Single points of access to fill the "GAP" for unattached patients in primary care: what makes paediatric users more likely to require a medical appointment?

Unattachment to a regular primary care professional can affect children's and adolescents' well-being, considering their unique health needs. Having no alternative, many turn to emergency departments for non-urgent conditions. To help unattached patients access healthcare services while on waitlists, Quebec's government implemented single access points in each administrative region across the province. Our study aimed to describe the paediatric population using single access points and identify associations between their characteristics and need for a medical appointment. Clinical-administrative data of 1,323 paediatric access point users in the Montérégie region from November 2022 to March 2023 were utilized to conduct bivariate and multivariable regression analyses. Our study showed that young age, assessment trajectory, and specific reasons for calling were more likely to necessitate a medical appointment. While access points improve accessibility to doctors, questions remain regarding the relevance of medical consultations, inequities, and possible security issues resulting from the overall process.

Heavy Burden of Toxic Dilated Cardiomyopathy Among Young Adults: A Retrospective Study and Review of the Literature.

BACKGROUND: Dilated cardiomyopathy (DCM) is a well described entity for heart failure (HF) with reduced left ventricular ejection fraction (LVEF). Recently, drugs and other substance of abuse have been recognised as potential triggers for DCM. The aim of this study was to assess the survival in patients ≤ 65 years of age with toxic cardiomyopathy (TCM). Left ventricular remodelling and the potential usefulness of left ventricular assist devices (LVADs) was also assessed. METHODS: This was a single-centre retrospective study from January 2003 to August 2019 of 553 patients ≤ 65 years old with LVEF < 40% at a tertiary-care cardiology centre. RESULTS: A total of 201 patients (36%) had a diagnosis of idiopathic DCM. Further analysis identified 38 patients (19%) for which a TCM was the most likely etiology (amphetamine [50%], cocaine [37%], anabolic steroids [8%], and energy drinks [5%]). Despite a mean LVEF of 17 ± 8% at presentation, most patients (n = 27; 71%) had event-free survival with guideline-directed medical therapy, and 61% (n = 23) recovered an LVEF ≥ 40% after a median follow-up of 21 ± 23 months. Seven patients (18%) required an LVAD and 1 patient (3%) a transplantation. All LVADs were explanted or decommissioned after partial or complete LVEF recovery after a median support time of 11 ± 4 months. CONCLUSIONS: TCM induced by substance abuse is a frequent cause of HF, accounting for almost 20% of patients ≤ 65 years of age with DCM of unknown etiology. Treatment must be tailored on an individual basis. Mechanical circulatory support demonstrated its usefulness in carefully selected patients.

Screening for asymptomatic diabetes and metabolic comorbidities in pediatric patients during therapy for acute lymphoblastic leukemia.

OBJECTIVES: Chronic metabolic disturbances related to cancer treatment are well reported among survivors of pediatric acute lymphoblastic leukemia (ALL). However, few studies have investigated the incidence of these complications during the phase of chemotherapy. We evaluated the incidence of acute metabolic complications occurring during therapy in our cohort of patients diagnosed with ALL. METHODS: A prospective study involving 50 ALL pediatric patients diagnosed and treated between 2012 and 2016 in our oncology unit. We collected weight, blood pressure, fasting plasma glucose and hemoglobin A1C (HBA1c) levels during the two years of therapy. RESULTS: Obesity and overweight occurred in 43 and 25%, respectively among patients and have been reached at 12 months of chemotherapy. About 26% of the patients developed high blood pressure and 14% experienced hyperglycemias without meeting diabetes criteria. There was a significant decrease of HBA1c levels between the beginning and the end of therapy (p<0.0001). CONCLUSIONS: Increase of body mass index in our ALL pediatric patients occurred during the first months of therapy and plateaued after a year of treatment. We should target this population for early obesity prevention. HbA1c levels measured during therapy did not reveal diabetes criteria. Hence, fasting blood glucose levels are sufficient to monitor ALL pediatric patients' glycemia.

Precise Chip-to-Chip Reagent Transfer for Cross-Reactivity-Free Multiplex Sandwich Immunoassays.

