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BACKGROUND: Transthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo. METHODS: In this phase 3, double-blind trial, we randomly assigned patients with transthyretin amyloid cardiomyopathy in a 2:1 ratio to receive acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo for 30 months. Efficacy was assessed in the patients who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. The four-step primary hierarchical analysis included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6-minute walk distance. We used the Finkelstein-Schoenfeld method to compare all potential pairs of patients within strata to generate a P value. Key secondary outcomes were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary, and the serum TTR level. RESULTS: A total of 632 patients underwent randomization. The primary analysis favored acoramidis over placebo (P<0.001); the corresponding win ratio was 1.8 (95% confidence interval [CI], 1.4 to 2.2), with 63.7% of pairwise comparisons favoring acoramidis and 35.9% favoring placebo. Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0%). The overall incidence of adverse events was similar in the acoramidis group and the placebo group (98.1% and 97.6%, respectively); serious adverse events were reported in 54.6% and 64.9% of the patients. CONCLUSIONS: In patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo. Adverse events were similar in the two groups. (Funded by BridgeBio Pharma; ATTRibute-CM ClinicalTrials.gov number, NCT03860935.).
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Amiloidose , Cardiomiopatias , Fármacos Cardiovasculares , Pré-Albumina , Humanos , Amiloidose/tratamento farmacológico , Amiloidose/patologia , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/patologia , Coração , Hospitalização , Pré-Albumina/efeitos dos fármacos , Pré-Albumina/uso terapêutico , Resultado do Tratamento , Método Duplo-Cego , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Peptídeo Natriurético Encefálico/análise , Estado FuncionalRESUMO
The first-generation Molecular Microscope (MMDx) system for heart transplant endomyocardial biopsies used expression of rejection-associated transcripts (RATs) to diagnose not only T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) but also acute injury. However, the ideal system should detect rejection without being influenced by injury, to permit analysis of the relationship between rejection and parenchymal injury. To achieve this, we developed a new rejection classification in an expanded cohort of 3230 biopsies: 1641 from INTERHEART (ClinicalTrials.gov NCT02670408), plus 1589 service biopsies added to improve the power of the machine learning algorithms. The new system used 6 rejection classifiers instead of RATs and generated 7 rejection archetypes: No rejection, 48%; Minor, 24%; TCMR1, 2.3%; TCMR2, 2.7%; TCMR/mixed, 2.7%; early-stage ABMR, 3.9%; and fully developed ABMR, 16%. Using rejection classifiers eliminated cross-reactions with acute injury, permitting separate assessment of rejection and injury. TCMR was associated with severe-recent injury and late atrophy-fibrosis and rarely had normal parenchyma. ABMR was better tolerated, seldom producing severe injury, but in later biopsies was often associated with atrophy-fibrosis, indicating long-term risk. Graft survival and left ventricular ejection fraction were reduced not only in hearts with TCMR but also in hearts with severe-recent injury and atrophy-fibrosis, even without rejection.
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Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Coração , Transplante de Coração/efeitos adversos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/patologia , Humanos , Masculino , Biópsia , Feminino , Pessoa de Meia-Idade , Seguimentos , Prognóstico , Miocárdio/patologia , Adulto , Fatores de RiscoRESUMO
"Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation, and the use of cardiovascular magnetic resonance (CMR) in the diagnosis and management of cardiovascular disease. The 2023 digital collection of cases are presented in this manuscript.
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Ivabradine is a pharmacologic agent that inhibits the funny current responsible for determining heart rate in the sinoatrial node. Ivabradine's clinical potential has been investigated in the context of heart failure since it is associated with reduced myocardial oxygen demand, enhanced diastolic filling, stroke volume, and coronary perfusion time; however, it is yet to demonstrate definitive mortality benefit. Alternative effects of ivabradine include modulation of the renin-angiotensin-aldosterone system, sympathetic activation, and endothelial function. Here, we review key clinical trials informing the clinical use of ivabradine and explore opportunities for leveraging its potential pleiotropic effects in other diseases, including treatment of hyperadrenergic states and mitigating complications of COVID-19 infection.
