The rare case of double valve surgery in a patient with factor VII deficiency.

Performing cardiac surgery on patients with bleeding diatheses poses significant challenges since these patients are at an increased risk for complications secondary to excessive bleeding. Despite its rarity, patients with factor VII (FVII) deficiency may require invasive procedures such as cardiac surgery. However, we lack guidelines on their pre-, peri-, and post-operative management. As FVII deficiency is rare, it seems unlikely to design and learn from large clinical studies. Instead, we need to base our clinical decision-making on single reported cases and registry data. Herein, we present the rare case of a patient with FVII deficiency who underwent double valve surgery. Pre-operatively, activated recombinant FVII (rFVIIa) was administered to reduce the risk of bleeding. Nevertheless, the patient experienced major bleeding. This case highlights the significance of FVII deficiency in patients undergoing cardiac surgery and emphasizes the importance of adequate and appropriate transfusion of blood products for these patients.

Coronary artery disease in post-menopausal women: are there appropriate means of assessment?

The recognition of sex differences in cardiovascular disease, particularly the manifestations of coronary artery disease (CAD) in post-menopausal women, has introduced new challenges in not only understanding disease mechanisms but also identifying appropriate clinical means of assessing the efficacy of management strategies. For example, the majority of treatment algorithms for CAD are derived from the study of males, focus on epicardial stenoses, and inadequately account for the small intramyocardial vessel disease in women. However, newer investigational modalities, including stress perfusion cardiac magnetic resonance imaging and positron emission tomography are providing enhanced diagnostic accuracy and prognostication for women with microvascular disease. Moreover, these investigations may soon be complemented by simpler screening tools such as retinal vasculature imaging, as well as novel biomarkers (e.g. heat shock protein 27). Hence, it is vital that robust, sex-specific cardiovascular imaging modalities and biomarkers continue to be developed and are incorporated into practice guidelines that are used to manage women with CAD, as well as gauge the efficacy of any new treatment modalities. This review provides an overview of some of the sex differences in CAD and highlights emerging advances in the investigation of CAD in post-menopausal women.

Heat shock protein 27 in the pathogenesis of COVID-19 and non-COVID acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure in intensive care units that has increased dramatically as a result of the COVID-19 pandemic. In both COVID-19 and non-COVID ARDS, the pathogenesis of lung injury involves local (pulmonary) and systemic inflammation, leading to impaired gas exchange, requirement for mechanical ventilation, and a high risk of mortality. Heat shock protein 27 (HSP27) is a chaperone protein expressed in times of cell stress with roles in modulation of systemic inflammation via the NF-κB pathway. Given its important role as a modulator of inflammation, we sought to investigate the role of HSP27 and its associated auto-antibodies in ARDS caused by both SARS-CoV-2 and non-COVID etiologies. A total of 68 patients admitted to the intensive care unit with ARDS requiring mechanical ventilation were enrolled in a prospective, observational study that included 22 non-COVID-19 and 46 COVID-19 patients. Blood plasma levels of HSP27, anti-HSP27 auto-antibody (AAB), and cytokine profiles were measured on days 1 and 3 of ICU admission along with clinical outcome measures. Patients with COVID-19 ARDS displayed significantly higher levels of HSP27 in plasma, and a higher ratio of HSP27:AAB on both day 1 and day 3 of ICU admission. In patients with COVID-19, higher levels of circulating HSP27 and HSP27:AAB ratio were associated with a more severe systemic inflammatory response and adverse clinical outcomes including more severe hypoxemic respiratory failure. These findings implicate HSP27 as a marker of advanced pathogenesis of disease contributing to the dysregulated systemic inflammation and worse clinical outcomes in COVID-19 ARDS, and therefore may represent a potential therapeutic target.

Apolipoprotein-induced conversion of phosphatidylcholine bilayer vesicles into nanodisks.

