Much work has been done on developing hierarchical composite end point analysis methods, which meaningfully measure the effect of a treatment for patients with heart failure. Two motivations for this work have been as follows: (1) trying to ensure that more severe outcomes are weighted more heavily in the analysis; (2) combining different types of end points such as death, number of recurrent hospitalizations, and continuous functional or biologic end points. Such methods include the win ratio, the win odds, and the proportion in favor of treatment. In this article, our focus is when all components are clinical end points such as death or hospitalizations and do not include continuous end points. We review these methods using HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training). We also describe recent methods for combining different clinical end points, which take into account the time a subject is in a particular clinical state. These include the pairwise win time, the restricted mean time in favor of treatment, the expected win time, and the expected win time against reference. We discuss the US Food and Drug Administration guidances and make general recommendations.

Induction therapy is the use of potent immunosuppression in the perioperative period with the intent to diminish rejection rates in at-risk patients or as a renal-protective strategy. The potent immunomodulatory effects of these agents must be balanced against the recipient's risk of infectious or malignant complications, among others. There is a notable lack of clinically useful risk stratification models that integrate these competing risks and guide the clinician in the use of these therapies. This review integrates the existing evidence on the utility and safety of various induction regimens and highlights the gaps of knowledge in the field. In addition, we frame the discussion in view of the changing landscape of heart transplantation where many unknowns remain, such as the impact of induction immunosuppression on patients bridged with mechanical circulatory devices or receiving organs from hepatitis C-positive or donation after circulatory death donors, among others.

Thresholds to define prognosis with hs-cTnI (high-sensitivity cardiac troponin I) have not been systematically addressed in wild-type transthyretin amyloid cardiomyopathy, in part because of the multiplicity of hs-cTnI assays. The aims of this study were: first, to assess the prognostic performance of hs-cTnI measured with different assays in patients with wild-type transthyretin amyloid cardiomyopathy and, second, to identify assay-specific hs-cTnI thresholds for prognosis that could be integrated into staging systems for risk stratification.

Hypertrophic cardiomyopathy (HCM) is associated with significant morbidity and mortality, including sudden cardiac death in the young. Its prevalence is estimated to be 1 in 500, although many people are undiagnosed. The ability to screen electrocardiograms for its presence could improve detection and enable earlier diagnosis. This study evaluated the accuracy of an artificial intelligence device (Viz HCM) in detecting HCM based on a 12-lead electrocardiogram.

Imaging markers of atherosclerotic inflammation are needed to enhance cardiovascular risk assessment and evaluate the impact of therapies. We sought to test the hypothesis that treatments impacting arterial inflammation can be evaluated using a simplified measure of periaortic fat attenuation (FA) assessed on noncontrast, nongated computed tomography of the descending thoracic aorta.

Hemodynamic response to escalation of vasoactive drugs has not been well-characterized in patients with cardiogenic shock (CS). We tested the hypothesis that lower diastolic perfusion pressure (DPP=diastolic blood pressure-right atrial pressure) was associated with more limited hemodynamic response to uptitration of vasoactive drugs and with possible benefit from early mechanical circulatory support in patients with CS.

A functionally significant myocardial bridge (MB) is an important cause of angina with nonobstructive coronary arteries. However, distinguishing a functionally significant versus incidental MB remains challenging. Resting and hyperemic intracoronary functional indices are available, but no studies have compared their diagnostic performance in MBs.

The effects of the aspirin-free strategy on bleeding and cardiovascular events were unknown in patients with high bleeding risk (HBR), with or without acute coronary syndrome (ACS), undergoing percutaneous coronary intervention.

Mortality due to ischemic heart disease (IHD) has declined in countries with high socioeconomic development. Whether these declines extend to other settings, and whether socioeconomic development influences IHD mortality among men and women differently, is unknown.

Disparities between metro and nonmetro areas exist in health outcomes. The effect of residing areas on mortality for patients with congenital heart disease remains unclear. We evaluated the relationship of residing areas with survival outcomes after congenital heart surgery (CHS).

