Hemodynamic Derangements Research Articles

Abstract 4137205: Management Patterns and Outcomes in the Use of Invasive Mechanical Ventilation for Patients with Cardiogenic Shock

Background: Approximately half of all patients with cardiogenic shock (CS) require invasive mechanical ventilation (IMV). While there have been significant advances in the management of patients requiring IMV based on data primarily derived from medical intensive care patients with respiratory failure, little is known regarding the management and outcomes of IMV in patients with CS. Methods: We conducted an analysis of patients treated for CS who required IMV at an academic safety net hospital from 2017-2023. Indications for IMV, ventilator settings, and medications were obtained from the medical record. The primary outcome was unsuccessful extubation, defined as reintubation within 48 hours of extubation. Results: A total of 110 patients with CS who received IMV were identified. Median age was 60yo; 28% of the cohort was female, 39% of Hispanic ethnicity, and 38% of Black race. Primary reasons for intubation included ongoing cardiac arrest (35%) and hypoxic respiratory failure (34%). Most patients were on minimal ventilator support at 24 hours after intubation (median FiO2 40% [IQR 30-50%], post-end expiratory pressure [PEEP] 5cm H2O [IQR 5-8]). Mechanical circulatory support (MCS) was present in 40% of patients at 24 hours post-intubation. Protocolized spontaneous breathing trials (SBTs) were delayed in 77% of patients, primarily due to hemodynamic instability (88%). Planned or unplanned extubation occurred in 63% of patients after a median of 4.8 days [IQR 2.1-8.0]. Ten percent of patients transferred hospitals while on IMV, while 27% were palliatively extubated or died on IMV. The majority (58%) of patients undergoing non-palliative extubation were on vasoactive medications preceding extubation, with only 2% on MCS. Most patients (58%) were extubated to nasal cannula or room air. A total of 13% of patients experienced unsuccessful extubation. Conclusions: In a cohort of patients with CS requiring IMV, most patients were on minimal ventilator settings within 24 hours yet remained intubated with SBTs delayed due to hemodynamic instability. Rates of failed extubation were comparable to published data from other forms of critical illness. Further work is necessary to determine optimal approaches to ventilator liberation and circulatory support in intubated patients with CS where hemodynamic derangements rather than respiratory insufficiency represent the primary barrier to extubation.

Primary inflammatory disease in heart failure with preserved ejection fraction

Abstract Background Inflammation plays a fundamental role in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of underlying systemic inflammatory diseases represented by rheumatoid arthritis. Purpose This study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and primary inflammatory diseases. Methods Consecutive patients undergoing hemodynamic exercise testing with concurrent expiratory gas analysis to evaluate dyspnea of unknown cause were identified. HFpEF was defined as left ventricular ejection fraction ≥50% and pulmonary capillary wedge pressure ≥15 mmHg (rest) or ≥25 mmHg (exercise). Patients with HFpEF were divided into groups with and without primary inflammatory diseases. Patients without inflammatory disease were divided into tertiles according to the value of C-reactive protein (CRP). Results Of 982 consecutively evaluated patients with HFpEF diagnosed (577 female, mean age 68 years), 79 (8%) had primary inflammatory disease. In multivariable logistic regression, female sex (OR 1.88; 95% CI 1.01-3.52), higher resting heart rate (OR 1.18; 95% CI 1.08-1.30), lower hemoglobin level (OR 0.84; 95% CI 0.70-0.99), absence of history of atrial fibrillation (OR 0.45; 95% CI 0.24-0.86) and absence of epicardial coronary artery disease (OR 0.45; 95% CI 0.22-0.93) were independently associated with inflammatory disease. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with inflammatory disease, reflected by lower arterial-venous oxygen content difference (Ca-vO2) at rest (4.2±0.7 mL/dL vs 4.6±1.0 mL/dL, P<.001) and during exercise (9.3±2.2 mL/dL vs 10.4±2.2 mL/dL, P<.001) (Figure 1A), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCO2 slope) was also more impaired (38.0±7.9 vs 36.2±7.3, P=.035). The HFpEF patients without inflammatory disease falling in the highest tertile of CRP) displayed lower Ca-vO2 during exercise, more closely resembling peripheral deficits observed in those with inflammatory disease (Figure 1B). During a median follow-up of 3.0 years, the composite outcome of all-cause deaths and HF hospitalization occurred in 127 patients (14%). Patients with HFpEF and inflammatory disease showed a higher incidence of composite outcome than those without (log-rank P=.030; Figure 2). Patients with inflammatory disease had higher risk of composite outcome compared to those without in adjusted analyses (HR 1.93; 95% CI 1.15-3.23), which was primarily attributable to higher risk of HF hospitalization (HR 2.85; 95% CI 1.08-7.52). Conclusion Patients with HFpEF and primary inflammatory disease have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared to those without.