Apolipoprotein mediated formation of nanodisks was studied in detail using apolipophorin III (apoLp-III), thereby providing insight in apolipoprotein-lipid binding interactions. The spontaneous solubilization of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles occured only in a very narrow temperature range at the gel-liquid-crystalline phase transition temperature, exhibiting a net exothermic interaction based on isothermal titration calorimetry analysis. The resulting nanodisks were protected from proteolysis by trypsin, endoproteinase Glu-C, chymotrypsin and elastase. DMPC solubilization and the simultaneous formation of nanodisks were promoted by increasing the vesicle diameter, protein to lipid ratio and concentration. Inclusion of cholesterol in DMPC dramatically enhanced the rate of nanodisk formation, presumably by stabilization of lattice defects which form the main insertion sites for apolipoprotein α-helices. The presence of fully saturated acyl chains with a length of 13 or 14 carbons in phosphatidylcholine allowed the spontaneous vesicle solubilization upon apolipoprotein addition. Nanodisks with C13:0-phosphatidylcholine were significantly smaller with a diameter of 11.7 ± 3.1nm compared to 18.5 ± 5.6 nm for DMPC nanodisks determined by transmission electron microscopy. Nanodisk formation was not observed when the phosphatidylcholine vesicles contained acyl chains of 15 or 16 carbons. However, using very high concentrations of lipid and protein (>10mg/ml), 1,2,-dipalmitoyl-sn-glycero-3-phosphocholine nanodisks could be produced spontaneously although the efficiency remained low.

Late Stent Thrombosis in a Patient with Endovascular Aortic Repair for Blunt Thoracic Aortic Injury.

Blunt thoracic aortic injury (BTAI) is associated with high mortality and morbidity. Thoracic endovascular aortic repair has become the recommended treatment modality given improved short-term results compared to open repair. We present a case of a 19-year-old male who presented with acute paralysis and multiorgan dysfunction from acute TEVAR thrombosis. Systemic thrombolysis, catheter-directed thrombolysis followed by aspiration thrombectomy, and angioplasty were initially successful in restoring perfusion. However, he developed progressive multiorgan failure related to prompt reocclusion within 48 hours. This case is the first to describe thrombolysis and angioplasty as a management strategy for acute TEVAR thrombosis. We also review the literature surrounding this uncommon complication.

Corrigendum to "Massive Acetaminophen Overdose Treated Successfully with N-Acetylcysteine, Fomepizole, and Hemodialysis".

[This corrects the article DOI: 10.1155/2021/6695967.].

Massive Acetaminophen Overdose Treated Successfully with N-Acetylcysteine, Fomepizole, and Hemodialysis.

Acetaminophen overdose is one of the most common causes of acute hepatic failure in the developed world. There is strong evidence for N-acetylcysteine (NAC) as a safe and effective antidote for acetaminophen toxicity. However, there is less clarity in the management of massive overdoses (acute, single ingestions > 500 mg/kg with 4-hour equivalent concentrations ~6000 µmol/L) which are often associated with metabolic acidosis and multiorgan dysfunction. In such ingestions, the role of adjuvant treatments such as fomepizole and extracorporeal removal is unclear. We present a case of a 20-year-old female presenting with an acute ingestion of over 120 grams (1764.7 mg/kg) and an acetaminophen concentration of 5880 µmol/L who developed refractory shock, decreased level of consciousness, and metabolic acidosis requiring mechanical ventilation and vasopressor support. She was treated with gastric decontamination with activated charcoal, IV NAC, fomepizole, and hemodialysis. The patient had complete clearance of acetaminophen by 32 hours after presentation and normalization of her acid base and hemodynamic status without any organ failure. This case highlights the potential benefit of a triple strategy of NAC, fomepizole, and early hemodialysis in massive acetaminophen overdose, potentially sparing complications of prolonged intubation and ICU hospitalization.

Review of Stereotactic Arrhythmia Radioablation Therapy for Cardiac Tachydysrhythmias.

