-
Acta Cardiologica Jun 2024Midodrine, an FDA-approved medication for orthostatic hypotension, is also used off-label to manage hypotension in dialysis patients, including those with heart failure....
BACKGROUND
Midodrine, an FDA-approved medication for orthostatic hypotension, is also used off-label to manage hypotension in dialysis patients, including those with heart failure. However, in patients with reduced ejection fraction (HFrEF) and/or right heart failure, midodrine is potentially harmful. No known studies examine the safety of midodrine in hospitalised kidney failure patients with HF.
METHODS
The TriNetX database was queried for hospitalised kidney failure patients with HFrEF and/or right heart failure who experienced hypotension (SBP < 110 mm Hg or MAP < 70 mm Hg). Excluding those needing critical care or vasopressors, we compared cohorts based on midodrine use, matching for comorbidities.
RESULTS
Analysis showed patients on midodrine had a higher 6-month mortality risk ratio (RR 1.53, 95% CI 1.037 to 2.246) and Hazard Ratio (HR 1.54, 95% CI 1.022 to 2.317) compared to those not on midodrine, indicating an association with increased mortality.
CONCLUSION
This study illuminates the complexities in treating hospitalised patients with kidney failure and HF. Our findings, drawn from an exploratory analysis, indicate that inpatient midodrine use is associated with increased 6-month mortality. This may reflect deleterious effects from vasoconstriction and/or unmeasured confounders in this vulnerable population. This investigation, utilising TriNetX, was limited by access to deidentified aggregate data, preventing detailed exploration of specifics such as timing, dosage, and indications for midodrine use. Moreover, given its observational nature, cause-effect relationship cannot be established. Our findings indicate an increased mortality associated with midodrine use for hypotension, underscoring the need for further research and consideration of alternative strategies.
PubMed: 38860595
DOI: 10.1080/00015385.2024.2365608 -
Life Sciences Aug 2024
Corrigendum to "Receptor-specific contributions of caveolae, PKC, and Src tyrosine kinase to serotonergic and adrenergic regulation of Kv channels and vasoconstriction" [Life Sci. 329 (2023) 121903].
PubMed: 38851942
DOI: 10.1016/j.lfs.2024.122771 -
Critical Reviews in Clinical Laboratory... Jun 2024Pulmonary arterial hypertension (PAH), one subtype of pulmonary hypertension (PH), is a life-threatening condition characterized by pulmonary arterial remodeling,... (Review)
Review
Pulmonary arterial hypertension (PAH), one subtype of pulmonary hypertension (PH), is a life-threatening condition characterized by pulmonary arterial remodeling, elevated pulmonary vascular resistance, and blood pressure in the pulmonary arteries, leading to right heart failure and increased mortality. The disease is marked by endothelial dysfunction, vasoconstriction, and vascular remodeling. The role of Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors, a class of medications originally developed for diabetes management, is increasingly being explored in the context of cardiovascular diseases, including PAH, due to their potential to modulate these pathophysiological processes. In this review, we systematically examine the burgeoning evidence from both basic and clinical studies that describe the effects of SGLT2 inhibitors on cardiovascular health, with a special emphasis on PAH. By delving into the complex interactions between these drugs and the potential pathobiology that underpins PH, this study seeks to uncover the mechanistic underpinnings that could justify the use of SGLT2 inhibitors as a novel therapeutic approach for PAH. We collate findings that illustrate how SGLT2 inhibitors may influence the normal function of pulmonary arteries, possibly alleviating the pathological hallmarks of PAH such as inflammation, oxidative stress, aberrant cellular proliferation, and so on. Our review thereby outlines a potential paradigm shift in PAH management, suggesting that these inhibitors could play a crucial role in modulating the disease's progression by targeting the potential dysfunctions that drive it. This comprehensive synthesis of existing research underscores the imperative need for further clinical trials to validate the efficacy of SGLT2 inhibitors in PAH and to integrate them into the therapeutic agents used against this challenging disease.
