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1.
Sensors (Basel) ; 24(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38894453

RESUMO

Heart failure (HF) admissions are burdensome, and the mainstay of prevention is the timely detection of impending fluid retention, creating a window for medical treatment intensification. This study evaluated the accuracy and performance of a Triage-HF-guided carepath in real-world ambulatory HF patients in daily clinical practice. In this prospective, observational study, 92 adult HF patients (71 males (78%), with a median age of 69 [IQR 59-75] years) with the Triage-HF algorithm activated in their cardiac implantable electronic devices (CIEDs), were monitored. Following high-risk alerts, an HF nurse contacted patients to identify signs and symptoms of fluid retention. The sensitivity and specificity were 83% and 97%, respectively. The positive predictive value was 89%, and negative predictive value was 94%. The unexplained alert rate was 0.05 alerts/patient year, and the false negative rate was 0.11 alerts/patient year. Ambulatory diuretics were initiated or escalated in 77% of high-risk alert episodes. In 23% (n = 6), admission was ultimately required. The median alert handling time was 2 days. Fifty-eight percent (n = 18) of high-risk alerts were classified as true positives in the first week, followed by 29% in the second-third weeks (n = 9), and 13% (n = 4) in the fourth-sixth weeks. Common sensory triggers included an elevated night ventricular rate (84%), OptiVol (71%), and reduced patient activity (71%). The CIED-based Triage-HF algorithm-driven carepath enables the timely detection of impending fluid retention in a contemporary ambulatory setting, providing an opportunity for clinical action.


Assuntos
Algoritmos , Insuficiência Cardíaca , Triagem , Humanos , Masculino , Insuficiência Cardíaca/terapia , Feminino , Idoso , Pessoa de Meia-Idade , Triagem/métodos , Estudos Prospectivos , Desfibriladores Implantáveis
2.
Eur J Cardiothorac Surg ; 65(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38603625

RESUMO

We present the case of a 52-year-old woman with cardiogenic shock and refractory right ventricular failure due to spontaneous dissection of the right coronary artery. She remained dependent on mechanical support for several weeks. Both a right ventricular assist device implant and a bidirectional cavopulmonary anastomosis were explored as long-term support options. A history of malignancy and possible right ventricular functional recovery resulted in a decision in favour of the bidirectional cavopulmonary anastomosis and concomitant tricuspid valve annuloplasty. Postoperatively her clinical condition improved significantly, and she could be discharged home. Echocardiography showed normalization of right ventricular dimensions and slight improvement of right ventricular function.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Feminino , Pessoa de Meia-Idade , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/etiologia , Infarto do Miocárdio/cirurgia , Infarto do Miocárdio/complicações , Disfunção Ventricular Direita/cirurgia , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia , Técnica de Fontan/efeitos adversos , Coração Auxiliar , Ventrículos do Coração/cirurgia , Ventrículos do Coração/diagnóstico por imagem
4.
J Am Coll Cardiol ; 83(15): 1403-1414, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38530688

