Outcomes and Complications after Left Ventricular Assist Device Implantation.

BACKGROUND: Heart transplantation is the treatment of choice for selected patients with end-stage heart failure. Persistent donor organ shortage causes a growing demand for mechanical circulatory support not only as a bridge to transplantation but mainly as a destination therapy (DT). METHODS: The aim of the study was to analyze the indications, comorbidities, and complications during the follow-up of all patients undergoing left ventricular assist device (LVAD) implantation with at least 12 months of follow-up time in one of the most experienced clinics in Poland between 2015 and 2023. RESULTS: There were 125 individuals with LVAD implantation, from which 90 had full 12 months of follow-up (85 males - 94%, 5 females - 6%), with a median age of 58 (50.25-63.75) years. The median body mass index was 27.12 (25.27-29.68). The etiology of heart failure was ischemic (n = 44, 49%), dilated cardiomyopathy (n = 44, 49%), and others. Preoperative echocardiography revealed a mean LV ejection fraction of 13.8% and a median LV dimension of 7.55 (6.92-8.2) cm. In 61 patients (68%), imaging confirmed pulmonary hypertension. Thirty-four patients (38%) had diabetes and 16 (18%) were active smokers. Median follow-up was 30 (17.25-42) months, with the longest period being about 82 months. 40 (44%) patients had kidney failure before LVAD implantation, and in 43 cases (48%), we observed relevant, transient deterioration of kidney function. Almost all patients (n = 82, 91%) suffered from anemia (Hb <13 g/dL in males and <12 g/dL in females) in different periods after LVAD implantation due to perioperative bleeding, gastrointestinal bleeding or unknown causes. The lowest Hb level was observed in the first week after LVAD implantation in 53 cases (58%). Median red cell concentrate transfusion demand before the discharge after surgery was 6 (2-8, 5) units. CONCLUSIONS: Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of DT. Anemia and kidney failure are the most frequent follow-up complications. Improved results and increased applicability and durability of LVADs have established this treatment option as an excellent alternative for patients with end-stage heart failure.

Driveline Infection in Patients With Left Ventricular Assist Devices Implanted as Destination Therapy.

BACKGROUND: Donor organ shortages cause increasing demand for mechanical circulatory support in patients with end-stage heart failure not only as a bridge to heart transplantation but mainly as a destination therapy. Improved results and increased applicability and durability of left ventricular assist devices (LVADs) have established this treatment option as an alternative to heart transplantation in selected patients. One of the most common complications after LVAD implantation is driveline infections (DLIs). METHODS: This study aimed to expand the understanding of DLI epidemiology and potential changes in implantation techniques regarding optimizing DLI prevention and treatment among all patients undergoing LVAD (Medtronic's Heartware HVAD and HeartMate 3 Abbott LVAD system) implantation with at least 12 months of follow-up time between 2015 and 2022. RESULTS: There were 120 individuals with LVAD implantation, of whom 90 had 12 months of follow-up (85 men [94%], 5 women [6%]) with a median age of 58 years (50.25-63.75). The median body mass index was 27.12 kg/m2 (25.27-29.68). Of the 90 patients, 43 had ischemic heart failure (48%), 43 had dilated cardiomyopathy (48%), and the remaining 3 had other etiologies (3%), such as postinflammatory, and the remaining 1 had congenital heart defect (1%). Preoperative echocardiography revealed a mean left ventricle ejection fraction of 13.8% and a median left ventricle dimension of 7.55 cm (6.92-8.2). Imaging confirmed pulmonary hypertension in 61 patients (68%). Thirty-four of the 90 patients had diabetes (38%), and 16 were active smokers (18%). Median follow-up was 30 months (17.25-42), with the longest period being 82 months. More than half of the patients (n = 52; 57%) experienced a DLI. The median time to the first episode of DLI was 13 months (6-25). The most common pathogen revealed in wound swab culture was methicillin-sensitive Staphylococcus aureus (n = 23; 44%), Pseudomonas aeruginosa (n = 9; 17%), Proteus mirabilis (n = 4; 7%), and others. We observed that deeper driveline implantation below the left rectus muscle and just above the posterior rectus sheath resulted in fewer DLIs and longer free-from-DLI follow-up time. There was no statistically significant difference in DLI frequency between patients with or without diabetes mellitus. CONCLUSIONS: Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of destination therapy. DLI is the most common complication after LVAD implantation. Optimal surgical techniques and early implementation of targeted antibiotics are crucial. Significant challenges remain in optimizing DLI prevention and treatment.

Simultaneous Determination of Selected Steroids with Neuroactive Effects in Human Serum by Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry.