PubMed: 38847284
DOI: 10.1080/10408363.2024.2361012 -
The International Journal of Angiology... Jun 2024Over the last 20 years, there has been a progressive increase in the incidence of pulmonary embolism (PE) diagnosis in the United States, Europe, and Australia.... (Review)
Review
Over the last 20 years, there has been a progressive increase in the incidence of pulmonary embolism (PE) diagnosis in the United States, Europe, and Australia. Increased use of computed tomography pulmonary angiography has likely contributed in part to this rising incidence. However, it is pertinent to note that the burden of comorbidities associated with PE, such as malignancy, obesity, and advanced age, has also increased over the past 20 years. Time-trend analysis in North American, European, and Asian populations suggests that mortality rates associated with PE have been declining. The reported improved survival rates in PE over the past 20 years are likely, at least in part, to be the result of better adherence to guidelines, improved risk stratification, and enhanced treatment. Factors contributing to the development of venous thromboembolism (VTE) include stasis of blood, hypercoagulability, endothelial injury, and inflammation. In 70 to 80% of cases of PE, the thrombi embolizes from the proximal deep veins of the lower extremities and pelvis. Strong risk factors for VTE include lower extremity fractures and surgeries, major trauma, and hospitalization within the previous 3 months for acute myocardial infarction or heart failure with atrial fibrillation. Acute PE causes several pathophysiological responses including hypoxemia and right ventricle (RV) failure. The latter is a result of pulmonary artery occlusion and associated vasoconstriction. Hemodynamic compromise from RV failure is the principal cause of poor outcome in patients with acute PE.
PubMed: 38846994
DOI: 10.1055/s-0044-1785487 -
Frontiers in Cardiovascular Medicine 2024Pulmonary hypertension (PH) is a pathological condition that affects approximately 1% of the population. The prognosis for many patients is poor, even after treatment....
INTRODUCTION
Pulmonary hypertension (PH) is a pathological condition that affects approximately 1% of the population. The prognosis for many patients is poor, even after treatment. Our knowledge about the pathophysiological mechanisms that cause or are involved in the progression of PH is incomplete. Additionally, the mechanism of action of many drugs used to treat pulmonary hypertension, including sotatercept, requires elucidation.
METHODS
Using our graph-powered knowledge mining software in combination with a very small patient metabolite data set, we demonstrate how we derive detailed mechanistic hypotheses on the mechanisms of PH pathophysiology and clinical drugs.
RESULTS
In PH patients, the concentration of hypoxanthine, 12(S)-HETE, glutamic acid, and sphingosine 1 phosphate is significantly higher, while the concentration of L-arginine and L-histidine is lower than in healthy controls. Using the graph-based data analysis, gene ontology, and semantic association capabilities of , led us to connect the differentially expressed metabolites with G-protein signaling and SRC. Then, we associated SRC with IL6 signaling. Subsequently, we found associations that connect SRC, and IL6 to activin and BMP signaling. Lastly, we analyzed the mechanisms of action of several existing and novel pharmacological treatments for PH. elucidated the interplay between G-protein, IL6, activin, and BMP signaling. Those pathways regulate hallmark pathophysiological processes of PH, including vasoconstriction, endothelial barrier function, cell proliferation, and apoptosis.
DISCUSSION
The results highlight the importance of SRC, ERK1, AKT, and MLC activity in PH. The molecular pathways affected by existing and novel treatments for PH also converge on these molecules. Importantly, sotatercept affects SRC, ERK1, AKT, and MLC simultaneously. The present study shows the power of mining knowledge graphs using 's diverse set of data analytics functionalities for developing knowledge-driven hypotheses on PH pathophysiological and drug mechanisms and their interactions. We believe that and our presented approach will be valuable for future mechanistic studies of PH, other diseases, and drugs.
PubMed: 38845688
DOI: 10.3389/fcvm.2024.1341145 -
The Journal of Physiology Jun 2024Heart failure with preserved ejection fraction (HFpEF) has been characterized by lower blood flow to exercising limbs and lower peak oxygen utilization ( ), possibly...
