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European Heart Journal. Case Reports Jun 2024There is limited evidence for the use of an intra-aortic balloon pump (IABP) in adult patients with a total cavopulmonary, or Fontan circulation.
BACKGROUND
There is limited evidence for the use of an intra-aortic balloon pump (IABP) in adult patients with a total cavopulmonary, or Fontan circulation.
CASE SUMMARY
A patient in his twenties with a Fontan circulation presented with sepsis, pneumonia, and pulmonary oedema. He was born with a hypoplastic left ventricle, atrioventricular septal defect, and hypoplastic aortic arch, and a total cavopulmonary circulation had been established within his first years of life. Standard of care treatment with antibiotics, non-invasive ventilatory support, loop diuretics, and vasopressors was initiated. Due to persistent pulmonary congestion and increasing general fatigue, an IABP was placed via a femoral artery to offload the failing systemic ventricle. Secondary to IABP treatment, mean arterial pressure rose, and vasodilatory nitroprusside could be introduced. Over 4 days of IABP treatment, the patient's general condition and ventricular systolic function improved significantly.
DISCUSSION
This case suggests that IABP treatment was important in the recovery of our patient with a Fontan circulation, pneumonia, and heart failure. We propose that during IABP treatment, an increase in stroke volume and a reduction in ventricular filling pressure is achieved, thereby increasing the transpulmonary pressure gradient that is central to pulmonary blood flow in Fontan patients. More definitive evidence is necessary to confirm our hypotheses.
PubMed: 38912116
DOI: 10.1093/ehjcr/ytae289 -
Pulmonary Circulation Apr 2024Pulmonary hypertension (PH) adds a substantial disease burden, including higher mortality, when associated with interstitial lung disease (ILD), a severe, chronic,...
Pulmonary hypertension (PH) adds a substantial disease burden, including higher mortality, when associated with interstitial lung disease (ILD), a severe, chronic, progressive condition. Yet little is known of the lived experiences, perspectives, priorities, and viewpoints of patients and carers living with PH-ILD. The Voice of the Patient meeting at the center of this qualitative research study aims to provide these difficult-to-obtain insights from a European perspective for the first time. The multistakeholder approach brought together four PH-ILD patients, three primary caregivers, two patient associations, clinical experts, sponsor representatives, and a facilitator. Of the six major themes identified in the thematic analysis, symptoms, and physical limitations were the most impactful. Shortness of breath was the most bothersome symptom affecting patients daily. Further symptoms included fatigue, cough, dizziness, syncope, edema, and palpitations. Physical limitations focused on reduced mobility, impacting patients' ability to perform daily tasks, hobbies, sports, and to enjoy travel. Existing antifibrotic and pulmonary arterial hypertension-targeted treatments were perceived as beneficial. However, despite advances in treatment, severe disease burdens and high unmet medical needs persist from the perspectives of patients. Most meaningful to patients' daily wellbeing was supplemental oxygen, enabling greater mobility. Patients and carers reported difficulties and barriers in navigating the healthcare system and obtaining adequate information to reduce their considerable uncertainties, documenting the substantial challenges that rare and complex conditions such as PH-ILD pose for routine clinical practice beyond PH expert centers and indicating an urgent need for high-quality patient- and clinician-directed information to support patient-centered care.
PubMed: 38911184
DOI: 10.1002/pul2.12405 -
Cardio-oncology (London, England) Jun 2024The anthracycline doxorubicin (DOX) is a highly effective anticancer agent, especially in breast cancer and lymphoma. However, DOX can cause cancer therapy-related...
BACKGROUND
The anthracycline doxorubicin (DOX) is a highly effective anticancer agent, especially in breast cancer and lymphoma. However, DOX can cause cancer therapy-related cardiovascular toxicity (CTR-CVT) in patients during treatment and in survivors. Current diagnostic criteria for CTR-CVT focus mainly on left ventricular systolic dysfunction, but a certain level of damage is required before it can be detected. As diastolic dysfunction often precedes systolic dysfunction, the current study aimed to identify functional and molecular markers of DOX-induced CTR-CVT with a focus on diastolic dysfunction.