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INTRODUCTION: Heart transplant (HT) recipients with prior exposure to cytomegalovirus (CMV R+) are considered intermediate risk for CMV-related complications. Consensus guidelines allow for either universal prophylaxis (UP) or preemptive therapy (PET) (serial CMV testing) approaches to CMV prevention in such patients. Whether an optimal approach to mitigate CMV related risks exists in this setting remains uncertain. We therefore assessed the utility of PET as compared to UP in CMV R+ HT recipients. METHODS: Retrospective analysis of all CMV R+ HT recipients from 6 U.S. centers between 2010 and 2018 was performed. The primary outcome was the development of CMV DNAemia or end-organ disease resulting in the initiation/escalation of anti-CMV therapy. The secondary outcome was CMV-related hospitalization. Additional outcomes included incidence of acute cellular rejection (ACR) ≥ grade 2R, death, cardiac allograft vasculopathy (CAV), and leukopenia. RESULTS: Of 563 CMV R+ HT recipients, 344 (61.1%) received UP. PET was associated with increased risk for the primary (adjusted HR 3.95, 95% CI: 2.65-5.88, p < .001) and secondary (adjusted HR 3.19, 95% CI: 1.47-6.94, p = .004) outcomes, and with increased ACR ≥ grade 2R (PET 59.4% vs. UP 34.4%, p < .001). Incidence of detectable CAV was similar at 1 year (PET 8.2% vs. UP 9.5%, p = .698). UP was associated with increased incidence of leukopenia within 6 months post-HT (PET 34.7% vs. UP 43.6%, p = .036). CONCLUSION: The use of a PET CMV prophylaxis strategy in intermediate risk HT recipients associated with increased risk of CMV infection and CMV-related hospitalization, and may associate with worse post-HT graft outcomes.
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Infecções por Citomegalovirus , Transplante de Coração , Leucopenia , Humanos , Antivirais/uso terapêutico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir , Transplante de Coração/efeitos adversos , Leucopenia/tratamento farmacológico , Estudos RetrospectivosRESUMO
INTRODUCTION: Analgesia Nociception Index (ANI) as a monitor of peri-operative nociception-anti-nociception balance has not been studied in paediatric neurosurgery. The objectives were to study the correlation between ANI (Mdoloris Education system) and revised FLACC (r-FLACC) score for the prediction of acute postoperative pain in paediatric population undergoing elective craniotomies and to compare the changes in ANI values with heart rate (HR), mean arterial pressure (MAP) and surgical plethysmographic index (SPI) during various time points of intraoperative noxious stimulation and before and after opioid administration. METHODS: This prospective observational pilot study included 14 patients between 2 and 12 years of age undergoing elective craniotomies. HR, MAP, SPI, ANI instantaneous (ANIi) and ANI mean (ANIm) values were recorded intraoperatively and before and after opioid administration. Postoperatively HR, MAP, ANIi and ANIm, and pain scores (r-FLACC scale) were recorded. RESULTS: There was a statistically significant negative correlation between ANIi and ANIm with r-FLACC during the time course of PACU stay (r = - 0.89, p < 0.001 and r = - 0.88 and p < 0.001 respectively). Intraoperatively, in patients with ANIi values < 50, with additional fentanyl administration, there was an increasing trend in values beyond 50, which was statistically significant (p < 0.05) at 3, 4, 5 and 10 min. The trend in changes of SPI after opioid administration was not found to be significant for patients irrespective of the baseline SPI values. CONCLUSION: The ANI is a reliable tool for objective assessment of acute postoperative pain as assessed by r-FLACC in children undergoing craniotomies for intracranial lesions. It may be used as a guide to nociception-antinociception balance during the peri-operative period in this population.
