Considerations for Advanced Heart Failure Consultation in Individuals With Fontan Circulation: Recommendations From ACTION.

Individuals with Fontan circulation are at risk of late mortality from both cardiac and noncardiac causes. Despite the known risk of mortality, referral indications for advanced heart failure care vary between centers, and many individuals die from Fontan circulation-related complications either after late consideration for advanced heart failure therapies or having never seen a heart failure specialist. There is a critical need for guidelines to direct appropriately timed referral for advanced heart failure consultation. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Fontan Committee has developed recommended thresholds for advanced heart failure referral to guide primary cardiologists. These recommendations are divided into 4 categories of clinical Fontan circulatory dysfunction including (1) cardiac/systemic ventricular dysfunction, (2) Fontan pathway dysfunction, (3) lymphatic dysfunction, and (4) extracardiac dysfunction.

Heart rate control with landiolol hydrochloride in infants with ventricular dysfunction and pulmonary hypertension.

AIMS: Sinus tachycardia potentially leads to a deterioration of cardiac function in critically ill infants. The ultrashort-acting beta-blocker landiolol hydrochloride is a new pharmacological option for a selective heart rate (HR) control in patients with sinus tachycardia and heart failure. METHODS AND RESULTS: This study was a monocentric retrospective medical chart review study at the University Children's Hospital Bonn (Germany) from 01 January 2018 until 30 June 2020. This study included a cohort of 62 term and preterm infants with a diagnosis of ventricular dysfunction and/or pulmonary hypertension (PH), in combination with preexisting tachycardia and treatment with landiolol hydrochloride. Infants were allocated to subgroups according to weeks of gestational age (GA): born at <35 weeks of GA (Group A) and born at >35 weeks of GA (Group B). Tachycardia was defined depending on GA (<35 weeks of GA: >170 b.p.m.; ≥ 35 weeks of GA: >150 b.p.m.). The primary endpoint was defined as percentage of patients achieving HR normalization during the first 24 h of landiolol treatment. Twenty-nine infants were allocated to Group A and 33 infants to Group B. The overall median GA of the infants was 35.3 (23.3/41.3), with 53% female infants. The primary endpoint was achieved in 57 patients (91.9%). The median time to reach target HR was 1.8 (0.3-24) h. The median starting dose of landiolol was 8.8 (3.9-25.3) µk/kg/min, with a median dosing during the first 24 h of landiolol treatment of 9.9 (2.8-35.4) µk/kg/min. The median landiolol dose while achieving the target HR was 10 (2.4-44.4) µk/kg/min. The right ventricular dysfunction improved significantly in both groups 24 h after onset of landiolol infusion (P = 0.001 in Group A and P = 0.045 in Group B). The left ventricular and biventricular dysfunction improved significantly 24 h after onset of landiolol infusion in infants of Group B (P = 0.004 and P = 0.006, respectively). The severity of PH improved significantly after 24 h in infants of Group A (P < 0.001). During landiolol treatment, no severe drug-related adverse event was noted. CONCLUSIONS: The use of landiolol hydrochloride for HR control of non-arrhythmic tachycardia in critically ill infants is well tolerated. Reduction of HR can be guided quickly and landiolol treatment is associated with an improvement of ventricular dysfunction and PH.

A Path FORWARD: Development of a Comprehensive Multidisciplinary Clinic to Create Health and Wellness for the Child and Adolescent with a Fontan Circulation.

Today, it is anticipated most individuals diagnosed with single-ventricle malformation will survive surgical reconstruction through a successful Fontan operation. As greater numbers of patients survive, so has the recognition that individuals with Fontan circulation face a variety of challenges. The goal of a normal quality and duration of life will not be reached by all. The hurdles fall into a variety of domains. From a cardiovascular perspective, the Fontan circulation is fundamentally flawed by its inherent nature of creating a state of chronically elevated venous pressure and congestion, accompanied by a relatively low cardiac output. Ventricular dysfunction, atrioventricular valve regurgitation, and arrhythmia may directly impact cardiac performance and can progress with time. Problems are not limited to the cardiovascular system. Fontan circulatory physiology impacts a multitude of biological processes and health parameters outside the heart. The lymphatic circulation is under strain manifesting as variable degrees of protein-rich lymph loss and immune system dysregulation. Organ system dysfunction develops through altered perfusion profiles. Liver fibrosis is ubiquitous, and a process of systemic fibrogenesis in response to circulatory stressors may affect other organs as well. Somatic growth and development can be delayed. Behavioral and mental health problems are common, presenting as clinically important levels of anxiety and depression. Most striking is the high variability in prevalence and magnitude of these complications within the population, indicating the likelihood of additional factors enhancing or mitigating their emergence. We propose that optimal care for the individual with single ventricle and a Fontan circulation is ideally offered in a comprehensive multidisciplinary manner, with attention to elements that are beyond cardiac management alone. In this report, we share the concepts, our experiences, and perspectives on development of a clinic model-the "Fontan rehabilitation, wellness and resilience development" or FORWARD program. We provide insights into the mechanics of our multidisciplinary model of care and the benefits offered serving our growing population of individuals with a Fontan circulation and their families.

