Assessing cardiac resynchronization therapy response in heart failure patients: a comparative analysis of efficacy and outcomes between transvenous and epicardial leads.

Cardiac resynchronization therapy (CRT) is an effective treatment for selected heart failure (HF) patients. Although transvenous implantation is the standard method, it is not feasible in some patients, so the epicardial lead emerges as an alternative. We aim to compare CRT response, procedure-related complications, and the occurrence of clinical outcomes between patients with transvenous and epicardial leads. In a single-center retrospective study, we enrolled consecutive HF patients submitted to CRT implantation with a defibrillator between 2013 and 2022. Clinical response was defined as an improvement of at least one of the New York Heart Association classes with no occurrence of cardiovascular death or HF hospitalization in the first year of follow-up. Echocardiographic response was attained with an increase in left ventricular ejection fraction 10% or a reduction of left ventricular end-diastolic volume >15% at 6-12 months after CRT implantation. Major adverse cardiovascular events (MACE) (cardiovascular mortality and HF hospitalization) and all-cause mortality were evaluated. From a total of 149 patients, 38% (n=57) received an epicardial lead. Clinical (63% versus 60%, p=0.679) and echocardiographic (63% versus 60%, p=0.679) responses were similar between the transvenous and epicardial groups. Patients in the transvenous group had a shorter hospital stay (2 versus 7 days, p<0.001). Procedure-related complications were comparable between groups (24% versus 28%, p=0.572), but left ventricular lead-related complications were more frequent in the transvenous group (14% versus 2%). During a median follow-up of 4.7 years, the rate of MACE was 30% (n=44), with no differences in both groups (p=0.591), neither regarding HF hospitalization (p=0.917) nor cardiovascular mortality (p=0.060). Nevertheless, the epicardial group had a higher rate of all-cause mortality (35% versus 20%, p=0.005), the majority occurring during long-term follow-up (>12 months), with no deaths in the postoperative period. Considering the comparable rates of CRT response, procedure-related complications, and MACE between groups, we conclude that epicardial lead is a feasible alternative for CRT when transvenous lead implantation is not possible. The occurrence of a higher number of all-cause deaths in epicardial patients in the long-term follow-up was mainly due to infectious complications (unrelated to the lead) and the progression of oncological/chronic diseases.

A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors.

BACKGROUND: This study aimed to evaluate the safety, pharmacokinetics (PKs), and preliminary activity of LY3405105, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), in patients with advanced solid tumors. MATERIALS AND METHODS: LY3405105 monotherapy was given once daily (QD; part A1) or thrice weekly (TIW; part A2) starting at 1 and 2 mg orally, respectively, and escalated per a Bayesian design in adult patients. The primary endpoint was safety, and secondary endpoints included PKs and antitumor activity. RESULTS: Fifty-four patients were enrolled: 43 in part A1 and 11 in part A2. Seven patients had dose-limiting toxicities, all in part A1 (45 mg: n = 3; 35 mg: n = 3; 25 mg: n = 1). Thirty-five patients (64.8%) reported at least one treatment-related adverse event (TRAE). TRAEs (≥10%) were diarrhea, nausea, fatigue, vomiting, abdominal pain, anemia, asthenia, and decreased platelet count. QD dosing showed sustained exposure with less peak-trough fluctuation compared to TIW dosing. Median time to maximum concentration was 1-2 hours and half-life was 15-19 hours. CDK7-target occupancy in skin and peripheral blood on day 15 was dose-dependent and reached near maximal occupancy of 75% at ≥15 mg QD. The maximum tolerated dose (MTD) was 20 mg QD. Twelve patients in part A1 (27.9%) and 5 patients in part A2 (45.5%) had a best overall response of stable disease. No complete response or partial response was observed. CONCLUSION: The MTD of LY3405105 monotherapy was 20 mg QD. The most common toxicities were gastrointestinal adverse events, myelosuppression, fatigue, and asthenia. Limited clinical activity was observed in this phase I trial, and there are no plans for further development. CLINICALTRIALS.GOV IDENTIFIER: NCT03770494.

Cardioneuroablation for severe neurocardiogenic syncope.

