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Journal of the American College of... Aug 2023Despite worsening heart failure (HF) being extremely common, expensive, and associated with substantial risk of death, there remain no dedicated clinical practice... (Review)
Review
Despite worsening heart failure (HF) being extremely common, expensive, and associated with substantial risk of death, there remain no dedicated clinical practice guidelines for the specific management of these patients. The lack of a management guideline is despite a rapidly evolving evidence-base, as a number of recent clinical trials have demonstrated multiple therapies to be safe and efficacious in this high-risk population. Herein, we propose a framework for treating worsening HF with reduced ejection fraction with the sense of urgency it deserves. This includes treating congestion; managing precipitants; and establishing a foundation of rapid-sequence, simultaneous, and/or in-hospital initiation of quadruple medical therapy for HF with reduced ejection fraction, with the top priority being at least low doses of all 4 medications. Moreover, to maximally reduce residual clinical risk, we further propose consideration of upfront simultaneous use of vericiguat (ie, quintuple medical therapy) and administration of intravenous iron for those who are iron deficient.
Topics: Humans; Stroke Volume; Ventricular Dysfunction, Left; Heart Failure
PubMed: 37532426
DOI: 10.1016/j.jacc.2023.04.057 -
Circulation Aug 2023Left ventricular (LV) systolic dysfunction is associated with a >8-fold increased risk of heart failure and a 2-fold risk of premature death. The use of ECG signals in...
BACKGROUND
Left ventricular (LV) systolic dysfunction is associated with a >8-fold increased risk of heart failure and a 2-fold risk of premature death. The use of ECG signals in screening for LV systolic dysfunction is limited by their availability to clinicians. We developed a novel deep learning-based approach that can use ECG images for the screening of LV systolic dysfunction.
METHODS
Using 12-lead ECGs plotted in multiple different formats, and corresponding echocardiographic data recorded within 15 days from the Yale New Haven Hospital between 2015 and 2021, we developed a convolutional neural network algorithm to detect an LV ejection fraction <40%. The model was validated within clinical settings at Yale New Haven Hospital and externally on ECG images from Cedars Sinai Medical Center in Los Angeles, CA; Lake Regional Hospital in Osage Beach, MO; Memorial Hermann Southeast Hospital in Houston, TX; and Methodist Cardiology Clinic of San Antonio, TX. In addition, it was validated in the prospective Brazilian Longitudinal Study of Adult Health. Gradient-weighted class activation mapping was used to localize class-discriminating signals on ECG images.
RESULTS
Overall, 385 601 ECGs with paired echocardiograms were used for model development. The model demonstrated high discrimination across various ECG image formats and calibrations in internal validation (area under receiving operation characteristics [AUROCs], 0.91; area under precision-recall curve [AUPRC], 0.55); and external sets of ECG images from Cedars Sinai (AUROC, 0.90 and AUPRC, 0.53), outpatient Yale New Haven Hospital clinics (AUROC, 0.94 and AUPRC, 0.77), Lake Regional Hospital (AUROC, 0.90 and AUPRC, 0.88), Memorial Hermann Southeast Hospital (AUROC, 0.91 and AUPRC 0.88), Methodist Cardiology Clinic (AUROC, 0.90 and AUPRC, 0.74), and Brazilian Longitudinal Study of Adult Health cohort (AUROC, 0.95 and AUPRC, 0.45). An ECG suggestive of LV systolic dysfunction portended >27-fold higher odds of LV systolic dysfunction on transthoracic echocardiogram (odds ratio, 27.5 [95% CI, 22.3-33.9] in the held-out set). Class-discriminative patterns localized to the anterior and anteroseptal leads (V and V), corresponding to the left ventricle regardless of the ECG layout. A positive ECG screen in individuals with an LV ejection fraction ≥40% at the time of initial assessment was associated with a 3.9-fold increased risk of developing incident LV systolic dysfunction in the future (hazard ratio, 3.9 [95% CI, 3.3-4.7]; median follow-up, 3.2 years).
CONCLUSIONS
We developed and externally validated a deep learning model that identifies LV systolic dysfunction from ECG images. This approach represents an automated and accessible screening strategy for LV systolic dysfunction, particularly in low-resource settings.
Topics: Adult; Humans; Prospective Studies; Longitudinal Studies; Electrocardiography; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 37489538
DOI: 10.1161/CIRCULATIONAHA.122.062646 -
Circulation Sep 2023Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date.