Cardiac tachyarrhythmias are a major cause of morbidity and mortality. Treatments for these tachyarrhythmias include antiarrhythmic drugs, catheter ablation, surgical ablation, cardiac implantable electronic devices, and cardiac transplantation. Each of these treatment approaches is effective in some patients but there is considerable room for improvement, particularly with respect to the most common of the tachydysrhythmias, atrial fibrillation, and the most dangerous of the tachydysrhythmias, ventricular tachycardia (VT) or ventricular fibrillation. Noninvasive stereotactic ablative radiation therapy is emerging as an effective treatment for refractory tachyarrhythmias. Animal models have shown successful ablation of arrhythmogenic myocardial substrates with minimal short-term complications. Studies of stereotactic radioablation involving patients with refractory VT have shown a reduction in VT recurrence and promising early safety data. In this review, we provide the background for the application of stereotactic arrhythmia radioablation therapy along with promising results from early applications of the technology.

Les tachyarythmies cardiaques sont une cause importante de morbidité et de mortalité. Les traitements employés comprennent des antiarythmiques, l'ablation par cathéter, l'ablation par chirurgie, l'implantation de dispositifs cardiaques électroniques et la transplantation cardiaque. Toutes ces démarches thérapeutiques sont efficaces dans certains cas, mais les traitements peuvent encore être largement améliorés, en particulier en ce qui concerne la fibrillation auriculaire, qui est la tachyarythmie la plus fréquente, et la tachycardie ventriculaire (TV, aussi appelée fibrillation ventriculaire), qui est la tachyarythmie la plus dangereuse. La radiochirurgie stéréotaxique non invasive se démarque de plus en plus comme traitement efficace des tachyarythmies réfractaires. Des substrats myocardiques arythmogènes ont pu être réséqués avec succès sur des modèles animaux, l'intervention n'ayant entraîné que des complications minimales de courte durée. Dans le cadre d'études menées auprès de patients présentant une TV réfractaire, la radiochirurgie stéréotaxique a permis de réduire le risque de récurrence de la TV, et les premières données sur l'innocuité du traitement sont encourageantes. Dans notre revue, nous précisons le cadre d'application de la radiochirurgie stéréotaxique visant à réséquer le tissu responsable de l'arythmie, et nous présentons les résultats prometteurs des premières applications de la technologie à cette fin.

Apolipophorin III interaction with model membranes composed of phosphatidylcholine and sphingomyelin using differential scanning calorimetry.

Apolipophorin III (apoLp-III) from Locusta migratoria was employed as a model apolipoprotein to gain insight into binding interactions with lipid vesicles. Differential scanning calorimetry (DSC) was used to measure the binding interaction of apoLp-III with liposomes composed of mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and sphingomyelin (SM). Association of apoLp-III with multilamellar liposomes occurred over a temperature range around the liquid crystalline phase transition (L(alpha)). Qualitative and quantitative data were obtained from changes in the lipid phase transition upon addition of apoLp-III. Eleven ratios of DMPC and SM were tested from pure DMPC to pure SM. Broadness of the phase transition (T(1/2)), melting temperature of the phase transition (T(m)) and enthalpy were used to determine the relative binding affinity to the liposomes. Multilamellar vesicles composed of 40% DMPC and 60% SM showed the greatest interaction with apoLp-III, indicated by large T(1/2) values. Pure DMPC showed the weakest interaction and liposomes with lower percentage of DMPC retained domains of pure DMPC, even upon apoLp-III binding indicating demixing of liposome lipids. Addition of apoLp-III to rehydrated liposomes was compared to codissolved trials, in which lipids were rehydrated in the presence of protein, forcing the protein to interact with the lipid system. Similar trends between the codissolved and non-codissolved trials were observed, indicating a similar binding affinity except for pure DMPC. These results suggested that surface defects due to non-ideal packing that occur at the phase transition temperature of the lipid mixtures are responsible for apolipoprotein-lipid interaction in DMPC/SM liposomes.

Apolipophorin III interaction with phosphatidylglycerol and lipopolysaccharide: A potential mechanism for antimicrobial activity.

