-
Circulation Research May 2021Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and... (Review)
Review
Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.
Topics: Acute Disease; Body Fluids; Cardio-Renal Syndrome; Cardiotoxins; Comorbidity; Heart Failure; Hospitalization; Humans; Inflammation Mediators; Myocardial Contraction; Natriuretic Peptide, Brain; Patient Discharge; Patient Readmission; Renin-Angiotensin System; Symptom Assessment; Vascular Resistance; Vasoconstriction; Vasodilator Agents
PubMed: 33983837
DOI: 10.1161/CIRCRESAHA.121.318186 -
Annals of the American Thoracic Society Feb 2018The hemodynamic effects of ventilation can be grouped into three concepts: 1) Spontaneous ventilation is exercise; 2) changes in lung volume alter autonomic tone and... (Review)
Review
The hemodynamic effects of ventilation can be grouped into three concepts: 1) Spontaneous ventilation is exercise; 2) changes in lung volume alter autonomic tone and pulmonary vascular resistance and can compress the heart in the cardiac fossa; and 3) spontaneous inspiratory efforts decrease intrathoracic pressure, increasing venous return and impeding left ventricular ejection, whereas positive-pressure ventilation decreases venous return and unloads left ventricular ejection. Spontaneous inspiratory efforts may induce acute left ventricular failure and cardiogenic pulmonary edema. Reversing the associated negative intrathoracic pressure swings by using noninvasive continuous positive airway pressure rapidly reverses acute cardiogenic pulmonary edema and improves survival. Additionally, in congestive heart failure, states increasing intrathoracic pressure may augment left ventricular ejection and improve cardiac output. Using the obligatory changes in venous return induced by positive pressure breathing, one can quantify the magnitude of associated decreases in venous flow and left ventricular ejection using various parameters, including vena caval diameter changes, left ventricular stroke volume variation, and arterial pulse pressure variation. These parameters vary in proportion to the level of cardiac preload reserve present, thus accurately predicting which critically ill patients will increase their cardiac output in response to fluid infusions and which will not. Common parameters include arterial pulse pressure variation and left ventricular stroke volume variation. This functional hemodynamic monitoring approach reflects a practical clinical application of heart-lung interactions.
Topics: Blood Pressure; Cardiovascular System; Hemodynamics; Humans; Lung Diseases; Myocardial Contraction; Oxygen Consumption; Positive-Pressure Respiration; Pulmonary Artery; Respiration; Vascular Resistance; Ventricular Function, Left
PubMed: 28820609
DOI: 10.1513/AnnalsATS.201704-339FR -
Journal of the American College of... Apr 2021The mechanisms responsible for the positive and unexpected cardiovascular effects of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor... (Review)
Review
The mechanisms responsible for the positive and unexpected cardiovascular effects of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes remain to be defined. It is likely that some of the beneficial cardiac effects of these antidiabetic drugs are mediated, in part, by altered myocardial metabolism. Common cardiometabolic disorders, including the metabolic (insulin resistance) syndrome and type 2 diabetes, are associated with altered substrate utilization and energy transduction by the myocardium, predisposing to the development of heart disease. Thus, the failing heart is characterized by a substrate shift toward glycolysis and ketone oxidation in an attempt to meet the high energetic demand of the constantly contracting heart. This review examines the metabolic pathways and clinical implications of myocardial substrate utilization in the normal heart and in cardiometabolic disorders, and discusses mechanisms by which antidiabetic drugs and metabolic interventions improve cardiac function in the failing heart.
Topics: Animals; Energy Metabolism; Glucagon-Like Peptide-1 Receptor; Heart Failure; Humans; Hypoglycemic Agents; Myocardial Contraction; Myocardium; Review Literature as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33888253
DOI: 10.1016/j.jacc.2021.02.057 -
Circulation Nov 2022Direct cardiac reprogramming of fibroblasts into cardiomyocytes has emerged as a promising strategy to remuscularize injured myocardium. However, it is insufficient to...
BACKGROUND
Direct cardiac reprogramming of fibroblasts into cardiomyocytes has emerged as a promising strategy to remuscularize injured myocardium. However, it is insufficient to generate functional induced cardiomyocytes from human fibroblasts using conventional reprogramming cocktails, and the underlying molecular mechanisms are not well studied.
