cardiac management. Aim: The purpose of this study was to assess the quality of life (QoL) among ACS patients who have undergone percutaneous coronary intervention (PCI). Methods: This cohort study included 145 consecutive male ACS patients between March 2021 and May 2022. Of these patients, 138 (mean age 54.3 ± 10.7 years) completed the QoL assessment using the short form-12 (SF-12) health survey questionnaire. Seventy (51%) of them presented with ST-segment elevation myocardial infarction (STEMI), 18 (13%) had non-STEMI, 39 (28%) had evolved MI, and 11 (8%) had unstable angina. Recruited patients' QoL data were assessed at various time points post-PCI. Results: At the end of the 12 months of follow-up, major clinical events (MCE) defined as death, sudden death, or re-acute myocardial infarction occurred in 54.9% of patients. Out of 7 MCE, four deaths and three re-AMIs had occurred. SF-12 physical component score was found to be significantly improved when compared to the mental component score, which seems to improve without reaching statistical significance over time. Among event-free ACS patients, we found a significant positive correlation between left ventricular ejection fraction and HRQoL. Conclusion: Improvement in HRQoL (physical component) was seen among ACS patients post-PCI. Relevance for Patients: QoL assessment outcomes should be considered in clinical settings, practice guidelines, and treatment modality post-PCI to improve QoL in post-ACS survivors.

Impact of calcium on the procedural techniques and outcomes of chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Coronary calcification is common and increases the difficulty of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the impact of calcium on procedural outcomes of 13,079 CTO PCIs performed in 12,799 patients at 46 US and non-US centers between 2012 and 2023. RESULTS: Moderate or severe calcification was present in 46.6% of CTO lesions. Patients whose lesions were calcified were older and more likely to have had prior coronary artery bypass graft surgery. Calcified lesions were more complex with higher J-CTO score (3.0 ± 1.1 vs. 1.9 ± 1.2; p < 0.001) and lower technical (83.0% vs. 89.9%; p < 0.001) and procedural (81.0% vs. 89.1%; p < 0.001) success rates compared with mildly calcified or non-calcified CTO lesions. The retrograde approach was more commonly used among cases with moderate/severe calcification (40.3% vs. 23.5%; p < 0.001). Balloon angioplasty (76.6%) was the most common lesion preparation technique for calcified lesions, followed by rotational atherectomy (7.3%), laser atherectomy (3.4%) and, intravascular lithotripsy (3.4%). The incidence of major adverse cardiovascular events (MACE) was higher in cases with moderate or severe calcification (3.0% vs. 1.2%; p < 0.001), as was the incidence of perforation (6.5% vs. 3.4%; p < 0.001). On multivariable analysis, the presence of moderate/severe calcification was independently associated with lower technical success (odds ratio, OR = 0.73, 95% CI: 0.63-0.84) and higher MACE (OR = 2.33, 95% CI: 1.66-3.27). CONCLUSIONS: Moderate/severe calcification was present in nearly half of CTO lesions, and was associated with higher utilization of the retrograde approach, lower technical and procedural success rates, and higher incidence of in-hospital MACE.

Prognostic value of heart rate variability in acute coronary syndrome.

OBJECTIVES: To assess the predictive value of pre-discharge heart rate variability (HRV) parameters in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI). METHODS: 145 consecutive male patients with ACS (aged 57.12 ± 10.81 years) were included in this study. Fifteen minutes electrocardiogram recording was done to measure time-domain [standard deviation of N-N intervals (SDNN), root-mean square differences of successive R-R intervals (rMSSD)] and frequency-domain [low-frequency (LF) power, high-frequency (HF) power and total power (TP)] HRV parameters before and after PCI. The primary end point was the occurrence of major clinical events (MCE) defined as death, sudden death or re-acute myocardial infarction at the end of 3 months follow-up. RESULTS: At a follow-up of 3 months, MCE occurred in 06 patients (4.14%) (Cardiac death was 3.01%, while that of sudden death was 1.13%). Out of six-MCE, four deaths and two re-AMIs occurred. Pre-discharge HRV values (SDNN, rMSSD, TP, LF and HF) were significantly lower in patients with ACS without MCE. Only total power HRV index (AUC=0.748; p=0.040) showed greater prognostic accuracy. CONCLUSIONS: In conclusion, study showed an increase in SDNN, rMSSD, LF, HF and TP after successful revascularization with PCI in patients who had MCE. The resultant sensitivity, specificity of HRV is still limited in the present study. Particularly, its sensitivity is higher (33-83%) with a modest specificity (61-72%).