METHODS
Male C57BL/6J mice were treated with saline or DOX (4 mg/kg, weekly i.p. injection) for 2 and 6 weeks (respectively cumulative dose of 8 and 24 mg/kg) (n = 8 per group at each time point). Cardiovascular function was longitudinally investigated using echocardiography and invasive left ventricular pressure measurements. Subsequently, at both timepoints, myocardial tissue was obtained for proteomics (liquid-chromatography with mass-spectrometry). A cohort of patients with CTR-CVT was used to complement the pre-clinical findings.
RESULTS
DOX-induced a reduction in left ventricular ejection fraction from 72 ± 2% to 55 ± 1% after 2 weeks (cumulative 8 mg/kg DOX). Diastolic dysfunction was demonstrated as prolonged relaxation (increased tau) and heart failure was evident from pulmonary edema after 6 weeks (cumulative 24 mg/kg DOX). Myocardial proteomic analysis revealed an increased expression of 12 proteins at week 6, with notable upregulation of SERPINA3N in the DOX-treated animals. The human ortholog SERPINA3 has previously been suggested as a marker in CTR-CVT. Upregulation of SERPINA3N was confirmed by western blot, immunohistochemistry, and qPCR in murine hearts. Thereby, SERPINA3N was most abundant in the endothelial cells. In patients, circulating SERPINA3 was increased in plasma of CTR-CVT patients but not in cardiac biopsies.
CONCLUSION
We showed that mice develop heart failure with impaired systolic and diastolic function as result of DOX treatment. Additionally, we could identify increased SERPINA3 levels in the mice as well as patients with DOX-induced CVT and demonstrated expression of SERPINA3 in the heart itself, suggesting that SERPINA3 could serve as a novel biomarker.
PubMed: 38909263
DOI: 10.1186/s40959-024-00241-1 -
Cell & Bioscience Jun 2024Clinical outcome after traumatic brain injury (TBI) is closely associated conditions of other organs, especially lungs as well as degree of brain injury. Even if there... (Review)
Review
Clinical outcome after traumatic brain injury (TBI) is closely associated conditions of other organs, especially lungs as well as degree of brain injury. Even if there is no direct lung damage, severe brain injury can enhance sympathetic tones on blood vessels and vascular resistance, resulting in neurogenic pulmonary edema. Conversely, lung damage can worsen brain damage by dysregulating immunity. These findings suggest the importance of brain-lung axis interactions in TBI. However, little research has been conducted on the topic. An advanced disease model using stem cell technology may be an alternative for investigating the brain and lungs simultaneously but separately, as they can be potential candidates for improving the clinical outcomes of TBI.In this review, we describe the importance of brain-lung axis interactions in TBI by focusing on the concepts and reproducibility of brain and lung organoids in vitro. We also summarize recent research using pluripotent stem cell-derived brain organoids and their preclinical applications in various brain disease conditions and explore how they mimic the brain-lung axis. Reviewing the current status and discussing the limitations and potential perspectives in organoid research may offer a better understanding of pathophysiological interactions between the brain and lung after TBI.
PubMed: 38909262
DOI: 10.1186/s13578-024-01252-2 -
Medicina 2024Takotsubo syndrome, was described in Japan in 1990, it is a stress cardiomyopathy, predominantly in women, usually postmenopausal. Cardiac hypokinesia occurs, with...
Takotsubo syndrome, was described in Japan in 1990, it is a stress cardiomyopathy, predominantly in women, usually postmenopausal. Cardiac hypokinesia occurs, with involvement of multiple coronary territories. In intensive care unit (ICU), it is considered underdiagnosed. Manifestations of severe dengue fever include cardiovascular involvement, mainly arrhythmias and systolic dysfunction. A case of a 72-year-old man is presented, who was hospitalized in ICU for dengue fever, with plateletopenia (15000 cells/mm3) and dehydration. After fluid management the patient reported respiratory discomfort, auscultating crackling rales. A pulmonary ultrasound was made where bilateral B lines were found with B7 pattern compatible with interstitial syndrome and pulmonary edema. Basal hyperkinesia, medial and apical hypokinesia with an image consistent with apical ballooning were observed in the transthoracic echocardiogram. The electrocardiogram showed complete right bundle branch block. Chagas serology was negative and quantitative troponin I was increased. In the context of severe dengue, a Takotsubo syndrome was diagnosed. The patient evolved favorably. After discharge, a normalization of the cardiac function was stated in ultrasound images. The case is of clinical importance due to the low association of these two diseases and the need to screen for cardiac involvement in severe dengue.
