Inter-season training effects on cardiovascular health in American-style football players.

BACKGROUND: Recent studies on American-style football (ASF) athletes raised questions about the impact of training on the cardiovascular phenotype, particularly among linemen players who engage mostly in static exercise during competition and who exhibit concentric cardiac remodeling, often considered maladaptive. We aimed to examine the cardiovascular adaptation to the inter-season mixed-team training program among ASF players. METHODS: A prospective, longitudinal, cohort study was conducted among competitive male ASF players from the University of Montreal before and after an inter-season training, which lasted 7 months. This program includes, for all players, combined dynamic and static exercises. Clinical and echocardiographic examinations were performed at both steps. Left atrial (LA) and ventricular (LV) morphological and functional changes were assessed using a multiparametric echocardiographic approach (2D and 3D-echo, Doppler, and speckle tracking). Two-way ANOVA was performed to analyze the impacts of time and field position (linemen versus non-linemen). RESULTS: Fifty-nine players (20 linemen and 39 non-linemen) were included. At baseline, linemen had higher blood pressure (65% were prehypertensive and 10% were hypertensive), thicker LV walls, lower LV systolic and diastolic functions, lower LA-reservoir and conduit functions than non-linemen. After training, linemen significantly reduced weight (Δ-3.4%, P < 0.001) and systolic blood pressure (Δ-4.5%, P < 0.001), whereas non-linemen maintained their weight and significantly increased their systolic (Δ+4.2%, P = 0.037) and diastolic (Δ+16%, P < 0.001) blood pressure ). Mixed training was associated with significant increases in 2D-LA volume (P < 0.001), 3D-LV end-diastolic volume (P < 0.001), 3D-LV mass (P < 0.001), and an improvement in LV systolic function, independently of the field position. Non-linemen remodeled their LV in a more concentric fashion and showed reductions in LV diastolic and LA reservoir functions. CONCLUSIONS: Our study underscored the influence of field position on cardiovascular adaptation among university-level ASF players, and emphasized the potential of inter-season training to modulate cardiovascular risk factors, particularly among linemen.

Revealing the true nature of a parachute mitral valve during an ultra-trail race.

Pre-participation screening and management of congenital cardiac valvulopathy in competitive athletes can be challenging, particularly within the context of ultra-endurance disciplines. A 55-year-old female athlete without a reported history of cardiac disease exhibited clinical signs of cardiogenic pulmonary edema during a 156 km ultra-trail race. The echocardiographic assessment revealed the presence of a parachute mitral valve, with no evidence of mitral stenosis or regurgitation at rest, but it demonstrated severe dynamic mitral stenosis during exercise. In competitive athletes, the detection of rare valvulopathy should prompt a comprehensive cardiac evaluation aimed at assessing the potential for dynamic valvular dysfunction.

Effects of a 20-Week High-Intensity Strength Training Program on Muscle Strength Gain and Cardiac Adaptation in Untrained Men: Preliminary Results of a Prospective Longitudinal Study.