Spermatogonial stem cells (SSCs) in buffalo (Bubalus bubalis) testis.

BACKGROUND: Water buffalo is an economically important livestock species and about half of its total world population exists in India. Development of stem cell technology in buffalo can find application in targeted genetic modification of this species. Testis has emerged as a source of pluripotent stem cells in mice and human; however, not much information is available in buffalo. OBJECTIVES AND METHODS: Pou5f1 (Oct 3/4) is a transcription factor expressed by pluripotent stem cells. Therefore, in the present study, expression of POU5F1 transcript and protein was examined in testes of both young and adult buffaloes by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical analysis. Further, using the testis transplantation assay, a functional assay for spermatogonial stem cells (SSCs), stem cell potential of gonocytes/spermatogonia isolated from prepubertal buffalo testis was also determined. RESULTS: Expression of POU5F1 transcript and protein was detected in prepubertal and adult buffalo testes. Western blot analysis revealed that the POU5F1 protein in the buffalo testis exists in two isoforms; large (∼47 kDa) and small (∼21 kDa). Immunohistochemical analysis revealed that POU5F1 expression in prepubertal buffalo testis was present in gonocytes/spermatogonia and absent from somatic cells. In the adult testis, POU5F1 expression was present primarily in post-meiotic germ cells such as round spermatids, weakly in spermatogonia and spermatocytes, and absent from elongated spermatids. POU5F1 protein expression was seen both in cytoplasm and nuclei of the stained germ cells. Stem cell potential of prepubertal buffalo gonocytes/spermatogonia was confirmed by the presence of colonized DBA-stained cells in the basal membrane of seminiferous tubules of xenotransplanted mice testis. CONCLUSION/SIGNIFICANCE: These findings strongly indicate that gonocytes/spermatogonia, isolated for prepubertal buffalo testis can be a potential target for establishing a germ stem cell line that would enable genetic modification of buffaloes.

Expression of vascular endothelial growth factor (VEGF) transcript and protein in the testis of several vertebrates, including endangered species.

Vascular endothelial growth factor (VEGF) is known to influence the testis function. To establish the role of VEGF in the testis of a variety of species, we analyzed the expression of VEGF transcript using human gene-specific primers by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis in the testes of 18 vertebrates, including a few endangered species. An amplicon of 566 bp representing VEGF(165) was identified in testis of all species in this study. Sequence analysis of these amplicons revealed 84 to 96% homology to available human VEGF sequence and to the VEGF sequences of other species in GenBank. Immunohistochemical analysis revealed expression of VEGF protein, primarily in Sertoli and Leydig cells and occasionally in the germ cells of the testis sections. It can be concluded from this study that expression of VEGF transcript is conserved in the testis of several vertebrates and may have a role in the process of spermatogenesis.

Gonadal status of male recipient mice influences germ cell development in immature buffalo testis tissue xenograft.

Growth and development of immature testis xenograft from various domestic mammals has been shown in mouse recipients; however, buffalo testis xenografts have not been reported to date. In this study, small fragments of testis tissue from 8-week-old buffalo calves were implanted subcutaneously onto the back of immunodeficient male mouse recipients, which were either castrated or left intact (non-castrated). The xenografts were retrieved and analyzed 12 and 24 weeks later. The grafted tissue survived and grew in both types of recipient with a significant increase in weight and seminiferous tubule diameter. Recovery of grafts from intact recipients 24 weeks post-grafting was significantly lower than that from the castrated recipients. Seminal vesicle indices and serum testosterone levels were lower in castrated recipients at both collection time points in comparison to the intact recipients and non-grafted intact mouse controls. Pachytene spermatocytes were the most advanced germ cells observed in grafts recovered from castrated recipients 24 weeks post-grafting. Complete spermatogenesis, as indicated by the presence of elongated spermatids, was present only in grafts from intact recipients collected 24 weeks post-grafting. However, significant number of germ cells with DNA damage was also detected in these grafts as indicated by TUNEL assay. The complete germ cell differentiation in xenografts from intact recipients may be attributed to efficient Sertoli cell maturation. These results suggest that germ cell differentiation in buffalo testis xenograft can be completed by altering the recipient gonadal status.