Common multiplex sandwich immunoassays suffer from cross-reactivity due to the mixing of detection antibodies and the combinatorial, undesired interaction between all reagents and analytes. Here we present the snap chip to perform antibody colocalization microarrays that eliminates undesirable interactions by running an array of singleplex assays realized by sequestering detection antibodies in individual nanodroplets. When detecting proteins in biological fluids, the absence of cross-reactivity allows a higher level of multiplexing, reduced background, increased sensitivity, and ensures accurate and specific results. The use of the snap chip is illustrated by measuring highly related analytes such as proteins isoforms and phospho-proteins, both particularly prone to cross-reactivity, in a single experiment. The main steps of the protocol are preparation of sample, incubation on an assay slide harboring the microarrayed capture antibodies, transfer of the microarrayed detection antibodies on their cognate spots, and measurement of the assay results by fluorescence.

Canadian Real-World Experience of Using Sacubitril/Valsartan in Patients With Heart Failure With Reduced Ejection Fraction: Insight From the PARASAIL Study.

BACKGROUND: To determine the effectiveness of sacubitril/valsartan 97/103 mg twice daily (b.i.d.) on tolerability, safety, and quality of life (QoL) in Canadian patients with heart failure with reduced ejection fraction in a real-life setting. METHODS: In Prospective, Multicenter, Open Label, Post-Approval Study Aimed at Characterizing the Use of LCZ696 at 97 mg Sacubitril/103 mg Valsartan bid in Patients With HFrEF (PARASAIL), an open-label, prospective, phase IV, multicentre study, outpatients with heart failure with reduced ejection fraction and New York Heart Association functional class II-III were followed up for 12 months. The suggested starting dose of sacubitril/valsartan was 24/26 mg b.i.d. replacing angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, with an uptitration to 97/103 mg b.i.d. or as per clinical judgement. The primary endpoint was the proportion of patients achieving the target dose of sacubitril/valsartan 97/103 mg b.i.d. after 6 months of treatment. RESULTS: For the 302 patients included, the mean age was 64.47 years, and a majority of patients (82.8%) belonged to New York Heart Association class II. Overall, 195 (64.6%) patients were on maximum dose of sacubitril/valsartan 97/103 mg b.i.d. after 6 months and 62.3% remained on this dose at month 12. Using patient global assessment, patients experienced an improvement in QoL. For Minnesota Living with Heart Failure Questionnaire scores, a significant decrease from the baseline was observed at weeks 4, 12, and 24 (P < 0.0001 for all), which indicated an improvement in QoL. The patient global assessment and Minnesota Living with Heart Failure Questionnaire results correlate with moderate but significant changes in Euro quality of life-5D visual analogue scale scores. CONCLUSIONS: Results of the PARASAIL study in a real-life setting have shown that most patients were on sacubitril/valsartan 97/103 mg b.i.d. and the treatment was well tolerated. The patient-reported outcomes showed an overall improvement in patients' QoL.

CONTEXTE: L'objectif était de déterminer, en contexte réel, l'efficacité de l'association sacubitril à 97 mg/valsartan à 103 mg, deux fois par jour, sous l'angle de la tolérabilité, de l'innocuité et de la qualité de vie (QV) chez des patients canadiens atteints d'insuffisance cardiaque avec fraction d'éjection réduite. MÉTHODOLOGIE: Au cours de l'étude multicentrique et prospective sans insu de phase IV PARASAIL ( P rospective, Multicenter, Open L a bel, Post-App r ov a l S tudy Ai med at Characterizing the Use of L CZ696 at 97 mg Sacubitril/103 mg Valsartan bid in Patients With HFrEF), des patients externes atteints d'insuffisance cardiaque de classe fonctionnelle II ou III selon la NYHA (New York Heart Association) avec fraction d'éjection réduite ont été suivis durant 12 mois. La dose initiale recommandée était de 24 mg de sacubitril/26 mg de valsartan, deux fois par jour, à la place d'un inhibiteur de l'enzyme de conversion de l'angiotensine ou d'un antagoniste des récepteurs de l'angiotensine; la dose devait être augmentée à 97 mg de sacubitril/103 mg de valsartan, deux fois par jour, ou selon le jugement du clinicien. Le critère d'évaluation principal était la proportion de patients chez qui la dose cible de 97 mg de sacubitril/103 mg de valsartan, deux fois par jour, se trouvait atteinte après six mois de traitement. RÉSULTATS: L'âge moyen des 302 patients admis était de 64,47 ans. La majorité de ces patients (82,8 %) présentaient une insuffisance cardiaque de classe II selon la NYHA. Globalement, 195 (64,6 %) patients prenaient la dose maximale de 97 mg de sacubitril/103 mg de valsartan, deux fois par jour, après six mois de traitement; 62,3 % continuaient de prendre cette dose à 12 mois de traitement. L'évaluation globale des patients indique une amélioration de leur QV. Les scores au Minnesota Living With Heart Failure Questionnaire avaient significativement diminué par rapport aux scores de départ aux semaines 4, 12 et 24 (p < 0,0001 à tous les temps d'évaluation), ce qui indique une amélioration de la QV. L'évaluation globale des patients et les scores au Minnesota Living With Heart Failure Questionnaire sont corrélés avec des variations modérées, mais significatives des scores de QV à l'échelle visuelle analogique du questionnaire EQ-5D. CONCLUSIONS: Les résultats obtenus en contexte réel au cours de l'étude PARASAIL montrent que la plupart des patients prenaient la dose de 97 mg de sacubitril/103 mg de valsartan, deux fois par jour, et que le traitement était bien toléré. Les résultats rapportés par les patients témoignent d'une amélioration globale de la QV de ces derniers.