Heart failure with preserved ejection fraction (HFpEF) has been characterized by lower blood flow to exercising limbs and lower peak oxygen utilization ( ), possibly associated with disease-related changes in sympathetic (α-adrenergic) signaling. Thus, in seven patients with HFpEF (70 ± 6 years, 3 female/4 male) and seven controls (CON) (66 ± 3 years, 3 female/4 male), we examined changes (%Δ) in leg blood flow (LBF, Doppler ultrasound) and leg to intra-arterial infusion of phentolamine (PHEN, α-adrenergic antagonist) or phenylephrine (PE, α-adrenergic agonist) at rest and during single-leg knee-extension exercise (0, 5 and 10 W). At rest, the PHEN-induced increase in LBF was not different between groups, but PE-induced reductions in LBF were lower in HFpEF (-16% ± 4% vs. -26% ± 5%, HFpEF vs. CON; P < 0.05). During exercise, the PHEN-induced increase in LBF was greater in HFpEF at 10 W (16% ± 8% vs. 8% ± 5%; P < 0.05). PHEN increased leg in HFpEF (10% ± 3%, 11% ± 6%, 15% ± 7% at 0, 5 and 10 W; P < 0.05) but not in controls (-1% ± 9%, -4% ± 2%, -1% ± 5%; P = 0.24). The 'magnitude of sympatholysis' (PE-induced %Δ LBF at rest - PE-induced %Δ LBF during exercise) was lower in patients with HFpEF (-6% ± 4%, -6% ± 6%, -7% ± 5% vs. -13% ± 6%, -17% ± 5%, -20% ± 5% at 0, 5 and 10 W; P < 0.05) and was positively related to LBF, leg oxygen delivery, leg , and the PHEN-induced increase in LBF (P < 0.05). Together, these data indicate that excessive α-adrenergic vasoconstriction restrains blood flow and limits of the exercising leg in patients with HFpEF, and is related to impaired functional sympatholysis in this patient group. KEY POINTS: Sympathetic (α-adrenergic)-mediated vasoconstriction is exaggerated during exercise in patients with heart failure with preserved ejection fraction (HFpEF), which may contribute to limitations of blood flow, oxygen delivery and oxygen utilization in the exercising muscle. The ability to adequately attenuate α-adrenergic vasoconstriction (i.e. functional sympatholysis) within the vasculature of the exercising muscle is impaired in patients with HFpEF. These observations extend our current understanding of HFpEF pathophysiology by implicating excessive α-adrenergic restraint and impaired functional sympatholysis as important contributors to disease-related impairments in exercising muscle blood flow and oxygen utilization in these patients.
PubMed: 38843407
DOI: 10.1113/JP285526 -
Der Nervenarzt Jun 2024Reversible cerebral vasoconstriction syndrome (RCVS) is a complex and etiologically diverse neurovascular disorder that typically presents with severe thunderclap... (Review)
Review
Reversible cerebral vasoconstriction syndrome (RCVS) is a complex and etiologically diverse neurovascular disorder that typically presents with severe thunderclap headaches (TCH) as the primary symptom, accompanied by reversible vasoconstriction of the cerebral arteries. The clinical course may include focal neurological deficits or epileptic seizures. There are two types: idiopathic RCVS and secondary RCVS, the latter triggered by various substances, medical interventions, or diseases. In clinical practice, various medical specialists may initially encounter this condition, underscoring the importance of accurate recognition and diagnosis of RCVS. The clinical course often appears monophasic and self-limiting, with recurrences reported in only 1.7% of cases annually. Complications such as cerebral hemorrhages and cerebral ischemia can lead to death in 5-10% of cases. This article utilizes a case study to explore RCVS, its complications, and the diagnostic procedures involved.
Topics: Humans; Vasospasm, Intracranial; Headache Disorders, Primary; Diagnosis, Differential; Stroke; Female; Cerebral Angiography; Syndrome; Rare Diseases; Middle Aged
PubMed: 38842549
DOI: 10.1007/s00115-024-01674-w -
Molecular & Cellular Proteomics : MCP Jun 2024Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder characterized by repetitive thunderclap headaches and reversible cerebral...
Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder characterized by repetitive thunderclap headaches and reversible cerebral vasoconstriction. The pathophysiological mechanism of this mysterious syndrome remains under-explored and there is no clinically available molecular biomarker. To provide insight into the pathogenesis of RCVS, this study reported the first landscape of dysregulated proteome of cerebrospinal fluid (CSF) in patients with RCVS (n = 21) compared to the age- and sex-matched controls (n = 20) using data-independent acquisition mass spectrometry (DIA-MS). Protein-protein interaction and functional enrichment analysis were employed to construct functional protein networks using the RCVS proteome. An RCVS-CSF proteome library resource of 1,054 proteins was established, which illuminated large groups of upregulated proteins enriched in the brain and blood-brain barrier (BBB). Personalized RCVS-CSF proteomic profiles from 17 RCVS patients and 20 controls reveal proteomic changes involving the complement system, adhesion molecules, and extracellular matrix, which may contribute to the disruption of BBB and dysregulation of neurovascular units. Moreover, an additional validation cohort validated a panel of biomarker candidates and a two-protein signature predicted by machine learning model to discriminate RCVS patients from controls with an area under the curve of 0.997. This study reveals the first RCVS proteome and a potential pathogenetic mechanism of BBB and neurovascular unit dysfunction. It also nominates potential biomarker candidates that are mechanistically plausible for RCVS, which may offer potential diagnostic and therapeutic opportunities beyond the clinical manifestations.