CT imaging of clinically significant abdominopelvic injuries in the damage control surgery patient.

Damage Control Surgery (DCS) refers to a staged laparotomy performed in patients who have suffered severe blunt or penetrating abdominopelvic trauma with the goal of managing critical injuries while avoiding life threatening metabolic derangements. Within 24h of the initial laparotomy, computed tomography (CT) is used to assess the full extent of injuries. The purpose of this study was to assess the incidence of clinically significant unknown abdominopelvic injuries which required further dedicated surgical or interventional radiology management and failed surgical repairs identified on CT following initial laparotomy. CT findings were correlated with surgical findings from the initial and subsequent staged laparotomy to determine known and unknown injuries. Frequency and percentage analyses was performed. Out of 63 patients who underwent DCS with an open abdomen following initial laparotomy and subsequent CT within 24h, a total of 13 clinically significant abdominopelvic injuries were identified in 12 patients. Seven clinically significant injuries were identified in seven patients (11.1% of patients) in surgically explored areas. Six clinically significant injuries were identified in six patients (9.5%) in surgically unexplored areas. Four instances of failed initial surgical repair were identified in four patients (6.3%) involving the liver and gastrointestinal tract. Overall, 23.8% of the DCS patient population had an actionable finding on the post laparotomy CT. CT demonstrated value for identifying the extent of clinically significant abdominopelvic injuries and evidence of failed initial surgical repair, which informed surgical planning for subsequent laparotomy. The authors advocate for performing CT in post-DCS patients with an open abdomen as soon as possible following correction of metabolic and hemodynamic derangements.

Quantification of extra-cardiac damage following acute myocardial infarction using cis- and trans-4-[18F]fluoro-L-proline PET imaging

The preclinical surgically-induced models of myocardial infarction (MI) have been extensively utilised for studying the wound healing response in the mammalian heart. It is well-established that these invasive procedures induce marked acute systemic inflammation and adverse haemodynamic derangements, which can result in extra-cardiac tissue injury and remodelling; however, the extent of this has not yet been robustly characterised. Here, using a rat permanent coronary artery ligation (PL) model of MI and the cis- and trans-4-[18F]fluoro-l-proline positron emission tomography (PET) probes, targeting active misfolded and triple-helical collagen biosynthesis, respectively, we conducted an exploratory time-course analysis of the associated extra-cardiac tissue remodelling post-injury. Our results showed an increased cis-4-[18F]fluoro-l-proline PET signal in the liver (P = 0.02; two sample t-test) and lung (P = 0.03; two sample t-test) at the acute day 7 timepoint in the MI group compared to the Sham group (n = 3-6), which was not apparent at the later timepoints (days 14, 28, and 84). Ex vivo quantification of the deposited collagen in extra-cardiac tissues using Sirius red histochemical staining and the total hydroxyproline assay validated the apparent time course trends observed with [18F]fluoro-l-proline PET. These findings suggest that the liver and lungs are susceptible to acute injury in the rat PL model of MI and align with numerous clinical reports of extracardiac injury in MI patients. Moreover, our results highlight the suitability of [18F]fluoro-l-proline PET as a systems-based imaging technique for investigating active collagen biosynthesis across multiple organs.

Challenges in the diagnosis and management of dry tamponade.

Dry tamponade is a rare complication of percutaneous coronary intervention. It encompasses a heterogenous pathophysiology and is used to describe hemodynamic compromise secondary to a coronary artery perforation, without free-flowing fluid in the pericardium. Tamponade physiology can result from compressive epicardial, intramyocardial, subepicardial hematomas, or dissecting intramyocardial hematomas. The diagnosis of dry tamponade requires hemodynamic derangement in the context of a compressive hematoma as demonstrated by imaging. Although echocardiography can often help identify dry tamponade, additional studies including right heart catheterization, computed tomography, or cardiac magnetic resonance imaging can inform the exact mechanism and help guide management. This article describes a case of dry tamponade, reviews the existing literature on the topic, and offers expert recommendations on diagnosis and management.