Neuroactive steroids are a group of steroid molecules that are involved in the regulation of functions of the nervous system. The nervous system is not only the site of their action, but their biosynthesis can also occur there. Neuroactive steroid levels depend not only on the physiological state of an individual (person's sex, age, diurnal variation, etc.), but they are also affected by various pathological processes in the nervous system (some neurological and psychiatric diseases or injuries), and new knowledge can be gained by monitoring these processes. The aim of our research was to develop and validate a comprehensive method for the simultaneous determination of selected steroids with neuroactive effects in human serum. The developed method enables high throughput and a sensitive quantitative analysis of nine neuroactive steroid substances (pregnenolone, progesterone, 5α-dihydroprogesterone, allopregnanolone, testosterone, 5α-dihydrotestosterone, androstenedione, dehydroepiandrosterone, and epiandrosterone) in 150 µL of human serum by ultrahigh-performance liquid chromatography with tandem mass spectrometry. The correlation coefficients above 0.999 indicated that the developed analytical procedure was linear in the range of 0.90 nmol/L to 28.46 µmol/L in human serum. The accuracy and precision of the method for all analytes ranged from 83 to 118% and from 0.9 to 14.1%, respectively. This described method could contribute to a deeper understanding of the pathophysiology of various diseases. Similarly, it can also be helpful in the search for new biomarkers and diagnostic options or therapeutic approaches.

Patients with Neurodegenerative Proteinopathies Exhibit Altered Tryptophan Metabolism in the Serum and Cerebrospinal Fluid.

Some pathological conditions affecting the human body can also disrupt metabolic pathways and thus alter the overall metabolic profile. Knowledge of metabolic disturbances in specific diseases could thus enable the differential diagnosis of otherwise similar conditions. This work therefore aimed to comprehensively characterize changes in tryptophan metabolism in selected neurodegenerative diseases. Levels of 18 tryptophan-related neuroactive substances were determined by high throughput and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry in time-linked blood serum and cerebrospinal fluid samples from 100 age-matched participants belonging to five cohorts: healthy volunteers (n = 21) and patients with Lewy body disease (Parkinson's disease and dementia with Lewy bodies; n = 31), four-repeat tauopathy (progressive supranuclear palsy and corticobasal syndrome; n = 10), multiple system atrophy (n = 13), and Alzheimer's disease (n = 25). Although these conditions have different pathologies and clinical symptoms, the discovery of new biomarkers is still important. The most statistically significant differences (with p-values of ≤0.05 to ≤0.0001) between the study cohorts were observed for three tryptophan metabolites: l-kynurenine in cerebrospinal fluid and 3-hydroxy-l-kynurenine and 5-hydroxy-l-tryptophan in blood serum. This led to the discovery of distinctive correlation patterns between the profiled cerebrospinal fluid and serum metabolites that could provide a basis for the differential diagnosis of neurodegenerative tauopathies and synucleinopathies. However, further large-scale studies are needed to determine the direct involvement of these metabolites in the studied neuropathologies, their response to medication, and their potential therapeutic relevance.

Preoperative and mid-term right ventricular systolic function assessment, at rest and during exercise, with speckle-tracking echocardiography after left ventricular assist device implantation.

OBJECTIVES: The study aimed to compare pre- and postoperative resting as well as postprocedural resting and exertional right ventricular speckle-tracking echocardiographic parameters at a mid-term follow-up after left ventricular assist device (LVAD) implantation. METHODS: Patients with implanted third-generation LVADs with hydrodynamic bearings were prospectively enrolled (NCT05063006). Myocardial deformation was evaluated before pump implantation and at least three months after the procedure, both at rest and during exercise. RESULTS: We included 22 patients, 7.3 months (IQR, 4.7-10.2) after the surgery. The mean age was 58.4 ± 7 years, 95.5% were men, and 45.5% had dilated cardiomyopathy. The RV strain analysis was feasible in all subjects both at rest and during exercise. The RV free wall strain (RVFWS) worsened from -13% (IQR, -17.3 to -10.9) to -11.3% (IQR, -12.9 to -6; p = 0.033) after LVAD implantation with a particular decline in the apical RV segment [-11.3% (IQR, -16.4 to -6.2) vs -7.8% (IQR, -11.7 to -3.9; p = 0.012)]. The RV four-chamber longitudinal strain (RV4CSL) remained unchanged [-8.5% (IQR, -10.8 to -6.9) vs -7.3% (IQR, -9.8 to -4.7; p = 0.184)]. Neither RVFWS (-11.3% (IQR, -12.9 to -6) vs -9.9% (IQR, -13.5 to -7.5; p = 0.077) nor RV4CSL [-7.3% (IQR, -9.8 to -4.7) vs -7.9% (IQR, -9.8 to -6.3; p = 0.548)] changed during the exercise test. CONCLUSIONS: In patients who are pump-supported, the right ventricular free wall strain tends to worsen after LVAD implantation and remains unchanged during a cycle ergometer stress test.