INTRODUCTION AND OBJECTIVES: Cardioneuroablation (CNA), a technique based on radiofrequency ablation of cardiac vagal ganglia, was developed to treat recurrent vasovagal syncope (VVS) with a predominant cardioinhibitory component, as an alternative to pacemaker implantation. The aim of our study was to evaluate the safety and success rate of CNA guided by extracardiac vagal stimulation in patients with highly symptomatic cardioinhibitory VVS. METHODS: Prospective study of patients who underwent anatomically guided CNA at two cardiology centers. All patients had a history of recurrent syncope with a predominant cardioinhibitory component and refractory to conventional measures. Acute success was determined by the absence or significant reduction of cardiac parasympathetic response to extracardiac vagal stimulation. The primary endpoint was the recurrence of syncope during follow-up. RESULTS: In total, 19 patients (13 males; mean age 37.8±12.9 years) were included. Ablation was acutely successful in all patients. One patient had a convulsive episode after the procedure, which was deemed unrelated to the ablation, requiring admission to intensive care but without sequelae. No other complications occurred. At a mean follow-up of 21.0±13.2 months (range 3-42 months), 17 patients remained free of syncope. The remaining two patients had recurrence of syncope and, despite undergoing a new ablation procedure, required pacemaker implantation during follow-up. CONCLUSION: Cardioneuroablation, confirmed by extracardiac vagal stimulation, appears to be an effective and safe treatment option for highly symptomatic patients with refractory VVS with a predominant cardioinhibitory component, providing a new potential approach as an alternative to pacemaker implantation.

Mitral annular disjunction: Beyond mitral valve prolapse.

Mitral annular disjunction (MAD) is an easily identifiable entity on transthoracic echocardiography, but is still poorly recognized or ignored. It is often associated with mitral valve prolapse and is itself a risk marker for ventricular arrhythmias and sudden cardiac death, but the management and risk stratification of these patients is not systematized. Two clinical cases of MAD associated with mitral valve prolapse and ventricular arrhythmias are presented. The first case is of a patient with a history of surgical intervention on the mitral valve due to Barlow's disease. He presented to the emergency department with sustained monomorphic ventricular tachycardia requiring emergent electrical cardioversion. MAD with transmural fibrosis at the level of the inferolateral wall was documented. The second report is of a young woman with palpitations and frequent premature ventricular contractions on Holter with documentation of valvular prolapse and MAD, and focuses on the risk stratification approach. The present article offers a review of the literature regarding the arrhythmic risk of MAD and mitral valve prolapse, as well as a review of risk stratification in these patients.

Flebite associada ao cateter venoso periférico em cardiologia: incidência, fatores de risco e custos associados / Phlebitis associated with peripheral venous catheter in cardiology: incidence, risk factors and associated costs

Objetivo: Determinar a incidência de flebite, fatores de risco associados e custos diretos de tratamento. Métodos: Estudo descritivo, correlacional, com análise de custo direto. Utilizaram-se dados da documentação dos enfermeiros entre janeiro 2019 e agosto 2021. Resultados: Incluíram-se 2.374 pessoas com cateter venoso periférico, com internamento na cardiologia. A incidência de flebite foi de 12,38%, das quais 78,23% eram de grau 1 de severidade. Verificou-se associação estatística entre o desenvolvimento de flebite e a administração de amiodarona endovenosa, dias de hospitalização e serviço de internamento. Estimaram-se 1662€ de custos adicionais ao tratamento da flebite, em material clínico e horas de cuidados de enfermagem. Conclusão: Os cuidados de enfermagem são eficazes na identificação precoce e tratamento da flebite, promovendo redução de custos adicionais e garantindo melhores cuidados e ganhos em saúde.

Objective: This study aimed to identify the incidence rate of phlebitis, associated risk factors and treatment direct costs. Methods: Descriptive, correlational study with direct cost analisys. Data from the nurses' clinical records between January 2019 and August 2021 were used. Results: Included 2,374 files of people with peripheral venous catheter who were admitted to Cardiology. The phlebitis incidence rate was 12.38% and regarding severity 78.23% were grade 1. The phlebitits was significantly related with intravenous amiodarone administration, length of stay and physical department. This represents €1662 of additional treatment costs, in clinical supplies and nursing time. Conclusion: Nursing care is effective in the early identification and treatment of phlebitis, reducing costs and improve clinical and economic outcomes.

Peritoneal dialysis modality transition and impact on phosphate and potassium serum levels.

