Role of per- and polyfluoroalkyl substances in the cardiorenal system: Unraveling crosstalk from the network of pollutants and phenotypes.

Although per- and polyfluoroalkyl substances (PFAS) have been frequently linked to cardiovascular and renal disease separately, evidence remains scarce regarding their systematic effect. Therefore, we recruited 546 newly diagnosed acute coronary syndrome (ACS) patients and detected seven myocardial enzymes and six kidney function biomarkers. Twelve PFAS were also assessed with ultra-high-performance liquid chromatography-tandem mass spectrometry. Generalized linear model and restricted cubic spline model were applied to single pollutant analysis. Quantile g-computation was used for mixture analysis. Network model was utilized to identify central and bridge nodes of pollutants and phenotypes. In the present study, perfluorohexane sulfonic acid was positively associated with uric acid (UA) (ß= 0.04, 95% confidence interval (CI): 0.01, 0.07), and perfluorobutanoic acid was negatively associated with estimated glomerular filtration rate (ß= -0.04, 95% CI: -0.07, -0.01) but positively associated with UA (ß= 0.03, 95% CI: 0.01, 0.06). In mixture analysis, each quantile increase in the PFAS mixture was significantly associated with UA (ß= 0.08, 95% CI: 0.04, 0.11). Network analysis revealed that perfluorooctanoate, UA, and myoglobin were denoted as bridge nodes, and the first principal component of lactate dehydrogenase and creatine kinase- myocardial band was identified as the node with the highest strength and expected influence. This study investigates the systematic impact of PFAS exposure through cardiorenal interaction network, which highlights that PFAS may serve as an upstream approach in UA-modulated cardiorenal network to affect cardiorenal system comprehensively.

Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes.

BACKGROUND: Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. METHODS: From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk. RESULTS: Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16-5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6-36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail. CONCLUSIONS: In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention. REGISTRATION: ClinicalTrials.gov Identifier: NCT01000701.

Ten-year clinical outcomes after drug-eluting stents implantation according to clinical presentation-Insights from the DECADE cooperation.

BACKGROUND: Investigations of very long-term outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) according to clinical presentation are scarce. Here, we investigated the 10-year clinical outcomes of patients undergoing DES-PCI according to clinical presentation. METHODS: Patient-level data from five randomized trials with 10-year follow-up after DES-PCI were pooled. Patients were dichotomized into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) groups as per clinical presentation. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST) and repeat revascularization involving the target lesion (TLR), target vessel (TVR) or non-target vessel (nTVR). RESULTS: Of the 9700 patients included in this analysis, 4557 presented with ACS and 5143 with CCS. Compared with CCS patients, ACS patients had a higher risk of all-cause death and nTVR in the first year, but comparable risk thereafter. In addition, ACS patients had a higher risk of MI [adjusted hazard ratio 1.21, 95% confidence interval (1.04-1.41)] and definite ST [adjusted hazard ratio 1.48, 95% confidence interval (1.14-1.92)], while the risk of TLR and TVR was not significantly different up to 10-year follow-up. CONCLUSIONS: Compared to CCS patients, ACS patients treated with PCI and DES implantation have an increased risk of all-cause death and repeat revascularization of remote vessels up to 1 year, with no significant differences thereafter and up to 10-year follow-up. ACS patients have a consistently higher risk of MI and definite ST. Whether these differences persist with current antithrombotic and secondary prevention therapies requires further investigation.

The Cost-Effectiveness of Early Invasive Procedures for Acute Coronary Syndrome in Low-Income Regions: A Prospective Cohort Study in Pakistan.