Apolipophorin III (apoLp-III) is a model insect apolipoprotein to study structure-function relationships of exchangeable apolipoproteins. The protein associates with lipoproteins to aid in the transport of neutral lipids, and also interacts with the bacterial membrane. To better understand a potential role as an antimicrobial protein, the binding interaction of apoLp-III from Locust migratoria and Galleria mellonella with phosphatidylglycerol and lipopolysaccharides was analyzed. ApoLp-III from either species induced a robust release of calcein from phosphatidylglycerol vesicles, but was ineffective for phosphatidylcholine vesicles with comparable side-chain architecture. Acetylation of L. migratoria apoLp-III lysine residues greatly reduced the calcein release from phosphatidylglycerol vesicles, indicating a critical role of lysine side-chains in phosphatidylglycerol vesicles interaction. Isothermal calorimetry provided Kd values of 0.26 µM (L. migratoria) and 0.50 µM (G. mellonella) for binding to dimyristoylphosphatidylglycerol vesicles, which is an order of magnitude stronger compared to zwitterionic vesicles. A strong preference of apoLp-III for dimyristoylphosphatidylglycerol vesicles was also observed with differential scanning calorimetry with a concentration dependent shift in the lipid phase transition temperature. Native PAGE analysis showed that LPS binding was significantly weaker for L. migratoria apoLp-III compared to G. mellonella apoLp-III. This difference was confirmed by fluorescence titration analysis of L. migratoria apoLp-III, which also indicated that acetylation of the apolipoprotein did not affect LPS binding. Taken together, the results indicate that apoLp-III phosphatidylglycerol interaction may follow a detergent model with an important electrostatic binding component. Since lipopolysaccharide binding was not affected by neutralization of apoLp-III lysine-side chains, the binding interaction may be distinctly different from that of phosphatidylglycerol.

Myocarditis and Eosinophilia: Three Cases of Hypereosinophilic Syndrome and Myocarditis.

Eosinophilic infiltration is a rare and underrecognized cause of myocarditis associated with prolonged eosinophilia. Before advanced imaging and routine biopsy, patients were diagnosed with an idiopathic cardiomyopathy with subsequent diagnosis made on autopsy. We present 3 cases of eosinophilic myocarditis diagnosed by cardiac biopsy classified as hypereosinophilic syndrome. Two patients presented with severe left ventricular dysfunction, and 1 patient presented with cardioembolic stroke. All patients were successfully treated with glucocorticoid therapy. Our cases highlight the importance of early diagnosis with endomyocardial biopsy and prompt immunosuppressive treatment.

L'infiltration par les éosinophiles est une cause rare et non reconnue de myocardite associée à une éosinophilie prolongée. Avant l'imagerie avancée et la biopsie systématique, le diagnostic de cardiomyopathie idiopathique était posé après l'autopsie des patients. Nous présentons 3 cas de myocardite à éosinophiles dont la biopsie cardiaque a permis de poser le diagnostic de syndrome d'hyperéosinophilie. Deux patients ont présenté une dysfonction grave du ventricule gauche, et 1 patient a présenté un accident vasculaire cérébral d'origine cardio-embolique. Le traitement par glucocorticoïdes s'est avéré réussi chez tous les patients. Nos cas montrent l'importance du diagnostic précoce par biopsie endomyocardique et du traitement immunosuppresseur hâtif.

Initiation of ivabradine in cardiogenic shock.

