-
American Heart Journal Jun 2024It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can...
PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.
BACKGROUND
It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions.
METHODS
This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance.
CONCLUSION
The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.
PubMed: 38942221
DOI: 10.1016/j.ahj.2024.06.004 -
Metabolism: Clinical and Experimental Jun 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are...
Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: systematic analysis from the global burden of disease study 2019.
OBJECTIVE
Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary.
METHODS
From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data.
RESULTS
Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average.
CONCLUSION
The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.
PubMed: 38942169
DOI: 10.1016/j.metabol.2024.155958 -
Europace : European Pacing,... Jun 2024Anticoagulation can prevent stroke and prolong lives in patients with atrial fibrillation (AF); However, anticoagulated patients with AF remain at risk of death. The aim...
AIMS
Anticoagulation can prevent stroke and prolong lives in patients with atrial fibrillation (AF); However, anticoagulated patients with AF remain at risk of death. The aim of this study was to investigate the causes of death and factors associated with all-cause and cardiovascular death in the XANTUS population.
METHODS AND RESULTS
Causes of death occurring within a year after rivaroxaban initiation in patients in the XANTUS program studies were adjudicated by a central adjudication committee and classified following international guidance.Baseline characteristics associated with all-cause or cardiovascular death were identified. Of 11,040 patients, 187 (1.7%) died. Almost half of these deaths were due to cardiovascular causes other than bleeding (n = 82, 43.9%), particularly heart failure (n = 38, 20.3%) and sudden or unwitnessed death (n = 24, 12.8%). Fatal stroke (n = 8, 4.3%), which was classified as a type of cardiovascular death, and fatal bleeding (n = 17, 9.1%) were less common causes of death. Independent factors associated with all-cause or cardiovascular death included age, AF type, body mass index, left ventricular ejection fraction, hospitalization at baseline, rivaroxaban dose, and anaemia.
CONCLUSION
The overall risk of death due to stroke or bleeding was low in XANTUS. Anticoagulated patients with AF remain at risk of death due to heart failure and sudden death. Potential interventions to reduce cardiovascular deaths in anticoagulated patients with AF, require further investigation, e.g. early rhythm control therapy and AF ablation.
PubMed: 38941511
DOI: 10.1093/europace/euae183 -
Interdisciplinary Cardiovascular and... Jun 2024Less invasive surgery has emerged as an option for aortic pathologies. The current study compared our experience on early postoperative results of patients with aortic...
OBJECTIVES
Less invasive surgery has emerged as an option for aortic pathologies. The current study compared our experience on early postoperative results of patients with aortic surgery between partial upper sternotomy (PUS) and full sternotomy (FS).
METHODS
We performed a retrospective analysis of the data of patients undergoing aortic root surgery with concomitant ascending aorta and hemiarch replacement. Exclusion criteria were type A aortic dissection and other concomitant major cardiac surgery. After propensity-score matching, we compared the perioperative outcomes of patients undergoing surgery with PUS vs FS.
RESULTS
161 patients operated on between January 2013 and September 2022 met the inclusion criteria (PUS: n = 22, FS: n = 139). Propensity score matching yielded 22 pairs with a balanced distribution of propensity scores and covariates between the compared groups. There was no evidence that PUS affects cardiopulmonary bypass [108(67-119) vs 113(87-148) min, p = 0.154; PUS vs FS] and circulatory arrest duration [9(7-10) vs 9(8-13) min, p = 0.264; PUS vs FS]. There was a reduced cross-clamp duration in the PUS group [88(58-96) vs 92(71-122) min, p = 0.032]. Cumulative sum charts (CUSUM) have shown consistently low cross-clamp and circulatory arrest duration for two experienced surgeons who performed 20 of the procedures in the PUS group (10 each). Perioperative mortality and morbidity were low, with no in-hospital mortality in the PUS group [0 vs 1(4.5%), p > 0.999] and absence of strokes in both groups.
CONCLUSIONS
In summary, our initial experience suggests that less invasive aortic root, ascending aorta, and hemiarch replacement via partial upper sternotomy could be performed in our patient cohort as safely as via full sternotomy. Advantages for the patient are reduced surgical trauma, improved cosmetic results, and-presumably-less pain.
PubMed: 38941507
DOI: 10.1093/icvts/ivae120 -
Stroke Jun 2024Angioedema without concomitant urticaria is a well-known complication of treatment with the recombinant tissue-type plasminogen activator (r-tPA) alteplase and its...
Angioedema without concomitant urticaria is a well-known complication of treatment with the recombinant tissue-type plasminogen activator (r-tPA) alteplase and its genetically modified variant tenecteplase. It is potentially lethal when causing airway obstruction and can require intubation. The latest guideline for the early management of patients with acute ischemic stroke from the American Heart Association/American Stroke Association advises to treat this complication initially by interfering with the histamine pathway. This article aims to clarify the pathophysiological mechanism of r-tPA-induced angioedema and provides several arguments that this condition is primarily bradykinin-mediated and hence should be treated initially by intervening with the bradykinin pathway. Second, other-less frequently reported-adverse symptoms after r-tPA therapy and their proposed pathophysiological mechanisms leading to specific treatment are described. This manuscript describes the need for an update of the section "3.5 IV alteplase" from the American Heart Association/American Stroke Association guideline to treat this r-tPA-induced angioedema adequately and prevent potentially fatal outcomes.