Background Acute coronary syndrome (ACS) is a significant cause of mortality and morbidity globally, necessitating effective intervention strategies. Early invasive procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are often recommended for high-risk patients. However, their cost-effectiveness in low-income regions remains uncertain, particularly in Pakistan, where healthcare resources are limited. Objective This study aims to evaluate the cost-effectiveness of early invasive procedures compared to standard care for ACS in low-income regions of Pakistan. Methods We conducted a prospective cohort study from January 1, 2021, to January 31, 2021, at four major hospitals in Pakistan: Army Cardiac Center Combined Military Hospital (CMH) Lahore, National Institute of Cardiovascular Diseases in Karachi, Lady Reading Hospital in Peshawar, and Mardan Medical Complex. The participants included 436 patients diagnosed with ACS aged 18 years or older and presenting within 24 hours of symptom onset. The patients were divided into two groups: the early invasive procedure group (n = 218) and the standard care group (n = 218). The primary outcome was the 30-day mortality rate. Secondary outcomes included recurrent myocardial infarctions, hospital readmissions, healthcare costs, and procedural complications. Data were analyzed using SPSS version 25.0 (IBM SPSS Statistics, Armonk, NY), employing descriptive statistics, chi-square tests, independent t-tests, and Kaplan-Meier survival analysis. Results The early invasive procedure group showed a mortality rate of 18 (8%) compared to 33 (15%) in the standard care group, demonstrating a significant reduction in mortality (p = 0.01). Additionally, the average healthcare cost was significantly lower in the early invasive group, with mean costs of Pakistani rupee (PKR) 187,200 (US dollar {USD} 1,200) compared to PKR 280,800 (USD 1,800) in the standard care group (p < 0.01). Recurrent myocardial infarctions occurred in 11 (5%) of the early invasive group versus 26 (12%) in the standard care group (p < 0.05). Hospital readmission rates were lower in the early invasive group, 22 (10%) compared to 39 (18%) in the standard care group (p < 0.05). Healthcare costs were significantly lower in the early invasive group, with mean costs of PKR 187,200 (USD 1,200) compared to PKR 280,800 (USD 1,800) in the standard care group (p < 0.01). Conclusion Early invasive procedures for ACS significantly improve survival rates, reduce complications, and lower healthcare costs in low-income regions of Pakistan. These findings suggest that such strategies should be considered in resource-limited settings to optimize patient outcomes and healthcare resource utilization.

One-Year Prognosis Difference of Myocardial Infarction With or Without Coronary Obstruction in Developing Countries: Insights From the Moroccan Experience.

Introduction: The debate remains open as to the difference in prevalence of mortality and occurrence of acute events in patients with Myocardial infarction with non-obstructive coronary arteries (MINOCA) and others with Myocardial infarction with coronary arteries disease (MI-CAD). Methods: We conducted a 2-year retrospective study for patients admitted for Acute coronary syndrome (ACS) to analyze the clinical and prognostic characteristics of patients with MINOCA versus MI-CAD. We defined 1-year all-cause mortality as the primary outcome, and the secondary outcome as a composite of 1-year readmission for myocardial infarction or acute heart failure (AHF). Results: Our study included 1077 patients, 95.3% with MI-CAD and 4.7% with MINOCA. At admission, 71.1% patient were diagnosed STEMI and 28.9% with NSTEMI. The difference between the 2 groups was found on age (P < .001), hypertension, diabetes with consecutive P-values of .007 and .001, as well as Ejection fraction (P < .001). For the outcomes studied, the difference was significant between the 2 groups for all events, and MINOCA patients had a better prognosis than MI-CAD patients, with adjusted hazard ratios (HR) for 1-year mortality (HR = 0.601 P = .004), for readmission for ACS (HR = 0.662; P = .002) and for readmission for AHF (HR = 0.539; P = .019). Conclusion: Despite the ambiguity in the genesis of MINOCA, the short- and long-term prognosis of these patients remains generally favorable.

Eligibility for marine omega-3 fatty acid supplementation after acute coronary syndromes.

Background and aims: The 2019 European Society of Cardiology guidelines for the management of dyslipidemia consider the use of high-dose marine omega-3 fatty acid (FA) eicosapentaenoic acid (EPA) supplementation (icosapent ethyl 2 × 2g/day) to lower residual cardiovascular risk in high-risk patients with hypertriglyceridemia. This study aimed to assess the eligibility for omega-3 FA-EPA supplementation in patients with acute coronary syndromes (ACS). Methods: In a prospective Swiss cohort of patients hospitalized for ACS, eligibility for marine omega-3 FA-EPA, defined as plasma triglyceride levels ranging from 1.5 to 5.6 mmol/l, was assessed at baseline and one-year follow-up and compared across subgroups. Lipid-lowering therapy intensification with statin and ezetimibe was modelled to simulate a hypothetical systematic treatment and its effect on omega-3 FA-EPA supplementation eligibility. Results: Of 2643 patients, 98 % were prescribed statin therapy at discharge, including 62 % at a high-intensity regimen; 93 % maintained it after one year, including 53 % at a high-intensity regimen. The use of ezetimibe was 3 % at discharge and 7 % at one year. Eligibility was observed in 32 % (32 % men, 29 % women) one year post-ACS. After modelling systematic treatment with statins, ezetimibe, and both, eligibility decreased to 31 %, 25 % and 24 %, respectively. Eligibility was higher in individuals aged <70 (34 vs 25 %), smokers (38 vs 28 %), diabetics (46 vs 29 %), hypertensive (35 vs 29 %), and obese patients (46 vs 22 % for normal weight), all with p-values <0.001. Conclusion: In a contemporary Swiss cohort of patients with ACS, up to 32 % would be eligible for omega-3 FA-EPA supplementation one year after ACS, highlighting an opportunity to mitigate residual cardiovascular risk in patients with ACS and hypertriglyceridemia.