Interatrial Shunting for Treating Acute and Chronic Left Heart Failure.

The creation of an interatrial shunt has emerged as a new therapy to decompress the left atrium in patients with acute and chronic left heart failure (HF). Current data support the safety of this therapy, and promising preliminary efficacy results have been reported in patients who are refractory to optimal medical/device therapy. This article aims to provide an updated overview and clinical perspective on interatrial shunting for treating different HF conditions, and highlights the potential challenges and future directions of this therapy.

Significant mitral regurgitation in patients undergoing TAVR: Mechanisms and imaging variables associated with improvement.

BACKGROUND: Significant mitral regurgitation (MR) is associated with poorer outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). Factors associated with MR improvement have not been studied thoroughly. METHODS: Retrospective analysis of consecutive patients treated with TAVR with more than mild MR at baseline. MR evolution was assessed at 1-3 and 6-12 months after intervention. MR severity and mechanisms were assessed by echocardiography. Mitral annulus calcification (MAC) was quantified using preoperative cardiac CT. RESULTS: From 674 consecutive TAVR recipients, 78 with more than mild MR had a 6-12 months follow-up. Following TAVR, MR improved in 34 patients (43%), remained stable in 38 (49%) and worsened in 6 (8%). Patients with MR improvement had greater tenting area (141 ± 56 vs. 99 ± 40 mm2 , P < 0.01), tenting height (7.2 ± 1.9 vs. 5.6 ± 1.9 mm, P < 0.01) and lower ejection fraction (43 ± 16 vs. 52 ± 14%, P = 0.01). MAC was frequent (87.7% of patients) and a trend in greater MAC was observed in patients without MR improvement (3560 ± 5587 vs. 2053 ± 2800, P = 0.16). In multivariable analysis, tenting area (OR per 10 mm2 increase: 1.012, 95% CI, 1.001-1.024 P = 0.039) and annulus calcifications associated with leaflet restriction (OR = 0.108, 95% CI, 0.012-0.956, P = 0.045) were independently associated with MR outcome after TAVR. CONCLUSION: Larger mitral valve tenting area was associated with more improvement of MR after TAVR whereas extensive MAC associated with leaflet restriction was associated with less improvement. This may help in the clinical decision-making process of TAVR candidates with concomitant MR.

Renal injury in pediatric anorexia nervosa: a retrospective study.

PURPOSE: Although primarily a mental health disorder, anorexia nervosa (AN) has many physical consequences. Among them, the consequences on kidney function are often underestimated. We evaluated renal function in adolescent AN inpatients and investigated the correlation between the GFR and intrinsic patient characteristics. METHODS: A single-center retrospective study was conducted on 51 patients hospitalized for the restrictive type of AN in 2013. Data were divided into: (1) medical history of AN; (2) growth parameters and vital signs upon admission; and (3) blood tests. The glomerular filtration rate (GFR) was calculated using the Cockroft-Gault, MAYO Clinical Quadratic (MCQ), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), the Modification of Diet in Renal Disease (MDRD), and Schwartz equations. RESULTS: The calculated percentages of patients with a GFR below 90 mL/min/1.73 m2 according to the different equations were as follows: Cockroft-Gault, 45%; MDRD, 28%; CKD-EPI, 14%; MCQ, 12%, and Schwartz, 4%. There was a strong association between the body mass index (BMI) and the GFR according to all equations (p < 0.0001). The lowest heart rate was significantly associated with a reduced GFR according to the Cockroft-Gault equation (p = 0.03). The GFR values did not differ significantly after rehydration. CONCLUSION: Clinicians should evaluate AN patients for renal complications, especially when the BMI and heart rate are very low. Dehydration was not solely responsible for renal impairment. LEVEL OF EVIDENCE: Level III, single-center retrospective cohort study.