Peritoneal dialysis (PD) modalities affect solute removal differently. However, the impacts of switching PD modalities on serum levels of biomarkers of different sizes are not known. Our objective was to analyze whether a change in the PD modality associates with the levels of two routine biochemical laboratories. In this multicentric prospective cohort study. we selected all patients who remained on a PD modality for at least 6 months and switched PD modality. Patients were also required to be treated with the same PD modality for at least 3 months before and after the modality change. The primary outcome was change in potassium and phosphate serum levels. We identified 737 eligible patients who switched their PD modality during the study. We found mean serum phosphate levels increased during the 3 months after switching from CAPD to APD and conversely decreased after switching to from APD to CAPD. In contrast, for potassium the difference in the mean serum levels was comparable between groups switching from CAPD to APD, and vice versa. In conclusion, CAPD seems to be as efficient as APD for the control of potassium serum levels, but more effective for the control of phosphate serum levels. The effect of a higher removal of middle size molecules as result of PD modalities in terms of clinical and patient-reported outcomes should be further explored.

Penile necrosis and calciphylaxis.

Penile necrosis is an uncommon condition associated, in most cases, with calciphylaxis, also known as calcific uremic arteriolopathy. It is a progressive disease found in approximately 1%-4% of patients with end stage renal disease. Patients with penile calciphylaxis present a mortality rate of up to 70%, with life expectancy of two-and a half months following the diagnosis. We report a severe calciphylaxis case that had to be submitted to a penectomy but survived the penile event.

Brugada syndrome: Eligibility for subcutaneous implantable cardioverter-defibrillator after exercise stress test.

INTRODUCTION: Brugada syndrome (BrS) is a channelopathy associated with ventricular arrhythmias and sudden cardiac death. In patients at high risk of sudden death, an implantable cardioverter-defibrillator is indicated. Subcutaneous implantable cardioverter-defibrillators (S-ICDs) are an alternative to transvenous systems, with reduced risk of infection and complications associated with system extraction or explantation. OBJECTIVE: To test electrocardiographic eligibility for S-ICD placement after exercise stress testing (EST) in patients with BrS. METHODS: The sample included 35 consecutive patients with BrS. Electrocardiographic eligibility was assessed using the Boston Scientific model 2889 EMBLEM™ S-ICD automated screening tool, in four phases: decubitus and orthostatism, and before and after EST. Those who had at least one acceptable vector in the four measurements were considered eligible. RESULTS: In this study, 71.4% of patients were male and mean age was 53.86±12 years. In screening prior to EST, 14.3% of patients (n=5) were not eligible for an S-ICD. There was a statistically significant association between ineligibility and presence of complete right bundle branch block and history of syncope. After EST, 16.7% of initially eligible patients no longer had eligible vectors (n=5). CONCLUSION: In this study, 16.7% of patients previously eligible for an S-ICD were no longer eligible after EST. This result demonstrates the importance of screening after EST in all patients with BrS and with indication for an S-ICD, and may influence decisions concerning which ICD to implant or whether to institute pharmacological measures that avoid inappropriate therapies.

Ciclo de Supervisão de Peter Nicklin num Cenário de Ensino Clínico de Enfermagem / Peter nicklin's supervision cycle in a nursing clinical practice scenario

Objetivo: Relatar cenário de supervisão clínica de estudante de enfermagem no primeiro ensino clínico, com base no ciclo de supervisão de Nicklin. Métodos: Relato de Experiência no ensino com análise crítica de um cenário de supervisão clínica de estudante de enfermagem, em contexto do primeiro ensino clínico, num serviço de medicina, com a duração de 10 semanas, com base no ciclo de supervisão de Nicklin. Resultados: Analisaram-se as práticas e foram identificados problemas de natureza cognitiva, técnica, comunicacional, comportamental, relacional, de gestão das emoções e de autocontrole. O plano de intervenção de supervisão baseou-se na mobilização estratégias supervisivas que permitissem concretizar objetivos no sentido da aquisição de competências nos domínios em que foram identificados problemas. A implementação do plano decorre a partir da avaliação intercalar, nas últimas cinco semanas de ensino clínico. Conclusão: Concluiu-se que o ciclo de supervisão clínica de Nicklin, cuja estrutura encontra paralelismos na metodologia científica do processo de enfermagem, possibilita a análise do processo de desenvolvimento de estudantes em ensino clínico, com base no método científico, o que permite uma supervisão estruturada e baseada na identificação e resolução dos problemas. (AU)

Objective: To report a clinical supervision scenario of a nursing student in the first clinical training based on Nicklin's supervision cycle. Methods: Teaching Experience Report with a critical analysis of a nursing student clinical supervision scenario, in the context of the first clinical training, in a medical ward, lasting 10 weeks, based on Nicklin's supervision cycle. Results: Practices were analysed and problems of a cognitive, technical, communicational, behavioural, relational, emotional management and self-control nature were identified. The supervisory intervention plan was based on the mobilization of supervisory strategies that would make possible to achieve objectives in the sense of acquiring skills in the areas in which problems were identified. The implementation of the plan takes place from the mid-term evaluation, in the last five weeks of clinical training. Conclusion: We concluded that Nicklin's clinical supervision cycle, whose structure finds parallels in the scientific methodology of the nursing process, allows the analysis of the students' development process in clinical training, based on the scientific method, which allows a supervision structured and based on the identification and resolution of problems. (AU)