Needs and Preferences for Remote-Delivered Mindfulness-Based Cognitive Therapy in Patients After Acute Coronary Syndrome: A Qualitative Study.

Background: Following acute coronary syndrome (ACS), up to 40% of patients report elevated depressive symptoms which is associated with a two-fold increase in mortality risk due to behavioral and biological mechanisms. Mindfulness-Based Cognitive Therapy (MBCT) delivered via synchronous group videoconferencing could help reduce depressive symptoms. Objective: To guide MBCT adaptation for ACS patients for a future clinical trial, this qualitative study aimed to explore ACS patients' (1) symptoms after ACS, (2) needs for behavioral health treatment, (3) perspectives on mindfulness intervention and group videoconference delivery, and (4) willingness to self-collect dried blood spots in a research study. Methods: We compared ACS patients with and without depressive symptoms to highlight particularly relevant treatment topics for patients developing depression following ACS experience. From 2/2019-11/2019, we conducted semi-structured individual telephone interviews with N = 23 patients after ACS (N = 13 with and N = 10 without elevated depressive symptoms; 63.4 (SD = 8.5) years, 87% male, 96% non-Hispanic white, 7.1 (SD = 7.5) years since ACS). In qualitative content analyses, four independent coders coded each interview. Results: Participants with depressive symptoms experienced emotional, physical, social, and health behavior problems, while those without depressive symptoms made positive health behavior changes and struggled with anxiety symptoms. Both groups were interested in a behavioral health treatment for emotional and social support. Most were willing to participate in a mindfulness group via videoconferencing; some preferred in-person, but accessibility and convenience outweighed these cons. Almost all were willing to self-collect dried blood spots and some were already familiar with this technique. Conclusion: ACS patients, especially those with depressive symptoms, need help managing a multitude of quality of life concerns that can be targeted with an adapted MBCT approach. A videoconference-delivered MBCT approach is of interest. Suggestions for adapting MBCT to target the needs of ACS patients are discussed.

Prognostic value of the monocyte-to-high-density lipoprotein-cholesterol ratio in ACS patients: A systematic review and meta-analysis.

BACKGROUND: Globally, diseases of the cardiovascular system stand as the principal contributors to mortality and are anticipated to show an upward trajectory. The occurrence of Acute Coronary Syndrome (ACS) has been linked to underlying inflammatory processes. The monocyte-to-high-density lipoprotein-cholesterol (MHR) ratio has garnered significant attention as a prognostic biomarker, encapsulating the synergistic roles of inflammation and lipid metabolism in the pathophysiology of cardiovascular diseases, including ACS. AIMS: This meta-analysis examines the prognostic MHR ratio in ACS patients. METHODS: We systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library databases to identify the relevant meta-analyses up to February 26, 2024. The findings were aggregated into risk ratios with 95% confidence intervals. RESULTS: Eleven studies, with 7421 patients, were included. Low MHR levels compared to high MHR levels were associated with statistically significantly lower in-hospital mortality (0.9% vs. 5.5%; respectively; p<0.001), 3-month mortality (4.4% vs. 11.2%; p = 0.02), 6-month follow-up mortality (4.0% vs. 10.2%; p = 0.03), 1-year mortality (4.2%, vs. 10.2%; p<0.001), as well as long-term follow-up mortality (7.5% vs. 13.7%; p<0.001). CONCLUSIONS: MHR has both good predictive properties for mortality and MACE (short- and long-term). Data indicate that MHR may improve in-hospital and long-term cardiovascular risk prediction. It may, therefore, be an effective tool for risk re-estimation and the selection of patients for whom intensive lipid-lowering treatment may be particularly useful.

