Left Ventricular Diastolic Failure Research Articles

Effect of mechanical tension on fibroblast transcriptome profile and regulatory mechanisms of myocardial collagen turnover.

Excess deposition of extracellular matrix in the myocardium is a predictor of reduced left ventricular function. Although reducing the hemodynamic load is known to improve myocardial fibrosis, the mechanisms underlying the reversal of the fibrosis have not been elucidated. We focused on the elasticity of myocardial tissue, which is assumed to influence the fibroblast phenotype. Normal and fibrotic myocardium were cultured in 16 kPa and 64 kPa silicone gel-coated dishes supplemented with recombinant TGFβ protein, respectively. Matrix-degrading myocardium was cultured in 64 kPa silicone gel-coated dishes with recombinant TGFβ protein and then in 16 kPa silicone gel-coated dishes. Cardiac fibroblasts were cultured in this three-part in vitro pathological models and compared. Fibroblasts differentiated into activated or matrix-degrading types in response to the pericellular environment. Comprehensive gene expression analysis of fibroblasts in each in vitro condition showed Selenbp1 to be one of the genes responsible for regulating differentiation of fibroblasts. In vitro knockdown of Selenbp1 enhanced fibroblast activation and inhibited conversion to the matrix-degrading form. In vivo knockdown of Selenbp1 resulted in structural changes in the left ventricle associated with progressive tissue fibrosis and left ventricular diastolic failure. Selenbp1 is involved in regulating fibroblast differentiation and appears to be one of the major molecules regulating collagen turnover in cardiac fibrosis.

Human Omentin-1 Administration Ameliorates Hypertensive Complications without Affecting Hypertension in Spontaneously Hypertensive Rats.

Hypertension is one of the major risk factors for cardiovascular diseases and is caused by various abnormalities including the contractility of blood vessels. Spontaneously hypertensive rats (SHR), whose systemic blood pressure increases with aging, are a frequently used animal model for investigating essential hypertension and related complications in humans due to the damage of several organs. Human omentin-1 is an adipocytokine consisting of 313 amino acids. Serum omentin-1 levels decreased in hypertensive patients compared with normotensive controls. Furthermore, omentin-1 knockout mice showed elevated blood pressure and impaired endothelial vasodilation. Taken together, we hypothesized that adipocytokine, human omentin-1 may improve the hypertension and its complications including heart and renal failure in the aged SHR (65-68-weeks-old). SHR were subcutaneously administered with human omentin-1 (18 μg/kg/day, 2 weeks). Human omentin-1 had no effect on body weight, heart rate, and systolic blood pressure in SHR. The measurement of isometric contraction revealed that human omentin-1 had no influence on the enhanced vasocontractile or impaired vasodilator responses in the isolated thoracic aorta from SHR. On the other hand, human omentin-1 tended to improve left ventricular diastolic failure and renal failure in SHR. In summary, human omentin-1 tended to improve hypertensive complications (heart and renal failure), while it had no influence on the severe hypertension in the aged SHR. The further study of human omentin-1 may lead to the development of therapeutic agents for hypertensive complications.

Left atrial strain: a sensitive whistleblower lost in translation

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the Netherlands Organisation for Scientific Research (NWO- ZonMw, VIDI grant 016.176.340 to J.L.) and the Dutch Heart Foundation (ERA-CVD JTC2018 grant 2018T094; Dr. Dekker Program grant 2015T082 to J.L.) Background Left atrial (LA) function measured by peak/reservoir strain (PLAS) has been shown to be of prognostic value in various cardiac pathologies, including heart failure (HF). However, the underlying mechanisms leading to reduced PLAS remain poorly understood. Purpose To investigate how various combinations of left ventricular (LV) systolic-, diastolic, and LA failure affect PLAS. Method The CircAdapt computational model of the human heart and circulation is used to simulate the abovementioned LV and LA substrates, starting from a healthy reference simulation. LV systolic failure was simulated by a 25% decrease of LV contractility and LV eccentric hypertrophy (simultaneous increase of LV wall mass and area by 30%). LV diastolic failure was simulated by increasing LV myocardial stiffness by 100%, impairing LV relaxation function (increasing relaxation time constant from 35ms to 60ms, and LV concentric remodeling (increasing LV wall mass by 30%). LA failure was simulated by a fully non-contractile LA myocardium. Results LV systolic failure was characterized by reduced LV GLS (21 to 12%) and LVEF (54 to 34%), with marginal increase in PLAS (42 to 46%; Figure top row, first vs second column). LV diastolic failure was characterized by reduced PLAS (42 to 23%; Figure first vs third and fourth columns) with LA dilation (i.e. peak LA volume: 50 to 80 ml). Furthermore, LV concentric remodeling increased LVEF (54 to 64%). LA failure led to LA dilation and reduction of PLAS, regardless of LV substrate. Lastly, LV diastolic dysfunction and LA failure did not affect LV GLS (Figure bottom row). Conclusion Simulations showed that acute LV systolic failure hardly affected PLAS, but predominantly decreased LV GLS and LVEF. On the contrary, both LV diastolic dysfunction and LA failure reduced PLAS, rather than LV GLS and LVEF. Hence, LA strain can be considered as a whistleblower sensitive to various LV and/or LA abnormalities, which may explain why it is a rather nonspecific diagnostic marker. Abstract Figure. LA and LV strain in various substrates

