scholarly journals Altered Hemodynamics and End-Organ Damage in Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (10) ◽  
pp. 998-1012 ◽  
Author(s):  
Frederik H. Verbrugge ◽  
Marco Guazzi ◽  
Jeffrey M. Testani ◽  
Barry A. Borlaug
Keyword(s):  
Heart Failure ◽  
Cardiac Myocyte ◽  
Organ Damage ◽  
Multiple Organ ◽  
Pulmonary Vascular Disease ◽  
Downstream Effects ◽  
Capillary Stress ◽  
Organ Systems ◽  
Patients With Heart Failure ◽  
Cardiac Filling

Heart failure is characterized by pathologic hemodynamic derangements, including elevated cardiac filling pressures (“backward” failure), which may or may not coexist with reduced cardiac output (“forward” failure). Even when normal during unstressed conditions such as rest, hemodynamics classically become abnormal during stressors such as exercise in patients with heart failure. This has important upstream and downstream effects on multiple organ systems, particularly with respect to the lungs and kidneys. Hemodynamic abnormalities in heart failure are affected by processes that extend well beyond the cardiac myocyte, including important roles for pericardial constraint, ventricular interaction, and altered venous capacity. Hemodynamic perturbations have widespread effects across multiple heart failure phenotypes, ranging from reduced to preserved ejection fraction, acute to chronic disease, and cardiogenic shock to preserved perfusion states. In the lung, hemodynamic derangements lead to the development of abnormalities in ventilatory control and efficiency, pulmonary congestion, capillary stress failure, and eventually pulmonary vascular disease. In the kidney, hemodynamic perturbations lead to sodium and water retention and worsening renal function. Improved understanding of the mechanisms by which altered hemodynamics in heart failure affect the lungs and kidneys is needed in order to design novel strategies to improve clinical outcomes.

scholarly journals Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart Failure

Circulation ◽  
2020 ◽  
Vol 141 (8) ◽  
pp. 678-693 ◽  
Author(s):  
Stephan Rosenkranz ◽  
Luke S. Howard ◽  
Mardi Gomberg-Maitland ◽  
Marius M. Hoeper
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Structural Changes ◽  
Immune Cell ◽  
Organ Damage ◽  
Multiple Organ ◽  
Clinical Syndrome ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Organ Systems

Pulmonary hypertension (PH) is a feature of a variety of diseases and continues to harbor high morbidity and mortality. The main consequence of PH is right-sided heart failure which causes a complex clinical syndrome affecting multiple organ systems including left heart, brain, kidneys, liver, gastrointestinal tract, skeletal muscle, as well as the endocrine, immune, and autonomic systems. Interorgan crosstalk and interdependent mechanisms include hemodynamic consequences such as reduced organ perfusion and congestion as well as maladaptive neurohormonal activation, oxidative stress, hormonal imbalance, and abnormal immune cell signaling. These mechanisms, which may occur in acute, chronic, or acute-on-chronic settings, are common and precipitate adverse functional and structural changes in multiple organs which contribute to increased morbidity and mortality. While the systemic character of PH and right-sided heart failure is often neglected or underestimated, such consequences place additional burden on patients and may represent treatable traits in addition to targeted therapy of PH and underlying causes. Here, we highlight the current state-of-the-art understanding of the systemic consequences of PH and right-sided heart failure on multiple organ systems, focusing on self-perpetuating pathophysiological mechanisms, aspects of increased susceptibility of organ damage, and their reciprocal impact on the course of the disease.

Abstract 12563: Retrospective Analysis of Cardiovascular Events With the Use of Immune Checkpoint Inhibitors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tushar Tarun ◽  
Brian P Bostick ◽  
Deepa Baswaraj ◽  
Nishchayjit Basra ◽  
Meeshal Khan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Retrospective Analysis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Multiple Organ ◽  
Fulminant Myocarditis ◽  
Organ Systems ◽  
History Of