Subclinical cardiovascular dysfunction in children and adolescents with asthma.

BACKGROUND: There is close association between asthma and cardiovascular functions as both diseases share common inflammatory pathways. The current study was aimed at investigating the risk factors, associated with endothelial and cardiac functions in children with newly-diagnosed mild-persistent asthma. METHODS: A total of 33 steroid-naive asthmatic children [median(interquartile-range); 9.1 years(7.8-13.5)] and 16 healthy controls [11.5 years(9.9-13.6)] were included. Their demographic, clinical and laboratory findings were recorded. Carotid Artery intima-media thickness (CIMT), stiffness, distensibility and strain were measured as atheroclerosis markers. Conventional and tissue Doppler imaging was performed to evaluate ventricular function. RESULTS: The patients with asthma had higher CIMT and stiffness and lower strain and distensibility compared to controls (p < 0.001 for all). There was a significant correlation between the duration of asthmatic symptoms and subclinical-atherosclerosis as well as peripheral eosinophil count (p < 0.001, p < 0.05). The patients had lower tricuspid-annular-plane-systolic-excursion (TAPSE), ejection time, and higher isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), and left ventricle myocardial performance index (LVMPI) than the control subjects (p < 0.001 for all). A positive correlation was also observed between the duration of asthmatic-symptoms and cardiac-function parameters. CONCLUSION: Children with mild persistent asthma had subclinical atherosclerosis and ventricular dysfunction even in the early stage of disease. Symptom duration was closely associated with both subclinical atherosclerosis and ventricular dysfunction. Myocardial performance index was abnormal in the asthmatic children when assessed by tissue Doppler Imaging even though they had normal ejection fraction in conventional echocardiography. Future prospective studies with larger sample sizes are needed to confirm these findings and to assess the possible protective effect of ICSs in the prevention of subclinical atherosclerosis.

Left atrial function analysis in patients with functional mitral regurgitation associated with dilated cardiomyopathy / Análise da função atrial esquerda em pacientes com insuficiência mitral funcional associada à miocardiopatia dilatada

BACKGROUND: Functional mitral regurgitation (FMR) is associated with dilated cardiomyopathy (DC), heart failure (HF), and worsening left atrial function (LAF). Patients with DC and FMR may present left atrial dysfunction resulting from both ventricular dysfunction and valve disease, but it is unknown whether the presence of valve disease will lead to greater LAF impairment. OBJECTIVE: This study aimed to evaluate the relationship between LAF parameters and FMR degree in patients with DC. METHODS: This cross-sectional observational study included 214 patients with DC, 46 without FMR (control group) and 168 with mild, moderate or severe FMR. An LAF analysis was performed by speckle tracking echocardiography (STE) and atrial volumetric variation. RESULTS: LAF analyzed by STE by means of reservoir strain, conduit strain and active contraction strain was reduced in the sample, with values of 14.3%, 8.49% and 5.92%, respectively. FMR degree was significantly associated with reservoir strain (0.27 ± 0.16 versus 0.15 ± 0.09; p < 0.001) and contraction strain (19.2 ± 7.3 versus 11.2 ± 2.7; p < 0.001). FMR was also associated with a reduced LAF assessed by volumetric analysis: total atrial emptying fraction of 0.51 ± 0.13 versus 0.34 ± 0.11 and active atrial emptying fraction of 0 .27 ± 0.16 versus 0.15 ± 0.09 (p < 0.001). CONCLUSION: In a population with DC, FMR was associated with reduced LAF assessed by STE and atrial volume variation.