Sleep problems and interpersonal violence in youth in care under the Quebec Child Welfare Society.

OBJECTIVE: The objective this study was to investigate the relative contributions of gender, common mental health symptoms, and experiences of interpersonal violence to the presence of sleep disturbances in Youth in Care under Child Welfare Society admitted to residential facilities. METHODS: A sample of 315 teenagers (14-18 years old) completed a self-reported questionnaire upon admission, followed by a medical consultation with a nurse and a physician. Information regarding experiences of interpersonal violence, mental health symptoms, and sleep disturbances was collected using a standardized questionnaire. RESULTS: Anxiety, ADHD symptoms, and sexual abuse were associated with sleep disturbances, F(10, 264) = 5.95, p < 0.001. Results from hierarchical regression analyses revealed that experiences of interpersonal violence, more specifically sexual abuse, were associated with sleep disturbances over and beyond gender and the presence of mental health symptoms. CONCLUSIONS: These results highlight practical implications for health professionals in terms of assessment and intervention for vulnerable youth exposed to interpersonal violence. Implications for research and practice are discussed.

Interatrial Shunting for Heart Failure: Early and Late Results From the First-in-Human Experience With the V-Wave System.

OBJECTIVES: This was a first-in-human study to assess the feasibility, safety, and exploratory efficacy of interatrial shunting for treating high-risk heart failure (HF) in patients with reduced and preserved ejection fraction. METHODS: A single-arm open-label study of patients with New York Heart Association functional class III or IV HF on optimal therapy was performed at 6 centers. The V-Wave shunt, an hourglass-shaped implant containing a 1-way bioprosthetic valve, was implanted by transseptal catheterization. Clinical, functional, echocardiographic, and hemodynamic evaluations were performed at baseline, 3 and 12 months, and annually (clinical follow-up) thereafter (median follow-up 28 months; interquartile range: 21 to 31 months). RESULTS: A total of 38 patients were enrolled (30 with HF with reduced ejection fraction and 8 with HF with preserved ejection fraction; mean age 66 ± 9 years; 97% and 3% in New York Heart Association functional classes III and IV, respectively), and the shunt device was successfully implanted in all cases without periprocedural mortality. The rate of major device- or procedure-related complications during the first 12 months was 2.6% (periprocedural cardiac tamponade in 1 patient). At 3- and 12-month follow-up, there were improvements in New York Heart Association functional class (classes I and II in 78% and 60% of patients, respectively), quality of life (improvements ≥5 points in 74% and 73% of patients, respectively), and 6-min walk distance (mean increases of 41 ± 63 m and 28 ± 83 m, respectively) (p < 0.02 for all, data available for 36 patients), without changes in objective measures of left- or right-sided function. All shunts were patent at 3 months, but 5 of 36 (14%) had occluded, and another 13 of 36 (36%) were stenotic at the valve by 12 months. Patients with widely patent shunts had lower long-term rates of death, left ventricular assist device placement or heart transplantation (p = 0.001), and HF hospitalization (p = 0.008), along with a reduction of pulmonary capillary wedge pressure (from 23.3 ± 5.4 mm Hg at baseline to 18.0 ± 4.0 mm Hg at 12 months; p = 0.011). CONCLUSIONS: Interatrial shunting with the V-Wave system was feasible and safe in patients with HF with reduced and preserved ejection fraction. Improvements in clinical and functional status were observed early and at 12 months despite attenuation of shunt patency in one-half of the patients. Patients with preserved shunt patency tended to maintain clinical benefit during longer term follow-up. Device modification that improves the durability of patency is likely worthwhile before confirmation of these findings in a randomized trial.

Usefulness of a titration algorithm for de novo users of sacubitril/valsartan in a tertiary centre heart failure clinic.