Fluids, Vasopressors, and Inotropes to Restore Heart–Vessel Coupling in Sepsis: Treatment Options and Perspectives

Sepsis is a complex syndrome with heterogeneous clinical presentation and outcome, characterized by an abnormal inflammatory response, potentially leading to multiorgan damage and hemodynamic instability. Early resuscitation with fluids and timely control of the source of sepsis are key treatment targets in septic patients. Recommendations on when to add vasopressors and inotropes are mostly empirical and anecdotal, therefore remaining a topic of debate. This narrative review was developed to present and discuss current options in the early management of hemodynamic derangement induced by sepsis. We discuss the strengths and drawbacks of the recommended treatment with fluids and how to optimize volume resuscitation in order to avoid fluid overload or under-resuscitation. The choice and timing of vasopressor use represent hot topics in the early management of septic patients. We describe the advantages and limitations of the early introduction of vasopressors and new catecholamine-sparing strategies. We conclude with a description of the inotropes, considering that the heart plays a key role in the pathophysiology of septic shock.

Evaluation and Management of Kidney Dysfunction in Advanced Heart Failure: A Scientific Statement From the American Heart Association.

Early identification of kidney dysfunction in patients with advanced heart failure is crucial for timely interventions. In addition to elevations in serum creatinine, kidney dysfunction encompasses inadequate maintenance of sodium and volume homeostasis, retention of uremic solutes, and disrupted endocrine functions. Hemodynamic derangements and maladaptive neurohormonal upregulations contribute to fluctuations in kidney indices and electrolytes that may recover with guideline-directed medical therapy. Quantifying the extent of underlying irreversible intrinsic kidney disease is crucial in predicting whether optimization of congestion and guideline-directed medical therapy can stabilize kidney function. This scientific statement focuses on clinical management of patients experiencing kidney dysfunction through the trajectory of advanced heart failure, with specific focus on (1) the conceptual framework for appropriate evaluation of kidney dysfunction within the context of clinical trajectories in advanced heart failure, including in the consideration of advanced heart failure therapies; (2) preoperative, perioperative, and postoperative approaches to evaluation and management of kidney disease for advanced surgical therapies (durable left ventricular assist device/heart transplantation) and kidney replacement therapies; and (3) the key concepts in palliative care and decision-making processes unique to individuals with concomitant advanced heart failure and kidney disease.

Heart transplantation under mechanical circulatory support for fulminant myocarditis: a Case Report

Fulminant myocarditis has been defined as the clinical manifestation of cardiac inflammation with rapid-onset heart failure and cardiogenic shock. We report on the case of a 17-year-old boy with hemodynamic derangement and cardiac arrest due to fulminant myocarditis. After about 2 h of intensive cardiopulmonary resuscitation, with 13 days of extracorporeal membrane oxygenation support, the patient finally bridged to orthotopic heart transplantation. The patient recovered uneventfully and was discharged 37 days after transplantation. The explanted heart revealed diffuse lymphocytic infiltration and myocyte necrosis in all four cardiac chamber walls confirming the diagnosis and identifying the underlying cause of fulminant myocarditis.

Dexmedetomidine as a total intravenous anesthetic in pediatric patients undergoing cleft lip and palate surgery: a case series

BackgroundSurgery for pediatric cleft lip and palate repair often utilizes high-dose opioids and inhaled anesthesia, thereby causing postoperative complications such as desaturation and/or severe agitation after anesthesia. These complications are detrimental to the child and medical personnel and cause tremendous psychologic stress to parents. Our aim is to decrease these complications through dexmedetomidine, an alpha-2 receptor agonist with anxiolytic, sympatholytic, and analgetic properties. Devoid of respiratory depressant effect, it allows patients to maintain effective ventilation and reduce agitation, postoperatively. Its unique anesthetic property may shed light on providing safe anesthesia and gentle emergence to this young, vulnerable population.Case presentationA total of 21 patients of Sundanese ethnicity, aged 3 months to 8 years (9 males and 12 females), underwent cleft lip or cleft palate surgery using total intravenous dexmedetomidine. Anesthesia was induced using sevoflurane, fentanyl, and propofol, and airway was secured. Intravenous dexmedetomidine 1.5 μg/kg was administered within 10 minutes, and a maintenance dose of 1.5 μg/kg/hour was continued as the sole anesthetic maintenance agent thereafter. Hemodynamics and anesthetic depth using Patient State Index (SEDLine™ monitor, Masimo Corporation, Irvine, CA, USA) were monitored carefully throughout the surgical procedure. Dexmedetomidine did not cause any hemodynamic derangements or postoperative complications in any of our patients. We found agitation in 9.5% (2/21) of patients.ConclusionDexmedetomidine can be used as a total intravenous anesthetic agent to maintain anesthesia and provide gentle emergence to infants and young children undergoing cleft lip and palate repair.

