American heart journal最新文献

The foramen ovale plays a vital role in sustaining life in-utero; however, a patent foramen ovale (PFO) after birth has been associated with pathologic sequelae in the systemic circulation including stroke/transient ischemic attack (TIA), migraine, high altitude pulmonary edema, decompression illness, platypnea–orthodeoxia syndrome (POS) and worsened severity of obstructive sleep apnea. Importantly, each of these conditions is most commonly observed among specific age groups: migraine in the 20 to 40s, stroke/TIA in the 30-50s and POS in patients >50 years of age. The common and central pathophysiologic mechanism in each of these conditions is PFO-mediated shunting of blood and its contents from the right to the left atrium. PFO-associated pathologies can therefore be divided into (1) paradoxical systemic embolization and (2) right to left shunting (RLS) of blood through the PFO. Missing in the extensive literature on these clinical syndromes are mechanistic explanations for the occurrence of RLS, including timing and the volume of blood shunted, the impact of age on RLS, and the specific anatomical pathway that blood takes from the venous system to the left atrium. Visualization of the flow pattern graphically illustrates the underlying RLS and provides a greater understanding of the critical flow dynamics that determine the frequency, volume, and pathway of flow. In the present review, we describe the important role of foramen ovale in in-utero physiology, flow visualization in patients with PFO, as well as contributing factors that work in concert with PFO to result in the diverse pathophysiological sequelae.

Background

About half of patients with severe aortic stenosis present with concomitant coronary artery disease. The optimal timing of percutaneous coronary intervention (PCI) and transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and concomitant coronary artery disease remains unknown.

Study design

The TAVI PCI trial is a prospective, international, multicenter, randomized, 2-arm, open-label study planning to enroll a total of 986 patients. It is designed to investigate whether the strategy “angiography-guided complete revascularization after (within 1-45 days) TAVI” is noninferior to the strategy “angiography-guided complete revascularization before (within 1-45 days) TAVI” using the Edwards SAPIEN 3 or 3 Ultra Transcatheter Heart Valve in patients with severe aortic stenosis and concomitant coronary artery disease. Patients are randomized in a 1:1 ratio to one of the 2 treatment strategies. The primary end point is a composite of all-cause death, nonfatal myocardial infarction, ischemia-driven revascularization, rehospitalization (valve- or procedure-related including heart failure), or life-threatening/disabling or major bleeding at 1 year.

Conclusions

The TAVI PCI trial tests the hypothesis that the strategy “PCI after TAVI” is noninferior to the strategy “PCI before TAVI” in patients with severe aortic stenosis and concomitant coronary artery disease.

Background

Atherosclerosis in more than 1 vs. 1 arterial bed is associated with increased risk for major adverse cardiovascular events (MACE). This study aimed to determine whether the risk of post percutaneous coronary intervention (PCI) MACE associated with polyvascular disease (PVD) differs by sex.

Methods

We analyzed 18,721 patients undergoing PCI at a tertiary-care center between 2012 and 2019. Polyvascular disease was defined as history of peripheral artery and/or cerebrovascular disease. The primary endpoint was MACE, a composite of all-cause death, myocardial infarction, or stroke at 1 year. Multivariate Cox regression was used to adjust for differences in baseline risk between patients with PVD vs. coronary artery disease (CAD) alone and interaction testing was used to assess risk modification by sex.

Results

Women represented 29.2% (N = 5,467) of the cohort and were more likely to have PVD than men (21.7% vs. 16.1%; P < .001). Among both sexes, patients with PVD were older with higher prevalence of comorbidities and cardiovascular risk factors. Women with PVD had the highest MACE rate (10.0%), followed by men with PVD (7.2%), women with CAD alone (5.0%), and men with CAD alone (3.6%). Adjusted analyses revealed similar relative MACE risk associated with PVD vs. CAD alone in women and men (adjusted hazard ratio [aHR] 1.54, 95% confidence interval [CI] 1.20-1.99; P < .001 and aHR 1.31, 95% CI 1.06-1.62; P = .014, respectively; p-interaction = 0.460).

