Cardiac magnetic resonance ventricular parameters correlate with cardiopulmonary fitness in patients with functional single ventricle.

Owing to advances in medical and surgical fields, patients with single ventricle (SV) have a greatly improved life expectancy. However, progressive functional deterioration is observed over time, with a decrease in cardiopulmonary fitness. This study aimed to identify, in patients with SV, the association between cardiac magnetic resonance imaging (CMR) parameters and change in cardiopulmonary fitness assessed by cardiopulmonary exercise test (CPET), and if certain thresholds could anticipate a decline in aerobic fitness. Patients with an SV physiology were retrospectively screened from 2011 and 2021 in a single-centre observational study. We evaluated (1) the correlation between baseline CMR and CPET parameters, (2) the association between baseline CMR results and change in peak oxygen uptake (peak VO2), and (3) the cut-off values of end-diastolic and end-systolic volume index in patients with an impaired cardiopulmonary fitness (low peak VO2 and/or high VE/VCO2 slope). 32 patients were included in the study. End-systolic volume index (r = 0.37, p = 0.03), end-diastolic volume index (r = 0.45, p = 0.01), and cardiac index (r = 0.46, p = 0.01) correlated with the VE/VCO2 slope. End-systolic ventricular volume (r = - 0.39, p = 0.01), end-diastolic ventricular volume (r = - 0.38, p = 0.01), and cardiac output (r = - 0.45, p < 0.01) inversely correlated with the peak VO2. In multivariate analysis, the cardiac index obtained from baseline CMR was inversely associated with the change in peak VO2 (p < 0.01). An end-diastolic volume index > 101 ml/m2 and an end-systolic volume index > 47 ml/m2 discriminated patients with impaired cardiopulmonary fitness. CMR parameters correlate with cardiopulmonary fitness in patients with SV and can therefore be useful for follow-up and therapeutic management of these patients.

Could a Multi-Marker and Machine Learning Approach Help Stratify Patients with Heart Failure?

Half of the patients with heart failure (HF) have preserved ejection fraction (HFpEF). To date, there are no specific markers to distinguish this subgroup. The main objective of this work was to stratify HF patients using current biochemical markers coupled with clinical data. The cohort study included HFpEF (n = 24) and heart failure with reduced ejection fraction (HFrEF) (n = 34) patients as usually considered in clinical practice based on cardiac imaging (EF ≥ 50% for HFpEF; EF < 50% for HFrEF). Routine blood tests consisted of measuring biomarkers of renal and heart functions, inflammation, and iron metabolism. A multi-test approach and analysis of peripheral blood samples aimed to establish a computerized Machine Learning strategy to provide a blood signature to distinguish HFpEF and HFrEF. Based on logistic regression, demographic characteristics and clinical biomarkers showed no statistical significance to differentiate the HFpEF and HFrEF patient subgroups. Hence a multivariate factorial discriminant analysis, performed blindly using the data set, allowed us to stratify the two HF groups. Consequently, a Machine Learning (ML) strategy was developed using the same variables in a genetic algorithm approach. ML provided very encouraging explorative results when considering the small size of the samples applied. The accuracy and the sensitivity were high for both validation and test groups (69% and 100%, 64% and 75%, respectively). Sensitivity was 100% for the validation and 75% for the test group, whereas specificity was 44% and 55% for the validation and test groups because of the small number of samples. Lastly, the precision was acceptable, with 58% in the validation and 60% in the test group. Combining biochemical and clinical markers is an excellent entry to develop a computer classification tool to diagnose HFpEF. This translational approach is a springboard for improving new personalized treatment methods and identifying "high-yield" populations for clinical trials.

Pheochromocytoma in a patient presenting with ventricular fibrillation and carotid dissection: a case report.