Nutritional Risk Assessment and Adverse Events in Patients Undergoing Left Ventricular Assist Device Implantation-A Retrospective Cohort Study Using Hospital Information System.

Clinical or subclinical malnutrition occurs in 30% to 70% of patients with advanced heart failure and increases the risk of postoperative adverse events. The main objective of this study was to assess the nutritional status of patients prior to left ventricular assist device (LVAD) implantation using different methods of malnutrition assessment and to evaluate the relationship between nutritional status and postoperative adverse events. A retrospective cohort study included 120 patients aged 26-74 years referred for LVAD surgery. Preoperative nutritional status (NRS-2002-Nutritional Risk Score 2002, NRI-Nutritional Risk Index, PNI-Prognostic Nutritional Index; TLC-total lymphocyte count) and postoperative adverse events were assessed. Moderate to severe malnutrition was found in 55.8%, 43.3%, 40.0%, and 20% of all patients, respectively, according to the PNI, NRI, TLC, and NRS-2002 scores. Patients with a TLC < 1200 cells/m3 had a higher risk of postoperative acute renal failure [hazard ratio (HR): 2.5; 95% confidence interval (95% CI): 1.01-6.3] and death during the observation period [HR = 2.1; 95% CI: 1.2-3.5]. Moderate to severe malnutrition was also associated with a significantly increased risk of in-hospital death [for the NRI score, HR = 4.9 (95% CI: 1.1-22.0); for the PNI score, HR = 5.0 (95% CI: 1.1-22.3)]. In conclusion, moderate to severe malnutrition prior to LVAD implantation has been identified as a risk factor for postoperative acute renal failure and mortality. Assessment of nutritional risk may improve patient selection and early initiation of nutritional support.

Cerebrospinal fluid and blood serum biomarkers in neurodegenerative proteinopathies: A prospective, open, cross-correlation study.

Neurodegenerative diseases are a broad heterogeneous group affecting the nervous system. They are characterized, from a pathophysiological perspective, by the selective involvement of a subpopulation of nerve cells with a consequent clinical picture of a disease. Clinical diagnoses of neurodegenerative diseases are quite challenging and often not completely accurate because of their marked heterogeneity and frequently overlapping clinical pictures. Efforts are being made to define sufficiently specific and sensitive markers for individual neurodegenerative diseases or groups of diseases in order to increase the accuracy and speed of clinical diagnosis. Thus said, this present research aimed to identify biomarkers in the cerebrospinal fluid (CSF) and serum (α-synuclein [α-syn], tau protein [t-tau], phosphorylated tau protein [p-tau], ß-amyloid [Aß], clusterin, chromogranin A [chromogrA], cystatin C [cyst C], neurofilament heavy chains [NFH], phosphorylated form of neurofilament heavy chains [pNF-H], and ratio of tau protein/amyloid beta [Ind tau/Aß]) that could help in the differential diagnosis and differentiation of the defined groups of α-synucleinopathies and four-repeat (4R-) tauopathies characterized by tau protein isoforms with four microtubule-binding domains. In this study, we analyzed a cohort of 229 patients divided into four groups: (1) Parkinson's disease (PD) + dementia with Lewy bodies (DLB) (n = 82), (2) multiple system atrophy (MSA) (n = 25), (3) progressive supranuclear palsy (PSP) + corticobasal syndrome (CBS) (n = 30), and (4) healthy controls (HC) (n = 92). We also focused on analyzing the biomarkers in relation to each other with the intention of determining whether they are useful in distinguishing among individual proteinopathies. Our results indicate that the proposed set of biomarkers, when evaluated in CSF, is likely to be useful for the differential diagnosis of MSA versus 4RT. However, these biomarkers do not seem to provide any useful diagnostic information when assessed in blood serum.

Quantitative Determination of Endogenous Tetrahydroisoquinolines, Potential Parkinson's Disease Biomarkers, in Mammals.

Current diagnostic options for Parkinson's disease are very limited and primarily based on characteristic clinical symptoms. Thus, there are urgent needs for reliable biomarkers that enable us to diagnose the disease in the early stages, differentiate it from other atypical Parkinsonian syndromes, monitor its progression, increase knowledge of its pathogenesis, and improve the development of potent therapies. A promising group of potential biomarkers are endogenous tetrahydroisoquinoline metabolites, which are thought to contribute to the multifactorial etiology of Parkinson's disease. The aim of this critical review is to highlight trends and limitations of available traditional and modern analytical techniques for sample pretreatment (extraction and derivatization procedures) and quantitative determination of tetrahydroisoquinoline derivatives in various types of mammalian fluids and tissues (urine, plasma, cerebrospinal fluid, brain tissue, liver tissue). Particular attention is paid to the most sensitive and specific analytical techniques, involving immunochemistry and gas or liquid chromatography coupled with mass spectrometric, fluorescence, or electrochemical detection. The review also includes a discussion of other relevant agents proposed and tested in Parkinson's disease.