Conclusion

Women and men derive similar excess risk of MACE from PVD after PCI. The heightened risk associated with PVD needs to be addressed with maximized use of secondary prevention in both sexes.

Background

The optimal duration of dual antiplatelet therapy after currently available drug-eluting stent (DES) implantation to prevent stent thrombosis (ST) remains controversial. Delayed healing is frequently identified as a leading cause of ST in the early phase. However, a thorough pathological investigation into strut coverage after currently available DES implantation is lacking—a gap addressed in the current study.

Methods

From our autopsy registry of 199 stented lesions, 4,713 struts from 66 currently available DES-stented lesions with an implant duration ≤370 days were histologically evaluated. Endothelial coverage was defined as the presence of luminal endothelial cells overlying struts and an underlying smooth muscle cell layer. The stented lesions were classified into acute coronary syndrome (ACS) (n = 40) and chronic coronary syndrome (CCS) (n = 26) groups and were compared. Endothelial coverage predictors were identified through logistic analysis.

Results

Although ACS and CCS lesions presented comparable clinical characteristics, including age, sex, and cause of death, the latter exhibited a significantly higher prevalence of chronic kidney disease and hemodialysis than the former (33.3% vs. 65.2%; P = .02, 7.7% vs. 30.4%; P = .02). The poststent implant median duration was significantly shorter in ACS lesions than in CCS lesions (13 [IQR 5-26 days] vs. 40 [IQR 16-233 days]; P < .01). The endothelial coverage percentage was 3.5% at 30 days and 27.7% at 90 days after currently available DES implantation. Multivariable logistic regression analysis implicated implant duration of ≤90 days (odds ratio [OR], 0.009; 95% confidence interval [CI], 0.006-0.012; P < .01), superficial calcification (OR, 0.11; 95% CI, 0.07-0.17; P < .01), ACS culprit site (OR, 0.29; 95% CI, 0.09-0.94; P = .039), and circumferentially durable polymer-coated DES (OR, 0.32; 95% CI, 0.24-0.41; P < .01) as delayed endothelial coverage predictors.

Conclusions

Endothelial coverage was limited at 90 days after currently available DES implantation, and the ACS culprit site and circumferentially durable polymer-coated DES were identified as independent predictors of delayed endothelial coverage. Our findings suggest the importance of underlying plaque morphology and stent technology for vessel healing after such implantation.

Background

Modern drug-eluting stents have seen significant improvements, yet still create a rigid cage within the coronary artery. There is a 2% to 4% annual incidence of target lesion failure (TLF) beyond 1 year, and half of the patients experience angina after 5 years. The DynamX bioadaptor is a sirolimus-eluting, thin (71 µm) cobalt-chromium platform with helical strands that unlock and separate after in vivo degradation of the bioresorbable polymer coating. This allows the vessel to return to normal physiological function and motion, along with compensatory adaptive remodeling, which may reduce the need for reintervention and alleviate angina following percutaneous coronary intervention (PCI).

Methods

The INFINITY-SWEDEHEART trial is a single-blind, registry-based randomized clinical trial (R-RCT) to evaluate the safety and effectiveness of the DynamX bioadaptor compared to the Resolute Onyx stent in the treatment of patients with ischemic heart disease with de novo native coronary artery lesions. The R-RCT framework allows for recruitment, randomization, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries integrated with the trial database. The primary objective is to demonstrate noninferiority in terms of freedom from TLF (cardiovascular death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year. Powered secondary endpoints will be tested sequentially for superiority from 6 months to the end of follow-up (5 years) for the following: 1) TLF in all subjects, 2) target vessel failure in all subjects, and 3) TLF in subjects with acute coronary syndrome (ACS). Subsequent superiority testing will be performed at a time determined depending on the number of events, ensuring sufficient statistical power. Change in angina-related symptoms, function and quality of life will be assessed using the Seattle Angina Questionnaire-short version. Predefined sub-groups will be analyzed. In total, 2400 patients have been randomized at 20 sites in Sweden. Available baseline characteristic reveal relatively old age (68 years) and a large proportion of ACS patients including 25% STEMI and 37% NSTEMI patients.