Objetivo: Informar el escenario de supervisión clínica de un estudiante de enfermería en la primera educación clínica, basado en el ciclo de supervisión de Nicklin. Métodos: Informe de experiencia docente con un análisis crítico del escenario de supervisión clínica de un estudiante de enfermería, en el contexto de la primera enseñanza clínica, en un servicio médico, con una duración de 10 semanas, basado en el ciclo de supervisión de Nicklin. Resultados: Se analizaron las prácticas y se identificaron problemas de naturaleza cognitiva, técnica, comunicacional, conductual, relacional, emocional y de autocontrol. El plan de intervención de supervisión se basó en la movilización de estrategias de supervisión que permitirían alcanzar objetivos en el sentido de adquirir habilidades en las áreas en las que se identificaron problemas. La implementación del plan se lleva a cabo desde la evaluación intermedia, en las últimas cinco semanas de enseñanza clínica. Conclusión: Se concluyó que el ciclo de supervisión clínica de Nicklin, cuya estructura encuentra paralelos en la metodología científica del proceso de enfermería, permite el análisis del proceso de desarrollo del estudiante en la enseñanza clínica, basado en el método científico, que permite la supervisión estructurado y basado en la identificación y resolución de problemas. (AU)

Post mortem genetic test, the clinical diagnosis is not fade with the death of the patient. / Teste genético post mortem, o diagnóstico clínico não se esgota com a morte do doente.

In up to one-third of cases of sudden death, the medico-legal autopsy finding is inconclusive, and the option to perform a molecular autopsy is covered in international guidelines. The importance of postmortem genetic testing lies in its ability to identify hereditary diseases, often those with an autosomal dominant transmission pattern, and, through consultations and screening of relatives, to identify family members with a pathogenic mutation, who are often asymptomatic, providing an opportunity to change the course of their lives. The authors present three clinical cases that highlight the importance of postmortem genetic studies and family studies, as well as the integration of the data obtained in a cardiology consultation, which may be for arrhythmology, coronary disease or cardiomyopathy, depending on the specific condition. This could modify the course of the disease in many relatives.

Importance of cardiac implantable eletronic devices in the diagnosis of Sleep Apnea Syndrome. / Importância dos dispositivos eletrónicos cardíacos implantáveis no diagnóstico da Síndrome da Apneia do Sono.

INTRODUCTION: Sleep Apnea Syndrome (SAS) is a prevalent respiratory disease with marked expression in the population with cardiovascular disease. The diagnosis is based on polysomnography. In patients with cardiac implantable electronic devices (CIED), the prevalence of SAS may reach 60%. The objective of this study was to evaluate the value of DEC in the SAS screening. METHODS: Prospective study that included patients with CIED with sleep apnea algorithm. The frequency response function was activated and simplified polygraphy was performed. The data of the device were collected on the day of the polygraph. RESULTS: The sample included 29 patients, with a mean age of 76.1 years, 71.4% of the male gender. The prevalence of SAS was 77%. For SAS, the agreement between polysomnography and the Pacemaker was Kappa = 0.54 (p = 0.001), 95% CI (0.28, 0.81) (moderate agreement); for moderate to severe SAS, the agreement was Kappa = 0.73 (p <0.001), 95% CI (0.49, 0.976) (substantial agreement). Severe SAS was obtained: sensitivity 60%, specificity 100%, positive predictive value 100%, negative predictive value 60% and diagnostic accuracy 75%; for moderate to severe SAS: sensitivity of 90%, specificity of 83%, positive predictive values of 90% and negative of 87.5%, with a diagnostic accuracy of 87.5%. CONCLUSION: SAS is highly prevalent in patients with CIED. The values obtained through these devices have a strong positive correlation with the Apnea-Hypopnea Índex, which makes them a good tool for the screening of severe SAS.

Bioclimatic modeling in the Last Glacial Maximum, Mid-Holocene and facing future climatic changes in the strawberry tree (Arbutus unedo L.).