Contemporary characteristics, outcomes and novel risk score for Takotsubo cardiomyopathy: a national inpatient sample analysis.

BACKGROUND: Takotsubo cardiomyopathy (TC) is an established differential diagnosis of myocardial infarction with non-obstructive coronaries with significant interest but limited data on prognostication. We reviewed the characteristics and in-hospital outcomes and developed a novel risk score for TC. METHODS: Using the National Inpatient Sample data from 2016 to 2020, we identified adult patients (≥18 years) with acute coronary syndrome (ACS) and TC. We divided the cohort into ACS with and without TC and retrieved baseline data. Multivariable regression analysis was conducted to identify factors associated with TC diagnosis and adverse outcomes, leading to the development of a risk-scoring system. RESULTS: Among 7 219 004 adult ACS admissions, 78 214 (1.0%) were diagnosed with TC, with a mean age of 68.2 years, 64 526 (82.5%) being female and 5475 (7.0%, compared with 8.4% for other ACS) in-hospital mortality events. Factors significantly associated with TC were female sex (OR 6.78 (95% CI 6.47 to 7.09), p<0.001) and chronic heart failure (OR 1.60 (95% CI 1.54 to 1.66), p<0.001). A novel risk score was developed, including the following parameters: male sex, age >70 years, non-white race, hypertension, hyperlipidemia, history of coronary artery bypass grafting, history of percutaneous coronary intervention, cardiac arrhythmias, renal failure, cardiogenic shock and vasopressor use. The area under curves for in-hospital mortality was 0.716 in the derivation and 0.725 in the validation cohorts. CONCLUSIONS: TC remains a high-risk diagnosis in a minority of ACS cases, with mortality rates similar to other ACS causes. Our novel risk score offers a valuable tool for risk stratification in patients with TC, but external validation is needed to confirm its utility.

Case Report: Pazopanib-induced acute coronary syndrome.

Introduction: Pazopanib is a tyrosine kinase inhibitor approved for the treatment of metastatic renal cell carcinoma and advanced soft-tissue sarcoma that functions by inhibiting vascular endothelial growth factor receptors. Although the package insert and current cardio-oncology guidelines indicate a risk of acute coronary syndrome (ACS) associated with pazopanib, the causative role of pazopanib in arterial thrombosis is unclear due to a lack of focused coronary disease evaluation in oncological clinical trials prior to pazopanib initiation. Herein we present an antecedent ischemic evaluation of a patient who was prescribed pazopanib to demonstrate the first reported case of ACS directly attributable to pazopanib. Case description: A 65-year-old woman with metastatic leiomyosarcoma presented to the hospital with ACS. Pazopanib had been initiated 8 months prior, and an ischemic evaluation 6 weeks prior to hospitalization indicated mild coronary artery disease (CAD). Emergent cardiac catheterization revealed a large thrombotic occlusion of the mid-left anterior descending coronary artery involving the secondary diagonal artery, which was treated with manual aspiration thrombectomy. Pazopanib was discontinued, and the patient was discharged from the hospital 12 days later. Discussion: Although pazopanib is associated with ACS, there is a lack of definitive data supporting this association. This case-based demonstration of pazopanib-induced ACS provides a discrete clinical example of this phenomenon. The patient's minimal atherosclerotic burden 6 weeks prior to her presentation for ACS strongly suggests causality attributable to pazopanib. Given the increased risk for ischemic heart disease, careful attention and an individualized risk assessment for CAD should be provided to patients who are prescribed pazopanib.

Efficacy of Danlou tablets in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a multicenter prospective cohort study.