Summary

The INFINITY-SWEDEHEART study is designed to evaluate the long-term safety and efficacy of the DynamX bioadaptor compared to the Resolute Onyx stent in a general PCI patient population.

Background

Blood pressure (BP) control among treated patients in Africa is very suboptimal, with low levels of combination therapy use and therapeutic inertia being among the major barriers to effective control of hypertension. The VERONICA-Nigeria study aims to evaluate, among Black African adults with hypertension, the effectiveness and safety of a triple pill-based treatment protocol compared to Nigeria hypertension treatment protocol (standard care protocol) for the treatment of hypertension.

Methods

This study involves a randomized, parallel-group and open-label trial. Adults with uncontrolled hypertension (n = 300), untreated or receiving monotherapy, with no contraindication to study treatments will be randomly assigned 1:1 to treatment with a triple pill based-treatment protocol or standard care protocol. Follow-up is for 6 months, with interim follow up visits at month 1, 2, and 3. In a noncomparative extension treatment period, participants completing the 6 months randomized period and on ≤3 BP-lowering drugs will receive treatment with the triple pill-based treatment protocol for 12 months. The primary outcome is change in home mean SBP from baseline to month 6, and key secondary efficacy outcome is percentage of participants with clinic BP <140/90 mmHg at month 6. The primary safety outcome is discontinuation of trial treatment due to adverse events from randomization to month 6. Economic evaluation will be conducted to assess the cost-effectiveness of the triple pill-based treatment protocol, and process evaluation will be conducted to understand the context in which the trial was conducted, implementation of the trial and interventions and mechanisms of effect, and potential barriers and facilitators to implementing the intervention in clinical practice.

Conclusion

The VERONICA-Nigeria trial will provide evidence of effectiveness and safety of the triple-based treatment protocol for the pharmacological management of hypertension, in Black African adults.

Trial Registration

PACTR202107579572114.

Background

The optimal assessment of systemic and lung decongestion during acute heart failure is not clearly defined. We evaluated whether inferior vena cava (IVC) and pulmonary ultrasound (CAVAL US) guided therapy is superior to standard care in reducing subclinical congestion at discharge in patients with AHF.

Methods

CAVAL US-AHF was an investigator-initiated, single-center, single-blind, randomized controlled trial. A daily quantitative ultrasound protocol using the 8-zone method was used and treatment was adjusted according to an algorithm. The primary endpoint was the presence of more than 5 B-lines and/or an increase in IVC diameter and collapsibility at discharge. And secondary endpoint exploratory outcome was the composite of readmission for HF, unplanned visit for worsening HF or death at 90 days

Results

Sixty patients were randomized to CAVAL US (n = 30) or control (n = 30). The primary endpoint was achieved in 4 patients (13.3%) in the CAVAL US group and 20 patients (66.6%) in the control group (P < .001). A significant reduction in HF readmission, unplanned visit for worsening HF or death at 90 days was seen in the CAVAL US group (13.3% vs 36.7%; log rank P = .038). Other endpoints such as NT-proBNP reduction at discharge showed a nonstatistically significant reduction in the CAVAL US group (48% IQR 27-67 vs 37% -3-59; P = .09). Safety outcomes were similar in both groups.

Conclusion

IVC and lung ultrasound-guided therapy in AHF patients significantly reduced subclinical congestion at discharge. CAVAL US-AHF provides preliminary evidence for the potential use of a simple technique to guide decongestive therapy during hospitalization for AHF, which may reduce the composite outcome at 90 days.

Introduction

Developing accurate models for predicting the risk of 30-day readmission is a major healthcare interest. Evidence suggests that models developed using machine learning (ML) may have better discrimination than conventional statistical models (CSM), but the calibration of such models is unclear.