AIMS: Ivabradine is a selective sinus node inhibitor indicated in patients with symptomatic chronic heart failure on stable guideline-recommended heart failure therapy including appropriate doses of beta-blockers. The use in cardiogenic shock remains off label and has been considered a contraindication due to the theoretical risk of attenuating compensatory tachycardia. Tachycardia, especially in the context of inotropic therapy, may be deleterious, resulting in increased myocardial oxygen consumption and reduction in diastolic filling. As ivabradine does not have negative inotropic action, it may present a potential means to manage tachycardia in cardiogenic shock. We present a case series of four patients with cardiogenic shock started on ivabradine who were unable to tolerate beta-blockers. METHODS AND RESULTS: Five patients identified with cardiogenic shock defined as a severe reduction in cardiac index (<2.0 L/min/m2 ) and elevated filling pressures on inotropic therapy were started on ivabradine in patients with sinus tachycardia [heart rate (HR) >100] who were intolerant to beta-blockers. Each patient had a cardiac magnetic resonance imaging, echocardiogram, and coronary angiogram for determination of aetiology. Invasive haemodynamics via pulmonary artery catheterization were measured during initiation and titration of ivabradine (baseline, 6, 12, 24, and 48 h after ivabradine administration) with continuous telemetry monitoring for any dysrhythmia or bradyarrhythmias. All patients tolerated ivabradine initiation, and at 24 h, an observed decrease in HR (106 ± 6.8 vs. 91.6 ± 6.4 b.p.m., P = 0.04), pulmonary arterial occlusion pressure (30.4 ± 4.8 vs. 24 ± 5.1 mmHg, P = 0.04), and right atrial pressure (16.8 ± 6.2 vs. 9 ± 4.3 mmHg, P = 0.0002). An improvement was observed in mixed venous oxygen saturation (SvO2 ) (51 ± 8.8 vs. 64.8 ± 5.3%, P < 0.04), stroke volume (37.2 ± 7.6 vs. 49.2 ± 12.9 mL, P < 0.04), and right and left ventricular stroke work index (Table 1). No significant changes were observed with mean arterial pressure (73.4 ± 7.5 vs. 75.8 ± 5.0 mmHg, P = 0.81) and thermodilution-derived cardiac index (1.7 ± 0.2 vs. 2.5 ± 0.7 L/min/m2 , P = 0.58). Inotropic support was weaned successfully in three of five patients (88 ± 30 h) with subsequent titration of beta-blocker therapy. Two patients improved clinically but ultimately required left ventricular assist device implantation. All patients were discharged alive from hospital at 17 ± 7.9 days following ivabradine initiation. CONCLUSIONS: In our small non-randomized series of patients in cardiogenic shock, ivabradine was safely used to reduce HR in patients previously intolerant of beta-blockade. There are limited data surrounding the use of ivabradine in cardiogenic shock, and future studies should be undertaken to determine the optimal HR in humans with cardiogenic shock and whether systematic limitation of peak HR may improve outcomes.

Monomorphic Ventricular Tachycardia as a Presentation of Giant Cell Myocarditis.

BACKGROUND: Idiopathic giant cell myocarditis (GCM) has a fulminant course and typically presents in middle-aged adults with acute heart failure or ventricular arrhythmia. It is a rare disorder which involves T lymphocyte-mediated myocardial inflammation. Diagnosis is challenging and requires a high index of suspicion since therapy may improve an otherwise uniformly fatal prognosis. CASE SUMMARY: A previously healthy 54-year-old female presented with hemodynamically significant ventricular arrhythmia (VA) and was found to have severe left ventricular dysfunction. Cardiac MRI demonstrated acute myocarditis, and endomyocardial biopsy showed giant cell myocarditis. She was treated with combined immunosuppressive therapy as well as guideline-directed medical therapy. A secondary prevention implantable cardioverter defibrillator (ICD) was implanted. DISCUSSION: GCM is a rare, lethal myocarditis subtype but is potentially treatable. Combined immunosuppression may achieve partial clinical remission in two-thirds of patients. VA is common, and patients should undergo ICD implantation. More research is needed to better understand this complex disease. LEARNING OBJECTIVES: Giant cell myocarditis is an incompletely understood, rare cause of myocarditis. Patients present predominately with heart failure and dysrhythmia. Diagnosis is confirmed by histopathology, and immunosuppression may improve outcomes. ICD implantation should be considered. In the absence of treatment, prognosis is poor with a median survival of three months.

Biophysical analyses and functional implications of the interaction between Heat Shock Protein 27 and antibodies to HSP27.

