Is the last before-death alert remote monitoring transmission in patients with heart failure life-threatening?

BACKGROUND: Remote monitoring (RM) of cardiac implantable electronic devices (CIED) allows for a regular analysis of the occurrence of arrhythmias and functioning of the devices. AIMS: To date, no study investigated the characteristics of the alert-triggered ultimate transmissions before death, which was the aim of the present analysis. METHODS: Patients monitored remotely in our center, whose baseline characteristics were obtained from the COMMIT-HF Registry (NCT02536443) were analyzed and divided according to the occurrence of alert transmissions during the RM. In patients who had an alert transmission, the last transmission was analyzed. All RM data were obtained from the software provided by four RM manufacturers. RESULTS: Of 1271 patients with CIEDs which transmitted at least one message to the RM center, 198 (15.6%) had no alert transmissions, while 1073 (84.4%) had at least one alert transmission. Respective mortality in patients with and without alerts during RM was 29.7% and 12.6%, respectively. In patients who had ever an alert, the last recorded transmission before death was scheduled in 166 patients and alert-triggered in 152 patients. The most frequent alert-triggered last transmissions were atrial fibrillation/flutter (39.4%) and ventricular tachyarrhythmias (26.8%). The median period from the last alert-triggered transmission to death was 10 days. CONCLUSION: This is the first analysis of the ultimate RM transmissions delivered by CIEDs before death. In approximately 85% of RM patients with CIEDs, at least one alert transmission occurred during the RM, and in patients who had ever an alert, almost half of the last transmissions before death were alert-triggered.

The impact of complications related to transvenous lead extraction on the 12-month prognosis: Insights from the SILCARD registry.

BACKGROUND: Scant data exist on long-term outcomes, including death, in patients with complica-tions related to transvenous lead extractions (TLE). AIMS: We sought to characterize the population and examine the outcomes including risk factors for in-hospital complications and 12-month mortality and morbidity related to the complications in a large administrative database of patients undergoing TLE. RESULTS: From the database of patients hospitalized for cardiovascular diseases and included in the Silesian Cardiovascular Database (SILCARD) registry, we selected the admissions of those who underwent TLE according to the appropriate ICD-9 codes. The patients were divided into two groups based on whether they did or did not manifest any complications during their hospitalization for the TLE procedure. Between 2007 and 2019, we found a total of 835 patients who underwent TLE. TLE-related complications occurred in 56 patients (6.7%) of the Complications-Yes group while no complications were recorded in 779 (93.3%) patients of the Complications-No group. A significant difference in the rate of all-cause mortality (23.9% vs. 6.5%; P <0.001) and major adverse cardiac events (MACE) (58.7% vs. 39.4%; P = 0.01) between the Complications-Yes and Complications-No groups were recorded. Multivariable analysis of the entire study population revealed that prior dialysis, chronic kidney disease, and ventricular tachycardia were independent factors of a higher risk of TLE-related in-hospital complications. Multivariable analysis of the patients discharged from the hospital after the TLE procedure showed that TLE-related complications, a history of heart failure, and older age independently affected 12-month mortality. CONCLUSIONS: The presence of TLE-related in-hospital complications increased 12-month mortality.

Oxidative Stress Markers in Hypertrophic Cardiomyopathy.

Background and Objectives: Hypertrophic cardiomyopathy (HCM) depends on the primary impairment of sarcomeres, but it can also be associated with secondary alterations in the heart related to oxidative stress. The present study aimed to examine oxidative-antioxidant disturbances in patients with HCM compared with control individuals. Materials and Methods: We enrolled 52 consecutive HCM patients and 97 controls without HCM. The groups were matched for age, body mass index, and sex. Peripheral blood was collected from all patients to determine the total antioxidant capacity (TAC), total oxidant status (TOS), lipid hydroperoxide (LPH), and malondialdehyde (MDA). The oxidative stress index (OSI) was defined as the ratio of the TOS level to the TAC level. Results: The median age was 52 years, and 58.4% were female. The area under the curve (AUC) indicated good predictive power for the TAC and TOS [AUC 0.77 (0.69-0.84) and 0.83 (0.76-0.90), respectively], as well as excellent predictive power for the OSI [AUC 0.87 (0.81-0.93)] for HCM detection. Lipid peroxidation markers also demonstrated good predictive power to detect HCM patients [AUCLPH = 0.73, AUCMDA = 0.79]. Conclusions: The TOS, the TAC, LPH levels, and MDA levels have good predictive power for HCM detection. The holistic assessment of oxidative stress by the OSI had excellent power and could identify patients with HCM.

Radiation therapy in patients with cardiac implantable electronic devices.