Background: Danlou tablets (DLTs) have been widely used to treat coronary heart disease in China. However, the benefits associated with DLT for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in routine practice require further investigation. Purpose: To investigate the effectiveness of DLT in patients with ACS undergoing PCI. Methods: This multicenter prospective cohort study for patients with ACS undergoing PCI was conducted in 40 centers in mainland China from February 2012 to December 2018. This trial is registered under ChiCTR-OOC-14005552. Patients were assigned to either the DLT group or the conventional medicine (CM) group based on whether they used DLT prior to enrollment. The duration of DLT use (1.5 g, three times a day) was 12 months. The primary endpoint comprised of cardiac death, non-fatal myocardial infarction, and urgent revascularization. Secondary endpoint included rehospitalization owing to ACS, heart failure, stroke, and other thrombotic events. The Seattle Angina Questionnaire (SAQ) was used to assess quality of life (QOL). Primary and secondary endpoints were followed up for 36 months, and the SAQ was followed up for 12 months. The Cox proportional hazards regression model was used to analyze the independent effect of DLT on primary and secondary endpoints. Propensity score matching (PSM) analyses were performed to mitigate bias. Survival estimation was performed using Kaplan-Meier survival curves and log-rank tests in the PSM cohort, and landmark analyses were used for further evaluation of primary and secondary endpoints. Subgroup analyses and interactions confirmed the robustness of the findings. Linear mixed effects models were used to assess the QOL. Results: Overall, 936 patients were enrolled in this cohort study, of whom 875 completed follow-up. The primary and secondary endpoints had no significantly difference between the DLT and CM groups after Cox proportional hazards models. Kaplan-Meier survival curves and log-rank tests performed in the PSM cohort also found no significant differences between the two groups on primary and secondary endpoints. However, landmark analysis showed significant benefit in the primary endpoint for the DLT group after 200 days (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.22-0.93, P = 0.03). Landmark analysis also showed a significant benefit in the secondary endpoint in the DLT group within 200 days (HR 0.33, 95% CI 0.15-0.73, P = 0.006). Moreover, DLT improves the SAQ summary score, and scores in the physical limitation, treatment satisfaction, and disease perception domains for patients with ACS undergoing PCI. Conclusions: DLT combined with conventional treatment reduced the risk of the primary endpoint after 200 days and the secondary endpoint within 200 days during the 3-year follow-up. Additionally, DLT can improve the QOL without adverse effects.

Clinical characteristics, management, diagnostic findings, and various etiologies of patients with Kounis syndrome. A systematic review.

BACKGROUND: Kounis syndrome (KS) is defined by the association of acute coronary syndrome secondary to an anaphylactic reaction. KS is often underdiagnosed, and new etiologies have been proposed. AIMS: To synthesize the available evidence on clinical profile, management, diagnosis, and etiologies in patients with KS. METHODS: A search was conducted in the following databases: PubMed, Scopus, EMBASE and Web of Science from inception to March 19th, 2024. Case reports, case series, and observational studies were included. Letters to the editor, editorials, comments, notes, narrative reviews, and systematic reviews were excluded. RESULTS: A total of 190 studies were included (174 case reports, 13 case series, and 3 observational studies, 214 patients). A predominance of male gender was observed (69.63 %). Mean age was 54.4 ± 16.5 years. The most common comorbidities were hypertension (33.64 %), diabetes (16.82 %), and dyslipidemia (16.35 %). The most frequent clinical manifestations were chest pain (66.35 %) and difficulty breathing (34.11 %). Three variants of KS were identified: type I or allergic coronary vasospasm was the most frequent (43.46 %), and type III, the least common (8.88 %). The most frequent etiology was drug use (38.32 %), primarily antibiotics (42.68 %), followed by animal stings or bites (26.17 %). The calculated KS rate was 11.12 per 1000 people. The mortality rate was 7.47 %, and the majority had a favorable outcome (86.92 %) after management. CONCLUSIONS: KS is a complex and underdiagnosed disease that should be considered as a differential diagnosis in acute coronary syndrome associated with an allergic reaction.

The first in-human study to evaluate the antiplatelet properties of the clopidogrel conjugate DT-678 in acute coronary syndrome patients and healthy volunteers.

BACKGROUND AND PURPOSE: DT-678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT-678 to overcome HTPR. EXPERIMENTAL APPROACH: A total of 300 consecutive ACS patients naive to P2Y12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600-mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT-678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT-678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3-mg DT-678 or 75-mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared. KEY RESULTS: Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3 mg of DT-678. CONCLUSION AND IMPLICATIONS: These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy.

Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Recombinant Neorudin, a New Anticoagulant Drug in Patients With Acute Coronary Syndrome.