Topics: Humans; Takotsubo Cardiomyopathy; Aged; Male; Dengue; Electrocardiography; Severe Dengue; Echocardiography
PubMed: 38907979
DOI: No ID Found -
Cureus May 2024The Gerbode defect is a rare ventricular septal defect (VSD) between the left ventricle (LV) and right atrium (RA). We describe a challenging case of a rare acquired...
The Gerbode defect is a rare ventricular septal defect (VSD) between the left ventricle (LV) and right atrium (RA). We describe a challenging case of a rare acquired Gerbode defect from infective endocarditis. A 73-year-old male presented for left lower extremity edema and shortness of breath with exertion. He was discharged from the hospital one week prior after being diagnosed with right hip septic arthritis. A transthoracic echocardiogram (TTE) did not demonstrate an abscess or vegetation, but was significant for severely elevated tricuspid regurgitation velocity and pulmonary artery (PA) systolic pressure of 70 mm Hg without structural changes to the right ventricle or RA. A transesophageal echocardiogram (TEE) was performed due to these abnormal values and demonstrated a VSD between the LV and RA. This type of defect is known as a Gerbode defect, which is suggestive of an aortic root abscess. The patient ultimately was transferred to a tertiary care center, and the Gerbode defect with aortic root abscess was confirmed by direct visualization. This case reports a unique case of an acquired Gerbode defect secondary to infective endocarditis. Our patient's defect was noted to be above the tricuspid valve, which essentially confirmed the etiology as a VSD. Although the TEE did not demonstrate a clear aortic root abscess, direct visualization during the surgical intervention confirmed this suspicion. Prompt diagnosis of the Gerbode defect allowed the patient to receive urgent surgical intervention. Gerbode defects are rare but clinically important complications of infective endocarditis. This case highlights the importance of maintaining a high level of suspicion, especially if the values obtained during TTE do not fully explain a patient's clinical presentation. A high level of suspicion leading to a timely diagnosis of this condition is essential in preventing further valvular destruction and allowing prompt surgical intervention.
PubMed: 38903337
DOI: 10.7759/cureus.60677 -
Frontiers in Neurology 2024Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid...
INTRODUCTION
Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage (SAH) in the Japanese population, as demonstrated by a recent randomized phase 3 trial. However, evidence to suggest clazosentan should be prioritized over the current standard of care to prevent cerebral vasospasm is still lacking. Therefore, we investigated the efficacy and safety of clazosentan in comparison with conventional postoperative management in real-world clinical practice.
METHODS
We conducted a single-center, retrospective, observational cohort study using prospectively collected data from consecutive patients with aneurysmal SAH. After clazosentan was approved for use in Japan, the conventional postoperative management protocol, composed of intravenous fasudil chloride and oral cilostazol (control group, April 2021 to March 2022), was changed to the clazosentan protocol (clazosentan group, April 2022 to March 2023). The primary endpoint was the incidence of vasospasm-related symptomatic infarction. The secondary endpoints were favorable functional outcomes (modified Rankin scale score < 3) at discharge, angiographic vasospasm, and the need for rescue therapy for delayed cerebral ischemia.