BACKGROUND: Pheochromocytoma is an endocrine tumour secreting catecholamines, most often revealed by clinical symptoms (headache, palpitations, diaphoresis, or resistant hypertension). Some cases of ventricular arrhythmias were described in the literature, without any formal link between arrhythmia and pheochromocytoma. CASE SUMMARY: We report a case of pheochromocytoma discovered after cardiac arrest due to ventricular fibrillation in a 46-year-old patient. The diagnosis was suggested by clinical symptoms (headache, palpitation, and diaphoresis) and suspected on the abdominal computed tomography scan. The diagnosis was corroborated by metaiodobenzylguanidine scintigraphy and finally confirmed by anatomopathological analysis of the operative specimen. The cerebral imaging showed a dissection of the left internal carotid artery and an intraparenchymal haematoma that might be secondary to a catecholaminergic discharge of phaeochromocytoma and severe hypertension. DISCUSSION: Since pheochromocytoma is accessible to curative treatment, its detection in case of cardiac arrest is essential to decrease the risk of arrhythmic recurrence.

In vitro correlation between the effective and geometric orifice area in aortic stenosis.

BACKGROUND: Planimetry of aortic stenosis can be performed when Doppler measurements are unavailable. We sought to evaluate if, as advised in guidelines, the geometric orifice area (GOA) threshold value of 1 cm² was concordant with the threshold of 1 cm² of the effective orifice area (EOA), and the factors influencing the contraction coefficient (EOA/GOA ratio). METHODS: In an in vitro mock circulatory system, we tested 6 degrees of AS severity (3 severe and 3 non-severe), and 3 levels of flow (<150 ml/s, 150-200 ml/s, >250 ml/s). The EOA was calculated by Doppler-echocardiography, and the GOA was measured with dedicated software after camera acquisition. RESULTS: In all but the very low flow condition, an EOA of 1 cm² corresponded to a GOA of 1.2 cm². The contraction coefficient increased with both the flow and the stenosis severity. For very severe stenoses, the EOA and the GOA were interchangeable. CONCLUSION: As observed in clinical studies, the GOA was larger than the EOA, and a GOA between 1 and 1.2 cm² should not discard the possibility of severe aortic stenosis.

P-hacking in clinical trials and how incentives shape the distribution of results across phases.

Clinical research should conform to high standards of ethical and scientific integrity, given that human lives are at stake. However, economic incentives can generate conflicts of interest for investigators, who may be inclined to withhold unfavorable results or even tamper with data in order to achieve desired outcomes. To shed light on the integrity of clinical trial results, this paper systematically analyzes the distribution of P values of primary outcomes for phase II and phase III drug trials reported to the ClinicalTrials.gov registry. First, we detect no bunching of results just above the classical 5% threshold for statistical significance. Second, a density-discontinuity test reveals an upward jump at the 5% threshold for phase III results by small industry sponsors. Third, we document a larger fraction of significant results in phase III compared to phase II. Linking trials across phases, we find that early favorable results increase the likelihood of continuing into the next phase. Once we take into account this selective continuation, we can explain almost completely the excess of significant results in phase III for trials conducted by large industry sponsors. For small industry sponsors, instead, part of the excess remains unexplained.

In Vitro Quantification of Mitral Regurgitation of Complex Geometry by the Modified Proximal Isovelocity Surface Area Method.

BACKGROUND: Doppler echocardiographic methods, such as the proximal isovelocity surface area (PISA) method, are used to quantify mitral regurgitations (MRs). However, their accuracy and reproducibility are still being discussed, especially in the case of MR of complex geometry. The aim of this study was to evaluate the accuracy of the PISA method depending on the shape and number of regurgitant flows. METHODS: First, various MR shapes and severities (central, oblong, and multiple-jet MR) were mimicked in a left heart simulator. The effective regurgitant orifice area (EROA) was calculated using the standard and modified PISA methods and was compared to a reference value obtained from an electromagnetic flowmeter. Second, in order to clinically validate the in vitro findings, 16 patients were examined with two-dimensional (2D) echocardiography. The results were analyzed by comparing the PISA method and the echocardiographic 2D quantitative volumetric method. RESULTS: Both hemicylindrical and hemiellipsoidal PISA assumptions improved the quantification of the EROA for oblong MR compared with the traditional PISA method (hemispherical PISA assumption: 11 ± 4.6 mm2, P < .01; hemicylindrical PISA assumption: 2 ± 0.8 mm2, P = .83; hemiellipsoidal PISA assumption: 6 ± 3.7 mm2, P = .05). In the case of multiple jets of different sizes, an improved EROA calculation was measured when both jets were considered (single hemispherical PISA assumption: 4.5 ± 0.7 mm2, P < .01; double hemispherical PISA assumption: 2 ± 1.1 mm2, P = .64). CONCLUSION: For a correct diagnosis of MR, the PISA geometry must be considered. A measurement of both PISA radius and PISA width is necessary for an accurate quantification of an oblong MR. In the case of a double-jet MR, a measurement of the two radii is recommended.