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Analgesia , Analgésicos Opioides , Humanos , Criança , Analgésicos Opioides/uso terapêutico , Nociceptividade/fisiologia , Estudos Prospectivos , Frequência Cardíaca/fisiologia , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , CraniotomiaRESUMO
BACKGROUND: After heart transplantation, endomyocardial biopsy (EMBx) is used to monitor for acute rejection (AR). Unfortunately, EMBx is invasive, and its conventional histological interpretation has limitations. This is a validation study to assess the performance of a sensitive blood biomarker-percent donor-derived cell-free DNA (%ddcfDNA)-for detection of AR in cardiac transplant recipients. METHODS: This multicenter, prospective cohort study recruited heart transplant subjects and collected plasma samples contemporaneously with EMBx for %ddcfDNA measurement by shotgun sequencing. Histopathology data were collected to define AR, its 2 phenotypes (acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), and controls without rejection. The primary analysis was to compare %ddcfDNA levels (median and interquartile range [IQR]) for AR, AMR, and ACR with controls and to determine %ddcfDNA test characteristics using receiver-operator characteristics analysis. RESULTS: The study included 171 subjects with median posttransplant follow-up of 17.7 months (IQR, 12.1-23.6), with 1392 EMBx, and 1834 %ddcfDNA measures available for analysis. Median %ddcfDNA levels decayed after surgery to 0.13% (IQR, 0.03%-0.21%) by 28 days. Also, %ddcfDNA increased again with AR compared with control values (0.38% [IQR, 0.31-0.83%], versus 0.03% [IQR, 0.01-0.14%]; P<0.001). The rise was detected 0.5 and 3.2 months before histopathologic diagnosis of ACR and AMR. The area under the receiver operator characteristic curve for AR was 0.92. A 0.25%ddcfDNA threshold had a negative predictive value for AR of 99% and would have safely eliminated 81% of EMBx. In addition, %ddcfDNA showed distinctive characteristics comparing AMR with ACR, including 5-fold higher levels (AMR ≥2, 1.68% [IQR, 0.49-2.79%] versus ACR grade ≥2R, 0.34% [IQR, 0.28-0.72%]), higher area under the receiver operator characteristic curve (0.95 versus 0.85), higher guanosine-cytosine content, and higher percentage of short ddcfDNA fragments. CONCLUSIONS: We found that %ddcfDNA detected AR with a high area under the receiver operator characteristic curve and negative predictive value. Monitoring with ddcfDNA demonstrated excellent performance characteristics for both ACR and AMR and led to earlier detection than the EMBx-based monitoring. This study supports the use of %ddcfDNA to monitor for AR in patients with heart transplant and paves the way for a clinical utility study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.
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Aloenxertos/transplante , Ácidos Nucleicos Livres/genética , Rejeição de Enxerto/fisiopatologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: To assess the outcomes of a single-center experience with percutaneous left ventricular assist device (LVAD) decommissioning. BACKGROUND: Patients with LVADs may eventually require their removal, either due to recovery of left ventricular function or recurrent complications. Traditionally, withdrawal of LVAD support has been managed with surgical device explantation, which carries significant procedural risks. Transcatheter LVAD decommissioning, with outflow graft occlusion and driveline transection, has recently been described as an alternative to surgical removal. METHODS: Here, we report on a retrospective cohort of five consecutive cases treated with transcatheter LVAD decommissioning. RESULTS: The procedure was effective in all cases, and no patient experienced procedure-related complications. At midterm follow-up, the three patients who had myocardial function recovery were alive and had not experienced heart failure-related symptoms or complications. CONCLUSION: Percutaneous LVAD decommissioning appears to be a safe and effective approach to LVAD treatment discontinuation.