Assessment the Incidence of Inferior Wall Myocardial Infarction, its Association with Right Ventricular Infarction and Function and its Clinical Outcome

Introduction: Myocardial infarction is one of the most common diagnoses in hospitalized patients. Myocardial infarction was previously thought to be a disease of mainly the left ventricle. Right ventricular infarction was just a pathological entity. Myocardial infarction may go undetected or may lead to catastrophic events leading to sudden cardiac death or causing severe hemodynamic derangements. Objective: To find out the Assessment the incidence of Inferior Wall Myocardial Infarction, its association with right ventricular infarction and function and its clinical outcome. Methods: The hospital based observational cross-sectional study was contacted at Department of Cardiology, Mymensingh Medical College Hospital, Bangladesh from 1st January 2022 to 30th January 2024. Conducted in intensive care unit, on an in-patient basis, consist of 50 cases of inferior wall MI. In patients with RVMI, the hospital death is high and major complications are greater. Right ventricular infarction leads to hemodynamic instability, atrio-ventricular conduction blocks, and in-hospital mortality in patients with inferior wall myocardial infarction. Results: Out of the total 150 cases of acute MI were included. The incidence of IMI among all the cases of AMI was 33.3%. In our study group of IMI RVI incidence was 30%. So, the incidence of RVI in all cases of AMI was 10%. There is a significant association between IWMI and RVMI and RVMI is seen in about 20% of cases and most common complication encountered was hypotension followed by complete heart block. The mean age of participants was 58.33 and maximum number of patients was in the age group of 40-60 (43%) and consists of 80% males and 20% females. Among them 51.4% was hypertensive, 22.8% were diabetic, 74.3% smokers, 11.42% were alcoholics. In this study 58.33% of patients with RVMI and 2% of patients without RVMI were presented with hypotension at the time of admission. Complete heart block seen in 13.33% of IWMI patients and Hypotension seen in 20% IWMI patients RVMI group. Right ventricular myocardial infarction seen in 20% of IWMI cases and TR is seen 66% of patients of IWMI with RVMI and 4% of patients of IWMI without RVMI. Conclusion: The incidence of mortality and complications can be reduced only when we are fully aware of the diagnosis and the complications that can occur in RVI. So, in all cases of IMI, RVI should be looked for by using simple and specific investigation like RPLs of ECG. Involvement of the right ventricle in inferior wall myocardial infarction significantly affects the mortality and morbidity and complications.

Autoimmune Disorders in Heart Failure With Preserved Ejection Fraction

BackgroundInflammation plays a fundamental role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of an underlying systemic inflammatory disease such as rheumatoid arthritis or systemic lupus erythematosus. ObjectivesThis study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and autoimmune or primary inflammatory disorders. MethodsOf 982 consecutively evaluated patients with HFpEF diagnosed, 79 (8.0%) had autoimmune disorders. HFpEF was defined by invasive cardiopulmonary hemodynamic exercise testing. ResultsFemale sex, higher heart rate, lower hemoglobin, absence of atrial fibrillation, and absence of coronary artery disease were independently associated with autoimmune disorders. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with autoimmune disorders, reflected by lower arterial-venous oxygen content difference at rest (4.2 ± 0.7 mL/dL vs 4.6 ± 1.0 mL/dL; P < 0.001) and during exercise (9.3 ± 2.2 mL/dL vs 10.4 ± 2.2 mL/dL; P < 0.001), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCo2 slope, regression slope relating minute ventilation to carbon dioxide output) was also more impaired (38.0 ± 7.9 vs 36.2 ± 7.3; P = 0.043). Patients with autoimmune disorders had a higher risk of death or heart failure (HF) hospitalization compared with those without in adjusted analyses (HR: 1.95 [95% CI: 1.17-3.27]; P = 0.011) over a median follow-up of 3.0 years, which was primarily attributable to higher risk of HF hospitalization (HR: 2.87 [95% CI: 1.09-7.57]; P = 0.033). ConclusionsPatients with HFpEF and autoimmune disorders have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared with those without.