PubMed: 38939926
DOI: 10.1161/STROKEAHA.124.047060 -
JACC. Advances Apr 2024Major adverse cardiovascular events (MACE) are a leading cause of morbidity and mortality among adults with type 2 diabetes. Currently, available MACE prediction models...
BACKGROUND
Major adverse cardiovascular events (MACE) are a leading cause of morbidity and mortality among adults with type 2 diabetes. Currently, available MACE prediction models have important limitations, including reliance on data that may not be routinely available, narrow focus on primary prevention, limited patient populations, and longtime horizons for risk prediction.
OBJECTIVES
The purpose of this study was to derive and internally validate a claims-based prediction model for 1-year risk of MACE in type 2 diabetes.
METHODS
Using medical and pharmacy claims for adults with type 2 diabetes enrolled in commercial, Medicare Advantage, and Medicare fee-for-service plans between 2014 and 2021, we derived and internally validated the annualized claims-based MACE estimator (ACME) model to predict the risk of MACE (nonfatal acute myocardial infarction, nonfatal stroke, and all-cause mortality). The Cox proportional hazards model was composed of 30 covariates, including patient age, sex, comorbidities, and medications.
RESULTS
The study cohort comprised 6,623,526 adults with type 2 diabetes, mean age 68.1 ± 10.6 years, 49.8% women, and 73.0% Non-Hispanic White. ACME had a concordance index of 0.74 (validation index range: 0.739-0.741). The predicted 1-year risk of the study cohort ranged from 0.4% to 99.9%, with a median risk of 3.4% (IQR: 2.3%-6.5%).
CONCLUSIONS
ACME was derived in a large usual care population, relies on routinely available data, and estimates short-term MACE risk. It can support population risk stratification at the health system and payer levels, participant identification for decentralized clinical trials of cardiovascular disease, and risk-stratified observational studies using real-world data.
PubMed: 38939660
DOI: 10.1016/j.jacadv.2024.100852 -
JACC. Advances Nov 2023Sex differences in the clinical presentation and outcomes of DeBakey type I/II (Stanford type A) acute aortic dissection (AAD) remain unclear.
BACKGROUND
Sex differences in the clinical presentation and outcomes of DeBakey type I/II (Stanford type A) acute aortic dissection (AAD) remain unclear.
OBJECTIVES
The authors aimed to determine the impact of sex on the clinical presentation and in-hospital outcomes of surgically or medically treated patients with type I/II AAD.
METHODS
We studied 3,089 patients with type I/II AAD enrolled in multicenter Japanese registry between 2013 and 2018. The patients were divided into 2 treatment groups: surgical and medical. Multivariable logistic regression was used to examine the association between sex and in-hospital mortality.
RESULTS
In the entire cohort, women were older and more likely to have hyperlipidemia, previous stroke, altered consciousness, and shock/hypotension at presentation than men. Women had higher proportions of intramural hematomas and type II dissections than men. In the surgical group (n = 2,543), men had higher rates of preoperative end-organ malperfusion ( = 0.003) and in-hospital mortality ( = 0.002) than women. Multivariable analysis revealed that male sex was associated with higher in-hospital mortality after surgery (OR: 1.71; 95% CI: 1.24-2.35; < 0.001). In the medical group (n = 546), women were older and had higher rates of cardiac tamponade ( = 0.004) and in-hospital mortality ( = 0.039) than men; no significant association between sex and in-hospital mortality was found after multivariable adjustment (OR: 0.95; 95% CI: 0.56-1.59; = 0.832).
CONCLUSIONS
Male sex was associated with higher in-hospital mortality for type I/II AAD in the surgical group but not in the medical group. Further research is needed to understand the mechanisms responsible for worse surgical outcomes in men.
PubMed: 38938720
DOI: 10.1016/j.jacadv.2023.100661 -
JACC. Advances Oct 2023Atrial fibrillation (AF) is highly prevalent among cancer patients. The role of traditional risk stratification scores in the context of different cancer types in these...
BACKGROUND
Atrial fibrillation (AF) is highly prevalent among cancer patients. The role of traditional risk stratification scores in the context of different cancer types in these patients remains unknown.
OBJECTIVES
The purpose of this study was to determine the discriminative accuracy of the CHADSVASc score for ischemic stroke using receiver operating characteristic and area under the curve.
METHODS
The National Readmission Database (2015-2019) was used to identify all AF patients stratified by the cancer diagnosis, type, and CHADSVASc category (low; moderate; high risk). Outcomes at 30-day readmission were compared between cancer and noncancer groups using hierarchical multivariable logistic regression to calculate adjusted odds ratios (aORs) and 95% CIs.