Introduction: Immune checkpoint inhibitors have emerged as a promising, novel therapy for multiple malignancies. Immune-related adverse reactions pose a serious concern with use of these agents and reportedly involve multiple organ systems, notably cardiotoxicity. Early identification and management of these adverse events is essential in the prevention of morbidity and mortality. Hypothesis: Immune checkpoint inhibitors cause multiple cardiotoxic effects, and patients with prior cardiac history have a higher likelihood of cardiotoxicity. Methods: 1. A retrospective analysis of 150 patients was performed who had received immunotherapy with either the cytotoxic T lymphocyte associated antigen 4 inhibitors (CTLA4) or with the programmed cell death inhibitors (PD1) or programmed death-ligand 1 (PD-L1) inhibitors for a period of two years at a Tertiary health Care from 7/1/2016-6/30/2018. 2. Patients' cardiac diagnoses prior to the initiation of therapy were noted and included, including history of heart failure, coronary artery disease, atrial fibrillation, and sudden cardiac arrest. 3. Patients’ clinic visits and hospitalizations with admitting and discharge diagnosis, electrocardiogram, echocardiogram, troponin T, and NT-proBNP were reviewed. Results: 6% of patients had new onset heart failure (both preserved and reduced), 1.3% had evidence of myocardial infarction, 2% had new atrial fibrillation with rapid ventricular rate, and 0.6% had fulminant myocarditis. Of patients with new cardiac events, 60% had a history of cardiac disease, which was significantly higher than in patients without (p< 0.05). There were no age or sex differences between the groups with and without cardiotoxicity. Conclusion: Immunotherapy with immune checkpoint inhibitors have broadened the horizon for treatment of multiple solid and hematological malignancies. Nonetheless, new adverse effects on multiple organ systems, specifically cardiac involvement, occur with these therapies, which are important and potentially detrimental toxicities. Patients with a history of prior cardiovascular disease have higher likelihood to develop cardiotoxicity.

Abstract 71: STAT3 Affects Myofibrillar Structure and Its Loss May Contribute to Heart Failure in Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Fouad Zouein ◽  
Carlos Zgheib ◽  
John Fuseler ◽  
John E Hall ◽  
Mazen Kurdi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Myocytes ◽  
Transcriptional Activity ◽  
Cardiac Myocyte ◽  
Early Stage ◽  
Systolic Dysfunction ◽  
Wild Type ◽  
Patients With Heart Failure ◽  
Protective Proteins ◽  
Fractional Shortening

How hypertension causes heart failure is not known. Since patients with heart failure have reduced cardiac STAT3 and STAT3 KO mice develop heart failure with age, we tested the hypothesis that reduced STAT3 transcriptional activity contributes at an early stage to remodeling that precedes heart failure in hypertension using SA mice with a STAT3 S727A mutation. SA and wild type (WT) mice received angiotensin (A) II (1000 ng/kg/min) or saline (S) for 17 days. Hearts of WT and SA mice had similar levels of STAT3-induced protective proteins Bcl-xL and SOD2, and unlike STAT3 KO mice, cardiac miR-199a levels were not increased in SA mice. AII increased systolic blood pressure measured by telemetry in SA (124 ± 1 to 167 ± 3) and WT (122 ± 3 to 162 ± 3) mice to the same extent. AII increased cardiac levels of cytokines (pg/μg protein) associated with heart failure in both WT and SA mice, but significantly less so (P<0.05) in SA mice; IL-6, 13.6 ± 1.4 vs. 9.1 ± 0.6; TGFβ, 56 ± 4 vs. 38 ± 3 and MCP1 35 ± 2 vs. 22 ± 2. Compared to WT mice, hearts of SA mice showed signs of developing systolic dysfunction with AII as seen by a significant (P<0.05) reduction in ejection fraction (63.7 ± 7.1 to 51.7 ± 6.9) and fractional shortening (34.3 ± 4.9 to 26.4 ± 4.3). AII caused fibrosis in the left ventricle of both WT and SA mice characterized by cardiac myocyte loss and increased % collagen: WT+S, 5.59 ± 0.34; WT+AII, 15.70 ± 1.87; SA+S, 6.70 ± 0.40; SA+AII, 16.50 ± 1.91. In WT+AII mice there was a nonsignificant trend towards a loss of myofibrillar content of cardiac myocytes, but an increase in the mass of the myofibrils (IOD/myofibrillar area). In contrast, cardiac myocytes of SA+AII mice had a significant (P<0.001) % loss in myofibrils (5.71 ± 0.28) compared to SA+S (0.75 ± 0.07), WT+S (0.80 ± 0.06) and WT+AII (1.54 ± 0.10) mice. In addition, the mass of the myofibrils in SA+AII mice (6.01 ± 0.07) was significantly less (P<0.001) than those of SA+S mice (6.46 ± 0.04), although greater than WT+S (4.85 ± 0.06) or WT+AII (5.27 ± 0.08) mice. Our findings reveal that STAT3 transcriptional activity is important for proper morphology of the myofibrils of cardiac myocytes. Loss of STAT3 activity may impair cardiac function in the hypertensive heart due to defective myofibrillar structure and remodeling that may lead to heart failure.

scholarly journals Neurological, neuropsychiatric and neurodevelopmental complications of COVID-19