Heat Shock Protein 27 (HSP27) is a small molecular chaperone that reduces the development of atherosclerosis by lowering plasma cholesterol levels as well as inflammation. Human studies show an inverse correlation between atherosclerotic burden and HSP27 expression, and are supported by murine models in which augmenting HSP27 levels curbs experimental atherogenesis. Natural HSP27 auto-antibodies (AAb) are found in human plasma, however their role in modulating the athero-protective effects of HSP27 is unknown. The purpose of this study is to characterize the biophysical interaction between human recombinant HSP27 and AAb. A validated polyclonal anti-HSP27 IgG antibody (PAb) was used to mimic natural AAb. Homology modeling and secondary structure prediction tools facilitated the design of HSP27 truncation and phosphorylation mutants. Secondary structural changes were identified using Circular Dichroism (CD) and Dynamic Light Scattering (DLS). Similar to prior structural investigations of HSP27, there was a predominance of α-helical content in the N-terminal truncation and dephosphorylation ("AA") mutants. The α-crystallin domain (ACD) predominantly consists of ß-strands, with the addition of the N-terminal increasing helical content and the C-terminal maintaining ß structure. With increasing ratios of PAb to HSP27 ß structure abundance and particle size increased, with a similar trend observed with the N-terminus, C-terminus and ACD peptides but an opposite trend with the phosphorylation peptides. Taken together, these studies provide insights into the interaction of HSP27 and its AAb that ultimately may aid in optimizing the design of HSP27 peptidomimetics with anti-atherogenic potential.

A case of hypertensive emergency, primary hypothyroidism and large pericardial effusion with early tamponade.

Thyroid hormones and the cardiovascular system are strongly intertwined with known risk of coronary disease, atrial fibrillation, and cardiomyopathy. Pericardial effusions are commonly seen in cases of severe hypothyroidism, however large to massive pericardial effusions with cardiac tamponade are exceptionally rare. We report a case of a patient presenting with hypertensive emergency and a concomitant diagnosis of primary hypothyroidism with a large pericardial effusion and early echocardiographic features of tamponade. Following pericardiocentesis, hypertension management, and thyroid replacement therapy the patient's symptoms improved with no recurrence of pericardial effusion. .

A Case of Palpitations Due to T-Wave Oversensing Caused by Sacubitril/Valsartan.

A 58-year-old man with previous mitral/aortic mechanical-valve replacement, aortic root repair, and coronary disease developed severe left-ventricular dysfunction following AV-node ablation/single-chamber pacemaker implantation for management of atrial fibrillation. He then underwent an upgrade to cardiac resynchronization therapy with a defibrillator. To manage his heart failure better, angiotensin-receptor blocker therapy was changed to sacubitril/valsartan, after which symptomatic palpitations with T-wave oversensing occurred. The resolved T-wave oversensing and palpitations stopped upon discontinuation of sacubitril/valsartan and recurred upon rechallenge, requiring a switch back to valsartan monotherapy. Our report presents the first known case of T-wave oversensing due to sacubitril/valsartan.

Kidney Function, ACE-Inhibitor/Angiotensin Receptor Blocker Use, and Survival Following Hospitalization for Heart Failure: A Cohort Study.

BACKGROUND: Angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACE-I/ARB) improve outcomes in patients with heart failure and reduced left-ventricular (LV) systolic function. However, these medications can cause a rise in serum creatinine and their benefits in patients with HF accompanied by kidney disease are less certain. OBJECTIVE: To characterize associations between estimated glomerular filtration rate (eGFR), patterns of ACE-Is and ARBs use, and 1-year survival following hospitalization for heart failure (HF). DESIGN: We formed a retrospective cohort study of patients admitted with HF and followed HF medication prescriptions using the pharmaceutical information network, stratified by discharge eGFR. SETTING: Cardiology services in 3 centers in Southern Alberta, Canada. PATIENTS: The study cohort included patients admitted to hospital with a clinical diagnosis of HF. MEASUREMENTS: eGFR was determined from inpatient laboratory data prior to discharge. Outpatient prescription data prior to and following the index hospitalization was obtained using the Pharmaceutical Information Network of Alberta and survival was determined from provincial vital statistics. METHODS: Characteristics of the HF cohort were obtained from the Admissions Module of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. Multivariable Cox proportional hazards models were used to evaluate the association between time-varying ACE-I/ARB use, and mortality, and to test whether eGFR modified this association. RESULTS: Totally, 1404 patients were included. Within the first 3 months following discharge, ACE-I/ARBs were used in 71%, 67%, 62%, and 52% for those with eGFR > 90, 45-89, 30-44, and < 30 mL/min/1.73 m2, respectively, with differences in use persisting after 1 year of follow-up. Patients with eGFR < 45 mL/min/1.73 m2 had significantly lower rates of ACE-I/ARB use following hospitalization. In adjusted models, ACE-I/ARB use following discharge was associated with 25% lower risk of mortality (Hazard Ratio [HR]: 0.75, 95% confidence interval [CI]: 0.61-0.92; P < 0.01), without evidence that this association differed by eGFR (P = 0.75). LIMITATIONS: LV function measurements were not available for the cohort. Due to the observation design of the study, treatment-selection bias may be present. CONCLUSION: Patients with HF and reduced eGFR at time of hospital discharge were less likely to receive ACE-I/ARB despite these medications being associated with lower mortality independent of eGFR. These findings demonstrate the need for further research on strategies for safe use of ACE-I and ARB in patients with HF and kidney disease.