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Insuficiência Cardíaca , Coração Auxiliar , Remoção de Dispositivo/métodos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
BACKGROUND: LVADs provide life-sustaining treatment for patients with heart failure, but their complexity allows for complications. One complication, LVAD outflow graft obstruction, may be misdiagnosed as intraluminal thrombus, when more often it is extraluminal compression from biodebris accumulation. It can often be treated endovascularly with stenting. This case series describes diagnostic and procedural techniques for the treatment of left ventricular assist device (LVAD) outflow graft obstruction. METHODS: We present four patients with LVADs who developed LVAD outflow graft obstruction within the bend relief-covered segment. All were initially diagnosed with computed tomographic angiography (CTA). All underwent invasive evaluation with intravascular ultrasound (IVUS), then were treated with stenting. After misdiagnosing a twist, we developed the technique of balloon "graftoplasty" to ensure suitability for stent delivery in subsequent cases. RESULTS: All patients presented with low-flow alarms and symptoms of low output, and were diagnosed with outflow graft obstruction by CTA. In all four, IVUS confirmed an extraluminal etiology. Patient 1 was treated with stenting and had a good outcome. Patient 2's obstruction was from twisting, rather than biodebris accumulation, and had sub-optimal stent expansion and ultimately required surgery. Balloon "graftoplasty" was used in subsequent cases to ensure subsequent stent expansion. Patients 3 and 4 were successfully stented. All improved after treatment. CONCLUSIONS: In patients with LVAD outflow graft obstruction, IVUS can distinguish intraluminal thrombus from extraluminal compression. Balloon "graftoplasty" can ensure that the outflow graft will respond to stenting. Many cases of LVAD outflow graft obstruction should be amenable to endovascular treatment.
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Insuficiência Cardíaca , Coração Auxiliar , Obstrução do Fluxo Ventricular Externo , Coração Auxiliar/efeitos adversos , Humanos , Stents , Resultado do TratamentoRESUMO
ABSTRACT: The transthyretin (TTR) amyloidoses result from misfolding of the protein leading to fibril formation and aggregation as amyloid deposits in predominantly the cardiovascular and nervous systems. Cardiac involvement can manifest as heart failure, arrhythmias, and valvular disease. Neurologic involvement can cause sensorimotor polyneuropathies, mononeuropathies, and dysautonomia. Previously, treatment has focused on management of these symptoms and disease sequelae, with a high rate of mortality due to the absence of disease-modifying therapies. In this article, we review novel treatments focusing on 3 mechanistic pathways: (1) silencing of the TTR gene to suppress production, (2) stabilizing of TTR tetramers to prevent misfolding, or (3) disrupting of existing TTR amyloid fibrils to promote reabsorption.
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Neuropatias Amiloides Familiares/terapia , Amiloide/efeitos dos fármacos , Cardiomiopatias/terapia , Fármacos Cardiovasculares/uso terapêutico , Terapia Genética , Miócitos Cardíacos/efeitos dos fármacos , Pré-Albumina/genética , Amiloide/metabolismo , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/metabolismo , Neuropatias Amiloides Familiares/patologia , Animais , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Fármacos Cardiovasculares/efeitos adversos , Inativação Gênica , Predisposição Genética para Doença , Humanos , Mutação , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fenótipo , Pré-Albumina/metabolismo , Estabilidade ProteicaRESUMO
In order to develop the antimicrobial and antitubercular agents, we have derived quinoline bearing dihydropyrimidine analogues 5a-o and structures of these compounds were determined by spectroscopic techniques. Further, we have calculated the molecular properties prediction and drug-likeness by Molinspiration property calculation toolkit and MolSoft software, respectively. The most active compound against Mycobacterium tuberculosis (5m, MIC = 0.20 µg/mL) also possessed a maximum drug-likeness model score (0.42). Compounds 5m, 5g and 5k were possessed promising antibacterial activity against tested bacterial species. Compound 5k was the only compound to have eye-catcher antifungal activity. Furthermore, the MTT cytotoxicity results on HeLa cells suggested lower cytotoxicity of biologically active compounds. Supramolecular interactions of the synthesized compounds has been assessed my means of molecular docking studies. Although all the synthesized compounds are showing preferably good interactions with their respective proteins, their binding free energies values suggest that these molecules are preferred for antitubercular activity rather than antimicrobial activity.