RESUMO

BACKGROUND: Heart failure (HF) is the principal cause of morbidity and mortality in adults with congenital heart disease (ACHD). Robust evidence-based treatment options are lacking. OBJECTIVES: This study aims to evaluate the safety, tolerability, and short-term HF-related effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in a real-world ACHD population. METHODS: All patients with ACHD treated with SGLT2i in 4 European ACHD centers were included in this retrospective study. Data were collected from 1 year before starting SGLT2i to the most recent follow-up. Data on side effects, discontinuation, mortality, and hospitalizations were collected. RESULTS: In total, 174 patients with ACHD were treated with SGLT2i from April 2016 to July 2023. The mean age was 48.7 ± 15.3 years, 72 (41.4%) were female, and 29 (16.7%) had type 2 diabetes mellitus. Ten (5.7%) patients had mild, 75 (43.1%) moderate, and 89 (51.1%) severe congenital heart disease. HF was the most frequent starting indication (n = 162, 93.1%), followed by type 2 diabetes (n = 11, 6.3%) and chronic kidney disease (n = 1, 0.6%). At median follow-up of 7.7 months (Q1-Q3: 3.9-13.2 months), 18 patients (10.3%) reported side effects, 12 (6.9%) permanently discontinued SGLT2i, and 4 (2.3%) died of SGLT2i-unrelated causes. A significant reduction in the HF hospitalization rate was observed from 6 months before to 6 months after starting SGLT2i (relative rate = 0.30; 95% CI: 0.14-0.62; P = 0.001). CONCLUSIONS: SGLT2i generally seem safe, well-tolerated, and potentially beneficial in patients with ACHD. SGLT2i was associated with a 3-fold reduction in the 6-month HF hospitalization rate. These results warrant prospective randomized investigation of the potential benefits of SGLT2i for patients with ACHD.


Assuntos
Cardiopatias Congênitas , Insuficiência Cardíaca , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiopatias Congênitas/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Estudos Retrospectivos
5.
Phys Chem Chem Phys ; 26(9): 7772-7782, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38374775

RESUMO

The conductive properties of fluorite-like structures KLn4Mo3O15F (Ln = La, Pr, Nd: KLM, KPM, KNM) have been studied theoretically and experimentally. Theoretical studies included the geometrical-topological analysis of voids and channels available for migration of working ions; bond valence site energy calculations of the oxygen ions' migration energy; quantum-chemical calculations for the estimation of the oxygen vacancies formation energy. Experimental measurements of conductivity were made using impedance spectroscopy and as a function of oxygen partial pressure. The total conductivity was ∼10-3 S cm-1 for KLM and ∼10-2 S cm-1 for KPM and KNM at 800 °C. Measurements with changes in partial pressure proved the mixed nature of electric transport in KLM, KPM, and KNM phases, with predominantly ionic conductivity. The measured ion transference numbers in air reached approximately 0.9 at 800 °C for the KPM and KNM ceramics. Also, evaluated proton transfer numbers were less than 10%, indicating a small contribution to the total conductivity.

6.
J Cardiovasc Dev Dis ; 11(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38392265

RESUMO

BACKGROUND: Survival and quality-of-life of left ventricular assist device (LVAD) recipients improved significantly because of growing experience and technological advances. However, LVAD-related complication rates, including recurrent episodes of congestion, remain high. Early detection of fluid retention to provide a time-window for medical intervention is the pillar in preventing hospitalizations. The multisensory HeartLogicTM algorithm accurately detected impending congestion in ambulant heart failure patients. The aim of the current study is to investigate the feasibility of HeartLogicTM-driven care in LVAD patients. METHODS: Consecutive LVAD destination therapy patients were followed-up according the structured HeartLogicTM-based heart failure carepath. An alert triggered a device check-up, and the heart failure team contacted the patient to evaluate for signs and symptoms of impending congestion. An alert was adjudicated as true positive or unexplained. An episode of congestion not preceded by an alert was deemed as a false negative. RESULTS: Data from 7 patients were included: the median age was 67 years [IQR 61-71], 71% were male and 71% had a non-ischemic aetiology. Total follow-up entailed 12 patient-years. All patients experienced at least one alert. In total, 33 alerts were observed. Majority of alerts (70%, n = 23) were driven by congestion and one alerts (15%) were clinically meaningful but not primarily fluid-retention-related (e.g., altered hemodynamic triggered by a pump thrombosis). Of all the alerts, five (15%) were classified as an unexplained alert, and during follow-up, four false negative episodes were documented. CONCLUSIONS: HeartLogicTM-driven care with continuous monitoring to detect impending fluid retention in LVAD patients was feasible and deserves further prospective validation.