BACKGROUND: As strength sports gain popularity, there is a growing need to explore the impact of sustained strength training on cardiac biventricular structure and function, an area that has received less attention compared to the well-established physiological cardiac adaptation to endurance training. OBJECTIVE: This study aims to implement a 20-week high-intensity strength training program to enhance maximal muscle strength and evaluate its impact on cardiac biventricular adaptation in healthy, untrained men. METHODS: A total of 27 healthy and untrained young men (mean age 22.8, SD 3.2 years) participated in a strength training program designed to increase muscle strength. The training program involved concentric, eccentric, and isometric exercise phases, conducted over a consecutive 20-week time frame with a frequency of 3 weekly training sessions. Participants were evaluated before and after 12 and 20 weeks of training through body composition analysis (bioelectrical impedance), a 12-lead resting electrocardiogram, 3D transthoracic echocardiography, cardiopulmonary exercise testing, and muscle isokinetic dynamometry. The progression of strength training loads was guided by 1-repetition maximum (RM) testing during the training program. RESULTS: Of the initial cohort, 22 participants completed the study protocol. No injuries were reported. The BMI (mean 69.8, SD 10.8 kg/m² vs mean 72, SD 11 kg/m²; P=.72) and the fat mass (mean 15.3%, SD 7.5% vs mean 16.5%, SD 7%; P=.87) remained unchanged after training. The strength training program led to significant gains in 1-RM exercise testing as early as 4 weeks into training for leg extension (mean 69.6, SD 17.7 kg vs mean 96.5, SD 31 kg; P<.001), leg curl (mean 43.2, SD 9.7 kg vs mean 52.8, SD 13.4 kg; P<.001), inclined press (mean 174.1, SD 41.1 kg vs mean 229.2, SD 50.4 kg; P<.001), butterfly (mean 26.3, SD 6.2 kg vs mean 32.5, SD 6.6 kg; P<.001), and curl biceps on desk (mean 22.9, SD 5.2 kg vs mean 29.6, SD 5.2 kg; P<.001). After 20 weeks, the 1-RM leg curl, bench press, pullover, butterfly, leg extension, curl biceps on desk, and inclined press showed significant mean percentage gains of +40%, +41.1%, +50.3%, +63.5%, +80.1%, +105%, and +106%, respectively (P<.001). Additionally, the isokinetic evaluation confirmed increases in maximal strength for the biceps (+9.2 Nm), triceps (+11.6 Nm), quadriceps (+46.8 Nm), and hamstrings (+25.3 Nm). In this paper, only the training and muscular aspects are presented; the cardiac analysis will be addressed separately. CONCLUSIONS: This study demonstrated that a short-term high-intensity strength training program was successful in achieving significant gains in muscle strength among previously untrained young men. We intend to use this protocol to gain a better understanding of the impact of high-intensity strength training on cardiac physiological remodeling, thereby providing new insights into the cardiac global response in strength athletes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04187170; https://clinicaltrials.gov/study/NCT04187170.

Sport resumption and quality of life after surgical correction of anomalous origin of a coronary artery from the opposite sinus.

Objectives: We sought to assess the resumption of sport, exercise performances, and quality of life (QoL) in adults and children after surgical repair of anomalous coronary arteries originating from the opposite sinus (ACAOS). Materials and methods: Patients who underwent surgical repair for ACAOS between 2002 and 2022 were retrospectively identified. Information about sports activity and exercise performance based on metabolic equivalents of task (METs) calculated at the last exercise stress test, were collected. QoL was assessed using age-appropriate questionnaires (Paediatric QoL Inventory, cardiac module version 3.0 for patients <18 years; SF-36 QoL Inventory for adults). Patients' METS and patients' QoL-scores were compared to reference population using the Wilcoxon test. Results: 45 patients were enrolled (males 71%, adults 49%, anomalous right coronary 84%). Median age at surgery was 15 years; median follow-up after surgery was 2.3 years [4 months-12 years]. All post-operative exercise stress tests were normal, METs and VO2 max patients' values did not differ from healthy children or adults (Exercise intensity: 12.5 ± 4.7 vs. 13.4 ± 2 METS, p = 0.3; VO2 max: 43.6 ± 16.6 vs. 46.9 ± 7 ml/kg/min, p = 0.37). For adults, QoL-scores were similar between ACAOS patients and controls. For children, there was no significant difference between the study patients' scores and those of the reference population, except for physical appearance proxy-report (p = 0.02). Conclusion: In our study, the practice of sports, exercise stress testing and QoL were not adversely affected after ACAOS repair.

Left atrial strain quantified after myocardial infarction is associated with early left ventricular remodeling.