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Anti-Infecciosos/síntese química , Antituberculosos/síntese química , Quinolinas/química , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Antituberculosos/metabolismo , Antituberculosos/farmacologia , Sítios de Ligação , Sobrevivência Celular/efeitos dos fármacos , DNA Girase/química , DNA Girase/metabolismo , Desenho de Fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HeLa , Humanos , Ligação de Hidrogênio , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Quinidina/análogos & derivados , Quinidina/química , Quinolinas/metabolismo , Quinolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
BACKGROUND: The incidence of hemodialysis (HD)-dependent renal failure after total artificial heart (TAH) implantation is high. We sought to determine the preoperative predictors of HD after TAH implantation. METHODS AND RESULTS: We studied 87 patients after TAH implantation at our institution between April 2006 and March 2017. Baseline clinical data were obtained from the medical records, and patients were followed until death or heart transplantation. We performed logistic regression analysis to identify predictors of HD after TAH implantation. Of the patients, 24 (28%) required postimplantation HD. Those requiring HD were more likely to have histories of coronary artery disease (58% vs 29%; Pâ¯=â¯0.01), required preoperative membrane oxygenation (33% vs 4.8%; Pâ¯=â¯0.001) and had lower baseline estimated glomerular filtration rates (54 ± 29 vs 67 ± 24 mL/min/1.73m2; Pâ¯=â¯0.04). Patients requiring HD were at a higher risk of death on device at 1 year (33% vs 5%, Pâ¯=â¯0.001; log rank test: P =0.001, hazard ratio 6.6 [95% CI:1.8-23], Pâ¯=â¯0.003). CONCLUSIONS: The incidence of postimplantation HD is high and is associated with increased likelihood of mortality. Lower baseline estimated glomerular filtration rates, histories of coronary artery disease and preoperative membrane oxygenation support are predictors of postimplantation requirement of HD. These data may help to identify patients at risk for adverse outcomes after TAH implantation.
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Insuficiência Cardíaca , Transplante de Coração , Coração Artificial , Insuficiência Renal , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Coração Artificial/efeitos adversos , Humanos , Diálise Renal/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: We studied longitudinal levels of angiotensin-II type 1 receptor antibody (AT1R-Ab) and their effects on adverse events (death, treated rejection and cardiac allograft vasculopathy) in patients who were bridged to heart transplant using a continuous flow left ventricular assist device (LVAD). METHODS AND RESULTS: Sera of 77 patients bridged to heart transplant (from 2009 to 2017) were tested for AT1R-Ab and CRP before and after LVAD. Elevated AT1R-Ab was defined as >10.0 U/mL. The median follow-up after transplant was 3.6 years (interquartile range, 2.2-5.6 years). After LVAD, AT1R-Ab levels increased from baseline and remained elevated until transplant. Freedom from adverse events at 5 years was lower in those with elevated AT1R-Ab levels at time of transplant. In an adjusted, multivariable Cox analysis, an AT1R-Ab level of >10 U/mL was associated with developing the primary end point (adjusted hazard ratio 3.4, 95% confidence interval 1.2-9.2, Pâ¯=â¯.017). Although C-reactive protein levels were high before and after LVAD placement, C-reactive protein did not correlate with AT1R-Ab. CONCLUSIONS: In LVAD patients bridged to heart transplant, an increased AT1R-Ab level at time of transplant was associated with poor outcomes after heart transplant. Post-LVAD AT1R-Ab elevations were not correlated with serum markers of systemic inflammation. Larger studies are needed to examine the pathologic role of AT1R-Ab in heart transplant.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Transplante de Coração/efeitos adversos , Coração Auxiliar/efeitos adversos , Humanos , Morbidade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Worsening heart failure (HF) and health-related quality of life (HRQOL) have been shown to impact the decision to proceed with left ventricular assist device (LVAD) implantation, but little is known about how socioeconomic factors influence expressed patient preference for LVAD. METHODS AND RESULTS: Ambulatory patients with advanced systolic HF (n=353) reviewed written information about LVAD therapy and completed a brief survey to indicate whether they would want an LVAD to treat their current level of HF. Ordinal logistic regression analyses identified clinical and demographic predictors of LVAD preference. Higher New York Heart Association (NYHA) class, worse HRQOL measured by Kansas City Cardiomyopathy Questionnaire, lower education level, and lower income were significant univariable predictors of patients wanting an LVAD. In the multivariable model, higher NYHA class (OR [odds ratio]: 1.43, CI [confidence interval]: 1.08-1.90, Pâ¯=â¯.013) and lower income level (OR: 2.10, CI: 1.18 - 3.76, Pâ¯=â¯.012 for <$40,000 vs >$80,000) remained significantly associated with wanting an LVAD. CONCLUSION: Among ambulatory patients with advanced systolic HF, treatment preference for LVAD was influenced by level of income independent of HF severity. Understanding the impact of socioeconomic factors on willingness to consider LVAD therapy may help tailor counseling towards individual needs.