7.
Nucleic Acids Res ; 52(D1): D950-D962, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37665017

RESUMO

The Open Genes database was created to enhance and simplify the search for potential aging therapy targets. We collected data on 2402 genes associated with aging and developed convenient tools for searching and comparing gene features. A comprehensive description of genes has been provided, including lifespan-extending interventions, age-related changes, longevity associations, gene evolution, associations with diseases and hallmarks of aging, and functions of gene products. For each experiment, we presented the necessary structured data for evaluating the experiment's quality and interpreting the study's findings. Our goal was to stay objective and precise while connecting a particular gene to human aging. We distinguished six types of studies and 12 criteria for adding genes to our database. Genes were classified according to the confidence level of the link between the gene and aging. All the data collected in a database are provided both by an API and a user interface. The database is publicly available on a website at https://open-genes.org/.


Assuntos
Envelhecimento , Bases de Dados Genéticas , Longevidade , Humanos , Envelhecimento/genética , Longevidade/genética , RNA
8.
CJC Pediatr Congenit Heart Dis ; 2(3): 124-133, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37969355

RESUMO

Background: Anomalous aortic origin of a right coronary artery (AAORCA) with an interarterial course merits further evaluation; however, robust risk assessment strategies for myocardial ischemia and sudden cardiac death are currently lacking. The aim of this study is to explore the potential role of fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and intravascular ultrasound (IVUS) in patients with AAORCA. Methods: Consecutive adult patients with AAORCA with an interarterial course were included. Computed tomography angiography, noninvasive ischemia detection, and FFR, iFR, and IVUS were performed at baseline and during adrenaline-induced stress. External compression was evaluated with IVUS. Results: Eight patients (63% female, mean age: 53 ± 9.5 years) were included. Five patients (63%) were symptomatic, and computed tomography angiography revealed high-risk anatomy of the AAORCA in all patients. Only in 1 (12.5%) patient FFR and iFR were positive; however, this was attributed at large to concomitant diffuse atherosclerosis. In 2 of 8 (25%), IVUS revealed external compression; however, the ostial coronary surface area remained unchanged. In all patients, a conservative treatment strategy was pursued. During a mean follow-up of 29.3 months (standard deviation ±2.6 months), symptoms spontaneously disappeared in 4 of 5 (80%) and no adverse cardiac events occurred in any of the patients. Conclusions: Despite the presence of high-risk anatomy in all patients, none had proven ischemia prompting a conservative treatment strategy. No adverse cardiac events occurred during follow-up, and in the majority of patients, symptoms spontaneously disappeared. Therefore, FFR, iFR, and IVUS with pharmacologic stress merit further investigation and might contribute to ischemia-based risk stratification and management strategies in adult patients with AAORCA.