STADE-HF (sST2 As a help for management of HF): a pilot study.

AIMS: Biomarkers are not recommended until now to guide the management of patients with heart failure (HF). Soluble suppression of tumorigenicity 2 (sST2) appears as a promising biomarker. The current study considered pre-discharged sST2 values as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to reduce hospital readmission. METHODS AND RESULTS: STADE-HF was a blinded prospective randomized controlled trial and included 123 patients admitted for acute HF. They were randomized into the usual treatment group (unknown sST2 level) or the interventional treatment group, for whom sST2 level was known and used on Day 4 of hospitalization to guide the treatment. The primary endpoint was the readmission rate for any cause at 1 month. It occurred in 10 patients (19%) in the usual group and 18 (32%) in the sST2 group without statistical difference (P = 0.11). Post hoc analysis in the whole group shows that the mean duration of hospitalization was lower in patients with low sST2 (<37 ng/mL) at admission vs. high sST2 (8.5 ± 9.5 vs. 14.8 ± 14.9 days, respectively, P = 0.003). In addition, a decrease in sST2 greater than 18% is significantly associated with a lower readmission rate. CONCLUSIONS: Soluble suppression of tumorigenicity 2-guided therapy over a short period of time does not reduce readmissions. However, sST2 was clearly associated with duration of hospitalization, and the decrease in sST2 was associated with decreased rehospitalizations. Long-term outcome using sST2-guided therapy deserves further investigations.

Management of valvulopathies with acute severe heart failure and cardiogenic shock.

Cardiogenic shock is a critical clinical situation, requiring rapid diagnosis, aetiological assessment and immediate initiation of therapy. In industrialized countries, aortic stenosis is the most frequent left-sided valvulopathy, followed by mitral regurgitation, aortic regurgitation and mitral stenosis. Severe valvulopathies leading to cardiogenic shock are not rare conditions, but few data are available on their optimal management. Therapeutic options for such critical conditions include inotropic agents, mechanical support (when feasible) and rapid valvular intervention. Although surgery remains the gold-standard treatment for severe valvular disease, mortality is frequently prohibitive in the setting of cardiogenic shock, necessitating consideration of alternative therapies. Percutaneous management of valvulopathies has emerged as an alternative treatment for patients deemed at high surgical risk in a stable condition. Although few published data are available, catheter-based interventions may be feasible in the cardiogenic shock setting. This review offers an overview of different valvulopathies in the cardiogenic shock setting, and summarizes the different therapeutic options currently available in such critical situations.

Which high-sensitivity troponin variable best characterizes infarct size and microvascular obstruction?

BACKGROUND: The link between hs-Tn and infarct size has already been proved in several articles. However few is known about the kinetic of the troponin and its link to the infarct characteristics, likewise MVO. Our primary objective was to study which hs-Tn characterizes the best infarction. METHODS AND RESULTS: We identified 29 consecutive STEMI patients to study. The kinetics of hs-TnT (Roche) and two different TnIs (hs-TnI from Abbott, s-TnI from Siemens) were evaluated for all patients. Area under curves (AUC), first peak (FP) and second peak (SP), for hs-TnT, were compared to IS and MVO size using contrast-enhanced cardiac magnetic resonance. For IS, statistically SP of hs-TnT presented the best correlation compared to other peak values [r=0.9 vs. 0.73 for FP hs-TnT; vs. 0.69 for hs-TnI; vs. 0.57 for s-TnI; respectively P<0.01, P<0.01, P<0.01]. For MVO size, statistically SP of hs-TnT presented the best correlation compared to other peak values [r=0.84 vs. 0.75 for FP hs-TnT; vs. 0.72 for hs-TnI; vs. 0.62 for s-TnI; respectively P=0.01, P<0.01, P<0.01]. The best AUC were archived by the hs-TnT (AUC=0.95) but there were no statistical differences when compared to other hs-Tn AUC. CONCLUSION: The SP of hs-TnT had the greatest level of correlation and therefore seems to be the best biological parameter to evaluate and characterize infarct size.