FUNDAMENTO: A insuficiência mitral funcional (IMF) está associada à miocardiopatia dilatada (MD), à insuficiência cardíaca (IC) e à piora da função atrial esquerda (FAE). A FAE pode decair tanto pela disfunção ventricular quanto pela valvopatia, mas não se sabe se esta leva a um prejuízo maior da FAE. OBJETIVO: Avaliar a relação entre a piora de parâmetros de FAE com o grau de IMF, em pacientes com MD. MÉTODOS: Trata-se de estudo observacional transversal, que incluiu 214 pacientes com MD, sendo 46 sem IMF (controle) e 168 com IMF discreta, moderada ou grave. A análise da FAE foi realizada por ecocardiografia por speckle tracking (STE) e por variação volumétrica atrial. RESULTADOS: A FAE, analisada por STE­ por meio do strain de reservatório, conduto e contração ativa ­ encontrou-se reduzida na amostra, com valores respectivos de 14,3%, 8,49% e 5,92%. O grau de IMF associou-se significativamente com os valores do strain de reservatório (0,27±0,16 versus 0,15±0,09; p <0,001. CONCLUSÃO: Em uma população com MD, a presença de IMF associa-se à redução da FAE de reservatório e de contração, avaliada por STE e pela variação volumétrica atrial.

Preoperative echocardiographic parameters predict primary graft dysfunction following pediatric lung transplantation.

The importance of preoperative cardiac function in pediatric lung transplantation is unknown. We hypothesized that worse preoperative right ventricular (RV) systolic and worse left ventricular (LV) diastolic function would be associated with a higher risk of primary graft dysfunction grade 3 (PGD 3) between 48 and 72 hours. We performed a single center, retrospective pilot study of children (<18 years) who had echocardiograms <1 year prior to lung transplantation between 2006 and 2019. Conventional and strain echocardiography parameters were measured, and PGD was graded. Area under the receiver operating characteristic (AUROC) curves and logistic regression were performed. Forty-one patients were included; 14 (34%) developed PGD 3 and were more likely to have pulmonary hypertension (PH) as the indication for transplant (P = .005). PGD 3 patients had worse RV global longitudinal strain (P = .01), RV free wall strain (FWS) (P = .003), RV fractional area change (P = .005), E/e' (P = .01) and lateral e' velocity (P = .004) but not tricuspid annular plane systolic excursion (P = .61). RV FWS (AUROC 0.79, 95% CI 0.62-0.95) and lateral e' velocity (AUROC 0.87, 95% CI 0.68-1.00) best discriminated PGD 3 development and showed the strongest association with PGD 3 (RV FWS OR 3.87 [95% CI 1.59-9.43], P = .003; lateral e' velocity OR 0.10 [95% CI 0.01-0.70], P = .02). These associations remained when separately adjusting for age, weight, primary PH diagnosis, ischemic time, and bypass time. In this pilot study, worse preoperative RV systolic and worse LV diastolic function were associated with PGD 3 and may be modifiable recipient risk factors in pediatric lung transplantation.

Metabolic Syndrome Exacerbates Pulmonary Hypertension due to Left Heart Disease.