2020 ◽  
pp. 000486742096147
Author(s):  
Christos Pantelis ◽  
Mahesh Jayaram ◽  
Anthony J Hannan ◽  
Robb Wesselingh ◽  
Jess Nithianantharajah ◽  
...  
Keyword(s):  
Organ Damage ◽  
Multiple Organ ◽  
Global Pandemic ◽  
Organ Systems ◽  
Future Challenges ◽  
The Central Nervous System ◽  
The Impact ◽  
Collaborative Efforts ◽  
The Brain

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19, and the Renin-Angiotensin System

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1350-1367 ◽  
Author(s):  
Matthew A. Sparks ◽  
Andrew M. South ◽  
Andrew D. Badley ◽  
Carissa M. Baker-Smith ◽  
Daniel Batlle ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Experimental Models ◽  
Multiple Organ ◽  
Host Cells ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Organ Systems

The coronavirus disease 2019 (COVID-19) pandemic is associated with significant morbidity and mortality throughout the world, predominantly due to lung and cardiovascular injury. The virus responsible for COVID-19—severe acute respiratory syndrome coronavirus 2—gains entry into host cells via ACE2 (angiotensin-converting enzyme 2). ACE2 is a primary enzyme within the key counter-regulatory pathway of the renin-angiotensin system (RAS), which acts to oppose the actions of Ang (angiotensin) II by generating Ang-(1–7) to reduce inflammation and fibrosis and mitigate end organ damage. As COVID-19 spans multiple organ systems linked to the cardiovascular system, it is imperative to understand clearly how severe acute respiratory syndrome coronavirus 2 may affect the multifaceted RAS. In addition, recognition of the role of ACE2 and the RAS in COVID-19 has renewed interest in its role in the pathophysiology of cardiovascular disease in general. We provide researchers with a framework of best practices in basic and clinical research to interrogate the RAS using appropriate methodology, especially those who are relatively new to the field. This is crucial, as there are many limitations inherent in investigating the RAS in experimental models and in humans. We discuss sound methodological approaches to quantifying enzyme content and activity (ACE, ACE2), peptides (Ang II, Ang-[1–7]), and receptors (types 1 and 2 Ang II receptors, Mas receptor). Our goal is to ensure appropriate research methodology for investigations of the RAS in patients with severe acute respiratory syndrome coronavirus 2 and COVID-19 to ensure optimal rigor and reproducibility and appropriate interpretation of results from these investigations.

scholarly journals The Cardioprotective Actions of Hydrogen Sulfide in Acute Myocardial Infarction and Heart Failure

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
David J. Polhemus ◽  
John W. Calvert ◽  
Javed Butler ◽  
David J. Lefer
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Hydrogen Sulfide ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Multiple Organ ◽  
Organ Systems ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

It has now become universally accepted that hydrogen sulfide (H2S), previously considered only as a lethal toxin, has robust cytoprotective actions in multiple organ systems. The diverse signaling profile of H2S impacts multiple pathways to exert cytoprotective actions in a number of pathological states. This paper will review the recently described cardioprotective actions of hydrogen sulfide in both myocardial ischemia/reperfusion injury and congestive heart failure.

[PP.27.14] PHEOCHROMOCYTOMA PRESENTED WITH ACUTE HEART FAILURE AND MULTIPLE ORGAN DAMAGE

2017 ◽  
Vol 35 ◽  
pp. e315
Author(s):  
I. Papadakis ◽  
M. Velegraki ◽  
P. Ioannou ◽  
V. Theodorakopoulou
Keyword(s):  
Heart Failure ◽  
Acute Heart Failure ◽  
Organ Damage ◽  
Multiple Organ

scholarly journals Hydraulic force is a novel mechanism of diastolic function that may contribute to decreased diastolic filling in HFpEF and facilitate filling in HFrEF

2021 ◽  
Vol 130 (4) ◽  
pp. 993-1000
Author(s):  
Katarina Steding-Ehrenborg ◽  
Erik Hedström ◽  
Marcus Carlsson ◽  
Elira Maksuti ◽  
Michael Broomé ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Physiological Mechanism ◽  
Diastolic Filling ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Hydraulic Force ◽  
Patients With Heart Failure ◽  
Cardiac Filling

It is a previously unrecognized physiological mechanism of the heart that diastolic filling occurs with the help of hydraulics. In patients with heart failure with preserved ejection fraction, atrial dilatation may cause the net hydraulic force to work against cardiac filling, thus further augmenting diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles, as in heart failure with reduced ejection fraction.

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