Hyperlactataemia is a marker of reduced exercise capacity in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with an array of central and peripheral haemodynamic and metabolic changes. The exact pathogenesis of exercise limitation in HFpEF remains uncertain. Our aim was to compare lactate accumulation and central haemodynamic responses to exercise in patients with HFpEF, non-cardiac dyspnoea (NCD), and healthy volunteers. Right heart catheterization with mixed venous blood gas and lactate measurements was performed at rest and during symptom-limited supine exercise. Multivariable analyses were conducted to determine the relationship between haemodynamic and biochemical parameters and their association with exercise capacity. Of 362 subjects, 198 (55%) had HFpEF, 103 (28%) had NCD, and 61 (17%) were healthy volunteers. This included 139 (70%) females with HFpEF, 77 (75%) in NCD (P=0.41 HFpEF vs. NCD), and 31 (51%) in healthy volunteers (P<0.001 HFpEF vs. volunteers). The median age was 71 (65, 75) years in HFpEF, 66 (57, 72) years in NCD, and 49 (38, 65) years in healthy volunteers (HFpEF vs. NCD or volunteer, both P<0.001). Peak workload was lower in HFpEF compared with healthy volunteers [52W (interquartile range 31-73), 150W (125-175), P<0.001], but not NCD [53W (33, 75), P=0.85]. Exercise lactate indexed to workload was higher in HFpEF at 0.08mmol/L/W (0.05-0.11), 0.06mmol/L/W (0.05-0.08; P=0.016) in NCD, and 0.04mmol/L/W (0.03-0.05; P<0.001) in volunteers. Exercise cardiac index was 4.5L/min/m2 (3.7-5.5) in HFpEF, 5.2L/min/m2 (4.3-6.2; P<0.001) in NCD, and 9.1L/min/m2 (8.0-9.9; P<0.001) in volunteers. Oxygen delivery in HFpEF was lower at 1553mL/min (1175-1986) vs. 1758mL/min (1361-2282; P=0.024) in NCD and 3117mL/min (2667-3502; P<0.001) in the volunteer group during exercise. Predictors of higher exercise lactate levels in HFpEF following adjustment included female sex and chronic kidney disease (both P<0.001). HFpEF is associated with reduced exercise capacity secondary to both central and peripheral factors that alter oxygen utilization. This results in hyperlactataemia. In HFpEF, plasma lactate responses to exercise may be a marker of haemodynamic and cardiometabolic derangements and represent an important target for future potential therapies.

Asystolic donor warm ischemia time is associated with development of postreperfusion syndrome in donation after circulatory death liver transplant.

Individual events during donation after circulatory death (DCD) procurement, such as hypotensive or hypoxic warm ischemia, or circulatory arrest are all a part of donor warm ischemia time (dWIT), and may have differing effects on the outcome of the liver graft. This study aimed to identify risk factors for postreperfusion syndrome (PRS), a state of severe hemodynamic derangement following graft reperfusion, and its impact on DCD liver transplantation (LT) outcomes. This was a retrospective analysis using 106 DCD LT. Detailed information for events during procurement (withdrawal of life support; systolic blood pressure<80mmHg; oxygen saturation<80%; circulatory arrest; aortic cold perfusion) and their association with the development of PRS were examined using logistic regression. The overall incidence of PRS was 26.4%, occurring in 28 patients. Independent risk factors for PRS were asystolic dWIT (odds ratio (OR) 3.65, 95% confidence interval (CI) 1.38-9.66) and MELD score (OR 1.06, 95% CI 1.01-1.10). Total bilirubin was significantly higher in the PRS group at postoperative day (POD) 1 (p=.02; 5.2mg/dL vs. 3.4mg/dL), POD 3 (p=.049; 4.5mg/dL vs. 2.8mg/dL), and POD 7 (p=.04; 3.1mg/dL vs. 1.9mg/dL). Renal replacement therapy after LT was more likely to be required in the PRS group (p=.01; 48.2%vs. 23.1%). Asystolic dWIT is a risk factor for the development of PRS in DCD LT. Our results suggest that asystolic dWIT should be considered when selecting DCD liver donors.

Glomerular Hyperfiltration and Th17 Responses Promote Glomerulosclerosis Following Nephron Loss

