Ablação septal por radiofrequência na cardiomiopatia hipertrófica obstrutiva: a troponina é bom marcador de sucesso terapêutico? / Radiofrequency septal ablation in obstructive hypertrophic cardiomyopathy: is troponin a good marker of therapeutic success?

NTRODUÇÃO: A terapia de redução septal na Cardiomiopatia Hipertrófica Obstrutiva (CMHO) é indicada quando há sintomas refratários à terapêutica otimizada. Dentre estas terapias, recentemente foi proposta a ablação septal por radiofrequência (RF) com cateteres utilizados na eletrofisiologia para ablação de arritmias atriais e ventriculares. A ablação por RF é realizada com auxílio de ecocardiograma transesofágico com melhor controle da área abordada e redução do risco de lesões ao sistema de condução. Este trabalho tem como intuito apresentar uma série de casos de pacientes com CMHO que foram abordados por meio de ablação septal por RF, avaliando-se se a elevação dos níveis séricos de troponina, se correlacionam com a redução do gradiente intraoperatório e sucesso terapêutico. MÉTODOS: Estudo observacional, do tipo coorte histórica por análise de prontuário. As variáveis foram descritas por estatísticas de posição e escala para variáveis contínuas e frequências absolutas e relativas para variáveis categóricas (ou categorizadas). As análises foram realizadas com auxílio do software R (R Core Team, 2022). E os testes de hipótese utilizarão nível de significância de 5%. RESULTADOS: Analisaram-se 36 pacientes, sendo 18 (50%) do sexo masculinos. A troponina foi dosada no pré-operatório e no pós-operatório imediato, porém foi realizada usando tipos diferentes entre os pacientes, seguindo descrita como número de vezes acima do valor de referência. Observou-se uma elevação acima dos valores de referência em 83,3% dos pacientes analisados, e antes do procedimento, dois pacientes já apresentavam troponina acima do valor de referência, e se mantiveram acima após. Também se observou uma redução do GVSVE no intraoperatório de 38.3mmHg [30.7 a 45.8] com p<0,01.O gráfico 1 apresenta a relação do logaritmo do número de vezes da troponina acima do valor de referência contra o gradiente máximo pós-procedimento e das respectivas diferenças em relação ao valor de base (pré-procedimento). A correlação de Spearman foi respectivamente 0,47 (p = 0,065), não evidenciando uma correlação entre os achados. Gráfico 1. Dispersão do logaritmo diferença do número de vezes da troponina acima do valor de referência contra a redução gradiente máximo pós-procedimento. CONCLUSÃO: Apesar dos valores de troponina estarem maiores pós procedimento, concluímos que a troponina não deve ser usada como marcador de sucesso terapêutico.

Ablação septal por radiofrequência na cardiomiopatia hipertrófica obstrutiva: a troponina é bom marcador de sucesso terapêutico? / Radiofrequency septal ablation in obstructive hypertrophic cardiomyopathy: is troponin a good marker of therapeutic success?

INTRODUÇÃO: A terapia de redução septal na Cardiomiopatia Hipertrófica Obstrutiva (CMHO) é indicada quando há sintomas refratários à terapêutica otimizada. Dentre estas terapias, recentemente foi proposta a ablação septal por radiofrequência (RF) com cateteres utilizados na eletrofisiologia para ablação de arritmias atriais e ventriculares. A ablação por RF é realizada com auxílio de ecocardiograma transesofágico com melhor controle da área abordada e redução do risco de lesões ao sistema de condução. Este trabalho tem como intuito apresentar uma série de casos de pacientes com CMHO que foram abordados por meio de ablação septal por RF, avaliando-se se a elevação dos níveisséricos de troponina, marcadores de injúria miocárdica,se correlacionam com a redução do gradiente intraoperatório e consequente sucesso terapêutico. MÉTODOS: Estudo observacional, do tipo coorte histórica por análise de prontuário.As variáveis foram descritas por estatísticas de posição e escala para variáveis contínuas e frequências absolutas e relativas para variáveis categóricas (ou categorizadas).As análisesforam realizadas com auxílio do software R (R Core Team, 2022). E os testes de hipótese utilizarão nível de significância de 5%. RESULTADOS: Foram analisados 36 pacientes, sendo 18 (50%) do sexo masculinos, com média de idade de 57.8 anos (DP 10.15 anos). A troponina foi dosada no pré-operatório e no pós-operatório imediato, sendo descrita como número de vezes acima do valor de referência. Observou-se uma elevação acima dos valores de referência em 83,3% dos pacientes analisados, e antes do procedimento, dois pacientesjá apresentavam troponina acima do valor de referência, e se mantiveram acima após. Também se observou uma redução do GVSVE no intraoperatório de 38.3mmHg [30.7 a 45.8] com p<0,01. O gráfico 1 apresenta a relação do logaritmo do número de vezes da troponina acima do valor de referência contra o gradiente máximo pós-procedimento e das respectivas diferenças em relação ao valor de base (pré-procedimento). A correlação de Spearman foi respectivamente 0,47 (p = 0,065), não evidenciando uma correlação entre os achados. CONCLUSÃO: Por ser a troponina um marcador de injúria miocárdica, poderia se correlacionar com a queda do GVSVE na ablação por RF. Todavia, não foi observada tal concordância, apesar dos valores de troponina estarem maiores pós procedimento. Concluímos que a troponina não deve ser usada como marcador de sucesso terapêutico.