Ambulatory Hemodynamic Monitoring of Pulmonary Hypertension

Elevated pulmonary artery pressure, typically called “pulmonary hypertension (PH)”, may occur owing to several pathophysiological conditions. The World Health Organization (WHO) proposed 5 classifications of PH, primarily based on causality, in order to guide research and provide a framework for therapeutic intervention. The WHO group II PH is most common and characterized by a mean pulmonary artery (PA) pressure higher than 25 mmHg that is associated with a pulmonary capillary wedge pressure greater than 15 mmHg. This hemodynamic profile suggests that PA pressure is elevated in cases of left ventricular (LV) failure, such as severe mitral valve disease (stenosis or regurgitation), LV diastolic failure, or LV systolic failure. Patients with elevated PA pressure experience abnormal dyspnea on exertion as well as severe symptoms such as dyspnea at rest. Further elevations in PA pressures can cause fluid to exudate fluid from the intravascular to the extravascular space, leading to pulmonary edema and severe, potentially life-threatening decompensation that require in-hospital care. Recently developed ambulatory implantable hemodynamic monitors help physicians remotely measure direct PA pressure from patients’ homes. Monitoring PA pressures allows healthcare specialists to monitor patient stability by evaluating the response to therapy adjustments, ultimately reducing hospitalization.

Dipeptidyl peptidase-4 inhibitors are associated with improved left ventricular diastolic function after acute myocardial infarction in diabetic patients.

Dipeptidyl peptidase-4 (DPP4) is an integral membrane glycoprotein that modulates the pathological state of diabetes mellitus (DM), and DPP4 inhibitors are a new class of anti-type-2 DM drugs. Recent preclinical studies have associated DPP4 inhibition with improved myocardial systolic and diastolic function. Based on preclinical findings, we investigated associations between the administration of DPP4 inhibitors and cardiac function after acute myocardial infarction (AMI) in a clinical setting. We enrolled 34 patients with diabetes who were treated for acute myocardial infarction at our hospital between January 2010 and December 2012. We retrospectively compared changes in cardiac parameters determined by trans-thoracic echocardiography between patients treated with (DPP4-I group; n=13) or without (non-DPP4-I group; n=21) a DPP4 inhibitor during follow-up. The values of E/e' and of e'/a' significantly decreased and increased, respectively, in the DPP4-I, compared with the non-DPP4-I group (-2.53±5.53 vs. 2.58±5.68, p=0.038 and 0.08±0.23 vs. -0.12±0.21, p=0.036, respectively). We concluded that DPP4 inhibitors could improve E/e' and e'/a' in patients with DM and AMI and thus might be effective for treating left ventricular diastolic failure.

Usefulness of Combined Bedside Lung Ultrasound and Echocardiography to Assess Weaning Failure From Mechanical Ventilation

Recognition of the cardiac origin of weaning failure is a crucial issue for successful discontinuation of mechanical ventilation. Bedside lung ultrasound and echocardiography have shown a potential in predicting weaning failure. Objective of this report was to describe the case of a patient repeatedly failing to wean from mechanical ventilation, where the combined use of lung ultrasound and echocardiography during a spontaneous breathing trial uncovered an unexpected cause of the failure. Case report. General ICU of a university teaching hospital. Single case, abdominal surgery postoperative patient, not predicted to experience a difficult weaning. Cardiovascular therapy adjustments consistent with lung ultrasound and echocardiography findings acquired during spontaneous breathing trials. All patient's standard hemodynamic and respiratory parameters, datasets from comprehensive lung ultrasound and echocardiographic examinations, and pertinent data from biochemistry exams, were collected during two spontaneous breathing trials. Data from beginning and end of each of the two ultrasound monitored weaning trials, and from the end of the successful weaning trial following therapy and the previously failed one, were analyzed and qualitatively compared. Lung ultrasound performed at the end of the failed spontaneous breathing trial showed a pattern consistent with increased extravascular lung water (diffuse, bilateral, symmetrical, homogeneous sonographic interstitial syndrome). Concurrent echocardiography diagnosed left ventricular diastolic failure. Ultrasound findings at the end of the successful weaning trial showed normalization of the lung pattern and improvement of the echocardiographic one. The patient eventually returned to spontaneous respiration and was discharged from the ICU. The use of bedside lung ultrasound and echocardiography disclosed left ventricular diastolic dysfunction as unexpected cardiogenic cause of weaning failure and lead to subsequent correct patient management.