CONTEXTE: Les inhibiteurs de l'enzyme de conversion de l'angiotensine (IECA) et les antagonistes des récepteurs de l'angiotensine (ARA) améliorent les résultats des patients atteints d'insuffisance cardiaque (IC) et d'une fonction systolique réduite du ventricule gauche. Ces médicaments peuvent cependant provoquer une hausse de la créatinine sérique et leurs bienfaits pour les patients atteints d'IC et de néphropathie sont plus incertains. OBJECTIF: L'étude visait à caractériser l'association entre le débit de filtration glomérulaire estimé (DFGe), les schémas d'utilisation des IECA/ARA, et la survie sur un an à la suite d'une hospitalisation pour IC. CONCEPTION DE L'ÉTUDE: Nous avons procédé à une étude de cohorte rétrospective à partir des données du réseau d'information pharmaceutique. La cohorte était constituée de patients admis pour IC et ayant suivi un traitement pour cette affection. La cohorte a été stratifiée sur la base du DFGe des patients à leur sortie de l'hôpital. CADRE: Le département de cardiologie de trois centres hospitaliers du sud de l'Alberta (Canada). SUJETS: La cohorte était constituée de patients admis à la suite d'un diagnostic d'IC. MESURES: Le DFGe a été déterminé en consultant les résultats de laboratoire des patients hospitalisés avant leur départ. L'information sur les prescriptions avant et après l'hospitalisation a été obtenue grâce au réseau d'information pharmaceutique de l'Alberta, et le taux de survie a été déterminé à l'aide des statistiques de vie de la province. MÉTHODOLOGIE: Les caractéristiques des patients ont été obtenues grâce au module d'admission de la base de données APPROACH (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease). Des modèles multivariés des risques proportionnels de Cox ont été employés pour évaluer l'association entre l'utilisation variable des IECA/ARA dans le temps et le taux de mortalité; de même que pour vérifier si le DFGe avait une incidence sur cette association. RÉSULTATS: Au total, 1404 patients ont été inclus à l'étude. Dans les trois mois suivant l'hospitalisation, les taux de prescriptions des IECA/ARA variaient entre les différentes strates de DFGe de la cohorte et s'établissaient à 71% (DFGe > 90 mL/min/1.73 m2), 67% (DFGe entre 45 et 89 mL/min/1.73 m2), 62% (DFGe entre 30 et 44 mL/min/1.73 m2), et 52% (DFGe < 30 mL/min/1.73 m2); et ces différences ont persisté après un an de suivi. Les patients dont le DFGe était inférieur à 45 mL/min/1.73 m2 présentaient des taux d'utilisation des IECA/ARA significativement inférieurs après leur séjour à l'hôpital. Dans les modèles ajustés, l'utilisation des IECA/ARA à la sortie de l'hôpital a été associée à un risque inférieur de 25% de la mortalité (RR: 0.75; IC 95%: 0.61-0.92; P < .01), sans preuve que cette association diffère selon le DFGe (P = .75). LIMITES: Les mesures de la fonction ventriculaire gauche n'étaient pas disponibles pour la cohorte. De plus, en raison de sa nature observationnelle, l'étude pourrait comporter des biais relatifs au choix du traitement. CONCLUSION: Les patients atteints d'IC et dont le DFGe était faible au moment du congé étaient moins susceptibles de se voir prescrire des IECA/ARA, bien que ces médicaments soient associés à de plus faibles taux de mortalité indépendamment de la valeur du DFGe. Ces résultats démontrent la nécessité de poursuivre la recherche de stratégies permettant une utilisation sûre des IECA/ARA chez les patients atteints de néphropathie et d'insuffisance cardiaque.