BACKGROUND: The number of patients with cardiac implantable electronic devices (CIEDs) treated with radiation therapy (RT) as an oncological treatment is expected to increase. AIMS: The aim of the study was to assess whether cancer treatment with radiation therapy is associated with any device dysfunctions and device­related threats in patients with CIEDs. METHODS: The risk of all patients with CIEDs undergoing RT was assessed according to guidelines. Device interrogations were performed before the first and after the last RT session. In patients at high risk and/or with an implantable cardioverter­defibrillator or cardiac resynchronization therapy with defibrillator (CRT­D), all sessions were supervised by a cardiologist, and device interrogations were performed before and after every single RT session. Device parameters and events were monitored during thewhole treatment. RESULTS: The study included 157 patients with CIEDs who had palliative (n = 71) or radical (n = 86) RT. Pacemakers were implanted in 113 patients, implantable cardioverter­defibrillators in 36, and CRT­D in 8. During the 2396 RT sessions (median [interquartile range], 5 [5-28] per patient) with cumulative dose up to 78 Gy per patient for the whole RT treatment and maximum energy beam up to 20 MV, 2 events potentially related to radiation were recorded. CONCLUSIONS: Radiation therapy in patients with CIEDs is not associated with substantial risk to the patients assuming the patients' management follows current guidelines.

Impaired Brain Energy Metabolism: Involvement in Depression and Hypothyroidism.

Although hypothyroidism appears to be an important factor in the pathogenesis of depression, the impact of thyroid hormones on the bioenergetics of the adult brain is still poorly known. Since metabolic changes are reported to be a key player in the manifestation of depressive disorder, we investigated whether there are differences in selected metabolic markers in the frontal cortex and hippocampus of Wistar Kyoto rats (WKY; an animal model of depression) compared to those of control Wistar rats and whether the induction of hypothyroidism by propylthiouracil (PTU) elicits similar effects in these animals or intensifies some parameters in the WKY rats. In our study, we used WKY rats as a model of depression since this strain exhibits lower levels of monoamines in the brain than control rats and exhibits behavioral and hormonal alterations resembling those of depression, including increased reactivity to stress. The findings indicate a decrease in glycolysis intensity in both brain structures in the WKY rats as well as in both strains under hypothyroidism conditions. Furthermore, hypothyroidism disrupted the connection between glycolysis and the Krebs cycle in the frontal cortex and hippocampus in the depression model used in this study. Decreased thyroid hormone action was also shown to attenuate oxidative phosphorylation, and this change was greater in the WKY rats. Our results suggest that both the depression and hypothyroidism models are characterized by similar impairments in brain energy metabolism and mitochondrial function and, additionally, that the co-occurrence of hypothyroidism and depression may exacerbate some of the metabolic changes observed in depression.

Multicentre early experience with totally subcutaneous cardioverter-defibrillators in Poland.

INTRODUCTION: Implantable cardioverter-defibrillators (ICD) have a strong position in the prevention of sudden death. Nowadays, the most commonly used high-energy cardiac devices are transvenous ICDs. A new technology of totally subcutaneous ICDs (S-ICD) was invented and recently introduced into clinical practice in order to reduce lead-related complications of conventional ICDs. The aim of this paper is to present early experience with this new technology implemented in a few centres in Poland. MATERIAL AND METHODS: Medical records of patients who had S-ICD-related interventions in Poland were retrospectively analysed. RESULTS: During the first year of S-ICD introduction into the Polish health system 18 patients underwent surgery connected with S-ICDs. Majority of them (17 patients) were implanted de novo. In one patient surgical revision of a device implanted abroad was performed. Most of patients (78%) had S-ICDs implanted for secondary prevention. Inability of transvenous system implantation due to venous access obstruction or high risk of infection related with transvenous leads accounted for 83% of indications for S-ICD. Only in three patients were S-ICDs implanted due to young age and active mode of life. The implantations of S-ICDs were performed without important early or late complications. During follow-up one patient had episodes of ventricular arrhythmia successfully terminated with high-energy shocks. One patient died due to progression of heart failure. CONCLUSIONS: S-ICD implantation procedure has been successfully and safely introduced in Polish clinical routine. Nevertheless, despite clear indications in recent ESC guidelines, this therapy is not directly reimbursed in Poland and needs individual application for refund.

Remote Supervision to Decrease Hospitalization Rate (RESULT) study in patients with implanted cardioverter-defibrillator.

AIMS: The number of patients with heart failure (HF) and implantable cardiac electronic devices has been growing steadily. Remote monitoring care (RC) of cardiac implantable electronic devices can facilitate patient-healthcare clinical interactions and prompt preventive activities to improve HF outcomes. However, studies that have investigated the efficacy of remote monitoring have shown mixed findings, with better results for the system including daily verification of transmission. The purpose of the RESULT study was to analyse the impact of remote monitoring on clinical outcomes in HF patients with implantable cardioverter-defibrillator [ICD/cardiac resynchronization therapy-defibrillator (CRT-D)] in real-life conditions. METHODS AND RESULTS: The RESULT is a prospective, single-centre, randomized trial. Patients with HF and de novo ICD or CRT-D implantation were randomized to undergo RC vs. in-office follow-ups (SC, standard care). The primary endpoint was a composite of all-cause death and hospitalization due to cardiovascular reasons within 12 months after randomization. We randomly assigned 600 eligible patients (299 in RC vs. 301 in SC). Baseline clinical and echocardiographic characteristics were well-balanced and similar in both arms. The incidence of the primary endpoint differed significantly between RC and SC and involved 39.5% and 48.5% of patients, respectively, (P = 0.048) within the 12-month follow-up. The rate of all-cause mortality was similar between the studied groups (6% vs. 6%, P = 0.9), whereas hospitalization rate due to cardiovascular reasons was higher in SC (37.1% vs. 45.5%, P = 0.045). CONCLUSION: Remote monitoring of HF patients with implanted ICD or CRT-D significantly reduced the primary endpoint rate, mostly as a result of a lower hospitalization rate in the RC arm (ClinicalTrials.gov Identifier: NCT02409225).