Increasing forest wildfires in Portugal remain a growing concern since forests in the Mediterranean region are vulnerable to recent global warming and reduction of precipitation. Therefore, a long-term negative effect is expected on the vegetation, with increasing drought and areas burnt by fires. The strawberry tree (Arbutus unedo L.) is particularly used in Portugal to produce a spirit by processing its fruits and is the main income for forestry owners. Other applications are possible due to the fruit and leaves' anti-oxidant properties and bioactive compounds production, with a potential for clinical and food uses. It is a sclerophyllous plant, dry-adapted and fire resistant, enduring the Mediterranean climate, and recently considered as a possibility for afforestation, to intensify forest discontinuity where pines and eucalypts monoculture dominate the region. To improve our knowledge about the species' spatial distribution we used 318 plots (the centroid of a 1 km2 square grid) measuring the species presence and nine environmental attributes. The seven bioclimatic variables most impacting on the species distribution and two topographic features, slope and altitude, were used. The past, current and future climate data were obtained through WorldClim. Finally, the vulnerability of the strawberry tree to the effects of global climate change was examined in the face of two emission scenarios (RCP 4.5 and 8.5), to predict distribution changes in the years 2050 and 2070, using a species distribution models (MaxEnt). The reduction of suitable habitat for this species is significant in the southern regions, considering the future scenarios of global warming. Central and northern mountainous regions are putative predicted refuges for this species. Forest policy and management should reflect the impact of climate change on the usable areas for forestry, particularly considering species adapted to the Mediterranean regions and wildfires, such as the strawberry tree. The distribution of the species in the Last Glacial Maximum (LGM) and Mid-Holocene (MH) agrees with previous genetic and paleontological studies in the region, which support putative refuges for the species. Two in the southern and coastal-central regions, since the LGM, and one in the east-central mountainous region, considered as cryptic refugia.

Impact of Renin-Angiotensin Aldosterone System Inhibition on Serum Potassium Levels among Peritoneal Dialysis Patients.

BACKGROUND: The chronic use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker has been associated with hyperkalemia in patients with reduced renal function even after the initiation of hemodialysis. Whether such medications may cause a similar effect in peritoneal dialysis patients is not well established. So, the aim of our study was to analyze the impact of renin-angiotensin-aldosterone inhibitors on the serum levels of potassium in a national cohort of peritoneal dialysis patients. METHOD: A prospective, observational, nationwide cohort study was conducted. We identified all incident patients on peritoneal dialysis that had angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) prescribed for at least 3 months and a similar period of time without these medications. Patients were divided into 4 groups: Groups I and III correspond to patients using, respectively, an ACEi or ARB and then got the drug suspended; Groups II and IV started peritoneal dialysis without the use of any renin-angiotensin aldosterone system inhibitor and then got, respectively, an ACEi or ARB introduced. Changes in potassium serum levels were compared using 2 statistical approaches: (1) the non-parametric Wilcoxon test for repeated measures and (2) a crossover analysis. RESULTS: Mean potassium serum levels at the first phase of the study for Groups I, II, III, and IV were, respectively, 4.46 ± 0.79, 4.33 ± 0.78, 4.41 ± 0.63, and 4.44 ± 0.56. Changes in mean potassium serum levels for Groups I, II, III, and IV were -0.10 ± 0.60, 0.02 ± 0.56, -0.06 ± 0.46, and 0.03 ± 0.50, respectively. CONCLUSION: The use of ACEi and ARB was not associated with a greater risk for hyperkalemia in stable peritoneal dialysis patients independently of residual renal function.

Racial and social disparities in the access to automated peritoneal dialysis - results of a national PD cohort.

The prevalence of patients on automated peritoneal dialysis (APD) is increasing worldwide and may be guided by clinical characteristics, financial issues and patient option. Whether socioeconomic factors at the patient level may influence the decision for the initial peritoneal dialysis (PD) modality is unknown. This is a prospective cohort study. The primary outcome of interest was the probability to start PD on APD. The inclusion criteria were adult patients incident in PD. Exclusion criteria were missing data for either race or initial PD modality. We used a mixed-model analysis clustering patients according to their PD center and region of the country. We included 3,901 patients of which 1,819 (46.6%) had APD as their first modality. We found a significant disparity for race and educational level with African American patients less likely to start on APD (Odds ratio 0.74 CI95% 0.58-0.94) compared to Whites whilst those with greater educational levels were more likely to start on APD (Odds ratio 3.70, CI95% 2.25-6.09) compared to illiterate patients. Limiting the use of APD in disadvantaged population may be unethical. Demographics and socioeconomic status should not be necessarily part of the decision-making process of PD modality choice.