Contexte: L'anomalie de naissance de l'artère coronaire droite à partir de l'aorte (AAORCA, anomalous aortic origin of a right coronary artery) combinée à un trajet interartériel mérite un examen plus approfondi. Cependant, on observe à l'heure actuelle des lacunes en ce qui a trait à l'emploi de stratégies fiables d'évaluation du risque d'ischémie myocardique et de mort subite d'origine cardiaque. L'objectif de cette étude est d'examiner le rôle potentiel de la mesure de la réserve coronarienne (MRC), de l'évaluation du rapport instantané sans onde (iFR, instantaneous wave-free ratio) et de l'échographie intravasculaire chez des patients présentant une AAORCA. Méthodologie: Des cas de patients adultes consécutifs présentant une AAORCA combinée à un trajet interartériel ont été inclus à l'étude. Une angiographie par tomodensitométrie (TDM), une détection non invasive de la présence d'une ischémie, la MRC, l'évaluation de l'iFR et l'échographie intravasculaire ont été effectuées au début de l'étude ainsi que lors d'un stress induit par l'adrénaline. La compression externe a également été évaluée au moyen d'une échographie intravasculaire. Résultats: Huit patients (63 % de sexe féminin; âge moyen de 53 ans ± 9,5 ans) ont participé à l'étude. Cinq patients (63 %) présentaient des symptômes, et l'angiographie par TDM a révélé une AAORCA à risque élevé chez tous les patients. Les résultats de la MRC et de l'évaluation de l'iFR étaient positifs chez seulement un patient (12,5 %), ce qui est attribuable en majeure partie à une athérosclérose diffuse concomitante. Chez deux patients (25 %), l'échographie intravasculaire a montré une compression externe de l'artère coronaire droite même si l'aire de l'ostium de l'artère n'avait pas changé. Une stratégie thérapeutique prudente a été employée pour tous les patients. Pendant la période de suivi qui a duré en moyenne 29,3 mois (écart-type : ± 2,6 mois), les symptômes se sont résorbés de manière spontanée chez quatre des cinq patients (80 %), et aucun événement cardiaque indésirable n'est survenu. Conclusion: Malgré une anatomie à risque élevé chez tous les patients, aucun d'entre eux ne présentait une ischémie connue, ce qui justifiait une stratégie thérapeutique prudente. Aucun événement cardiaque indésirable n'est survenu durant la période de suivi, et les symptômes se sont résorbés de manière spontanée chez la majorité des patients. À la lumière de ces renseignements, la MRC, l'évaluation de l'iFR et l'échographie intravasculaire lors d'un stress pharmacologique devraient faire l'objet d'autres études et pourraient éventuellement être utiles dans la stratification du risque d'ischémie et dans le choix des stratégies de prise en charge des patients adultes présentant une AAORCA.

9.
Plants (Basel) ; 12(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37836145

RESUMO

Researchers are looking for the most effective ways to extract the bioactive substances of Juniperus communis L. berries, which are capable of displaying the greatest range of biological activity, namely antimicrobial potential "against phytopathogens", antioxidant activity and nematocidal activity. This study provides detailed information on the chemical activity, group composition and biological activity of the extracts of juniper berries of 1- and 2-year maturity (JB1 and JB2), which were obtained by using different solvents (pentane, chloroform, acetone, methanol and 70% ethanol) under various extraction conditions (maceration and ultrasound-assisted maceration (US)). Seventy percent ethanol and acetone extracts of juniper berries were analyzed via gas chromatography-mass spectrometry, and they contained monoterpenes, sesquiterpenes, polysaccharides, steroids, fatty acid esters and bicyclic monoterpenes. The antimicrobial activity was higher in the berries of 1-year maturity, while the acetone extract obtained via ultrasound-assisted maceration was the most bioactive in relation to the phytopathogens. Depending on the extraction method and the choice of solvent, the antioxidant activity with the use of US decreased by 1.5-1.9 times compared to the extracts obtained via maceration. An analysis of the nematocidal activity showed that the sensitivity to the action of extracts in Caenorhabditis elegans was significantly higher than in Caenorhabditis briggsae, particularly for the acetone extract obtained from the juniper berries of 1-year maturity.

11.
Int J Mol Sci ; 24(18)2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37762675

RESUMO

Among the plants that exhibit significant or established pharmacological activity, the genus Artemisia L. deserves special attention. This genus comprises over 500 species belonging to the largest Asteraceae family. Our study aimed at providing a comprehensive evaluation of the phytochemical composition of the ethanol extracts of five different Artemisia L. species (collected from the southwest of the Russian Federation) and their antimicrobial and nematocide activity as follows: A. annua cv. Novichok., A. dracunculus cv. Smaragd, A. santonica cv. Citral, A. abrotanum cv. Euxin, and A. scoparia cv. Tavrida. The study of the ethanol extracts of the five different Artemisia L. species using the methods of gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-MS/MS) allowed establishing their phytochemical profile. The obtained data on the of five different Artemisia L. species ethanol extracts' phytochemical composition were used to predict the antibacterial and antifungal activity against phytopathogenic microorganisms and nematocidal activity against the free-living soil nematode Caenorhabditis elegans. The major compounds found in the composition of the Artemisia L. ethanol extracts were monoterpenes, sesquiterpenes, flavonoids, flavonoid glycosides, coumarins, and phenolic acids. The antibacterial and antifungal activity of the extracts began to manifest at a concentration of 150 µg/mL. The A. dracunculus cv. Smaragd extract had a selective effect against Gram-positive R. iranicus and B. subtilis bacteria, whereas the A. scoparia cv. Tavrida extract had a selective effect against Gram-negative A. tumefaciens and X. arboricola bacteria and A. solani, R. solani and F. graminearum fungi. The A. annua cv. Novichok, A. dracunculus cv. Smaragd, and A. santonica cv. Citral extracts in the concentration range of 31.3-1000 µg/mL caused the death of nematodes. It was established that A. annua cv. Novichok affects the UNC-63 protein, the molecular target of which is the nicotine receptor of the N-subtype.