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Insuficiência Cardíaca , Coração Auxiliar , Insuficiência Cardíaca/terapia , Humanos , Estudos Prospectivos , Qualidade de Vida , Fatores Socioeconômicos , Resultado do TratamentoRESUMO
BACKGROUND: Canagliflozin reduces hospitalizations for heart failure (HF) in type 2 diabetes mellitus (T2DM). Its effect on cardiorespiratory fitness and cardiac function in patients with established HF with reduced ejection fraction (HFrEF) is unknown. METHODS: We conducted a double-blind randomized controlled trial of canagliflozin 100 mg or sitagliptin 100 mg daily for 12 weeks in 88 patients, and measured peak oxygen consumption (VO2 ) and minute ventilation/carbon dioxide production (VE/VCO2 ) slope (co-primary endpoints for repeated measure ANOVA time_x_group interaction), lean peak VO2 , ventilatory anaerobic threshold (VAT), cardiac function and quality of life (ie, Minnesota Living with Heart Failure Questionnaire [MLHFQ]), at baseline and 12-week follow-up. RESULTS: The study was terminated early due to the new guidelines recommending canagliflozin over sitagliptin in HF: 17 patients were assigned to canagliflozin and 19 to sitagliptin, total of 36 patients. There were no significant changes in peak VO2 and VE/VCO2 slope between the two groups (P = .083 and P = .98, respectively). Canagliflozin improved lean peak VO2 (+2.4 mL kgLM-1 min-1 , P = .036), VAT (+1.5 mL kg-1 min-1 , P = .012) and VO2 matched for respiratory exchange ratio (+2.4 mL Kg-1 min-1 , P = .002) compared to sitagliptin. Canagliflozin also reduced MLHFQ score (-12.1, P = .018). CONCLUSIONS: In this small and short-term study of patients with T2DM and HFrEF, interrupted early after only 36 patients, canagliflozin did not improve the primary endpoints of peak VO2 or VE/VCO2 slope compared to sitagliptin, while showing favourable trends observed on several additional surrogate endpoints such as lean peak VO2 , VAT and quality of life.
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Canagliflozina/uso terapêutico , Aptidão Cardiorrespiratória , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Consumo de Oxigênio/efeitos dos fármacos , Qualidade de Vida , Fosfato de Sitagliptina/uso terapêutico , Biomarcadores/análise , Diabetes Mellitus Tipo 2/patologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume SistólicoRESUMO
AIM: Our study aimed to examine factors that contribute to cognitive dysfunction in patients with heart failure (HF). BACKGROUND: Although a majority of patients with HF have mild to moderate cognitive impairment, little is known about factors that influence progressive cognitive decline in this population. METHODS: We examined the influence of physiological factors (NYHA functional class II - IV, ejection fraction, co-morbidity burden, polypharmacy), psychosocial factors (anxiety, depression, evaluation for advanced therapy), and associated toxicities (anticholinergic drug burden), on cognitive dysfunction. Data were analyzed using mean (SE) for continuous variables and frequency and percent for categorical variables. Differences between NYHA functional classification (Class II vs. Class III/IV) were examined using Chi Square. Linear regression models were used to assess associations among model variables. RESULTS: Of the 113 participants with HF, Class III-IV HF were more cognitively impaired than those with NYHA Class II (p < 0.0001), had higher anxiety (p = 0.002), and depression (p = 0.003), and lower EF (p = 0.041). A majority of participants had a moderate anticholinergic drug burden, and NYHA Class III/IV participants had significantly higher medication counts than Class II participants (p = 0.034). Regression analysis found that NYHA Class III/IV, anxiety, depression and evaluation for advanced therapy significantly influenced cognitive dysfunction. CONCLUSIONS: Findings support a high prevalence of cognitive dysfunction, anxiety, and depression in NYHA class II-IV with a greater level of cognitive dysfunction in class III/IV patients.