BACKGROUND: A reduction in the rate of death and hospitalisations in patients with heart failure (HF) with reduced ejection fraction receiving sacubitril/valsartan compared to enalapril was demonstrated in the PARADIGM-HF study. However, tolerability when initiating and optimising sacubitril/valsartan treatment in real clinical practice is unknown. METHODS: We performed a prospective cohort study of clinical and biochemical parameters of the first 100 patients receiving sacubitril/valsartan in a tertiary HF clinic. Patients had titration of the molecule guided by an algorithm developed by pharmacists and cardiologists in the clinic. The objective was to evaluate the proportion of patients reaching the maximal dosage, the time to reach maximal dosage, and the rate of adverse events, as well as the required modification of other HF therapy during the sacubitril/valsartan titration. RESULTS: Forty-six per cent of patients reached the sacubitril/valsartan maximal dose of 97/103 mg (200 mg) twice daily and 73% received at least 49/51 mg (100 mg) twice daily. Mean titration time was 30 ± 9 days. Symptomatic hypotension, renal dysfunction (increase in creatinine level > 30%) and hyperkalaemia (potassium level > 5.5 mmol/l) occurred in nine, four and 2% of patients, respectively. Background HF pharmacological treatment remained stable during the sacubitril/valsartan titration but daily dosage of furosemide was reduced by 13% (p = 0.0005). CONCLUSIONS: This algorithm is a safe and easy-to-use tool in daily clinical practice for the introduction and titration of sacubitril/valsartan. Almost half of the patients reached the maximal dose, with a tolerability profile in line with the original study.

Dynamic left ventricular dyssynchrony and severe mitral regurgitation caused by exercise: should we go beyond the guidelines?

Guidelines for cardiac resynchronization therapy (CRT) have been established, but there may be a subgroup of patients not identified in these guidelines who may benefit from this therapy. We report a patient with a dynamic left ventricular dyssynchrony and severe mitral regurgitation caused by exercise successfully treated with CRT. Exercise testing should be considered in patients with left ventricular ejection fraction <35% and QRS <130 ms with severe heart failure symptoms that are unexplained by rest echocardiography evaluation in order to rule out ischemia and/or dynamic left ventricular dyssynchrony. In the presence of exercise-induced left ventricular bundle branch block, the implantation of CRT should be contemplated.

Long-Term Outcomes Following Surgical Aortic Bioprosthesis Implantation.

BACKGROUND: Few data exist on long-term outcomes and structural valve degeneration (SVD) in consecutive unselected patients undergoing surgical aortic valve replacement (SAVR). OBJECTIVES: The goal of this study was to determine the long-term outcomes of a contemporary cohort of consecutive unselected SAVR recipients with a focus on evaluating clinical outcomes and SVD based on echocardiographic criteria. METHODS: A total of 672 consecutive patients (mean age: 72 ± 8 years; 61.5% male) undergoing SAVR with a bioprosthesis between 2002 and 2004 were included. Baseline and follow-up data were prospectively collected in a dedicated database. Baseline post-operative echocardiographic data were obtained in the 624 patients alive at hospital discharge and in 209 patients at 10 years (87% of the patients at risk). SVD was defined as subclinical (increase >10 mm Hg in mean transvalvular gradient + decrease >0.3 cm2 in valve area and/or new-onset mild or moderate aortic regurgitation) and clinically relevant (increase >20 mm Hg in mean transvalvular gradient + decrease >0.6 cm2 in valve area and/or new-onset moderate-to-severe aortic regurgitation). RESULTS: At a median follow-up of 10 years (interquartile range: 5 to 13 years), 432 patients (64.3%) had died. Older age, left ventricular dysfunction, atrial fibrillation, chronic obstructive pulmonary disease, greater body mass index, and diabetes mellitus were associated with an increased mortality risk (p < 0.05 for all). Clinically relevant SVD occurred in 6.6% of patients; 30.1% of patients had subclinical SVD. A greater body mass index and the use of a specific aortic bioprosthesis were independently associated with clinically relevant SVD (p < 0.05 for both), and 83% of these patients underwent aortic valve reintervention (valve-in-valve transcatheter aortic valve replacement in 44% of them). CONCLUSIONS: The 10-year mortality rate in elderly SAVR recipients of a bioprosthetic valve was considerable, chiefly determined by their older age and the presence of comorbidities. Clinically relevant SVD was infrequent, but close to one third of the population exhibited subclinical SVD. These results provide contemporary data on long-term clinical outcomes and SVD post-SAVR, and they should be taken into consideration when evaluating late clinical outcomes and valve durability after transcatheter aortic valve replacement.