Assuntos
Anti-Infecciosos , Araceae , Artemisia , Animais , Etanol , Antifúngicos , Espectrometria de Massas em Tandem , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antinematódeos , Caenorhabditis elegans , Flavonoides , Extratos Vegetais/farmacologia
12.
Nanomaterials (Basel) ; 13(17)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37686919

RESUMO

Photopharmacology is a booming research area requiring a new generation of agents possessing simultaneous functions of photoswitching and pharmacophore. It is important that any practical implementation of photopharmacology ideally requires spatial control of the medicinal treatment zone. Thus, advances in the study of substances meeting all the listed requirements will lead to breakthrough research in the coming years. In this study, CQDs@phosphonate nanohybrids are presented for the first time and combine biocompatible and nontoxic luminescent carbon quantum dots (CQDs) with photoactive phosphonate enabling inhibition of butyrylcholinesterase (BChE), which is a prognostic marker of numerous diseases. The conjunction of these components in hybrids maintains photoswitching and provides enhancement of BChE inhibition. After laser irradiation with a wavelength of 266 nm, CQDs@phosphonate hybrids demonstrate a drastic increase of butyrylcholinesterase inhibition from 38% up to almost 100% and a simultaneous luminescence decrease. All the listed hybrid properties are demonstrated not only for in vitro experiments but also for complex biological samples, i.e., chicken breast. Thus, the most important achievement is the demonstration of hybrids characterized by a remarkable combination of all-in-one properties important for photopharmacology: (i) bioactivity toward butyrylcholinesterase inhibition, (ii) strong change of inhibition degree as a result of laser irradiation, luminescence as an indicator of (iii) bioactivity state, and of (iv) spatial localization on the surface of a sample.

13.
J Clin Med ; 12(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37685719

RESUMO

Implantable cardioverter defibrillators (ICDs) significantly contribute to the prevention of sudden cardiac death in selected patients. However, it is essential to identify those who are likely to not have benefit from an ICD and to defer a pulse generator exchange. Easily implementable guidelines for individual risk stratification and decision making are lacking. This study investigates the 1-year mortality of patients who underwent an ICD or cardiac resynchronization therapy with defibrillator function (CRT-D) pulse generator replacement in a contemporary real-world tertiary hospital setting. The cause of death and patient- and procedure-related factors are stratified, and predictive values for 1-year mortality are evaluated. Patients with a follow-up of ≥365 days (or prior mortality) after an ICD or CRT-D exchange at the Leiden University Medical Center from 1 January 2018 until 31 December 2021 were eligible. In total, 588 patients were included (77% male, 69 [60-76] years old, 59% primary prevention, 46% ischemic cardiomyopathy and 37% mildly reduced left ventricular ejection fraction (LVEF)). Patients undergoing a CRT-D replacement or upgrade had a significantly higher 1-year all-cause mortality (10.7% and 11.9%, respectively) compared to patients undergoing ICD (2.8%) exchange (p = 0.002). LVEF ≤ 30%, New York Heart Association class ≥ 3, estimated glomerular filtration rate ≤ 30 mL/min/m2 and haemoglobin ≤ 7 mmol/L were independently associated with mortality within 1 year after pulse generator replacement. There is a growing need for prospectively validated risk scores to weight individualized risk of mortality with the expected ICD therapy benefit and to support a well-informed, shared decision-making process.