Brain Metabolic Alterations in Rats Showing Depression-Like and Obesity Phenotypes.

Current data suggest an important role of brain metabolic disturbances in the pathogenesis of depression and obesity, diseases that frequently co-occur. Our aim was to determine whether there are changes in markers characterizing glucose metabolism in prenatal stress (PS; animal model of depression), in rats fed a high-fat diet (HFD), and especially in the model of depression and obesity co-occurrence. The changes in glucose-6-phosphate, glycogen, glucose transporters (GLUT1, GLUT4), glucagon-like peptide-1 receptor (GLP-1R), and mitochondrial complexes levels in the frontal cortex and/or hippocampus were observed. In the case of the coexistence of depression and obesity, the most important changes were (1) the decrease in the membrane form of GLUT4, which may suggest weaker insulin action in the frontal cortex, and (2) the diminished GLP-1R, which could cause neurodegenerative changes in the hippocampus. However, presented results suggested that HFD weakened the PS effect of uncoupling oxidative phosphorylation in the frontal cortex.

Inflammatory Consequences of Maternal Diabetes on the Offspring Brain: a Hippocampal Organotypic Culture Study.

Gestational diabetes is a disorder associated with abnormal chronic inflammation that poses a risk to the developing fetus. We investigated the effects of experimentally induced diabetes (streptozotocin model) in Wistar female rats on the inflammatory status of the hippocampi of their offspring. Additionally, the impact of antidiabetic drugs (metformin and glyburide) on inflammatory processes was evaluated. Organotypic hippocampal cultures (OHCs) were prepared from the brains of the 7-day-old rat offspring of control and diabetic mother rats. On the 7th day in vitro, the cultures were pretreated with metformin (3 µM) or glyburide (1 µM) and then stimulated for 24 h with lipopolysaccharide (LPS, 1 µg/ml). The OHCs obtained from the offspring of diabetic mothers were characterized by the increased mortality of cells and an enhanced susceptibility to damage caused by LPS. Although we showed that LPS stimulated the secretion of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α) in the control and diabetic cultures, the levels of IL-1ß and IL-6 in the OHC medium obtained from the offspring of diabetic mothers were more pronounced. In the diabetic cultures, enhanced levels of TLR-4 and the overactivation of the NLRP3 inflammasome were demonstrated. Metformin and glyburide pretreatment normalized the LPS-induced IL-1ß secretion in the control and diabetic cultures. Furthermore, glyburide diminished both: LPS-induced IL-6 and TNF-α secretion in the control and diabetic cultures and increased NF-κB p65 subunit phosphorylation. Glyburide also diminished the levels of the NLRP3 subunit and caspase-1, but only in the diabetic cultures. The results showed that maternal diabetes affected inflammatory processes in the offspring brain and increased hippocampal sensitivity to the LPS-induced inflammatory response. The use of antidiabetic agents, especially glyburide, had a beneficial impact on the changes caused by maternal diabetes.

Hypothalamic insulin and glucagon-like peptide-1 levels in an animal model of depression and their effect on corticotropin-releasing hormone promoter gene activity in a hypothalamic cell line.

BACKGROUND: In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex - brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions. METHODS: Adult male PS rats were subjected to acute stress and/or received orally glucose. Levels of hormones and their receptors were assayed with ELISA method. In vitro studies were performed on mHypoA-2/12 hypothalamic cell line, stably transfected with CRH promoter coupled with luciferase. RESULTS: PS has reduced GLP-1 and GLP-1R levels, attenuated glucose-induced increase in insulin concentration and increased the amount of phosphorylated IR in the hypothalamus of animals subjected to additional stress stimuli, and also decreased the GLP-1R level in the hippocampus. In vitro studies demonstrated that insulin is capable of increasing CRH promoter activity in the condition of stimulation of the cAMP/PKA pathway in the applied cellular model. CONCLUSION: Prenatal stress may act as a preconditioning factor, affecting the concentrations of hormones such as insulin and GLP-1 in the hypothalamus in response to adverse stimuli. The decreased GLP-1R level in the hippocampus could be linked with the disturbances in neuronal plasticity.