A case report of QT prolongation with glycopyrronium bromide in a patient with chronic tamoxifen use.

BACKGROUND: Glycopyrronium bromide has recently been approved as a once daily maintenance inhalation therapy for moderate to severe chronic obstructive pulmonary disease (COPD). Efficacy and safety trial data have found rare cases of significant QT prolongation. To our knowledge, we describe the first case report of QT prolongation >600 ms with initiation of glycopyrronium bromide in a real world setting. CASE PRESENTATION: A 78-year-old female with moderate COPD recently started on glycopyrronium bromide, presented to Emergency Department (ED) with syncope. Her past medical history was significant for a left total mastectomy and she had been on Tamoxifen for 9 months. One day prior to her presentation, she had visited a naturopathic clinic for a vitamin infusion resulting in emesis. The following day she continued to feel dizzy and had a witnessed syncopal episode without any reported cardiac or neurological symptoms preceding the event or after regaining consciousness. In the emergency department, she reported dizziness and was found to be hypotensive. Her symptoms completely resolved with intravenous fluids. Lab work was normal however her electrocardiogram (ECG) demonstrated a QTc interval of 603 and 631 ms (Friderica and Bazett's respectively) with a normal QT interval on her baseline ECG prior to initiating Tamoxifen. She was admitted to the Cardiology service for further work-up of QT prolongation. Her syncope was felt to be due to orthostatic hypotension and the QT prolongation secondary to medications, which were both discontinued during her admission. After 2 days, her QT interval normalized consistent with the half-life of Glycopyrronium bromide (13-57 h) compared to Tamoxifen (8-14 days). CONCLUSION: Glycopyrronium bromide is guideline recommended as first line therapy for prevention of exacerbation in moderate to severe COPD however safety data had been limited to select populations. This case report highlights the need for future studies to identify high-risk populations at potential risk of life-threatening arrhythmias who may benefit from periodic ECG surveillance.

Relationships among achieved heart rate, ß-blocker dose and long-term outcomes in patients with heart failure with atrial fibrillation.

OBJECTIVE: Higher ß-blocker dose and lower heart rate are associated with decreased mortality in patients with systolic heart failure (HF) and sinus rhythm. However, in the 30% of patients with HF with atrial fibrillation (AF), whether ß-blocker dose or heart rate predict mortality is less clear. We assessed the association between ß-blocker dose, heart rate and all-cause mortality in patients with HF and AF. METHODS: We performed a retrospective cohort study in 935 patients (60% men, mean age 74, 44.7% with reduced left ventricular ejection fraction (LVEF)) discharged with concurrent diagnoses of HF and AF. We used Cox models to test independent associations between higher versus lower predischarge heart rate (dichotomised at 70/min) and higher versus lower ß-blocker dose (dichotomised at 50% of the evidence-based target), with the primary composite end point of mortality or cardiovascular rehospitalisation over a median of 2.9 years. All analyses were stratified by the presence of left ventricular systolic dysfunction (LVEF≤40%). RESULTS: After adjustment for covariates, neither ß-blocker dose nor predischarge heart rate was associated with the primary composite end point. However, tachycardia at admission (heart rate >120/min) was associated with a reduced risk of the composite outcome in patients with both reduced LVEF (adjusted HR 0.67, 95% CI 0.52 to 0.88, p<0.01) and preserved LVEF (adjusted HR 0.79, 95% CI 0.64 to 0.98, p=0.04). CONCLUSIONS: We found no associations between predischarge heart rate or ß-blocker dosage and clinical outcomes in patients with recent hospitalisations for HF and AF.