Speckle-Tracking Echocardiography in Children With Duchenne Muscular Dystrophy: A Prospective Multicenter Controlled Cross-Sectional Study.

BACKGROUND: Prognosis of Duchenne muscular dystrophy (DMD) is related to cardiac dysfunction. Speckle-tracking echocardiographic (STE) imaging is emerging as a noninvasive functional biomarker to consider in the early detection of DMD-related cardiomyopathy. However, STE analysis has not been assessed in a prospectively controlled study, especially in presymptomatic children with DMD, and no study has used STE analysis in all three displacements (longitudinal, radial, and circumferential) and for both ventricles. METHODS: This prospective controlled study enrolled 108 boys, 36 of whom had DMD (mean age, 11 ± 3.8 years) and 72 of whom were age-matched control subjects in a 1:2 case-control design. Conventional echocardiographic variables were collected for the left and right ventricles. STE analyses were performed in the longitudinal, radial, and circumferential displacements for the left ventricle and in the free wall longitudinal displacement for the right ventricle. The effect of age on the evolution of two-dimensional strain in children with DMD was studied by adding an interaction term, DMD × age, in the models. RESULTS: Conventional echocardiographic measures were normal in both groups. Left ventricular (LV) ejection fraction ranged from 45% to 76% (mean, 63 ± 6%) in the DMD group and from 55% to 76% (mean, 64 ± 5%) in the control group. Global LV strain mean measures were significantly worse in the DMD group for the longitudinal (-16.8 ± 3.9% vs -20.6 ± 2.6%, P < .0001), radial (22.7 ± 11.3% vs 31.7 ± 14%, P = .002), and circumferential (-16.5 ± 3.8% vs -20.3 ± 3.1%, P < .0001) displacements. The decrease of global LV longitudinal strain with age in children with DMD was 0.34% per year more marked than that in control subjects. The LV inferolateral and anterolateral segments were specifically impaired, especially in the basal area. Right ventricular function evaluated using conventional echocardiography and STE analysis was normal and not different between children with DMD and control subjects. CONCLUSIONS: The existence of altered LV strain despite normal LV function in children with DMD represents an important perspective for future pediatric drug trials in DMD-related cardiomyopathy prevention.

Potential Uses of Sacubitril/Valsartan: Need for Data on Efficacy and Safety.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been the cornerstone for the treatment of heart failure (HF) with reduced ejection fraction for decades. According to recent and promising studies, sacubitril/valsartan (SV) might be efficient in alternative indications in the area of HF with preserved left ventricular ejection fraction, chronic kidney disease, and so on. This review briefly summarizes these promising therapeutic options regarding SV and the potential limits and pitfalls for its use in routine practice (due to cognitive uncertainties).

Low-flow, low-gradient severe aortic stenosis despite normal ejection fraction is associated with severe left ventricular dysfunction as assessed by speckle-tracking echocardiography: a multicenter study.

BACKGROUND: Low-flow low-gradient (LFLG) is sometimes observed in severe aortic stenosis (AS) despite normal ejection fraction, but its frequency and mechanisms are still debated. We aimed to describe the characteristics of patients with LFLG AS and assess the presence of longitudinal left ventricular dysfunction in these patients. METHODS AND RESULTS: In a multicenter prospective study, 340 consecutive patients with severe AS and normal ejection fraction were studied. Longitudinal left ventricular function was assessed by 2D-strain and global afterload by valvulo-arterial impedance. Patients were classified according to flow and gradient: low flow was defined as a stroke volume index ≤35 mL/m(2), low gradient as a mean gradient ≤40 mm Hg. Most patients (n=258, 75.9%) presented with high-gradient AS, and 82 patients (24.1%) with low-gradient AS. Among the latter, 52 (15.3%) presented with normal flow and low gradient and 30 (8.8%) with LFLG. As compared with normal flow and low gradient, patients with LFLG had more severe AS (aortic valve area=0.7±0.12 cm(2) versus 0.86±0.14 cm(2)), higher valvulo-arterial impedance (5.5±1.1 versus 4±0.8 mm Hg/mL/m(2)), and worse longitudinal left ventricular function (basal longitudinal strain=-11.6±3.4 versus -14.8±3%; P<0.001 for all). CONCLUSIONS: LFLG AS is observed in 9% of patients with severe AS and normal ejection fraction and is associated with high global afterload and reduced longitudinal systolic function. Patients with normal-flow low-gradient AS are more frequent and present with less severe AS, normal afterload, and less severe longitudinal dysfunction. Severe left ventricular longitudinal dysfunction is a new explanation to the concept of LFLG AS.