RATIONALE: Pulmonary hypertension (PH) due to left heart disease (LHD), or group 2 PH, is the most prevalent form of PH worldwide. PH due to LHD is often associated with metabolic syndrome (MetS). In 12% to 13% of cases, patients with PH due to LHD display vascular remodeling of pulmonary arteries (PAs) associated with poor prognosis. Unfortunately, the underlying mechanisms remain unknown; PH-targeted therapies for this group are nonexistent, and the development of a new preclinical model is crucial. Among the numerous pathways dysregulated in MetS, inflammation plays also a critical role in both PH and vascular remodeling. OBJECTIVE: We hypothesized that MetS and inflammation may trigger the development of vascular remodeling in group 2 PH. METHODS AND RESULTS: Using supracoronary aortic banding, we induced diastolic dysfunction in rats. Then we induced MetS by a combination of high-fat diet and olanzapine treatment. We used metformin treatment and anti-IL-6 (interleukin-6) antibodies to inhibit the IL-6 pathway. Compared with sham conditions, only supracoronary aortic banding+MetS rats developed precapillary PH, as measured by both echocardiography and right/left heart catheterization. PH in supracoronary aortic banding+MetS was associated with macrophage accumulation and increased IL-6 production in lung. PH was also associated with STAT3 (signal transducer and activator of transcription 3) activation and increased proliferation of PA smooth muscle cells, which contributes to remodeling of distal PA. We reported macrophage accumulation, increased IL-6 levels, and STAT3 activation in the lung of group 2 PH patients. In vitro, IL-6 activates STAT3 and induces human PA smooth muscle cell proliferation. Metformin treatment decreased inflammation, IL-6 levels, STAT3 activation, and human PA smooth muscle cell proliferation. In vivo, in the supracoronary aortic banding+MetS animals, reducing IL-6, either by anti-IL-6 antibody or metformin treatment, reversed pulmonary vascular remodeling and improve PH due to LHD. CONCLUSIONS: We developed a new preclinical model of group 2 PH by combining MetS with LHD. We showed that MetS exacerbates group 2 PH. We provided evidence for the importance of the IL-6-STAT3 pathway in our experimental model of group 2 PH and human patients.

Sacubitril/valsartan in chronic kidney disease, the nephrologist point of view. / Experiencia clínica con sacubitrilo/valsartán en pacientes con insuficiencia renal: la visión del nefrólogo.

BACKGROUND AND OBJECTIVES: Sacubitril/valsartan reduces cardiovascular morbidity and mortality in patients with systolic dysfunction. The aim of the present study was to assess the evolution of chronic kidney disease (CKD) patients after initiating sacubitril/valsartan. MATERIAL AND METHODS: We included 66 consecutive CKD patients with systolic dysfunction followed up in outpatient care. Patients had to meet the inclusion criteria of having a New York Heart Association class ii to iv, receiving maximum tolerated doses of optimal medical therapy and CKD stages 1 to 4. At baseline, comorbidities and epidemiological data were collected and low doses of sacubitril/valsartan were initiated. At month 1 and 3, doses of sacubitril/valsartan were increased up to the maximum doses if tolerated. In each visit, renal function and cardiac biomarkers were recorded. All the data were analyzed at the end of follow up (6 months). RESULTS: Of the 66 patients, 42 (63%) were men, with a mean age of 73±15 years. Mean creatinine at baseline was 1.42±0.5 mg/dL (glomerular filtration rate estimated by CKD-EPI was 50±19 mL/min/1.73 m2) and mean left ventricular ejection fraction (LVEF) was 31±9%. At the end of follow up, LVEF improved from 31±9% to 39±15% (P <0.001). After one month of treatment, renal function improved up to 53±21 mL/min/1.73 m2, P=0.005. For the remaining follow-up time, glomerular filtration rate remained stable (mean at end of follow-up 51±18 mL/min/1.73 m2). Seven patients (10.6%) withdrew from treatment. CONCLUSION: In our experience, sacubitril/valsartan is safe in CKD, offering stability in CKD progression after 6 months.

Cardiac Magnetic Resonance Evaluation of Pulmonary Transit Time and Blood Volume in Adult Congenital Heart disease.

BACKGROUND: Management of adults with repaired congenital heart disease (CHD) is still challenging. Heart failure secondary to residual anatomical sequels or arrhythmic events is not rare in this population. MRI has emerged as an accurate tool to quantify pulmonary transit time (PTT) of intravenous contrast agents and pulmonary blood volume (PBV). PURPOSE: To determine the relationship between PTT, and conventional indexes of ventricular dysfunction and heart failure in a cohort of adults with CHD and to assess its association with adverse outcomes. STUDY TYPE: Retrospective. SUBJECTS: 89 adult CHD patients (56 males, age 34 ± 11 years) and 14 age- and sex-matched healthy subjects. FIELD STRENGTH/SEQUENCE: First-pass perfusion and standard sequences for ventricular volumes and function and flow analysis at 1.5T. ASSESSMENT: PTT was calculated as the time required for a bolus of contrast agent to pass from the right ventricle to the left atrium, expressed both in seconds (PTTS) and number of heartbeats (PTTB). The pulmonary blood volume index (PBVI) was measured by the product of PTTB and the pulmonary artery stroke volumes. STATISTICAL TESTS: Student's independent t-test analysis of variance (ANOVA) and Mann-Whitney nonparametric; Pearson's or Spearman's correlation; Kaplan-Meier method. RESULTS: PTTS and PTTB were significantly higher in patients than in controls (7.6 ± 3 vs. 5.6 ± 1.2 sec, P = 0.01 and 8 ± 3 vs. 6 ± 1 bpm, P = 0.01, respectively). PTTS showed negative correlation with left ventricle ejection fraction (LVEF) and cardiac index (CI) (r = -0.3, P = 0.004, and r = -0.4, P < 0.001, respectively) as well as with left ventricle and atrial volumes. By Kaplan-Meier survival analysis, PTTB >8 bpm was associated with significant increased risk of adverse outcome at mid-term follow-up. Moreover, patients with both increased PTTB and PBV have higher amino-terminal portion of the prohormone brain natriuretic peptide (NT-proBNP) and lower LVEF. DATA CONCLUSION: PTT is prolonged in adult CHD in comparison with healthy subjects, likely reflecting reduced CI and ventricular dysfunction. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:779-786.