Outcomes in Patients With HeartMate3 Versus HeartWare Ventricular Assist Device Implanted as Destination Therapy.

BACKGROUND: Donor organ shortage caused a growing interest in mechanical circulatory support not only as a bridge to transplant but also as a destination therapy. Improved results and increased applicability and durability of left ventricular assist devices (LVADs) have established this treatment option as an alternative for patients with end-stage heart failure. METHODS: The aim of the study was to compare the early results, major complications, and the follow up of all patients undergoing HeartMate3 (HM3) LVAD and HeartWare Ventricular Assist Device (HVAD) system implantation in one of the most experienced Clinic in Poland between 2015 and 2020. RESULTS: There were 78 individuals (72 male, 92%; 6 female, 8%), with median age 57 years (range, 50-62 years). Until 2020 we implanted 47 (60%) HVADs and 31 (40%) HM3 LVADs. Patient characteristics were comparable between both groups apart from median left ventricle diameter (8.2 cm [range, 7.4-8.4 cm] in HM3 group vs 7.2 cm [range, 6.7-7.9 cm] in HVAD group; P < .01) The overall survival was 53.2% in the HVAD group and 77.4% in the HM3 group (P =.03). Mean survival time was higher in HM3 group (2.97 years [range, 2.43-3.5 years] vs 2.51 years [range, 1.94-3.08 years]; P < .05). Mean complication-free survival time was also higher in the HM3 group (2.16 years [range, 1.55-2.76] vs 1.61 [range, 1.16-2.06 years]; P < .05), with overall complication-free rate of 54.8% for HM3 vs 29.8% for HVAD (P = .27). Median hospitalization time was comparable (31 days [range, 25-39 days] in the HM3 group vs 32 days [range, 24-38 days] in the HVAD group; P = .49). CONCLUSIONS: Patients supported with the HM3 had significantly fewer major complications than HVAD. Moreover, the HVAD was associated with higher mortality.

Echo-guided left ventricular assist device speed optimisation for exercise maximisation.

OBJECTIVE: Current generation left ventricular assist devices (LVADs) operate with a fixed rotation speed and no automated speed adjustment function. This study evaluates the concept of physiological pump speed optimisation based on aortic valve opening (AVO) imaging during a cardiopulmonary exercise test (CPET). METHODS: This prospective crossover study (NCT05063006) enrolled patients with implanted third-generation LVADs with hydrodynamic bearing. After resting speed optimisation, patients were randomised to a fixed-modified speed or modified-fixed speed CPET sequence. Fixed speed CPET maintained baseline pump settings. During the modified speed CPET, the LVAD speed was continuously altered to preserve periodic AVO. RESULTS: We included 22 patients, the mean age was 58.4±7 years, 4.5% were women and 54.5% had ischaemic cardiomyopathy. Exertional AVO assessment was feasible in all subjects. Maintaining periodic AVO allowed to safely raise the pump speed from 2900 (IQR 2640-3000) to 3440 revolutions per minute (RPM) (IQR 3100-3700; p<0.001). As a result, peak oxygen consumption increased from 11.1±2.4 to 12.8±2.8 mL/kg/min (p<0.001) and maximum workload from 1.1 (IQR 0.9-1.5) to 1.2 W/kg (IQR 0.9-1.7; p=0.028). The Borg scale exertion level decreased from 15.2±1.5 to 13.5±1.2 (p=0.005). CONCLUSIONS: Transthoracic AVO imaging is possible during CPETs in patients with LVAD. Dynamic echo-guided pump speed adjustment based on the AVO improves exercise tolerance and augments peak oxygen consumption and maximum workload.

Analytical Methods for the Determination of Neuroactive Steroids.

Neuroactive steroids are a family of all steroid-based compounds, of both natural and synthetic origin, which can affect the nervous system functions. Their biosynthesis occurs directly in the nervous system (so-called neurosteroids) or in peripheral endocrine tissues (hormonal steroids). Steroid hormone levels may fluctuate due to physiological changes during life and various pathological conditions affecting individuals. A deeper understanding of neuroactive steroids' production, in addition to reliable monitoring of their levels in various biological matrices, may be useful in the prevention, diagnosis, monitoring, and treatment of some neurodegenerative and psychiatric diseases. The aim of this review is to highlight the most relevant methods currently available for analysis of neuroactive steroids, with an emphasis on immunoanalytical methods and gas, or liquid chromatography combined with mass spectrometry.