BACKGROUND: Left ventricular remodeling (LVR) is common and associated with adverse outcome after ST-elevation myocardial infarction (STEMI). We aimed to investigate the association between left atrial (LA) mechanical function using speckle tracking imaging and early LVR at follow-up in STEMI patients. METHODS: Baseline 3D thoracic echocardiograms were performed within 48 h following admission and at a median follow-up of 7 months after STEMI. A > 20% increase in the left ventricular (LV) end-diastolic volume compared to baseline at follow-up was defined as LVR. LA global longitudinal strain was evaluated for the reservoir, conduit, and contraction (LASct) phases. RESULTS: A total of 121 patients without clinical heart failure (HF) were prospectively included, between June 2015 and October 2018 (age 58.3 ± 12.5 years, male 98 (81%)). Baseline and follow-up LV ejection fraction (LVEF) were 46.8% [41.0, 52.9] and 52.1% [45.8, 57.0] respectively (p < .001). Compared to other patients, those with LVR had significantly lower values of LASct at baseline (-7.4% [-10.1, -6.5] vs. -9.9% [-12.8, -8.1], p < .01), both on univariate and baseline LV volumes-adjusted analyses. Baseline LA strain for reservoir and conduit phases were not associated with significant LVR at follow-up. Intra- and interobserver analysis showed good reproducibility of LA strain. CONCLUSIONS: Baseline LASct may help identifying patients without HF after STEMI who are at higher risk of further early LVR and subsequent HF and who may benefit from more intensive management.

Age impacts left atrial functional remodeling in athletes.

AIM: Age-associated changes in cardiac filling and function are well known in the general population. Yet, the effect of aging on left atrial (LA) function, and its interaction with left ventricular (LV) adaptation, remain less described when combined with high-intensity chronic training. We aimed to analyze the effects of aging on LA and LV functions in trained athletes. METHODS AND RESULTS: Ninety-five healthy highly-trained athletes referred for resting echocardiography were included. Two groups of athletes were retrospectively defined based on age: young athletes aged <35 years (n = 54), and master athletes aged ≥35 years (n = 41). All subjects were questioned about their sports practice. Echocardiographic analysis of LV systolic and diastolic functions (2D-echo, 3D-echo, and Doppler), as well as LA 2D dimensions and phasic deformations assessed by speckle tracking, were analyzed. Master athletes (mean age = 46.3 ± 8.3 years, mean duration of sustained training = 13.7 ± 8.9 years) exhibited significantly stiffer LV and LA with reduced LV early diastolic functional parameters (ratio E/A, peak e', and ratio e'/a'), LA reservoir and conduit strain, whereas LA volume, LA contractile strain and LV peak a' were higher, compared to young athletes. Multivariate regression analysis confirmed that age was predictive of peak e', LA reservoir strain and LA conduit strain, independently of training variables. LA phasic strains were strongly associated with LV diastolic function. CONCLUSIONS: Regardless of chronic sports practice, master athletes exhibited age-related changes in LA function closely coupled to LV diastolic properties, which led to LV filling shifts to late diastole.

Study of the Kinetics of the Determinants of Performance During a Mountain Ultramarathon: Multidisciplinary Protocol of the First Trail Scientifique de Clécy 2021.

BACKGROUND: The growing interest of the scientific community in trail running has highlighted the acute effects of practice at the time of these races on isolated aspects of physiological and structural systems; biological, physiological, cognitive, and muscular functions; and the psychological state of athletes. However, no integrative study has been conducted under these conditions with so many participants and monitoring of pre-, per-, and postrace variables for up to 10 days over a distance close to 100 miles. OBJECTIVE: The aim of this study was to evaluate the kinetics of the performance parameters during a 156 km trail run and 6000 m of elevation gain in pre-, per-, and postrace conditions. The general hypothesis is based on significant alterations in the psychological, physiological, mechanical, biological, and cognitive parameters. METHODS: The Trail Scientifique de Clécy took place on November 11, 2021. This prospective experimental study provides a comprehensive exploration of the constraints and adaptations of psychophysiological and sociological variables assessed in real race conditions during a trail running of 156 km on hilly ground and 6000 m of elevation gain (D+). The study protocol allowed for repeatability of study measurements under the same experimental conditions during the race, with the race being divided into 6 identical loops of 26 km and 1000 m D+. Measurements were conducted the day before and the morning of the race, at the end of each lap, after a pit stop, and up to 10 days after the race. A total of 55 participants were included, 43 (78%) men and 12 (22%) women, who were experienced in ultra-trail-running events and with no contraindications to the practice of this sport. RESULTS: The launch of the study was authorized on October 26, 2021, under the trial number 21-0166 after a favorable opinion from the Comité de Protection des Personnes Ouest III (21.09.61/SIRIPH 2G 21.01586.000009). Of the 55 runners enrolled, 41 (75%) completed the race and 14 (25%) dropped out for various reasons, including gastric problems, hypothermia, fatigue, and musculoskeletal injuries. All the measurements for each team were completed in full. The race times (ie, excluding the measurements) ranged from 17.8206 hours for the first runner to 35.9225 hours for the last runner. The average time to complete all measurements for each lap was 64 (SD 3) minutes. CONCLUSIONS: The Trail Scientifique de Clécy, by its protocol, allowed for a multidisciplinary approach to the discipline. This approach will allow for the explanation of the studied parameters in relation to each other and observation of the systems of dependence and independence. The initial results are expected in June 2022. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/38027.