Diffuse skin hyperpigmentation in CD30+ lymphoproliferation

CD30+ T-cell lymphoproliferative disorders (LD) comprise two main groups of diseases: CD30+ LD of the skin and systemic anaplastic large cell lymphoma (ALCL). The main feature of these disorders is the expression of CD30. We present a patient with an unusual clinical presentation of CD30+ lymphoproliferative disease in a 54-year old Caucasian male who presented with generalized lymphadenopathy and pronounced skin hyperpigmentation. In the lymph nodes and skin, CD30+ lymphoproliferation (ALCL) was diagnosed. The Prussian blue staining identified that the pigment responsible for the skin color was hemosiderin. Chemotherapy was started but the patient’s condition progressively worsened and he died a week after the first cycle. The complete color transformation of the entire skin due to hemosiderin accumulation is, to the best of our knowledge, the first reported observation in a CD30+ lymphoproliferation/ALCL patient. We speculate that hemosiderin-loaded macrophages resulted from the paraneoplastic process by some still unknown mechanism.

Not Just Big Kids

Atrial septal defects (ASDs), allowing blood to directly communicate between systemic and pulmonary arterial circulations at the atrial level, are among the most common congenital cardiac anomalies seen in the adult population. The degree of shunting across an ASD is directly related to the area of the ASD and inversely related to the compliance of the combined atrial-ventricular chambers on either side of the heart. Under normal physiological conditions, there is net left-to-right shunting across an ASD, as the left ventricle is far less compliant than the right ventricle. This shunt of fully oxygenated blood back to the right atrium results in a volume load to the right-sided heart chambers and to the pulmonary vasculature; if left untreated, large-volume left-to-right shunting can result in atrial arrhythmias, right ventricular diastolic and systolic failure, worsened functional class, decreased exercise capacity, left ventricular diastolic failure, and, uncommonly, development of pulmonary arterial hypertension.1 The indication to treat an ASD is typically related to its hemodynamic significance and its effects on the right ventricle. National care guidelines denote ASD closure with class IA recommendation in patients with evidence …

The use of B‐type natriuretic peptide in the management of elderly patients with acute dyspnoea ( J Intern Med 2005;258:77–85)

Dear Sir, The findings of the above study [1] would have been more readily applicable to routine clinical practice if the radiographic stigmata of acute left ventricular failure (LVF) had also been documented, using parameters which have not only been found to be positively correlated with B-type atrial natriuretic factor, but have also proved to be highly predictive of LVF itself [2]. Coupled with a categorization of the patients into those with subnormal left ventricular ejection fraction (LVEF) and those with intact LVEF, the inclusion of radiographic stigmata as well as the radiographic response to antifailure therapy would have considerably enhanced our understanding of left ventricular diastolic failure in addition to validating the therapeutic trial as an alternative diagnostic tool in the evaluation of the acutely breathless patient with normal LVEF. No conflict of interest was declared.

Doppler echocardiographic investigation of left ventricular diastolic function in preterm infants with and without a patent ductus arteriosus

We studied the influence of preload augmentation on Doppler-derived left ventricular diastolic function parameters in infants with a birth weight <1500 g. In 44 neonates with a closed duct and 29 neonates with an open ductus arteriosus a complete echocardiographic study including Doppler investigations of the mitral inflow signals and analysis of diastolic time intervals was performed. Neonates with an open duct had a lower median gestational age (27.1 vs. 29, P<0.01), a higher cardiac index (425 vs. 260 ml/min/kg, P<0.001), and a different M-mode left atrial to aortic diameter ratio (1.36 vs. 0.79, P<0.001), but birth weight, age at examination (6.6 vs. 7.9 days), and heart rate were similar compared to the neonates with a closed duct. Main differences in diastolic indexes existed in early and atrial filling integrals and peak velocities, early filling acceleration time, and isovolumic relaxation time. Most informative in neonates with an open ductus peak early filling velocity (41.2 vs. 30.4 cm, P<0.01) and peak atrial filling velocity (49.2 vs. 35.9, P<0.001) are higher, and isovolumic relaxation time is shorter (45 vs. 53 ms, P<0.001) than in closed duct peers. Isovolumic relaxation time is inversely correlated with the cardiac index (R = -0.78). These parameter changes can be interpreted as incipient left ventricular diastolic failure in extremely low birth weight infants in the presence of a preload challenge. The coincidence of higher peak velocities with a shortened isovolumic relaxation time is very likely a result of left atrial pressure elevation. Preload mismatch has to be considered in preterm infants with a persistent ductus arteriosus. The results of this study can be helpful to find the indication for PDA-closure and to adjust volume replacement therapy, and catecholamine medication to a level appropriate for the individual cardiac performance.