Down-regulation of the transcription factor ZAC1 upon pre- and postconditioning protects against I/R injury in the mouse myocardium.

AIMS: Myocardial infarction leads to heart failure and death. Ischaemic preconditioning (PreC) and postconditioning (PostC) reduce infarct size in animal models and human. Zac1 was identified as the only gene related to apoptosis and jointly down-regulated upon PreC and PostC. The aim of our study was to investigate the role of Zac1 down-regulation during ischaemia-reperfusion (I/R) in vivo. METHODS AND RESULTS: C57BL/6 mice were submitted to myocardial I/R injury, PreC, or PostC protocols. QPCR and immunochemistry showed that Zac1 expression was down-regulated both at the transcriptional and the protein levels upon PreC and PostC. Zac1(-/-) Knockout mice (n = 7) developed smaller infarcts (54%) than Zac1(+/+) littermates (n = 8) and decreased apoptosis (61.7%) in the ischaemic part of the left ventricle during I/R (Zac1(-/-), n = 6 vs. Zac1(+/+), n = 7; P = 0.0012). Mutants showed under control conditions a decrease of 53.9% in mRNA of Daxx, a pro-apoptotic protein playing a key role in I/R injuries (4.81 ± 0.77, n = 4 Zac1(-/-) mice vs. 10.44 ± 3.5, n = 7 Zac1(+/+) mice; P = 0.0121). CONCLUSION: Our study shows for the first time that Zac1 is down-regulated both at the transcriptional and protein levels upon PreC and PostC in wild-type mice. Moreover, inactivation of Zac1 in vivo is associated with a decreased amount of Daxx transcripts and, upon I/R injury, decreased infarct size and apoptosis. Altogether, our results show that Zac1 down-regulation plays a key role during cardioprotection against I/R injury and support the concept that cardioprotection regulates a network of interacting pro-apoptotic genes including Zac1 and Daxx.

Short-run economic effects of the Scottish smoking ban.

BACKGROUND: We estimated the short-run economic impacts of the Scottish smoking ban on public houses. Previous findings on the effect of smoking bans on the hospitality sector have mainly focused on the United States. These studies have mostly found no negative economic effects of such legislation on the hospitality sector in the long run. However, differences in the social use of public houses in Great Britain in comparison with the United States may lead to different findings. METHODS: We used a quasi-experimental research design that compared the sales and number of customers in public houses located in Scotland before and after the Scottish smoking ban was introduced, relative to a control group of establishments across the English border where no ban was imposed. To perform this analysis, we collected data on 2724 pubs, 1590 in Scotland and 1134 in Northern England by phone interviews using quota sampling. RESULTS: We found that the Scottish ban led to a 10% decrease in sales [P = 0.02, 95% confidence interval (CI) -19% to -2%] and a 14% decrease in customers (P = 0.02, 95% CI -26% to -2%). CONCLUSION: Our study suggests that the Scottish smoking ban had a negative economic impact on public houses, at least in the short run, due in part to a drop in the number of customers.

Taxes, Cigarette Consumption, and Smoking Intensity.

This paper analyses the compensatory behavior of smokers. Exploiting data on cotinine concentration--a metabolite of nicotine--measured in a large population of smokers over time, we show that smokers compensate for tax hikes by extracting more nicotine per cigarette. Our study makes two important contributions. First, as smoking a given cigarette more intensively is detrimental to health, our results question the usefulness of tax increases. Second, we develop a model of rational addiction where agents can also adjust their intensity of smoking, and we show that the previous empirical results suffer from estimation biases.

Socio-economic status and health: causality and pathways

This paper, investigates the conclusions of further by replicating their methodology on two different panel data sets. It discusses some of he assumptions and implications underlying the conclusions made by Adams et al. (2002) and reinterpret their results and the results of this paper in terms of pathways from SES to health and mortality.