PubMed: 38839039
DOI: 10.1016/j.mcpro.2024.100794 -
Alternative Therapies in Health and... Jun 2024The objective of this study is to evaluate the effectiveness of targeted nursing measures in relieving swollen limb pain after extremity fractures. The term "targeted...
OBJECTIVE
The objective of this study is to evaluate the effectiveness of targeted nursing measures in relieving swollen limb pain after extremity fractures. The term "targeted nursing measures" refers to specific nursing interventions and care strategies that are designed to address the issue of swollen limb pain in patients with extremity fractures.
METHODS
Patients with extremity fractures treated in our hospital between January 2020 and December 2021 were recruited for eligibility assessment, and 100 patients were eventually included and assigned alternately at the time of admission to receive routine care, namely standard nursing interventions commonly provided to individuals with extremity fractures (These interventions included preoperative assessment, vital sign monitoring, postoperative status monitoring, local ice application, elevation of the affected limb, functional exercise, pain relief measures, postoperative nutrition, medication administration, and general health instruction) (routine group) or targeted care, namely care measures tailored to address swollen limb pain. (These targeted care measures included health education regarding the causes of limb fractures, precautions, causes of swollen limb pain after fractures, and treatment methods, decongestion care, ice compresses to promote vasoconstriction and reduce pain and swelling, psychological counseling to relieve negative emotions, and targeted rehabilitation training supervision) (targeted group), with 50 patients in each group. Outcome measures included swelling, pain, emotional state, and nursing satisfaction.
RESULTS
Targeted care resulted in better mitigation of swelling versus routine care (P < .05). Patients with targeted care had significantly lower visual analog scale (VAS) scores, self-rating anxiety scale (SAS) scores, and Hamilton depression scale (HAMD) scores, and higher Connor-Davidson resilience scale (CD-RISC) scores versus those with routine care (P < .05). Targeted care was associated with significantly higher nursing satisfaction versus routine care (P < .05).
CONCLUSION
Targeted care rapidly relieves the degree of swelling and pain of patients with extremity fractures and ameliorates their emotional state, thereby promoting health recovery and effectively improving patient satisfaction.
PubMed: 38836723
DOI: No ID Found -
The American Surgeon Jun 2024Before the 20th century, peripheral artery disease (PAD) manifested as extreme pain, chronic wounds, and, eventually, gangrene requiring amputation. Despite this, it was...
Before the 20th century, peripheral artery disease (PAD) manifested as extreme pain, chronic wounds, and, eventually, gangrene requiring amputation. Despite this, it was rarely diagnosed. However, at the turn of the century, Western medicine shifted focus from infectious to chronic illnesses, and with this change, physicians' engagement with PAD transformed. Aiming to mitigate long-term injury, physicians now worked to identify and treat vessel disease to restore meaningful blood circulation. This article explores the development and deployment of a new device resulting from this refocus, the PAssive VAscular EXerciser (PAVAEX) Boot, and its role as a creative response to a previously intractable clinical problem. The PAVAEX Boot, designed in 1933 by vascular surgeons Louis G. Herrmann and Mont R. Reid, was one of the few interventions for PAD at the time. Based on the observation that continuous negative pressure results in vasoconstriction, while short bursts transiently increase blood flow, the PAVAEX Boot utilized intermittent negative pressure to enhance peripheral vascular perfusion. Well-marketed and praised throughout the 1930s, it vanished from public writing and academic literature just 20 years later. However, negative pressure wound therapy resurged in the late 20th century, and though its inventors failed to recognize the precedent of the PAVAEX Boot, many of these devices and therapies are rooted in identical theories. We examine why the PAVAEX Boot faded from use and argue that the device remains a crucial advancement in negative pressure therapy.
PubMed: 38830241
DOI: 10.1177/00031348241259041