Snap Chip for Cross-reactivity-free and Spotter-free Multiplexed Sandwich Immunoassays.

Multiplexed protein analysis has shown superior diagnostic sensitivity and accuracy compared to single proteins. Antibody microarrays allow for thousands of micro-scale immunoassays performed simultaneously on a single chip. Sandwich assay format improves assay specificity by detecting each target with two antibodies, but suffers from cross-reactivity between reagents thus limiting their multiplexing capabilities. Antibody colocalization microarray (ACM) has been developed for cross-reactivity-free multiplexed protein detection, but requires an expensive spotter on-site for microarray fabrication during assays. In this work, we demonstrate a snap chip technology that transfers reagent from microarray-to-microarray by simply snapping two chips together, thus no spotter is needed during the sample incubation and subsequent application of detection antibodies (dAbs) upon storage of pre-spotted slides, dissociating the slide preparation from assay execution. Both single and double transfer methods are presented to achieve accurate alignment between the two microarrays and the slide fabrication for both methods are described. Results show that <40 µm alignment has been achieved with double transfer, reaching an array density of 625 spots/cm2. A 50-plexed immunoassay has been conducted to demonstrate the usability of the snap chip in multiplexed protein analysis. Limits of detection of 35 proteins are in the range of pg/mL.

Unidirectional left-to-right interatrial shunting for treatment of patients with heart failure with reduced ejection fraction: a safety and proof-of-principle cohort study.

BACKGROUND: In patients with heart failure, interventions to reduce elevated left atrial pressure improve symptoms and reduce the risk of hospital admission. We aimed to assess the safety and potential efficacy of therapeutic left-to-right interatrial shunting in patients with heart failure with reduced ejection fraction. METHODS: We did this proof-of-principle cohort study at one centre in Canada. Patients (aged ≥18 years) with New York Heart Association (NYHA) class III chronic heart failure with reduced ejection fraction were enrolled under the Canadian special access programme. Shunt implants were done after transseptal catheterisation with transoesophageal echocardiographic guidance under general anaesthesia. Patients had clinical and echocardiography evaluations at baseline and months 1 and 3 after shunt implantation. FINDINGS: Between Oct 10, 2013, and March 27, 2015, we enrolled ten patients. The device was successfully implanted in all patients; no device-related or procedural adverse events occurred during follow-up. Transoesophageal echocardiography at 1 month showed that all shunts were patent, with no thrombosis or migration. From baseline to 3 month follow-up, we recorded improvements in NYHA classification (from class III to class II in seven [78%] of nine patients, from class III to class I in one [11%] patient, and no change in one [11%] patient; p=0·0004); quality of life, as assessed by the Duke Activity Status Index (from a mean score of 13 [SD 6·2] to 24·8 [12·9]; p=0·016) and the Kansas City Cardiomyopathy Questionnaire (from a mean score of 44·3 [SD 9·8] to 79·1 [13·0]; p=0·0001); and 6 min walk test distance (from a mean of 244 m [SD 112] to 318 m [134]; p=0·016). Pulmonary capillary wedge pressure was reduced from a mean of 23 mm Hg (SD 5) at baseline to 17 mm Hg (8) at 3 months (p=0·035), with no changes in right atrial pressure, pulmonary arterial pressure, or pulmonary resistance. No patient was admitted to hospital for worsening heart failure. One (10%) patient was admitted to hospital with gastrointestinal bleeding at month 1; one (10%) patient died after incessant ventricular tachycardia storm, which led to terminal heart failure 2 months post-procedure. INTERPRETATION: This first-in-man experience with an implanted left-to-right interatrial shunt demonstrates initial safety and early beneficial clinical and haemodynamic outcomes in patients with heart failure with reduced ejection fraction. Further large-scale randomised studies are warranted. FUNDING: V-Wave.

Risk factors of mortality after surgical correction of ventricular septal defect following myocardial infarction: Retrospective analysis and review of the literature.