Objectives

To compare models developed using ML with those developed using CSM to predict 30-day readmission for cardiovascular and noncardiovascular causes in HF patients.

Methods

We retrospectively enrolled 10,919 patients with HF (> 18 years) discharged alive from a hospital or emergency department (2004-2007) in Ontario, Canada. The study sample was randomly divided into training and validation sets in a 2:1 ratio. CSMs to predict 30-day readmission were developed using Fine-Gray subdistribution hazards regression (treating death as a competing risk), and the ML algorithm employed random survival forests for competing risks (RSF-CR). Models were evaluated in the validation set using both discrimination and calibration metrics.

Results

In the validation sample of 3602 patients, RSF-CR (c-statistic=0.620) showed similar discrimination to the Fine-Gray competing risk model (c-statistic=0.621) for 30-day cardiovascular readmission. In contrast, for 30-day noncardiovascular readmission, the Fine-Gray model (c-statistic=0.641) slightly outperformed the RSF-CR model (c-statistic=0.632). For both outcomes, The Fine-Gray model displayed better calibration than RSF-CR using calibration plots of observed vs predicted risks across the deciles of predicted risk.

Conclusions

Fine-Gray models had similar discrimination but superior calibration to the RSF-CR model, highlighting the importance of reporting calibration metrics for ML-based prediction models. The discrimination was modest in all readmission prediction models regardless of the methods used.

Out-of-hospital cardiac arrest (OHCA) occurs in nearly 350,000 people each year in the United States (US). Despite advances in pre and in-hospital care, OHCA survival remains low and is highly variable across systems and regions. The critical barrier to improving cardiac arrest outcomes is not a lack of knowledge about effective interventions, but rather the widespread lack of systems of care to deliver interventions known to be successful. The RAndomized Cluster Evaluation of Cardiac ARrest Systems (RACE-CARS) trial is a 7-year pragmatic, cluster-randomized trial of 62 counties (57 clusters) in North Carolina using an established registry and is testing whether implementation of a customized set of strategically targeted community-based interventions improves survival to hospital discharge with good neurologic function in OHCA relative to control/standard care. The multifaceted intervention comprises rapid cardiac arrest recognition and systematic bystander CPR instructions by 9-1-1 telecommunicators, comprehensive community CPR training and enhanced early automated external defibrillator (AED) use prior to emergency medical systems (EMS) arrival. Approximately 20,000 patients are expected to be enrolled in the RACE CARS Trial over 4 years of the assessment period. The primary endpoint is survival to hospital discharge with good neurologic outcome defined as a cerebral performance category (CPC) of 1 or 2. Secondary outcomes include the rate of bystander CPR, defibrillation prior to arrival of EMS, and quality of life. We aim to identify successful community- and systems-based strategies to improve outcomes of OHCA using a cluster randomized-controlled trial design that aims to provide a high level of evidence for future application.

Background

Our objective was to determine the number of major cardiovascular events (MACE, nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and deaths from any cause that could be prevented across varying nationwide uptake of semaglutide 2.4 mg SC weekly for the secondary prevention of cardiovascular disease.

Methods

Using a nationally representative cross-sectional study of participants in the 2017-2018 and 2019-March 2020 cycles of the National Health and Nutrition Examination Survey in the U.S. (NHANES), we estimated the number of MACE and deaths from any cause potentially prevented over a four-year period among participants meeting SELECT trial inclusion criteria.

Results

In a sample of n = 216 individuals (corresponding to 4,473,681 adults in the U.S. population) potentially eligible for this therapy, a total of 356,329 MACE and 232,808 all-cause mortality events were expected without semaglutide over 4 years and 35,633 MACE and 22,117 all-cause mortality events would be prevented with 50% uptake of semaglutide.

Conclusions

Approximately 4.5 million adults in the U.S. are forecasted to be eligible for semaglutide 2.4mg SC weekly therapy, with substantial impact on CVD and mortality if accessible and broadly used.