High-dose of potent statins may not be sufficient to achieve therapeutic goals of ldlc and non-hdl cholesterol in patients at very high cardiovascular risk

INTRODUCTION High-dose of potente statins are first-line and mandatory therapy to reduce LDL-c among very high cardiovascular risk patients. The Brazilian Guideline on Dyslipidemia and Prevention of Atherosclerosis of the Brazilian Society of Cardiology (SBC) recommends a target of LDL-c below 50mg/dL or non-HDL cholesterol (NHDLc) <80mg/dL. OBJECTIVE Evaluate the amount of very high-risk patients using the initial treatment recommended by the brazilian guideline that achieved the LDL-c and NHDLc therapeutic goals. METHODS This is a crosssectional observational study that included 1122 very high cardiovascular risk patients (significant atherosclerotic disease with or without clinical events or obstruction ≥ 50% in any arterial territory), treated in outpatients clinics between January and March of 2022, in a tertiary care hospital in Brazil, using atorvastatin 40 mg or 80 mg daily. Exclusion criteria were: use of atorvastatin in a dose lower than 40mg/daily or use of other statins. Data from the electronic medical record were collected regarding lipid profile, such as LDL-c and NHDLc, age and sex. RESULTS A total of 1122 patients were evaluated and 1012 were included. Mean age was 68.8 years (SD 9.2), 634 (62.4%) were men. Regarding statin use, 613 (60.6%) patients used atorvastatin 80mg/daily and 399 (39.4%) used atorvastatin 40mg/daily. Average LDL-c was 83.1mg/dL (SD 29.5) and NHDLc was 113.5mg/dL (SD 35). The mean TC was 152 mg/dL (SD 29.5), HDL-c was 39.5 (SD 11.8) and of TG was 154.9 (SD 85.6). Ninety two (9%) patients had LDL-c <50 mg/dL and 133 (13.14%) patients had NHDLc <80mg/dL. CONCLUSION The low amount of patients in this population that achieved LDL-c and NHDLc target shows that with high-intensity statins monotherapy may not be sufficient. These data suggest that in very high-risk patients, combined lipid-lowering therapy, in the initial phase, should be considered.

A unique natural selective kappa-opioid receptor agonist, salvinorin A, and its roles in human therapeutics.

Until the mid-60s, only the Mazatecs, an indigenous group from Oaxaca, Mexico, used Salvia Divinorum (S. divinorum) due to its hallucinogen properties. Later it was found that the hallucinogen effects of this plant were caused by the presence of a neoclerodane diterpene Salvinorin A (salvinorin A), which is a highly selective agonist of kappa-opioid receptor (KOR) that cause more intense hallucinations than the common hallucinogens as lysergic acid, mushrooms, ecstasy and others. In fact, smoking of only 200-500 µg of S. divinorum leaves is enough to produce these effects thus making it the most potent natural occurring hallucinogen known. Due to its legal status in various countries, this compound has gained a worldwide popularity as a drug of abuse with an easy access through smartshops and internet. Furthermore, salvinorin A gathered an increased interest in the scientific community thanks to its unique structure and properties, and various studies demonstrated that salvinorin A has antinociceptive, antidepressant, in some circumstances pro-depressant and anti-addictive effects that have yielded potential new avenues for research underlying salvinorin A and its semi-synthetic analogs as therapeutic agents.

Shared and divergent pathways for flower abscission are triggered by gibberellic acid and carbon starvation in seedless Vitis vinifera L.