RESULTS
The analysis included 100 and 81 patients in the control and clazosentan groups, respectively. The incidence of vasospasm-related symptomatic infarction was significantly lower in the clazosentan group than in the control group (6.2% vs. 16%, = 0.032). Multiple logistic analyses demonstrated that the use of clazosentan was independently associated with fewer incidence of vasospasm-related symptomatic infarct (23.8% vs. 47.5%, odds ratio 0.34 [0.12-0.97], = 0.032). Clazosentan was significantly associated with favorable outcomes at discharge (79% vs. 66%, = 0.037). Moreover, both the incidence of angiographic vasospasm (25.9% vs. 44%, = 0.013) and the need for rescue therapy (16.1% vs. 34%, = 0.006) was lower in the clazosentan group. The occurrence of pulmonary edema was significantly higher with clazosentan use (19.8% vs. 5%, = 0.002), which did not result in morbidity.
CONCLUSION
A postoperative management protocol centering on clazosentan was associated with the reduced vasospasm-related symptomatic infarction and improved clinical outcomes compared to the conventional management protocol in Japanese clinical practice. Clazosentan might be a promising treatment option for counteracting cerebral vasospasm after aneurysmal SAH.
PubMed: 38903164
DOI: 10.3389/fneur.2024.1413632 -
BioRxiv : the Preprint Server For... Feb 2024Septic shock, in humans and in our well-established animal model, is associated with increases in biventricular end diastolic volume (EDV) and decreases in ejection...
BACKGROUND
Septic shock, in humans and in our well-established animal model, is associated with increases in biventricular end diastolic volume (EDV) and decreases in ejection fraction (EF). These abnormalities occur over 2 days and reverse within 10 days. Septic non-survivors do not develop an increase in EDV. The mechanism for this cardiac dysfunction and EDV differences is unknown.
METHODS
Purpose-bred beagles randomized to receive intrabronchial (n=27) or saline (n=6) were provided standard ICU care including sedation, mechanical ventilation, and fluid resuscitation to a pulmonary arterial occlusion pressure of over 10mmHg. No catecholamines were administered. Over 96h, cardiac magnetic resonance imaging, echocardiograms, and invasive hemodynamics were serially performed, and laboratory data was collected. Tissue was obtained at 66h from six septic animals.
RESULTS
From 0-96h after bacterial challenge, septic animals controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%) which was more pronounced at 48h in non-survivors than survivors. On histology, edema was located predominantly in myocytes, the interstitium, and endothelial cells. Edema was associated with significantly worse biventricular function (lower EFs), ventricular-arterial coupling, and circumferential strain. In septic animals, from 0-24h, the EDV decreased from baseline and, despite cardiac filling pressures being similar, decreased significantly more in non-survivors. From 24-48h, all septic animals had increases in biventricular chamber sizes. Survivors biventricular EDVs were significantly greater than baseline and in non-survivors, where biventricular EDVs were not different from baseline. Preload, afterload, or HR differences did not explain these differential serial changes in chamber size.
CONCLUSION
Systolic and diastolic cardiac dysfunction during sepsis is associated with ventricular wall edema. Rather than differences in preload, afterload, or heart rate, structural alterations to the ventricular wall best account for the volume changes associated with outcome during sepsis. In non-survivors, from 0-24h, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part explain, the EDV increases from 24-48h. However, these changes continued and even accelerated into the recovery phase consistent with a reparative process rather than ongoing injury.
CLINICAL PERSPECTIVE
Utilizing multimodal imaging and hemodynamics, we demonstrate the cardiac changes of sepsis have injury and reparative phases.The injury phase (0-24h) has EDV decreases more profound in non-survivors and is associated with worse ventricular compliance, myocardial edema, and diastolic dysfunction.The recovery phase has left ventricular mass loss with wall thinning in survivors that explains the EDV increases (24-96h). These progressed into the EF recovery phase consistent with a reparative process removing damaged tissue.This is the first controlled CMR sepsis study supporting ventricular wall edema is a fundamental aspect of sepsis pathophysiology and dry mass loss a reparative mechanism. Despite optimizing filling pressures, the cardiac changes in ventricular wall structure and function associated with survival and non-survival in sepsis still occurred, thereby discounting fluid resuscitation as the major factor of therapeutic importance for cardiac function and survival.The changes reported here have potential implications for sepsis treatment especially in the field of fluid resuscitation. These findings yield new understanding into the pathophysiology of sepsis cardiac dysfunction and allow for novel phenotyping and prognosticating of the syndrome with ventricular compliance and EDVs. This also offers potentially high yielding targets for research for new therapeutic approaches for sepsis and heart failure.