Cardiovascular magnetic resonance imaging feature tracking: Impact of training on observer performance and reproducibility.

BACKGROUND: Cardiovascular magnetic resonance feature tracking (CMR-FT) is increasingly used for myocardial deformation assessment including ventricular strain, showing prognostic value beyond established risk markers if used in experienced centres. Little is known about the impact of appropriate training on CMR-FT performance. Consequently, this study aimed to evaluate the impact of training on observer variance using different commercially available CMR-FT software. METHODS: Intra- and inter-observer reproducibility was assessed prior to and after dedicated one-hour observer training. Employed FT software included 3 different commercially available platforms (TomTec, Medis, Circle). Left (LV) and right (RV) ventricular global longitudinal as well as LV circumferential and radial strains (GLS, GCS and GRS) were studied in 12 heart failure patients and 12 healthy volunteers. RESULTS: Training improved intra- and inter-observer reproducibility. GCS and LV GLS showed the highest reproducibility before (ICC >0.86 and >0.81) and after training (ICC >0.91 and >0.92). RV GLS and GRS were more susceptible to tracking inaccuracies and reproducibility was lower. Inter-observer reproducibility was lower than intra-observer reproducibility prior to training with more pronounced improvements after training. Before training, LV strain reproducibility was lower in healthy volunteers as compared to patients with no differences after training. Whilst LV strain reproducibility was sufficient within individual software solutions inter-software comparisons revealed considerable software related variance. CONCLUSION: Observer experience is an important source of variance in CMR-FT derived strain assessment. Dedicated observer training significantly improves reproducibility with most profound benefits in states of high myocardial contractility and potential to facilitate widespread clinical implementation due to optimized robustness and diagnostic performance.

Myocardial constructive work is impaired in hypertrophic cardiomyopathy and predicts left ventricular fibrosis.

BACKGROUND: The estimation of myocardial work by pressure strain loops (PSLs) is a totally new non-invasive approach to assess myocardial performance, and its role in patients with hypertrophic cardiomyopathy is unknown. The aims of the present study are therefore: (a) to compare myocardial work in patients with non-obstructive hypertrophic cardiomyopathy (HCM) and in a subset of age-matched healthy controls and (b) to assess the correlation between myocardial work and left ventricular (LV) fibrosis. DESIGN: Eighty-two patients with non-obstructive HCM (58 ± 14 years) and 20 age-matched healthy subjects (58 ± 7 years, P = 0.99) underwent standard and speckle-tracking echocardiography to assess myocardial dimensions and deformation parameters. PSLs analysis was used to estimate global myocardial constructive work (GCW) and wasted work (GWW). LV fibrosis was estimated at cardiac magnetic resonance (CMR) by qualitative assessment of late gadolinium enhancement (LGE), and significant fibrosis was defined as LGE in ≥2 LV segments. RESULTS: Global constructive work (1599 ± 423 vs 2248 ± 249 mm Hg%, P < 0.0001) was significantly reduced in HCM compared to the control group. No difference was observed in GWW (141 ± 125 vs 101 ± 88 mm Hg%, P = 0.18) and LV ejection fraction (LVEF) (63 ± 13 vs 66 ± 4% P = 0.17) between the two groups. In HCM, GCW was the only predictor of LV fibrosis at multivariable analysis (OR 1.01, 95% CI: 0.99-1.08, P = 0.04). A cutoff value of 1623 mm Hg% (AUC 0.80, 95% CI: 0.66-0.93, P < 0.0001) was able to predict myocardial fibrosis with a good sensitivity and fair specificity (82% and 67%, respectively). CONCLUSIONS: Global constructive work is significantly reduced in HCM despite normal LVEF and is associated with the LV fibrosis as assessed by LGE.