Definition of left ventricular remodelling following ST-elevation myocardial infarction: a systematic review of cardiac magnetic resonance studies in the past decade.

An increase in left ventricular volumes between baseline and follow-up imaging is the main criteria for the quantification of left ventricular remodelling (LVR) after ST-elevation myocardial infarction (STEMI), but without consensual definition. We aimed to review the criteria used for the definition of LVR based on cardiac magnetic resonance imaging (CMR) in STEMI patients. A systematic literature search was conducted using MEDLINE and the Cochrane Library from January 2010 to August 2019. Thirty-seven studies involving 4209 patients were included. Among these studies, 30 (81%) used a cut-off value for defining LVR, with a pooled LVR prevalence estimate of 22.8%, 95% CI [19.4-26.7%] and a major between-study heterogeneity (I2 = 82%). The seven remaining studies (19%) defined LVR as a continuous variable. The definition of LVR using CMR following STEMI is highly variable, among studies including highly selected patients. A 20% increase or a 15% increase in left ventricular volumes between a baseline and a follow-up CMR imaging were the two most common criterion (13 [35%] and 9 [24%] studies, respectively). The most frequent LVR criterion was a 20% increase in end-diastolic volumes or a 15% increase in end-systolic volumes. A composite cut-off value of a 12 to 15% increase in end-systolic volume and a 12 to 20% increase in end-diastolic volume using a follow-up CMR imaging 3 months after STEMI might be proposed as a consensual cut-off for defining adverse LVR for future large-sized, prospective studies with serial CMR imaging and long-term follow-up in unselected patients.

Divergent synthesis and biological evaluation of 2-(trifluoromethyl)pyridines as virulence-attenuating inverse agonists targeting PqsR.

A short and divergent route towards new derivatives of 2-(trifluoromethyl)pyridines as potent inverse agonists of the bacterial target PqsR against Pseudomonas aeruginosa (PA) infections is described. This Gram-negative pathogen causes severe nosocomial infections and common antibiotic treatment options are rendered ineffective due to resistance issues. Based on an earlier identified optimized hit, we conducted derivatization and rigidification attempts employing two central building blocks. The western part of the molecule is built up via a 2-(trifluoromethyl)pyridine head group equipped with a terminal alkyne. The eastern section is then introduced through aryliode motifs exploiting Sonogashira as well as Suzuki-type chemistry. Subsequent modification provided quick access to an array of compounds, allowed for deep SAR insights, and enabled to optimize the hit scaffold into a lead structure of nanomolar potency combined with favorable in vitro ADME/T features.

Volumetric parcellation of the cardiac right ventricle for regional geometric and functional assessment.