RESULTS
A total of 6,996,088 AF patients were identified at index admission. Of these, 4,242,630 (642,237 cancer, 3,600,393 noncancer) were readmitted at 30 days. Cancer patients (92.1%) had a higher proportion of high CHADSVASc scores compared with their noncancer counterparts (89.8%, < 0.001). The 30-day readmission rate and incidence of major bleeding in cancer patients were significantly higher compared with their corresponding noncancer group across all CHADSVASc categories. Among the different cancer types, hematological and lung cancer had a high propensity for major bleeding. The odds of ischemic stroke were lower in the cancer group across high (1.9% vs 2.4%; aOR: 0.78; 95% CI: 0.76-0.79; < 0.0001), moderate (0.8% vs 1.3%; aOR: 0.57; 95% CI: 0.50-0.64; < 0.0001), and low (0.4% vs 0.9%; aOR: 0.46; 95% CI: 0.34-0.62; < 0.0001) risk category relative to the noncancer group irrespective of type of cancer. CHADSVASc category had a statistically significant discriminatory accuracy for ischemic stroke in both cancer and noncancer patients.
CONCLUSIONS
Cancer patients with AF are at a higher risk of readmission and major bleeding. The risk of ischemic stroke during readmission appears to be lower than noncancer patients. These findings may have implications for anticoagulant therapy in cancer patients.
PubMed: 38938329
DOI: 10.1016/j.jacadv.2023.100609 -
JACC. Advances Jun 2023Evidence is mixed regarding the most appropriate type of valve prosthesis for surgical aortic valve replacement (AVR) in patients 50 to 69 years. American and European...
BACKGROUND
Evidence is mixed regarding the most appropriate type of valve prosthesis for surgical aortic valve replacement (AVR) in patients 50 to 69 years. American and European guidelines differ.
OBJECTIVES
The purpose of this study was to determine the long-term all-cause mortality and complication rates after AVR in patients aged 50 to 69 years according to implantation of a Perimount bioprosthetic valve or a mechanical valve.
METHODS
In this nationwide observational cohort study, all patients aged 50 to 69 years who underwent primary surgical AVR in Sweden 2003 to 2018 using a Perimount bioprosthesis or mechanical valve were identified from the SWEDEHEART register. Primary outcome; all-cause mortality, secondary outcomes; major bleeding, aortic valve reintervention, heart failure hospitalization, and stroke. National health-data registers were used to ascertain outcomes. Regression standardization addressed confounding.
RESULTS
A total of 6,907 patients aged 50 to 69 years were included (Perimount group, n = 3,831 and mechanical valve group, n = 3,076) and 74% were men. The use of bioprostheses increased during the study period. At 15 years of follow-up, the estimated cumulative incidence of all-cause mortality was 37% (95% CI: 35%-40%) vs 45% (95% CI: 42%-48%) in the mechanical and Perimount groups, respectively (survival difference -7.9% [95% CI: -11% to -4.6%]). Patients with mechanical valves had a lower risk of aortic valve reintervention but a higher risk for bleeding. Survival difference at 15 years in ages 50 to 59 years was -15% (95% CI: -8.4% to -21%).
CONCLUSIONS
In patients aged 50 to 69 years who underwent surgical AVR, survival was better in those who received mechanical compared to Perimount bioprosthetic valves. While valve choice should be guided by individual patient factors and patient preference rather than by chronological age, the substantial survival advantage observed in patients with mechanical valves in ages 50 to 59 years must be recognized.
PubMed: 38938255
DOI: 10.1016/j.jacadv.2023.100359 -
Journal of Separation Science Jun 2024Short-chain fatty acids (SCFAs) are organic acids with carbon atoms less than six, released through fermentation products by intestinal microbiome, having multiple...
Short-chain fatty acids (SCFAs) are organic acids with carbon atoms less than six, released through fermentation products by intestinal microbiome, having multiple physiological activities. Considering weak acidity and high volatility, derivatization or liquid-liquid extraction is essential, which is time consuming. Headspace-solid-phase dynamic extraction (HS-SPDE) coupled with gas chromatography-mass spectrometry is automated and effortless to determine SCFAs in rat feces. The extraction procedure is performed by aspirating and discharging the headspace cyclically through a steel needle, coated with an inner polyethylene glycol sorbent. The key parameters of SPDE were optimized including coating type, incubation time and temperature, and number of extraction strokes. Besides, salting-out was conducted. Then, a method by HS-SPDE-GC-MS was established and validated. It only took 3-min incubation time, 4.5 min extraction time, and 13 min chromatographic separation in a run. The recovery, linearity, limit of quantification, and stability were evaluated. Then, the proposed method was applied to analyze rat feces including 18 rats with liver injury and 23 normal controls. Mann-Whitney U test indicated that the concentrations of six SCFAs in normal rat feces were higher than those with liver injury. This method provides a choice for fast, solvent-free, automated, and high-throughput analysis of SCFAs.
Topics: Animals; Gas Chromatography-Mass Spectrometry; Feces; Rats; Fatty Acids, Volatile; Solid Phase Extraction; Male; Rats, Sprague-Dawley
PubMed: 38937913
DOI: 10.1002/jssc.202400032