Objective: Chronic kidney disease (CKD) affects 37 million Americans resulting in $87 billion healthcare cost annually. Impaired renal autoregulation in obesity, diabetes and hypertension causes elevated glomerular capillary pressure and whole-kidney hyperfiltration, leading to progressive glomerulosclerosis and CKD. In advanced CKD with less than 50% functional nephron mass, single-nephron hyperfiltration causes further nephron loss, ultimately leading to hypofiltration and end-state kidney disease. Increased renal perfusion pressure directly drives T cell infiltration to the kidney. We and others have shown that T helper (Th) 17 cells promote vascular stiffening in hypertension and renal interstitial fibrosis after ischemia-reperfusion injury, but their roles in glomerulosclerosis and CKD are poorly understood. We hypothesized that glomerular hypertension and hyperfiltration promote renal fibrosis through Th17-mediated immune responses. Methods: We investigated the causal roles of glomerular hyperfiltration and Th17 responses in a mouse CKD model induced by reduced kidney mass (RKM), which involved right kidney nephrectomy and partial renal artery ligation in the left kidney such that the functional renal mass is reduced by ~ 5/6. Male 129/S6 mice received sham or RKM surgery at 8 weeks of age, and blood pressure (BP, by radiotelemetry), glomerular filtration rate (GFR, by transcutaneous FITC-sinistrin) and serum/urine CKD markers were assessed at baseline (BL) and week 1, 2, 3, 4, 8, and 12 post-surgery. Results: BP and GFR of RKM mice were identical to sham controls at BL (n=4-6). Immediately after the RKM procedure, GFR dropped to 22% of BL, consistent with the extent of renal mass ablation. BP increased by 29 mmHg first week after 5/6 ablation (144 ± 8 vs BL 112 ± 2 mmHg, p&lt;0.05, 2-way ANOVA), exposing the remnant nephrons to increased renal perfusion pressure. Serum creatinine, blood urea nitrogen and urinary albumin were significantly elevated by week 2. BP and CKD markers remained elevated through week 12 in the 5/6 ablation mice. The GFR of ablated mice gradually increased to 38% of BL at day 3, 57% at week 1 and 68% at week 2, suggesting that systemic hypertension and impaired renal autoregulation may have caused substantial single-nephron hyperfiltration in the remnant kidney mass. GFR plateaued at ~ 70% of BL in week 3-4 then declined to 48% at week 8-12 when glomerular, interstitial, and microvascular fibrosis developed as evidence by Periodic Acid Schiff and Picro Sirius Red staining. Supporting a causal role of hemodynamic derangements in CKD progression, calcium channel blocker amlodipine, a potent vasodilator, dose dependently (5-10 mg/kg/day, n=7-9) exacerbated glomerular hyperfiltration, glomerulosclerosis and mortality despite marked BP-lowering effects. Importantly, the adaptive increase of GFR in the first 2 weeks post 5/6 ablation was accompanied by significant increase of renal Th17 cells, which not only preceded the infiltration of CD11b+ myeloid cells, F4/80+ monocyte/macrophages and T regulatory cells, but also the glomerulosclerosis and GFR decline in week 8. Conclusions: Our data suggest that glomerular hyperfiltration causes progressive nephron loss and kidney fibrosis, at least in part, through Th17-mediated renal inflammation. To further establish causality, ongoing studies will assess if Th17 blockade ameliorates glomerulosclerosis and retard CKD progression. Funding: This work was supported by NIDDK R01 DK094907, R01 DK113632, R01 DK128677 to THL, and K01 DK126972 to JW. JW is also supported by an American Heart Association Second Century Early Faculty Independence Award (23SCEFIA1148464), a University of Rochester Environmental Health Science Center pilot award (Prime sponsor: NIEHS P30ES001247), and a University of Rochester Program for Advanced Immune Bioimaging Pilot Award (Prime Sponsor: NIAID P01AI102851). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiac magnetic resonance imaging in heart transplant recipients with biopsy-negative graft dysfunction.

Graft dysfunction (GD) after heart transplantation (HTx) can develop without evidence of cell- or antibody-mediated rejection. Cardiac magnetic resonance imaging (CMR) has an evolving role in detecting rejection; however, its role in biopsy-negative GD has not been described. This study examines CMR findings, evaluates outcomes based on CMR results, and seeks to identify the possibility of rejection missed through endomyocardial biopsy by using CMR in HTx recipients with biopsy-negative GD. HTx recipients with GD [defined as a decrease in left ventricular ejection fraction (LVEF) by >5% and LVEF<50%] in the absence of rejection by biopsy or allograft vasculopathy and who underwent CMR were included in the study. The primary outcome was a composite of all-cause mortality, re-transplantation, or persistent LVEF<50%. Overall, 34 HTx recipients developed biopsy-negative GD and underwent CMR. Left ventricular late gadolinium enhancement (LGE) on CMR was observed in 16 patients with two distinct patterns: diffuse epicardial (n=13) and patchy (n=3) patterns. Patients with LGE developed GD later after HTx [4 (1.4-6.8) vs. 0.8 (0.3-1.2) years, P<0.001], were more often symptomatic (88% vs. 56%, P=0.06), and had greater haemodynamic derangement (pulmonary capillary wedge pressure: 19±7 vs. 13±3mmHg, P=0.002) as compared with those without LGE. No significant difference was observed in the primary composite outcome between patients with LGE and those without LGE (50% vs. 38% of patients with events, P=0.515). During a median follow-up of 3.8years, mean LVEF improved similarly in the LGE-negative (37-55%) and LGE-positive groups (32-55%) (P=0.16). Biopsy-negative GD occurs with and without LGE when assessed by CMR, indicative of possible rejection/inflammation occurring only in a subset of patients. Irrespective of LGE, LVEF improvement occurs in most GD patients, suggesting that other neurohormonal or immunomodulatory mechanisms may also contribute to GD development.

The Pathogenesis and Impact of Arterial Stiffening in Hypertension: The 2023 John H. Laragh Research Award.