Spermatogonial stem cells in the testis of an endangered bovid: Indian black buck (Antilope cervicapra L.).

Numerous wild bovids are facing threat of extinction owing to the loss of habitat and various other reasons. Spermatogonial stem cells (SSCs) represent the only germline stem cells in adult body that are capable of self-renewal and that can undergo differentiation to produce haploid germ cells. SSCs can, therefore, serve as a useful resource for preservation of germplasm of threatened and endangered mammals. The Indian black buck (Antilope cervicapra L.) is a small Indian antelope that is listed as endangered by the Indian Wildlife Protection Act, 1972. Immunohistochemical analysis of testes tissues of black buck revealed the presence of spermatogonia that were specifically stained by lectin-Dolichos biflorus agglutinin (DBA). The expression of pluripotent cell-specific markers, NANOG and stage-specific embryonic antigen-1 (SSEA-1), was detected in spermatogonia. Interestingly, the expression of POU5F1 (OCT3/4) was absent from spermatogonia, however, it was detected in differentiating cells such as spermatocytes and round spermatids but not in elongated spermatids. The expression of NANOG protein was also present in spermatocytes but absent in round and elongated spermatids. Using the testis transplantation assay, stem cell potential of black buck spermatogonia was confirmed as indicated by the presence of colonized DBA-stained cells in the basal membrane of seminiferous tubules of xenotransplanted mice testis. The findings from this study suggest the presence of SSCs in the testis of an endangered bovid for the first time and open new possibility to explore the use of SSCs in conservation.

Spermatogonia-specific proteins expressed in prepubertal buffalo (Bubalus bubalis) testis and their utilization for isolation and in vitro cultivation of spermatogonia.

Buffalo is an economically important livestock species in Asia. Little is known about male germ line technology owing to lack of sufficient understanding regarding expression of germ- and somatic-cell specific-proteins in the testis. In this study, we identified UCHL-1 (PGP 9.5) and lectin- Dolichos biflorus agglutinin (DBA) as specific markers for spermatogonia in buffalo testis. Expression of germ-cell and pluripotency-specific proteins such as DDX4 (VASA) and POU5F1 (OCT3/4) were also present in spermatogonia. Interestingly, the expression of somatic cell-specific proteins such as VIMENTIN and GATA4 were also detected in germ cells. Using two-step enzymatic digestion followed by differential plating and Percoll density-gradient centrifugation, an approximately 55% spermatogonia-enriched cell population could be obtained from the prepubertal buffalo testis. Isolated spermatogonia could survive and proliferate in vitro in DMEM/F12 medium containing 10% fetal bovine serum in the absence of any specific growth factors for a week. Cultured spermatogonia showed DBA affinity and expressed DDX4 and POU5F1. These results may help to establish a long-term culture system for buffalo spermatogonia.

Microbial metabolism. Part 8. The pyranocoumarin, decursin.

Microbial transformation of the cancer chemopreventive agent, decursin (1) with Sepedonium chrysospermem (ATCC 13378) yielded two metabolites, (+)-decursinol (2) and (-)-cis-decursidinol (3). The structures were established by spectroscopic data.

Long-term mortality of patients admitted to the intensive care unit for gastrointestinal bleeding.

OBJECTIVES: Long-term mortality data for gastrointestinal (GI) bleeders is scarce in the literature. The aim of this prospective study was to determine the long-term mortality of patients admitted to two intensive care units with a primary diagnosis of GI bleeding. METHODS: The charts of patients admitted to the medical intensive care unit (MICU) with GI bleeding were reviewed and the data of the patients' first day in the MICU was used to calculate APACHE III and Charlson scores. A GI bleeding score was computed by combining endoscopic findings and units of blood transfused during patients' MICU stay. Mortality data was obtained from the Vital Statistics Department of Montgomery County, Dayton, OH. Survival data and predictability of mortality based on these scores were assessed. RESULTS: Mean age of the 66 patient cohort was 58.6 years. Twenty-six of 51 patients with upper GI bleeding, five of seven patients with lower GI bleeding, and four of eight patients with unknown site of bleeding died within 7 years. Charlson score correlated significantly with the mortality prediction, whereas the APACHE III and bleeding scores did not. CONCLUSIONS: All-cause and GI bleeding-related 7-year mortality for patients admitted to the MICU with GI bleeding was lower than the rates cited in the literature. The Charlson score was helpful in predicting mortality.