14.
J Clin Med ; 12(14)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37510913

RESUMO

INTRODUCTION: Increasing survival of adult congenital heart disease (ACHD) patients comes at the price of a range of late complications-arrhythmias, heart failure, and valvular dysfunction. Transcatheter valve interventions have become a legitimate alternative to conventional surgical treatment in selected acquired heart disease patients. However, literature on technical aspects, hemodynamic effects, and clinical outcomes of percutaneous atrioventricular (AV) valve interventions in ACHD patients is scarce. METHOD: This is a descriptive cohort from CAHAL (Center of Congenital Heart Disease Amsterdam-Leiden). ACHD patients with severe AV valve regurgitation who underwent a transcatheter intervention in the period 2020-2022 were included. Demographic, clinical, procedural, and follow-up data were collected from patient records. RESULTS: Five ACHD patients with severe or torrential AV valve regurgitation are described. Two patients underwent a transcatheter edge-to-edge repair (TEER), one patient underwent a valve-in-valve procedure, one patient received a Cardioband system, and one patient received both a Cardioband system and TEER. No periprocedural complications occurred. Post-procedural AV valve regurgitation as well as NYHA functional class improved in all patients. The median post-procedural NYHA functional class improved from 3.0 (IQR [2.5-4.0]) to 2.0 (IQR [1.5-2.5]). One patient died 9 months after the procedure due to advanced heart failure with multiorgan dysfunction. CONCLUSION: Transcatheter valve repair is feasible and safe in selected complex ACHD patients. A dedicated heart team is essential for determining an individualized treatment strategy as well as pre- and periprocedural imaging to address the underlying mechanism(s) of AV regurgitation and guide the transcatheter intervention. Long-term follow-up is essential to evaluate the clinical outcomes of transcatheter AV valve repair in ACHD patients.

15.
Front Cardiovasc Med ; 10: 1093201, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37435053

RESUMO

Aims: Given the compelling evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the conventional heart failure population, SGLT2i deserve exploration in systemic right ventricular (sRV) failure. The initial experience with dapagliflozin in sRV failure patients is described, with a focus on tolerability and short-term effects on clinical outcomes. Methods and results: Ten patients (70% female, median age 50 years [46.5-52]) with symptomatic sRV failure who received dapagliflozin 10 mg per day on top of optimal medical therapy between 04-2021 and 01-2023 were included. Within 4 weeks, no significant changes in blood pressure, electrolytes, or serum glucose occurred. Creatinine and estimated glomerular filtration rate (eGFR) showed a slight decline (88 ± 17 to 97 ± 23 µmol/L, p = 0.036, and 72 ± 14 vs. 66 ± 16 ml/min/1.73m2, p = 0.020, respectively). At 6 months follow-up (n = 8), median NT-proBNP decreased significantly from 736.6 [589.3-1193.3] to 531.6 [400.8-1018] ng/L (p = 0.012). Creatinine and eGFR recovered to baseline levels. There were no significant changes in echocardiographic systolic sRV or left ventricular function. New York Heart Association class improved significantly in 4 out of 8 patients (p = 0.046), who also showed an improvement in the 6-minute walk test or bicycle exercise test performance. One female patient developed an uncomplicated urinary tract infection. No patients discontinued treatment. Conclusion: Dapagliflozin was well-tolerated in this small cohort of sRV failure patients. While the early results on the reduction of NT-proBNP and clinical outcome parameters are encouraging, large-scale prospective studies are warranted to thoroughly evaluate the effects of SGLT2i in the growing sRV failure population.