PubMed: 38903100
DOI: 10.1101/2024.02.05.578971 -
Danish Medical Journal Jun 2024Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute...
INTRODUCTION
Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute heart failure (AHF). While the diuretic effect of loop diuretics is well established, it remains unclear how furosemide influences pulmonary congestion and cardiac filling pressures in the hyperacute phase before significant diuresis occurs.
METHODS
This was a prospective study of adult patients with AHF and objective signs of pulmonary congestion admitted to the cardiac ward. Remote dielectric sensing (ReDS) will directly measure lung fluid content, and cardiac filling pressures will be assessed by echocardiography with Doppler and strain analysis.
CONCLUSIONS
This study will examine if furosemide leads to a hyperacute reduction in pulmonary congestion assessed by ReDS independent of diuretic effects in patients with AHF. We hypothesise that the haemodynamic effect of furosemide shown on pulmonary congestion may explain the subjective instant relief in patients with AHF receiving furosemide.
FUNDING
Dr. Grand's salary during this project is supported by a research grant from the Danish Cardiovascular Academy funded by Novo Nordisk Foundation grant number NNF20SA0067242 and by the Danish Heart Foundation.
TRIAL REGISTRATION
This protocol was approved by the Scientific Ethical Committee, H-23029822, and the Danish Data Protection Agency P-2013-14703. The protocol was registered with ClinicalTrial.org on 29 August 2023 (Identifier: NCT06024889).
Topics: Furosemide; Humans; Heart Failure; Prospective Studies; Pulmonary Edema; Diuretics; Acute Disease; Remote Sensing Technology; Female; Male; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 38903022
DOI: 10.61409/A11230697 -
Frontiers in Pharmacology 2024Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of... (Review)
Review
BACKGROUND AND OBJECTIVES
Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of high altitude. Its main mechanism is the organism's tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on the holistic concept. TCM has made remarkable achievements in the treatment of many mountain sicknesses. This review outlines the pathogenesis of AMS in modern and traditional medicine, the progress of animal models of AMS, and summarizes the therapeutic effects of TCM on AMS.
METHODS
Using the keywords "traditional Chinese medicine," "herbal medicine," "acute mountain sickness," "high-altitude pulmonary edema," "high-altitude cerebral edema," "acute hypobaric hypoxia," and "high-altitude," all relevant TCM literature published up to November 2023 were collected from Scopus, Web of Science, PubMed, and China National Knowledge Infrastructure databases, and the key information was analyzed.
RESULTS
We systematically summarised the effects of acute hypobaric hypoxia on the tissues of the organism, the study of the methodology for the establishment of an animal model of AMS, and retrieved 18 proprietary Chinese medicines for the clinical treatment of AMS. The therapeutic principle of medicines is mainly invigorating qi, activating blood and removing stasis. The components of botanical drugs mainly include salidroside, ginsenoside Rg1, and tetrahydrocurcumin. The mechanism of action of TCM in the treatment of AMS is mainly through the regulation of HIF-1α/NF-κB signaling pathway, inhibition of inflammatory response and oxidative stress, and enhancement of energy metabolism.
CONCLUSION
The main pathogenesis of AMS is unclear. Still, TCM formulas and components have been used to treat AMS through multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, salidroside, and ginsenoside Rg1. These components generally exert anti-AMS pharmacological effects by inhibiting the expression of VEGF, concentration of MDA and pro-inflammatory factors, down-regulating NF-κB/NLRP3 pathway, and promoting SOD and Na + -K + -ATPase activities, which attenuates acute hypobaric hypoxia-induced tissue injury. This review comprehensively analyses the application of TCM in AMS and makes suggestions for more in-depth studies in the future, aiming to provide some ideas and insights for subsequent studies.
PubMed: 38895636
DOI: 10.3389/fphar.2024.1393209