BACKGROUND: Rupture of the ventricular septum following acute myocardial infarction (AMI) is an uncommon but serious complication, usually leading to congestive heart failure and cardiogenic shock. Surgical repair is the only definitive treatment for this condition. METHODS: We review our experience of surgical repair of post-infarction ventricular septal defects (VSDs), analyze the associated risk factors and outcomes, and do a complete review of the literature. A retrospective study was performed on 34 consecutive patients who had undergone surgical repair for VSDs following AMI from December 1991 to July 2014. Preoperative, clinical and echocardiographic variables were studied by uni-and multivariate analyses. RESULTS: Mortality was analyzed for the entire group of patients. Mean age was 69 ± 7 years with 44% women. VSDs were anterior in 11 (32%) and posterior in 23 (68%) patients. A majority, 24 (71%) patients were in cardiogenic shock. Median interval from myocardial infarction to VSDs repair was 7 days. The 30 days operative mortality was 65%. Mortality within the posterior VSDs group was 74% and the anterior VSDs group was 46% (P=0.14). Concomitant coronary artery bypass graft (CABG) did not influence early or late survival. Multivariate analysis identified older age (HR=1.11, P=0.0001) and shorter time between AMI and surgery (HR=0.90, P=0.015) as independent predictors of 30-day and long-term mortality. CONCLUSION: In conclusion, surgical repair of post-AMI VSDs carries a high operative mortality. An algorithm of treatment for the management of these patients is suggested.

Clinical Presentation and Value of Echocardiography in the Diagnosis of Freestyle Aortic Bioprosthesis Leaflet Tears: A Retrospective Study.

BACKGROUND: The unique design of the Freestyle stentless aortic bioprosthesis has led to different mechanisms of failure, particularly leaflet tearing. The aim of this retrospective study was to review the clinical presentation and echocardiographic data of symptomatic patients with leaflet tears and significant aortic regurgitation (AR) following implantation of the Freestyle bioprosthesis. METHODS: Between January 1993 and May 2011, a total of 430 consecutive patients was identified at the authors' institution who had undergone primary aortic valve replacement with a Freestyle stentless aortic bioprosthesis. Clinical and echocardiographic data were collected prospectively for all patients. Structural valve deterioration was the major cause of bioprosthetic valve failure. RESULTS: Twenty symptomatic patients presented with significant AR due to leaflet tears in the absence of more than mild valvular calcification. At presentation, all patients complained of dyspnea. Some 50% of patients (n = 10) presented with acute pulmonary edema, and 10% (n = 2) with cardiogenic shock. A leaflet tear was initially diagnosed using transthoracic echocardiography in five cases (25%), using transesophageal echocardiography (TEE) in eight cases (40%), or at surgery in seven cases (35%). An appropriate diagnosis of leaflet tearing was recognized at surgery in more than one-third of patients. Consequently, clinicians must be aware of the variety of clinical presentations and should have a high degree of suspicion regarding leaflet tears in patients who have received a Freestyle stentless aortic bioprosthesis and present with moderate to severe AR. CONCLUSIONS: For the optimal management of patients with Freestyle stentless aortic bioprosthesis and new moderate to severe AR, TEE should be considered in all patients.

Evaluating mixtures of 14 hygroscopic additives to improve antibody microarray performance.

Microarrays allow the miniaturization and multiplexing of biological assays while only requiring minute amounts of samples. As a consequence of the small volumes used for spotting and the assays, evaporation often deteriorates the quality, reproducibility of spots, and the overall assay performance. Glycerol is commonly added to antibody microarray printing buffers to decrease evaporation; however, it often decreases the binding of antibodies to the surface, thereby negatively affecting assay sensitivity. Here, combinations of 14 hygroscopic chemicals were used as additives to printing buffers for contact-printed antibody microarrays on four different surface chemistries. The ability of the additives to suppress evaporation was quantified by measuring the residual buffer volume in open quill pins over time. The seven best additives were then printed either individually or as a 1:1 mixture of two additives, and the homogeneity, intensity, and reproducibility of both the spotted protein and of a fluorescently labeled analyte in an assay were quantified. Among the 28 combinations on the four slides, many were found to outperform glycerol, and the best additive mixtures were further evaluated by changing the ratio of the two additives. We observed that the optimal additive mixture was dependent on the slide chemistry, and that it was possible to increase the binding of antibodies to the surface threefold compared to 50 % glycerol, while decreasing whole-slide coefficient of variation to 5.9 %. For the two best slides, improvements were made for both the limit of detection (1.6× and 5.9×, respectively) and the quantification range (1.2× and 2.1×, respectively). The additive mixtures identified here thus help improve assay reproducibility and performance, and might be beneficial to all types of microarrays that suffer from evaporation of the printing buffers.