Fifty years ago, Dr. John Laragh brought forward the "vasoconstriction-volume hypothesis" of hypertension. This is Ohm's Law in blood pressure regulation, explicating hypertension as a consequence of increased peripheral vascular resistance, cardiac output, or both. Resistance vessels, those of a diameter less than 200 μm, determines mean arterial pressure by controlling peripheral vascular resistance. In comparison, large capacitance arteries, particularly the aorta, confines the systolic and diastolic blood pressure in physiological range through the "windkessel effect." Loss of this cushioning function results in aortic stiffening and isolated systolic hypertension, both of which are independently associated with increased risk for coronary, cerebral, and renal diseases. Aortic stiffening is both a cause and a consequence of hypertension. On one hand, aortic stiffness precedes the onset of hypertension in populations and experimental models, and hemodynamic derangements related to aortic stiffening contributes to the development of hypertension by promoting renal dysfunction. On the other hand, the vasculature itself is a hypertensive target organ and hypertensive mechanical stretch directly induces the pathogenesis of aortic adventitial remodeling. Various cell types, including bone marrow-derived circulating fibrocytes, vascular stem cell antigen-1 positive progenitors, and endothelial to mesenchymal transition, and to a lesser extent resident fibroblasts, contribute to adventitial matrix deposition and aortic stiffening in hypertension. Vascular smooth muscle stiffness is another important contributor of aortic stiffening. Understanding the roles of immune components and specific signal pathways in the pathogenesis aortic stiffening paves the path to novel antihypertensive and anti-fibrosis therapies.

Efficacy of ketamine and thiopentone sodium with modified electroconvulsive therapy in depressive disorder: An observational study

Background: The first-line treatment for people with acute mania, mood disorders, severe depression, and catatonia is electroconvulsive therapy (ECT). The goal of anesthesia during ECT is to cause unconsciousness, and the drugs administered should not have any effect on seizures. Because all anesthetics have some ability to change seizures, the kind of anesthetic used in modified ECT becomes crucial. This study aimed to assess the hemodynamic profile during modified ECT and the effects of ketamine and thiopentone sodium on seizure duration. Aims and Objectives: The aim of the study was to compare the outcome of ECT, such as hemodynamics, improvement in depression, and duration of seizure, with ketamine versus thiopentone sodium in depressive disorder. Materials and Methods: A prospective observational study was conducted with 50 randomly selected depression patients after obtaining permission from the Institutional Ethics Committee and consent from the patients and attendants from June 2021 to November 2022. All 50 cases were equally divided into group K and group T. To obtain the data, a predesigned, semi-structured questionnaire was used along with the Hamilton rating scale for depression and ECT. The Chi-square test was used to measure the association between two categorical variables. A P &lt; 0.05 was considered statistically significant. Results: The mean heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and saturation of peripheral oxygen are higher in group K than in group T, and the mean difference was significant between group K and group T. Groups had a statistically significant association with increased secretions, nausea and vomiting, and headache, but not with gender, ASA grade, and number of ECT sessions. Conclusion: Compared to ketamine, thiopentone sodium was found to have minimal hemodynamic derangements, a decrease in seizure duration, and side effects.

Decreased levels of plasmacytoid dendritic cells predict survival in critically ill patients

Abstract Background Critically ill patients admitted to intensive care units (ICUs) exhibit high mortality rates and suffer from a broad variety of life-threatening conditions. Irrespective of the initial cause of hospitalization, many of them experience systemic immune dysregulation accompanied by strong inflammatory activation and subsequent anti-inflammatory response resulting in immune paralysis. Dendritic cells (DCs) are the most potent antigen-presenting cells and play a pivotal role in regulating the immune response by linking the innate to the adaptive immune system. Previous studies already highlighted their prognostic value in sepsis and infectious diseases. Purpose DCs may be useful as a biomarker in intensive care medicine. Thus, the aim of this study was to analyse whether DCs or their respective subsets are associated with 30-day mortality in a cohort of unselected patients admitted to a medical ICU with cardiovascular focus. Methods 231 patients admitted to a tertiary care medical ICU were consecutively included in this single-centre prospective observational study. Patient characteristics and vital parameters were assessed within 24 hours following ICU admission and 72 hours thereafter. Additionally, blood was drawn at both time points. Subsequently, flow cytometry was utilized for the analysis of DCs and their respective subsets. Patients were prospectively followed up for 30 days or until the primary study endpoint, defined as mortality, was reached. Results In the study cohort, low percentages of total DCs were significantly associated with sepsis, respiratory failure, and the presence of shock. Percentages of plasmacytoid dendritic cells (pDCs) were inversely correlated with routinely assessed markers of inflammation, organ dysfunction and hemodynamic derangement. In particular, pDCs at admission showed the most robust association with survival in univariate analysis with a hazard ratio (HR) of 6.5 (95% confidence interval [CI]: 2.5 – 17.2, p &amp;lt; 0.001) comparing the first to the third tertile. In multivariate analysis, pDCs remained a strong and independent predictor of 30-day mortality after adjustment for demographic and clinical variables with an adjusted HR of 4.20 (1.3 - 13.3, p = 0.015). Corresponding Kaplan-Meier curves showing survival according to tertiles of pDCs at day 0 are displayed in figure 2 (log-rank test: p &amp;lt; 0.001). Conclusion We observed low percentages of DCs in patients admitted to an ICU suffering from sepsis, respiratory failure, and cardiogenic shock, which potentially contributes to the excessive immune response in critically ill patients. In our cohort, pDCs were identified as the most robust subset to predict 30-day mortality.Figure 1Figure 2