METHODS
To discover potential missing factors for human direct reprogramming, we performed transcriptomic comparison between human induced cardiomyocytes and functional cardiomyocytes.
RESULTS
We identified (T-box transcription factor 20) as the top cardiac gene that is unable to be activated by the MGT133 reprogramming cocktail (, , , and ). TBX20 is required for normal heart development and cardiac function in adult cardiomyocytes, yet its role in cardiac reprogramming remains undefined. We show that the addition of TBX20 to the MGT133 cocktail (MGT+TBX20) promotes cardiac reprogramming and activates genes associated with cardiac contractility, maturation, and ventricular heart. Human induced cardiomyocytes produced with MGT+TBX20 demonstrated more frequent beating, calcium oscillation, and higher energy metabolism as evidenced by increased mitochondria numbers and mitochondrial respiration. Mechanistically, comprehensive transcriptomic, chromatin occupancy, and epigenomic studies revealed that TBX20 colocalizes with MGT reprogramming factors at cardiac gene enhancers associated with heart contraction, promotes chromatin binding and co-occupancy of MGT factors at these loci, and synergizes with MGT for more robust activation of target gene transcription.
CONCLUSIONS
TBX20 consolidates MGT cardiac reprogramming factors to activate cardiac enhancers to promote cardiac cell fate conversion. Human induced cardiomyocytes generated with TBX20 showed enhanced cardiac function in contractility and mitochondrial respiration.
Topics: Humans; Cellular Reprogramming; Chromatin; Fibroblasts; Mitochondria; Myocardium; Myocytes, Cardiac; T-Box Domain Proteins; Myocardial Contraction; Cardiovascular Agents
PubMed: 36102189
DOI: 10.1161/CIRCULATIONAHA.122.059713 -
Journal of Cardiology Jun 2019Diastolic filling of the heart is a complex sequence of multiple inter-related events consisting of processes such as ventricular relaxation, erectile coronary effect,... (Review)
Review
Diastolic filling of the heart is a complex sequence of multiple inter-related events consisting of processes such as ventricular relaxation, erectile coronary effect, visco-elastic forces of the myocardium, ventricular interaction, myocardial stress strain relationships, pericardial restraint, passive filling, and atrial contraction. However, in order to understand diastolic filling from a clinical aspect, a simplified foundation can be used which divides the cardiac cycle into contraction, relaxation, passive filling, and filling at atrial contraction. The mitral flow velocity curves are representative of the relative driving pressure between left atrium and left ventricle and allow one to grade the progression of diastolic dysfunction which occurs in disease states. Doppler tissue imaging is necessary as a surrogate of ventricular relaxation to further determine the stages of diastolic dysfunction in patients with preserved ejection fraction. These Doppler flow velocity curves can be applied to understanding diastolic filling of the heart in patients with both reduced ejection fraction and preserved ejection fraction.
Topics: Cardiomyopathies; Diastole; Echocardiography, Doppler; Female; Heart Atria; Heart Ventricles; Humans; Male; Myocardial Contraction; Ventricular Dysfunction; Ventricular Function
PubMed: 30922613
DOI: 10.1016/j.jjcc.2019.03.002 -
Journal of the American College of... Jan 2017In pulmonary hypertension, the right ventricle adapts to the increasing vascular load by enhancing contractility ("coupling") to maintain flow. Ventriculoarterial... (Review)
Review
In pulmonary hypertension, the right ventricle adapts to the increasing vascular load by enhancing contractility ("coupling") to maintain flow. Ventriculoarterial coupling implies that stroke volume changes little while preserving ventricular efficiency. Ultimately, a phase develops where ventricular dilation occurs in an attempt to limit the reduction in stroke volume, with uncoupling and increased wall stress as a consequence. With pressure-volume analysis, we separately describe the changing properties of the pulmonary vascular system and the right ventricle, as well as their coupling, as important concepts for understanding the changes that occur in pulmonary hypertension. On the basis of the unique properties of the pulmonary circulation, we show how all relevant physiological parameters can be derived using an integrative approach. Because coupling is maintained by hypertrophy until the end stage of the disease, when progressive dilation begins, right ventricular volume is the essential parameter to measure in follow-up of patients with pulmonary hypertension.