16.
Eur Heart J Case Rep ; 7(4): ytad176, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37123657

RESUMO

Background: Patients with a univentricular heart form a morphological heterogenous group of patients at the most severe end of the congenital heart disease (CHD) spectrum. Over the past decades, more awareness and knowledge has been raised on the genetic contributions to CHD. To date, only a limited number of genes have been identified in the hypoplastic heart, mainly in left-sided hypoplasia. There is still much more to be elucidated in this field. Case summary: Here, we present a follow-up report of a case of an adult patient after Fontan palliation, born with a.o. tricuspid atresia with hypoplastic right ventricle and pulmonary stenosis. This patient encountered a myriad of late sequalae involving multiple organ systems during the course of his young adult life, including refractory protein losing enteropathy (PLE). Concomitant extracardiac anomalies, in addition to the complex CHD and its complications, prompted for genetic evaluation. Whole exome sequencing showed a variant of uncertain significance in the BRAF gene [NM_004333.4:c.1897T > C p.(Tyr633His)], associated with Noonan spectrum disorders, that is also infamous for lymphoedema and PLE. The variant regards an evolutionarily highly conserved amino acid and is assumed pathogenic according to all prediction programmes. The mutation was most likely de novo. Discussion: Genetic screening can provide new insights in the complex and varied phenotype of the (adult) Fontan patient and in the myriad of complications encountered. Adult CHD cardiologists should be aware of genetic syndromes underlying a CHD, concomitant extracardiac anomalies, and a complex clinical course with a broad spectrum of late sequelae.

17.
Heart ; 109(20): 1525-1532, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37169551

RESUMO

OBJECTIVE: Patients with a systemic right ventricle (sRV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are prone to sRV dysfunction. Pharmacological options for sRV failure remain poorly defined. This study aims to investigate the tolerability and effects of sacubitril/valsartan on sRV failure in adult patients with sRV. METHODS: In this two-centre, prospective cohort study, all consecutive adult patients with symptomatic heart failure and at least moderately reduced sRV systolic function were initiated on sacubitril/valsartan and underwent structured follow-up. RESULTS: Data of 40 patients were included (40% female, 30% ccTGA, median age 48 (44-53) years). Five patients discontinued therapy during titration. Median follow-up was 24 (12-36) months. The maximal dose was tolerated by 49% of patients. No episodes of hyperkalaemia or renal function decline occurred. Six-minute walking distance increased significantly after 6 months of treatment (569±16 to 597±16 m, p=0.016). Serum N-terminal-prohormone brain natriuretic peptide (NT-proBNP) levels decreased significantly after 3 months (567 (374-1134) to 404 (226-633) ng/L, p<0.001). Small, yet consistent echocardiographic improvements in sRV function were observed after 6 months (sRV global longitudinal strain: -11.1±0.5% to -12.6±0.7%, p<0.001, and fractional area change: 20% (16%-24%) to 26% (19%-30%), p<0.001). The linear mixed-effects model illustrated that after first follow-up moment, no time effect was present for the parameters. CONCLUSIONS: Treatment with sacubitril/valsartan was associated with a low rate of adverse effects in this adult sRV cohort. Persisting improvement in 6-minute walking test distance, NT-proBNP levels and echocardiographic parameters of sRV function was observed in an on-treatment analysis and showed no differential response based on sex or anatomy.