Global strain and dyssynchrony of the single ventricle predict adverse cardiac events after the Fontan procedure: Analysis using feature-tracking cine magnetic resonance imaging.

BACKGROUND: The aim of this study was to determine whether major adverse cardiac events (MACE) during the late phase of the Fontan procedure could be predicted by strain measurements of single ventricles using cardiac magnetic resonance imaging with feature tracking (CMR-FT). METHODS: One hundred adolescent patients who underwent the Fontan procedure (mean age, 21 years) were examined retrospectively with CMR-FT to assess the systemic single-ventricle function. Vertical long-axis cine imaging was divided into six myocardial segments. Global longitudinal strain (GLS) was determined by averaging the peak strain values of each of the six segments. The dyssynchrony index was defined as the standard deviation of the time to peak strain for six segments. The primary outcome was MACE, defined as cardiac death and unscheduled hospitalization. RESULTS: MACE occurred in 18 patients during a mean follow-up of 62 months. According to the multivariate logistic regression analysis results for potential predictor variables, GLS and the dyssynchrony index are independent predictors of MACE. Patients with GLS ≥11.8% had significantly higher MACE-free rates than did those with GLS <11.8% [log-rank value, 14.15; p = 0.0002; hazard ratio, 6.82; 95% confidence interval (CI), 2.51-18.56]. Patients with a dyssynchrony index <63.5 ms had significantly higher MACE-free rates than did those with dyssynchrony index ≥63.5 ms (log-rank value, 28.17; p < 0.0001; hazard ratio, 21.69; 95% CI, 6.96-67.56). CONCLUSION: GLS and the dyssynchrony index found using CMR-FT are independent predictors of MACE for adolescent patients after the Fontan procedure and provide information regarding risk stratification beyond clinical parameters and biomarkers.

Pre-excitation induced ventricular dysfunction and successful berlin heart explantation after accessory pathway ablation.

A 13 kg, 20 month-old, Caucasian girl, presented with cardiomyopathy, biventricular dysfunction and pre-excitation on electrocardiogram. She had normal intracardiac anatomy with severely dilated left ventricle and severely diminished biventricular function (Fig. 1). She was treated with milrinone and epinephrine infusions, mechanical ventilation and listed for heart transplant. She underwent Berlin Heart EXCOR biventricular assist device (BiVAD) placement (30 ml LVAD and 25 ml RVAD pumps). No supraventricular tachycardia (SVT) was inducible or noted during her hospitalization. First ablation attempt without BiVAD support was unsuccessful; however, 18 days post BiVAD implantation, another electrophysiology study and successful radiofrequency ablation of a right anterolateral accessory pathway was performed on BiVAD support. After successful ablation and loss of pre-excitation, the cardiac dysfunction rapidly improved with initial improvement noted as early as 48 h after the successful ablation. Due to recovery of cardiac function, a BiVAD wean protocol was initiated and BiVAD explantation was performed 48 days after the implant (30 days after the successful ablation). To the best of our knowledge, this is the first report of successful BiVAD explantation.

Survival to Stage II with Ventricular Dysfunction: Secondary Analysis of the Single Ventricle Reconstruction Trial.