Topics: Cardiac Volume; Follow-Up Studies; Heart Ventricles; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Magnetic Resonance Imaging; Myocardial Contraction; Pulmonary Artery; Pulmonary Circulation; Risk Factors; Stroke Volume
PubMed: 28081831
DOI: 10.1016/j.jacc.2016.10.047 -
International Journal of Molecular... Oct 2021Inherited cardiomyopathies form a heterogenous group of disorders that affect the structure and function of the heart. Defects in the genes encoding sarcomeric proteins... (Review)
Review
Inherited cardiomyopathies form a heterogenous group of disorders that affect the structure and function of the heart. Defects in the genes encoding sarcomeric proteins are associated with various perturbations that induce contractile dysfunction and promote disease development. In this review we aimed to outline the functional consequences of the major inherited cardiomyopathies in terms of myocardial contraction and kinetics, and to highlight the structural and functional alterations in some sarcomeric variants that have been demonstrated to be involved in the pathogenesis of the inherited cardiomyopathies. A particular focus was made on mutation-induced alterations in cardiomyocyte mechanics. Since no disease-specific treatments for familial cardiomyopathies exist, several novel agents have been developed to modulate sarcomere contractility. Understanding the molecular basis of the disease opens new avenues for the development of new therapies. Furthermore, the earlier the awareness of the genetic defect, the better the clinical prognostication would be for patients and the better the prevention of development of the disease.
Topics: Animals; Cardiomyopathies; Humans; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Sarcomeres
PubMed: 34681814
DOI: 10.3390/ijms222011154 -
The Journal of Physiology Apr 2020
Topics: Arrhythmias, Cardiac; Heart Failure; Humans; Models, Cardiovascular; Myocardial Contraction
PubMed: 31998965
DOI: 10.1113/JP279385 -
Current Cardiology Reviews 2022The Myocardial Performance Index (MPI) or Tei index, presented by Tei in 1995, is the ratio of the sum of the duration of the isovolumetric contraction time (ICT) and... (Review)
Review
The Myocardial Performance Index (MPI) or Tei index, presented by Tei in 1995, is the ratio of the sum of the duration of the isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) to the duration of the ejection time (ET). The Modified Myocardial Performance Index (Mod-MPI), proposed in 2005, is considered a reliable and useful tool in the study of fetal heart function in several conditions, such as growth restriction, twin-twin transfusion syndrome, maternal diabetes, preeclampsia, intrahepatic cholestasis of pregnancy, and adverse perinatal outcomes. Nevertheless, clinical translation is currently limited by poorly standardised methodology as variations in the technique, machine settings, caliper placement, and specific training required can result in significantly different MPI values. This review aims to provide a survey of the relevant literature on MPI, present a strict methodology and technical considerations, and propose future research.
Topics: Female; Fetal Heart; Humans; Myocardial Contraction; Pregnancy; Ultrasonography, Prenatal
PubMed: 34961451
DOI: 10.2174/1573403X18666211227145856 -
Progress in Biophysics and Molecular... Jan 2021Well over a century ago, Otto Frank, working at Carl Ludwig's Institute of Physiology in Munich, studying the isolated, blood-perfused, frog heart preparation,... (Review)
Review
Well over a century ago, Otto Frank, working at Carl Ludwig's Institute of Physiology in Munich, studying the isolated, blood-perfused, frog heart preparation, demonstrated that there are two distinct pressure-volume relations in the heart: one for isovolumic twitches and a second (located inferiorly) for afterloaded twitches. Whereas Starling, working at UCL two decades later, referenced Frank's publication (to the extent of re-printing its seminal Figure), he appeared not to have tested Frank's finding. Hence, he remained silent with respect to Franks' contention that cardiac pressure-volume relations are contraction-mode-dependent. Instead, he concluded that "The energy of contraction, however measured, is a function of the length of the muscle fibre" - a conclusion that has become known (at least in the English-speaking world) as 'Starling's Law of the Heart'. This provides us with at least three conundra: (i) why did Starling present only one pressure-volume relation whereas Frank had previously found two, (ii) why, then, do we speak of The Frank-Starling relation, and (iii) how did Frank become largely forgotten for twelve decades among English speakers? This review will attempt to address and comment on these conundra.
Topics: Blood Pressure; Cardiac Output; Cardiac Volume; Heart; History, 19th Century; History, 20th Century; Humans; Models, Cardiovascular; Myocardial Contraction
PubMed: 32407748
DOI: 10.1016/j.pbiomolbio.2020.04.003