Exercise intolerance is a hallmark of heart failure with preserved ejection fraction (HFpEF) and is characterized by skeletal muscle (SkM) dysfunction with impaired oxidative capacity. To maintain oxidative capacity, the SkM secretes myokines such as musclin, which has been shown to potentiate NP (natriuretic peptide) signaling and induce PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1 alpha) signaling. We sought to investigate the role of musclin in SkM dysfunction in HFpEF. For this study, we selected the oxidative-predominant SkM soleus in HFpEF mice and vastus lateralis from patients with HFpEF.

The left atrium (LA) maintains a dynamic interaction with the left ventricle (LV). LA forward and reverse remodeling affect prognosis in patients with chronic heart failure. We examined LA reverse remodeling in patients supported with LV assist devices (LVADs) and investigated a potential impact on clinical outcomes.

Microvascular injury in the course of acute ST-segment-elevation myocardial infarction (STEMI) has been identified as determinant of adverse outcomes and manifests as microvascular obstruction (MVO). MVO has long been regarded as a transient finding, vanishing within a few weeks after infarction. However, recent studies have shown that it may persist beyond the early phase, resulting in adverse remodeling. However, its clinical implications remain unclear. This study aims to evaluate the association of MVO persistence and major adverse cardiac events after STEMI.

Computed tomography (CT) attenuation correction scans are an intrinsic part of positron emission tomography (PET) myocardial perfusion imaging using PET/CT, but anatomic information is rarely derived from these ultralow-dose CT scans. We aimed to assess the association between deep learning-derived cardiac chamber volumes (right atrial, right ventricular, left ventricular, and left atrial) and mass (left ventricular) from these scans with myocardial flow reserve and heart failure hospitalization.

The "open vein hypothesis" postulates that early thrombus clearance and restoration of venous blood flow may prevent postthrombotic syndrome after proximal deep vein thrombosis. Since its proposal several decades ago, new insights from basic and clinical studies have motivated a re-evaluation and refinement of this hypothesis. According to data from these studies, susceptibility to postthrombotic syndrome occurs as a result of differences in genetic composition, thrombophilic conditions, predilection to inflammation and fibrosis, endogenous fibrinolytic capability, timing of symptom presentation and treatment initiation, and efficacy of antithrombotic therapy. Although initial restoration of an open vein appears to be beneficial for selected patient groups, freedom from postthrombotic syndrome is more likely in the setting of long-term venous patency, reduced recurrent thrombotic episodes, and reduced perithrombotic (eg, vein wall and valve) inflammation. These underlying biological mechanisms need further elucidation, with a long-term goal of personalizing treatment by mapping the individuals' clinical presentation with their underlying risk factors and assessing time-dependent biological processes that occur as a clinical venous thrombosis resolves. This scientific statement (1) highlights historical fundamentals of the open vein hypothesis and then showcases new research insights into the pathophysiological factors driving postthrombotic syndrome; (2) discusses advantages and disadvantages of imaging modalities for deep vein thrombosis used in clinical practice, including the potential to depict thrombus chronicity and status of vein wall injury; (3) proposes measures to develop integrated multidisciplinary care for deep vein thrombosis focused on the reduction of postthrombotic syndrome; and (4) identifies priority areas and questions for further research.

Exercise improves functional outcomes in patients with diabetic cardiomyopathy (DiaCM). The molecular mechanism underlying cardiac benefits of exercise in DiaCM remains incompletely understood. N6-methyladenosine (m6A) is the most common form of messenger RNA modification in eukaryotes and has been implicated in cardiac development and disease. However, the role of m6A in DiaCM and in the mitigating effects of exercise on this disease are unclear.

Hypothyroidism leads to multiple organ dysfunction, with the heart the most affected. However, the pathologic mechanism of hypothyroidism-induced heart failure remains to be completely elucidated. Thyroid hormone replacement therapy enhances myocardium systolic function but increases the occurrence of arrythmias. There is an urgent need to explore these mechanisms in detail and to discover and develop drugs that can target and manage heart failure in patients with hypothyroidism.