Ventricular dysfunction affects survival in patients with single right ventricle (RV), and remains one of the primary indications for heart transplantation. Since it is challenging to predict the capacity of patients with ventricular dysfunction to proceed to the stage II procedure, we sought to identify factors that would be associated with death or heart transplantation without achieving stage II for single RV patients with ventricular dysfunction after Norwood procedure. The Single Ventricle Reconstruction (SVR) trial public-use database was used. Patients with a RV ejection fraction less than 44% or a RV fractional area of change less than 35% on the post-Norwood echocardiogram were included. Parametric risk hazard analysis was used to identify risk factors for death or transplantation without achieving stage II. Of 365 patients with ventricular function measurements on the post-Norwood echocardiogram, 123 (34%) patients had RV dysfunction. The transplantation-free survival was significantly lower for those with ventricular dysfunction compared to those with normal function (log rank Chi-square = 4.23, p = 0.04). Furthermore, having a Blalock-Taussig (BT) shunt, a large RV, a post-Norwood infectious complication, and a surgeon who performs five or less Norwood per year were independent risk factors for death or transplantation without achieving stage II. The predicted 6-month transplantation-free survival for patients with all four identified risk factors was 1% (70% CI 0-13%). Early heart transplantation referral might be considered for post-Norwood patients with BT shunt and RV dysfunction, especially if other high-risk features are present.

Comparative Safety of Sulfonylureas and the Risk of Sudden Cardiac Arrest and Ventricular Arrhythmia.

OBJECTIVE: To examine the association between individual antidiabetic sulfonylureas and outpatient-originating sudden cardiac arrest and ventricular arrhythmia (SCA/VA). RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using 1999-2010 U.S. Medicaid claims from five large states. Exposures were determined by incident use of glyburide, glimepiride, or glipizide. Glipizide served as the reference exposure, as its effects are believed to be highly pancreas specific. Outcomes were ascertained by a validated ICD-9-based algorithm indicative of SCA/VA (positive predictive value ∼85%). Potential confounding was addressed by adjustment for multinomial high-dimensional propensity scores included as continuous variables in a Cox proportional hazards model. RESULTS: Of sulfonylurea users under study (N = 519,272), 60.3% were female and 34.9% non-Hispanic Caucasian, and the median age was 58.0 years. In 176,889 person-years of sulfonylurea exposure, we identified 632 SCA/VA events (50.5% were immediately fatal) for a crude incidence rate of 3.6 per 1,000 person-years. Compared with glipizide, propensity score-adjusted hazard ratios for SCA/VA were 0.82 (95% CI 0.69-0.98) for glyburide and 1.10 (0.89-1.36) for glimepiride. Numerous secondary analyses showed a very similar effect estimate for glyburide; yet, not all CIs excluded the null. CONCLUSIONS: Glyburide may be associated with a lower risk of SCA/VA than glipizide, consistent with a very small clinical trial suggesting that glyburide may reduce ventricular tachycardia and isolated ventricular premature complexes. This potential benefit must be contextualized by considering putative effects of different sulfonylureas on other cardiovascular end points, cerebrovascular end points, all-cause death, and hypoglycemia.

Outcomes of a total cavopulmonary connection in patients with impaired ventricular function.

OBJECTIVES: Our aim was to evaluate outcomes following a total cavopulmonary connection (TCPC) in patients with preoperatively impaired ventricular function (VF). METHODS: Of 483 consecutive TCPC patients, 44 (9.1%) had impaired VF (ejection fraction <50%, Group A), and 439 patients had normal VF (ejection fraction ≥50%, Group B). We compared the clinical outcomes between the groups. RESULTS: The median age at TCPC was 2.8 (interquartile range 1.9-8.3) years in Group A and 2.3 (1.8-3.5) years in Group B (P = 0.025). An atrioventricular valve (AVV) operation prior to (38.6 vs 27.1%, P < 0.001) and concomitant with (31.8 vs 12.1%, P < 0.001) the TCPC was performed more frequently in Group A. The median intensive care unit stay (7.0 vs 7.0 days, P = 0.737) and 30-day survival (97.7 vs 98.4%, P = 0.737) were not significantly different between groups. Freedom from death, transplantation (P = 0.115) and catheter intervention (P = 0.603) showed no difference between groups. However, freedom from cardiac reoperation was significantly lower in Group A (P < 0.001). VF was resolved in 22 of the 39 (56.4%) survivors in Group A. The recovered patients had a lower incidence of AVV reoperation (0 vs 6, P = 0.002) and pacemaker rhythm (0 vs 5, P = 0.006). CONCLUSIONS: In patients planned for TCPC, impaired VF is often associated with AVV regurgitation. TCPC can be performed with low risk and comparable clinical results except for cardiac reoperation in patients with impaired VF when compared to patients with normal VF. Following TCPC, VF recovers in half of the survivors. A competent AVV and sinus rhythm are prerequisites for recovery.