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Disfunção Cognitiva , Insuficiência Cardíaca , Ansiedade , Insuficiência Cardíaca/complicações , Humanos , PrevalênciaRESUMO
BACKGROUND: Left ventricular assist devices (LVADs) have revolutionized the treatment of advanced heart failure, but proliferation of device therapy has unmasked potential complications. Reports have emerged of outflow graft narrowing due to extrinsic compression. METHODS AND RESULTS: The records of patients with LVADs that had been implanted at our institution were reviewed. Those who had postimplantation computed tomography angiographies sufficient to analyze the outflow graft lumen were identified, and the studies were analyzed to characterize the outflow graft lumen. We identified 241 patients; 110 (46%) had suitable computed tomography angiographies. Of those, 15 (14%) had evidence of outflow graft lumen narrowing, all in HeartMate devices and all within the portion covered by the bend relief. Of the 15, 3 underwent invasive examination, all without intraluminal thrombus but, rather, with biodebris between the bend relief and the outflow graft. Patients with HeartWare devices had a wide range of biodebris accumulation surrounding the outflow graft but no cases of lumen narrowing. On multivariable analysis, 1) time from device implant to scan, 2) nonischemic cardiomyopathy and 3) age at implant were significantly associated with higher risk of graft narrowing. CONCLUSION: Outflow graft narrowing can be seen in a number of patients with HeartMate LVADs within the portion covered by the bend relief. In the limited number of patients who underwent invasive evaluation, the narrowing was found to arise from extrinsic compression rather than intraluminal thrombus. The clinical significance of this requires further investigation.
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Oclusão de Enxerto Vascular , Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Implantação de Prótese , Reoperação , Angiografia por Tomografia Computadorizada/métodos , Angiografia por Tomografia Computadorizada/estatística & dados numéricos , Análise de Falha de Equipamento , Feminino , Oclusão de Enxerto Vascular/diagnóstico , Oclusão de Enxerto Vascular/epidemiologia , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/terapia , Coração Auxiliar/efeitos adversos , Coração Auxiliar/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Desenho de Prótese , Implantação de Prótese/efeitos adversos , Implantação de Prótese/métodos , Reoperação/instrumentação , Reoperação/métodos , Reoperação/estatística & dados numéricos , Stents , Estados Unidos/epidemiologiaRESUMO
Mechanical circulatory support is now widely accepted as a viable long-term treatment option for patients with end-stage heart failure (HF). As the range of indications for the implantation of ventricular assist devices grows, so does the number of patients living in the community with durable support. Because of their underlying disease and comorbidities, in addition to the presence of mechanical support, these patients are at a high risk for medical urgencies and emergencies (Table 1). Thus, it is the responsibility of clinicians to understand the basics of their emergency care. This consensus document represents a collaborative effort by the Heart Failure Society of America, the Society for Academic Emergency Medicine, and the International Society for Heart and Lung Transplantation (ISHLT) to educate practicing clinicians about the emergency management of patients with ventricular assist devices. The target audience includes HF specialists and emergency medicine physicians, as well as general cardiologists and community-based providers.