18.
J Card Fail ; 29(11): 1522-1530, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37220824

RESUMO

BACKGROUND: The implantable cardiac defibrillator-based HeartLogic algorithm aims to detect impending fluid retention in patients with heart failure (HF). Studies show that HeartLogic is safe to integrate into clinical practice. The current study investigates whether HeartLogic provides clinical benefit on top of standard care and device telemonitoring in patients with HF. METHODS: A multicenter, retrospective, propensity-matched cohort analysis was performed in patients with HF and implantable cardiac defibrillators, and it compared HeartLogic to conventional telemonitoring. The primary endpoint was the number of worsening HF events. Hospitalizations and ambulatory visits due to HF were also evaluated. RESULTS: Propensity score matching yielded 127 pairs (median age 68 years, 80% male). Worsening HF events occurred more frequently in the control group (2; IQR 0-4) compared to the HeartLogic group (1; IQR 0-3; P = 0.004). The number of HF hospitalization days was higher in controls than in the HeartLogic group (8; IQR 5-12 vs 5; IQR 2-7; P = 0.023), and ambulatory visits for diuretic escalation were more frequent in the control group than in the HeartLogic group (2; IQR 0-3 vs 1; IQR 0-2; P = 0.0001). CONCLUSION: Integrating the HeartLogic algorithm in a well-equipped HF care path on top of standard care is associated with fewer worsening HF events and shorter duration of fluid retention-related hospitalizations.


Assuntos
Desfibriladores Implantáveis , Insuficiência Cardíaca , Humanos , Masculino , Idoso , Feminino , Estudos Retrospectivos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Estudos de Coortes , Hospitalização
19.
J Cardiovasc Dev Dis ; 10(4)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37103059

RESUMO

In the transposition of the great arteries (TGA), alterations in hemodynamics and oxygen saturation could result in fibrotic remodeling, but histological studies are scarce. We aimed to investigate fibrosis and innervation state in the full spectrum of TGA and correlate findings to clinical literature. Twenty-two human postmortem TGA hearts, including TGA without surgical correction (n = 8), after Mustard/Senning (n = 6), and arterial switch operation (ASO, n = 8), were studied. In newborn uncorrected TGA specimens (1 day-1.5 months), significantly more interstitial fibrosis (8.6% ± 3.0) was observed compared to control hearts (5.4% ± 0.8, p = 0.016). After the Mustard/Senning procedure, the amount of interstitial fibrosis was significantly higher (19.8% ± 5.1, p = 0.002), remarkably more in the subpulmonary left ventricle (LV) than in the systemic right ventricle (RV). In TGA-ASO, an increased amount of fibrosis was found in one adult specimen. The amount of innervation was diminished from 3 days after ASO (0.034% ± 0.017) compared to uncorrected TGA (0.082% ± 0.026, p = 0.036). In conclusion, in these selected postmortem TGA specimens, diffuse interstitial fibrosis was already present in newborn hearts, suggesting that altered oxygen saturations may already impact myocardial structure in the fetal phase. TGA-Mustard/Senning specimens showed diffuse myocardial fibrosis in the systemic RV and, remarkably, in the LV. Post-ASO, decreased uptake of nerve staining was observed, implicating (partial) myocardial denervation after ASO.

20.
J Cardiovasc Dev Dis ; 10(3)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36975893

RESUMO

Baffle leaks are a frequently encountered and often overlooked complication after the atrial switch procedure for transposition of the great arteries. Baffle leaks are present in up to 50% of non-selected patients, and while they initially may not cause clear symptoms, they can complicate the hemodynamic course and influence the prognosis in this complex patient group. A shunt from the pulmonary venous atrium (PVA) to the systemic venous atrium (SVA) can lead to pulmonary overflow and subpulmonary left ventricular (LV) volume overload, while a shunt from the SVA to the PVA can result in (exercise-associated) cyanosis and paradoxical embolism. We report three cases of baffle leaks in patients with systemic right ventricular (sRV) failure late after the atrial switch procedure. Two symptomatic patients who presented with exercise-associated cyanosis due to SVA to PVA shunting over the baffle leak underwent successful percutaneous baffle leak closure with a septal occluder device. One patient with overt sRV failure and signs of subpulmonary LV volume overload due to PVA to SVA shunting was managed conservatively, as baffle leak closure was expected to lead to an increase in sRV end-diastolic pressure and aggravation of sRV dysfunction. These three cases illustrate the considerations made, challenges faced, and necessity of a patient-tailored approach when addressing baffle leaks.

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