BACKGROUND: Abscission is a highly coordinated developmental process by which plants control vegetative and reproductive organs load. Aiming at get new insights on flower abscission regulation, changes in the global transcriptome, metabolome and physiology were analyzed in 'Thompson Seedless' grapevine (Vitis vinifera L.) inflorescences, using gibberellic acid (GAc) spraying and shading as abscission stimuli, applied at bloom. RESULTS: Natural flower drop rates increased from 63.1% in non-treated vines to 83% and 99% in response to GAc and shade treatments, respectively. Both treatments had a broad effect on inflorescences metabolism. Specific impacts from shade included photosynthesis inhibition, associated nutritional stress, carbon/nitrogen imbalance and cell division repression, whereas GAc spraying induced energetic metabolism simultaneously with induction of nucleotide biosynthesis and carbon metabolism, therefore, disclosing alternative mechanisms to regulate abscission. Regarding secondary metabolism, changes in flavonoid metabolism were the most represented metabolic pathways in the samples collected following GAc treatment while phenylpropanoid and stilbenoid related pathways were predominantly affected in the inflorescences by the shade treatment. However, both GAc and shade treated inflorescences revealed also shared pathways, that involved the regulation of putrescine catabolism, the repression of gibberellin biosynthesis, the induction of auxin biosynthesis and the activation of ethylene signaling pathways and antioxidant mechanisms, although often the quantitative changes occurred on specific transcripts and metabolites of the pathways. CONCLUSIONS: Globally, the results suggest that chemical and environmental cues induced contrasting effects on inflorescence metabolism, triggering flower abscission by different mechanisms and pinpointing the participation of novel abscission regulators. Grapevine showed to be considered a valid model to study molecular pathways of flower abscission competence acquisition, noticeably responding to independent stimuli.

Molecular candidates for early-stage flower-to-fruit transition in stenospermocarpic table grape (Vitis vinifera L.) inflorescences ascribed by differential transcriptome and metabolome profiles.

Flower-to-fruit transition depends of nutrient availability and regulation at the molecular level by sugar and hormone signalling crosstalk. However, in most species, the identities of fruit initiation regulators and their targets are largely unknown. To ascertain the main pathways involved in stenospermocarpic table grape fruit set, comprehensive transcriptional and metabolomic analyses were conducted specifically targeting the early phase of this developmental stage in 'Thompson Seedless'. The high-throughput analyses performed disclosed the involvement of 496 differentially expressed genes and 28 differently accumulated metabolites in the sampled inflorescences. Our data show broad transcriptome reprogramming of molecule transporters, globally down-regulating gene expression, and suggest that regulation of sugar- and hormone-mediated pathways determines the downstream activation of berry development. The most affected gene was the SWEET14 sugar transporter. Hormone-related transcription changes were observed associated with increased indole-3-acetic acid, stimulation of ethylene and gibberellin metabolisms and cytokinin degradation, and regulation of MADS-box and AP2-like ethylene-responsive transcription factor expression. Secondary metabolism, the most representative biological process at transcriptome level, was predominantly repressed. The results add to the knowledge of molecular events occurring in grapevine inflorescence fruit set and provide a list of candidates, paving the way for genetic manipulation aimed at model research and plant breeding.

Flower abscission in Vitis vinifera L. triggered by gibberellic acid and shade discloses differences in the underlying metabolic pathways.

Understanding abscission is both a biological and an agronomic challenge. Flower abscission induced independently by shade and gibberellic acid (GAc) sprays was monitored in grapevine (Vitis vinifera L.) growing under a soilless greenhouse system during two seasonal growing conditions, in an early and late production cycle. Physiological and metabolic changes triggered by each of the two distinct stimuli were determined. Environmental conditions exerted a significant effect on fruit set as showed by the higher natural drop rate recorded in the late production cycle with respect to the early cycle. Shade and GAc treatments increased the percentage of flower drop compared to the control, and at a similar degree, during the late production cycle. The reduction of leaf gas exchanges under shade conditions was not observed in GAc treated vines. The metabolic profile assessed in samples collected during the late cycle differently affected primary and secondary metabolisms and showed that most of the treatment-resulting variations occurred in opposite trends in inflorescences unbalanced in either hormonal or energy deficit abscission-inducing signals. Particularly concerning carbohydrates metabolism, sucrose, glucose, tricarboxylic acid metabolites and intermediates of the raffinose family oligosaccharides pathway were lower in shaded and higher in GAc samples. Altered oxidative stress remediation mechanisms and indolacetic acid (IAA) concentration were identified as abscission signatures common to both stimuli. According to the global analysis performed, we report that grape flower abscission mechanisms triggered by GAc application and C-starvation are not based on the same metabolic pathways.