Functional volume distribution in tricuspid regurgitation associated right heart failure

Abstract Background Tricuspid regurgitation (TR) associated right heart failure is a significant challenge, and while tricuspid edge-to-edge repair (TEER) has been suggested to improve outcomes, patients remain at substantial residual risk. Thus, adjunctive therapies to treat associated right heart failure are warranted. Sympathetically mediated venoconstriction with subsequent changes in functional volume distribution with increases in stressed blood volume (SBV) ( the volume compartment which generates intravascular pressure) has been shown to importantly mediate hemodynamic derangements in heart failure and might pose an attractive adjunctive treatment target (e.g. by means of splanchnic denervation). Objectives This study aimed to elucidate the determinants of unfavorable functional volume distribution in patients with TR-associated right heart failure and investigate the prognostic role of SBV after TEER. Methods and Results A total of 279 patients underwent right heart catheterization (RHC) prior to TEER. SBV was estimated (eSBV) from hemodynamic variables fit to an extensively validated and comprehensive cardiovascular model. eSBV was associated with obesity, renal and hepatic dysfunction, and cardiac remodeling (p &amp;lt; 0.05 for all). Hemodynamically, eSBV correlated with pulmonary artery (PA) and cardiac filling pressures, as well as right ventricular-PA coupling (p &amp;lt; 0.05 for all). After TEER, patients with eSBV above the median demonstrated less reduction in right atrial pressures, peripheral edema, and ascites compared to lower eSBV patients (p &amp;lt; 0.05 for all). Higher eSBV was a powerful predictor of the occurrence of death and heart failure hospitalization during a median follow-up of 618 days (p &amp;lt; 0.05 for all) independent of all clinical, imaging, and invasive hemodynamic parameters. Conclusion In severe TR, eSBV is associated with obesity, renal and liver dysfunction, more severe heart failure, attenuated reduction of venous congestion after TEER, as well as adverse clinical outcomes. Estimation of SBV should be incorporated in future trials in the field to identify patients in need of adjunctive therapies and test its role as a potential treatment target.

Thyroid dysfunction in pediatric Fontan patients is associated with unfavorable hemodynamic status and severity of protein-losing enteropathy: A report from the Fontan care network

BackgroundThyroid dysfunction may have adverse effects on Fontan hemodynamics. Data on thyroid function in pediatric Fontan patients with or without protein-losing enteropathy (PLE) are limited. MethodsThis retrospective multicenter study included 67 Fontan patients (median age 10.9 years; 35.8% female; 28.4% PLE) in whom thyroid function testing was performed. ResultsSubclinical hypothyroidism (SHT) was present in 16 (23.9%) patients. Subjects with SHT had significantly lower systolic blood pressure (p = 0.014) and body weight z-score (p = 0.006), were in a worse New York Heart Association (NYHA) functional class (p = 0.004), were more often pacing dependent (p = 0.007), and were more likely to have PLE (p = 0.033, 8/19 (42.1%) patients). Serum thyroid stimulating hormone (TSH) levels were significantly higher in patients with NYHA class ≥ II (p = 0.005), significant atrioventricular valve regurgitation (p = 0.023), elevated serum natriuretic peptides (p = 0.031), and in those with PLE (p = 0.002). Patients with active PLE had significantly higher TSH levels than those in remission (p = 0.003). A strong inverse relationship was found between lower free triiodothyronine (fT3) levels and natriuretic peptides (r: −0.599, p = 0.040). Using binary logistic regression analysis we found that worse NYHA class was an independent predictor of SHT (OR 4.2; 95% CI 1.1–16.1, p = 0.036). ConclusionsSubclinical thyroid dysfunction is common in Fontan, particularly in patients with hemodynamic derangements and PLE. Future studies are needed to address the prognostic implications of thyroid dysfunction in the Fontan population.