METHODS
Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies.
RESULTS
Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82-1.30]; =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes.
CONCLUSIONS
PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT01920048.
Topics: Humans; Male; Aged; Female; Stroke Volume; Death, Sudden, Cardiac; Ventricular Function, Left; Arrhythmias, Cardiac; Ventricular Dysfunction, Left; Defibrillators, Implantable; Treatment Outcome
PubMed: 37555345
DOI: 10.1161/CIRCULATIONAHA.123.065300 -
Critical Care (London, England) Sep 2023The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory...
BACKGROUND AND AIMS
The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD.
METHODS
The relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9 mice for therapeutic and mechanistic studies on endotoxemia-induced cardiac dysfunction in mice.
RESULTS
In sepsis patients, elevated plasma S100A8/A9 was associated with left-ventricular (LV) systolic dysfunction and increased SOFA score. In wild-type mice, 5 mg/kg of bacterial lipopolysaccharide (LPS) induced rapid plasma S100A8/A9 increase and acute LV dysfunction. Two ABR-238901 doses (30 mg/kg) administered intraperitoneally with a 6 h interval, starting directly after LPS or at a later time-point when LV dysfunction is fully established, efficiently prevented and reversed the phenotype, respectively. In contrast, dexamethasone did not improve cardiac function compared to PBS-treated endotoxemic controls. S100A8/A9 inhibition potently reduced systemic levels of inflammatory mediators, prevented upregulation of inflammatory genes and restored mitochondrial function in the myocardium. The S100A9 mice were protected against LPS-induced LV dysfunction to an extent comparable with pharmacologic S100A8/A9 blockade. The ABR-238901 treatment did not induce an additional improvement of LV function in the S100A9 mice, confirming target specificity.
CONCLUSION
Elevated S100A8/A9 is associated with the development of LV dysfunction in severe sepsis patients and in a mouse model of endotoxemia. Pharmacological blockade of S100A8/A9 with ABR-238901 has potent anti-inflammatory effects, mitigates myocardial dysfunction and might represent a novel therapeutic strategy for patients with severe sepsis.
Topics: Animals; Humans; Mice; Calgranulin A; Calgranulin B; Endotoxemia; Heart Diseases; Inflammation; Lipopolysaccharides; Myocardium; Ventricular Dysfunction, Left
PubMed: 37773186
DOI: 10.1186/s13054-023-04652-x -
JAMA Cardiology Dec 2023In the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, percutaneous coronary intervention (PCI) did not improve outcomes for patients with...
IMPORTANCE
In the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, percutaneous coronary intervention (PCI) did not improve outcomes for patients with ischemic left ventricular dysfunction. Whether myocardial viability testing had prognostic utility for these patients or identified a subpopulation who may benefit from PCI remained unclear.
OBJECTIVE
To determine the effect of the extent of viable and nonviable myocardium on the effectiveness of PCI, prognosis, and improvement in left ventricular function.
DESIGN, SETTING, AND PARTICIPANTS
Prospective open-label randomized clinical trial recruiting between August 28, 2013, and March 19, 2020, with a median follow-up of 3.4 years (IQR, 2.3-5.0 years). A total of 40 secondary and tertiary care centers in the United Kingdom were included. Of 700 randomly assigned patients, 610 with left ventricular ejection fraction less than or equal to 35%, extensive coronary artery disease, and evidence of viability in at least 4 myocardial segments that were dysfunctional at rest and who underwent blinded core laboratory viability characterization were included. Data analysis was conducted from March 31, 2022, to May 1, 2023.
INTERVENTION
Percutaneous coronary intervention in addition to optimal medical therapy.
MAIN OUTCOMES AND MEASURES
Blinded core laboratory analysis was performed of cardiac magnetic resonance imaging scans and dobutamine stress echocardiograms to quantify the extent of viable and nonviable myocardium, expressed as an absolute percentage of left ventricular mass. The primary outcome of this subgroup analysis was the composite of all-cause death or hospitalization for heart failure. Secondary outcomes were all-cause death, cardiovascular death, hospitalization for heart failure, and improved left ventricular function at 6 months.