This study evaluated the safety, tolerability, pharmacodynamics, and pharmacokinetics of recombinant neorudin (EPR-hirudin [EH]) in patients with acute coronary syndrome (ACS), providing a basis for further therapeutic research. This open-label, single-center, nonrandomized, nonblinded, and noncontrolled trial categorized 24 patients with nonprogressive ACS who met the screening criteria into 3 groups. They received an intravenous injection of neorudin (0.4 mg/kg), followed by an intravenous drip at doses of 0.15, 0.30, and 0.45 mg/kg/h for 3 days in the low-, medium-, and high-dose groups, respectively. The safety, tolerability, pharmacodynamics, and pharmacokinetics of EH were assessed after treatment, indicating that neorudin was safe and well tolerated in nonprogressive ACS. No serious adverse events or clinical composite end points were observed. The activated partial thromboplastin time and thrombin time increased significantly and dose dependently following EH administration across all groups compared to pretreatment values. Conversely, thrombin activity significantly decreased after drug administration but returned to baseline levels shortly after drug withdrawal. Within the administered dose range, neorudin exposure increased with the dose, and its half-life was approximately 2 hours. Neorudin was found to be safe and tolerable for treating patients with nonprogressive ACS, demonstrating therapeutic efficacy at doses up to 0.45 mg/kg/h over a 3-day period.

Optimal medical therapy, clinical outcome and its predictors in patients with acute coronary syndrome after discharge with secondary prevention medications at University of Gondar Comprehensive Specialized Hospital, North West Ethiopia, 2023: A retrospective follow-up study.

BACKGROUND: The life-threatening diseases known as ACS (acute coronary syndrome) continue to produce considerable rates of morbidity and mortality despite breakthroughs in therapy. The study determined clinical outcome and its predictors in patients at the University of Gondar Comprehensive and Specialized Hospital (UOGCSH), North West Ethiopia. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study design was employed at UOGCSH from January 31, 2018 to February 1, 2023. The hospital used a systematic random sampling procedure to select study participants from the medical records of patients in chronic cardiac follow-up clinics. MAIN OUTCOME MEASURES: Exposures were optimal medical therapy (OMT) versus non-optimal medical therapy collected from May to August 2023. Descriptive and analytical statistics were employed to compare study groups. A binary logistic regression model was employed to identify candidate variables for further analysis. Cox's proportional hazard model and log-rank test were employed, with a P-value < 0.05 used to evaluate statistical significance. A five-year all-cause mortality after discharge estimate was displayed by using Kaplan-Meier curves. RESULTS: Among 422 patients with ACS [mean age, 61.56 (SD = 9.686) years; 54.7% male], of whom only 59.2% (250) received optimal medical therapy at discharge. Age ≥ 65, atrial fibrillation, chronic kidney diseases, and cardiogenic shock were negative independent predictors of optimal medical therapy. On the other hand, male sex was independently associated with the use of optimal medical therapy. All-cause mortality occurred in 16.6% (n = 70) and major adverse cardiac events occurred in 30.8% (n = 130) of patients with a 95% CI of 0.132-0.205 and 0.264-0.355, respectively. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality (aHR: 0.431, 95% CI: 0.222-0.835; P = 0.013). CONCLUSION: This study revealed that the use of preventive OMT in patients discharged with acute coronary syndrome was associated with a reduction in all-cause mortality. However, the use of this OMT is suboptimal.

Safety and efficacy of PCSK9 inhibitors and effect on coronary plaque phenotype in statin-treated patients following acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: Acute coronary syndrome continues to be a significant cardiovascular issue. Statins are commonly acknowledged as medications that reduce LDL-C levels and stabilize plaques. Nevertheless, their efficacy is limited. Presently, PCSK9 inhibitors are suggested to be advantageous in patients who are already receiving statin treatment. The study seeks to assess the safety and effectiveness of PCSK9 inhibitors in individuals who have been treated with statins after experiencing acute coronary syndrome (ACS), as well as investigate the impact on the characteristics of coronary plaque. METHODS: Articles were identified from PubMed, Cochrane Central Register of Controlled Trials, and ProQuest. Our analysis comprised trials and observational studies that compared the plaque phenotype, lipid profile, and safety outcomes between PCSK9 inhibitors and a control group in patients with acute coronary syndrome who were already being treated with statins. The random-effect model was used to measure the pooled effect, which was presented in terms of mean difference, standardized mean difference, and risk ratio. RESULTS: Acquired 12 studies that fulfilled our criteria. The addition of PCSK9 inhibitors ameliorates the plaque phenotype significantly in terms of percent atheroma volume (P = 0.02), total atheroma volume (P < 0.010), fibrous cap thickness (P < 0.00001), lipid arc (P < 0.00001), quantitative flow ratio (P = 0.003), and diameter of stenosis (P = 0.0003) but not in lipid/lesion length (P = 0.17). The administration of PCSK9 inhibitors led to a considerable improvement in all lipid profiles (P < 0.00001). Regarding safety analysis, there is no substantial disparity in the likelihood of non-serious side events (RR 1.21; P = 0.2), however, a significant reduction in the risk of serious adverse effects (RR 0.77; P = 0.04) in the PCSK9 inhibitor group. CONCLUSIONS: The addition of PCSK9 inhibitors compared to statin-only treatment led to a majority of patients experiencing significant benefits in terms of safety and efficacy following ACS.