RESULTS
The mean (SD) age of the participants was 69.3 (9.0) years. In the PCI group, 258 (87%) were male, and in the optimal medical therapy group, 277 (88%) were male. The primary outcome occurred in 107 of 295 participants assigned to PCI and 114 of 315 participants assigned to optimal medical therapy alone. There was no interaction between the extent of viable or nonviable myocardium and the effect of PCI on the primary or any secondary outcome. Across the study population, the extent of viable myocardium was not associated with the primary outcome (hazard ratio per 10% increase, 0.98; 95% CI, 0.93-1.04) or any secondary outcome. The extent of nonviable myocardium was associated with the primary outcome (hazard ratio, 1.07; 95% CI, 1.00-1.15), all-cause death, cardiovascular death, and improvement in left ventricular function.
CONCLUSIONS AND RELEVANCE
This study found that viability testing does not identify patients with ischemic cardiomyopathy who benefit from PCI. The extent of nonviable myocardium, but not the extent of viable myocardium, is associated with event-free survival and likelihood of improvement of left ventricular function.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01920048.
Topics: Humans; Male; Aged; Female; Stroke Volume; Prospective Studies; Percutaneous Coronary Intervention; Follow-Up Studies; Ventricular Function, Left; Heart Failure; Ventricular Dysfunction, Left
PubMed: 37878295
DOI: 10.1001/jamacardio.2023.3803 -
Redox Biology Nov 2023In acute sympathetic stress, catecholamine overload can lead to stress cardiomyopathy. We tested the hypothesis that cardiomyocyte NOX4 (NADPH oxidase 4)-dependent...
In acute sympathetic stress, catecholamine overload can lead to stress cardiomyopathy. We tested the hypothesis that cardiomyocyte NOX4 (NADPH oxidase 4)-dependent mitochondrial oxidative stress mediates inflammation and diastolic dysfunction in stress cardiomyopathy. Isoproterenol (ISO; 5 mg/kg) injection induced sympathetic stress in wild-type and cardiomyocyte (CM)-specific Nox4 knockout (Nox4) mice. Wild-type mice treated with ISO showed higher CM NOX4 expression, HO levels, inflammasome activation, and IL18, IL6, CCL2, and TNFα levels than Nox4 mice. Spectral flow cytometry and t-SNE analysis of cardiac cell suspensions showed significant increases in pro-inflammatory and pro-fibrotic embryonic-derived resident (CCR2MHCIICX3CR1) macrophages in wild-type mice 3 days after ISO treatment, whereas Nox4 mice had a higher proportion of embryonic-derived resident tissue-repair (CCR2MHCIICX3CR1) macrophages. A significant increase in cardiac fibroblast activation and interstitial collagen deposition and a restrictive pattern of diastolic dysfunction with increased filling pressure was observed in wild-type hearts compared with Nox4 7 days post-ISO. A selective NOX4 inhibitor, GKT137831, reduced myocardial mitochondrial ROS, macrophage infiltration, and fibrosis in ISO-injected wild-type mice, and preserved diastolic function. Our data suggest sympathetic overstimulation induces resident macrophage (CCR2MHCII) activation and myocardial inflammation, resulting in fibrosis and impaired diastolic function mediated by CM NOX4-dependent ROS.
Topics: Animals; Mice; Fibrosis; Hydrogen Peroxide; Inflammation; Myocytes, Cardiac; NADPH Oxidase 4; NADPH Oxidases; Reactive Oxygen Species; Takotsubo Cardiomyopathy
PubMed: 37871532
DOI: 10.1016/j.redox.2023.102937 -
Frontiers in Immunology 2023Takotsubo syndrome (TTS) is a disorder characterized by transient cardiac dysfunction with ventricular regional wall motion abnormalities, primarily thought to be caused... (Review)
Review
Takotsubo syndrome (TTS) is a disorder characterized by transient cardiac dysfunction with ventricular regional wall motion abnormalities, primarily thought to be caused by the effects of a sudden catecholamine surge on the heart. Although the majority of patients exhibit prompt recovery of their cardiac dysfunction, TTS remains associated with increased mortality rates acutely and at long-term, and there is currently no cure for TTS. Inflammation has been shown to play a key role in determining outcomes in TTS patients, as well as in the early pathogenesis of the disorder. There are also cases of TTS patients that have been successfully treated with anti-inflammatory therapies, supporting the importance of the inflammatory response in TTS. In this article, we provide a comprehensive review of the available clinical and pre-clinical literature on the immune response in TTS, in an effort to not only better understand the pathophysiology of TTS but also to generate insights on the treatment of patients with this disorder.
Topics: Humans; Takotsubo Cardiomyopathy; Heart; Catecholamines; Heart Ventricles; Inflammation
PubMed: 37868970
DOI: 10.3389/fimmu.2023.1254011 -
Revista Espanola de Cardiologia... Oct 2023Major international practice guidelines recommend the use of a combination of 4 medication classes in the treatment of patients with heart failure with reduced ejection... (Review)
Review
Major international practice guidelines recommend the use of a combination of 4 medication classes in the treatment of patients with heart failure with reduced ejection fraction (HFrEF) but do not specify how these treatments should be introduced and up-titrated. Consequently, many patients with HFrEF do not receive an optimized treatment regimen. This review proposes a pragmatic algorithm for treatment optimization designed to be easily applied in routine practice. The first goal is to ensure that all 4 recommended medication classes are initiated as early as possible to establish effective therapy, even at a low dose. This is considered preferable to starting fewer medications at a maximum dose. The second goal is to ensure that the intervals between the introduction of different medications and between different titration steps are as short as possible to ensure patient safety. Specific proposals are made for older patients (> 75 years) who are frail, and for those with cardiac rhythm disorders. Application of this algorithm should allow an optimal treatment protocol to be achieved within 2-months in most patients, which should the treatment goal in HFrEF.
Topics: Humans; Heart Failure; Stroke Volume; Ventricular Dysfunction, Left
PubMed: 36914024
DOI: 10.1016/j.rec.2023.03.005 -
Romanian Journal of Internal Medicine =... Dec 2023The Stroke-Heart syndrome is a major chapter in neurocardiology. Both brain-heart and stroke-heart correlations are based on neurophysiological studies that define and... (Review)
Review
The Stroke-Heart syndrome is a major chapter in neurocardiology. Both brain-heart and stroke-heart correlations are based on neurophysiological studies that define and describe the relation between the central autonomic system and cardiac function and it will be presented in this narrative review. The Stroke-Heart syndrome groups the entire spectrum of cardiac changes - clinical, ECG, echocardiographic, biological, morphological - that occur in the first 30 days from the onset of stroke, especially in the first days. Their presence significantly marks the evolution and prognosis of stroke. The damage resulted from hypothalamus-pituitary-adrenal axis activation and high catecholamine release (adrenergic storm) targets mainly the myocyte and the microcirculation.The Takotsubo syndrome and Stunned myocardium are distinct forms of neurogenic myocardial ischemia - with changes in ECG, parietal motility, and biological markers - usually reversible although evolution towards cardiac dysfunction is also possible. The concept of Stroke-Heart syndrome and the brain-heart correlation brought new scientific information regarding stress cardiomyopathy or neurogenic myocardial injury.
Topics: Humans; Takotsubo Cardiomyopathy; Myocardial Stunning; Echocardiography; Stroke; Catecholamines
PubMed: 37540842
DOI: 10.2478/rjim-2023-0020 -
Current Opinion in Pulmonary Medicine Sep 2023The purpose of this review is to provide an overview of assessment of right ventricular function in the context of pulmonary hypertension and pulmonary arterial... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide an overview of assessment of right ventricular function in the context of pulmonary hypertension and pulmonary arterial hypertension (PAH). We will review unique features of right ventricular anatomy, delineation of cause of pulmonary hypertension through careful right ventricular assessment, echocardiographic and hemodynamic evaluation, and the importance of this assessment in prognosis.
RECENT FINDINGS
The importance of performance in prognosis and risk assessment in patients with pulmonary hypertension has been continually emphasized in ongoing research. Representative parameters of right ventricular function have been shown to be predictive of prognosis in patients with pulmonary hypertension. Further, the importance of serial right ventricular assessment in risk assessment and prognosis has remained an emerging theme.
SUMMARY
Careful evaluation of right ventricular function is paramount in assessing the cause of pulmonary hypertension and severity of disease. Further, it has prognostic significance, as many representative parameters of right ventricular function have been linked with mortality. In our opinion, right ventricular function should be assessed serially throughout the course of treatment in pulmonary hypertension, and baseline parameters in addition to dynamic changes should be incorporated into risk assessment. Achieving normal or near-normal right ventricular performance may serve as a principal goal in the treatment of pulmonary hypertension.
Topics: Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Prognosis; Familial Primary Pulmonary Hypertension; Echocardiography; Ventricular Dysfunction, Right
PubMed: 37410491
DOI: 10.1097/MCP.0000000000000980