IVUS-Guided vs Angiography-Guided PCI in Patients With Diabetes With Acute Coronary Syndromes: The IVUS-ACS Trial.

BACKGROUND: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) reduces the risk for clinical events in patients with acute coronary syndromes (ACS), compared with angiographic guidance. However, the benefits of IVUS guidance in high-risk patients with diabetes with ACS is uncertain. OBJECTIVES: The aim of this prespecified stratified subgroup analysis from the IVUS-ACS randomized trial was to determine the effectiveness of IVUS-guided PCI vs angiography-guided PCI in patients with diabetes with ACS. METHODS: From August 20, 2019, to October 27, 2022, 1,105 patients with diabetes with ACS were randomized, including 554 patients in the IVUS-guided group and 551 in the angiography-guided group. The primary endpoint was the rate of target vessel failure (TVF) at 1 year, defined as the composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. RESULTS: At 1-year follow-up, TVF occurred in 20 patients in the IVUS guidance group and in 46 patients in the angiographic guidance group (Kaplan-Meier rates 3.6% vs 8.3%; HR: 0.46; 95% CI: 0.27-0.81; P = 0.007), driven by a reduction in clinically driven target vessel revascularization (0.9% vs 3.8%; P = 0.003). IVUS-guided PCI also reduced the risk for TVF without procedural myocardial infarction (2.0% vs 6.7%; HR: 0.29; 95% CI: 0.15-0.57; P < 0.001) and all-cause mortality (HR: 0.30; 95% CI: 0.10-0.93; P = 0.037). There were no significant differences in the rates of stent thrombosis or major bleeding between the groups. CONCLUSIONS: In the large-scale IVUS-ACS trial, IVUS-guided PCI improved 1-year clinical outcomes in high-risk patients with diabetes with ACS. (1-Month vs 12-Month DAPT for ACS Patients Who Underwent PCI Stratified by IVUS: IVUS-ACS and ULTIMATE-DAPT Trials; NCT03971500).

ST-segment elevation in V1-4 in takotsubo cardiomyopathy with ventricular septal perforation: A case report and literature review.

Background: Takotsubo cardiomyopathy (TCM) is a nonischemic cardiomyopathy characterized by chest pain, typically manifesting transient left ventricular (LV) apical akinesis, and ischemic electrocardiographic changes, mimicking acute coronary syndrome (ACS). Although ventricular septal perforation (VSP) is a rare complication of TCM, it is potentially life-threatening if left untreated. Whether the conventional electrocardiographic criteria for TCM are beneficial, even in patients of TCM with VSP, remains unclear. Case presentation: An 87-year-old woman was admitted for worsening dyspnea. Elevated serum cardiac enzyme levels, LV dysfunction on echocardiography, and ST-segment elevation in leads V1-4 on electrocardiogram were initially suggestive of ACS. An emergency coronary angiography revealed 90 % focal stenosis of the mid-portion of the right coronary artery (RCA) with Thrombolysis in Myocardial Infarction flow grade 2. However, left ventriculography revealed LV apical ballooning with a coexisting left-to-right shunting, which was beyond single RCA distributions, leading to a final diagnosis of TCM with VSP. Repeat echocardiography confirmed VSP and right ventricular involvement with severe pulmonary hypertension. Following successful percutaneous coronary intervention with a drug-eluting stent for RCA stenosis, the patient was managed with medical treatment without surgical intervention. Eventually, VSP and associated pulmonary hypertension markedly improved along with the normalization of the patient's cardiac structure and function. The patient's clinical course was uneventful at the 1-year follow-up. Conclusions: Herein, we describe the case of TCM with VSP that we successfully managed with medical treatments. Our case highlights the significance of elucidating this rare complication of TCM, pitfalls of the conventional electrocardiographic diagnostic criteria for TCM, and potential of this unique electrocardiographic pattern for identifying TCM-associated VSP.