3D echocardiography is an increasingly popular tool for assessing cardiac remodelling in the right ventricle (RV). It allows quantification of the cardiac chambers without any geometric assumptions, which is the main weakness of 2D echocardiography. However, regional quantification of geometry and function is limited by the lower spatial and temporal resolution and the scarcity of identifiable anatomical landmarks, especially within the ventricular cavity. We developed a technique for regionally assessing the volume of 3 relevant RV volumetric regions: apical, inlet and outflow. The proposed parcellation method is based on the geodesic distances to anatomical landmarks that are easily identifiable in the images: the apex and the tricuspid and pulmonary valves, each associated to a region. Based on these distances, we define a partition in the endocardium at end-diastole (ED). This partition is then interpolated to the blood cavity using the Laplace equation, which allows to compute regional volumes. For obtaining an end-systole (ES) partition, the endocardial partition is transported from ED to ES using a commercial image-based tracking software, and then the interpolation process is repeated. We assessed the intra- and inter-observer reproducibility using a 10-subjects dataset containing repeated quantifications of the same images, obtaining intra- and inter- observer errors (7-12% and 10-23% respectively). Finally, we propose a novel synthetic mesh generation algorithm that deforms a template mesh imposing a user-defined strain to a template mesh. We used this method to create a new dataset for involving distinct types of remodelling that were used to assess the sensitivity of the parcellation method to identify volume changes affecting different parts. We show that the parcellation method is adequate for capturing local circumferential and global circumferential and longitudinal RV remodelling, which are the most clinically relevant cases.

Is plasma concentration of coenzyme Q10 a predictive marker for left ventricular remodelling after revascularization for ST-segment elevation myocardial infarction?

BACKGROUND: Left ventricular remodelling that frequently occurs after acute myocardial infarction is associated with an increased risk of heart failure and cardiovascular death. Although several risk factors have been identified, there is still no marker in clinical use to predict left ventricular remodelling. Plasma concentration of coenzyme Q10, which plays a key role in mitochondrial energy production and as an antioxidant, seems to be negatively correlated with left ventricular function after acute myocardial infarction. OBJECTIVE: The goal of our study was to determine whether the plasma coenzyme Q10 baseline concentrations at time of the ST-elevation myocardial infarction (STEMI) could predict left ventricular remodelling at six months' follow-up. METHODS: Sixty-eight patients who were admitted to hospital for STEMI and successfully revascularized with primary percutaneous coronary intervention were recruited. All patients underwent a 3D-echocardiography examination within the first four days after percutaneous coronary intervention and six months later then divided into two groups based on the presence or not of left ventricular remodelling. Plasma coenzyme Q10 concentration at the time of percutaneous coronary intervention was determined using high-performance liquid chromatography-tandem mass spectrometry. RESULTS: While we found similar plasma coenzyme Q10 concentrations compared with other studies, no association was evidenced between coenzyme Q10 concentrations and left ventricular remodelling (P = 0.89). CONCLUSION: We found no evidence for using plasma coenzyme Q10 concentration as an early prediction marker of left ventricular remodelling after STEMI.

Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction.

BACKGROUND: Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF). Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF). METHODS: We aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion and no clinical sign of HF. Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and after a median follow-up of 7 months. We compared 3 groups: a group with a low-level of plasma neprilysin (< 125 pg/mL, i.e. the lower limit of detection of the assay) and the two other groups were defined as being below or above the median value of the remaining samples. RESULTS: Median age was 58.5 ± 12.8 years and 56 (82.4%) were men. Median LVEF was 45.0 ± 8.5%. Baseline characteristics were comparable between groups (low-level of neprilysin group [≤125 pg/mL, n = 38], medium-level of neprilysin group [126-450 pg/mL, n = 15] and a high-level group [> 450 pg/mL, n = 15]). At baseline there was a non-significant trend towards lower end-diastolic volume (p = 0.07) but significantly lower LVEF in the high neprilysin group (46.4 ± 8.3%, 47.1 ± 8.1% and 39.1 ± 6.9%, p < 0.01). At follow-up, the magnitude of LVEF increase was significantly more important in the high neprilysin group compared to the other groups (p = 0.022 for relative change in LVEF and 6.6 ± 7.3%, 3.6 ± 9.0% and 11.3 ± 8.4%, p = 0.031 for absolute change in LVEF) resulting in similar LVEF levels at follow-up between all groups (53.0 ± 8.9%, 50.6 ± 9.7% and 50.4 ± 9.9%, p = 0.55). CONCLUSIONS: Initial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up. Future studies will have to assess the role of neprilysin in the setting of STEMI and the potential benefit of its blockade.

Usefulness of a personalized algorithm-based discharge checklist in patients hospitalized for acute heart failure.

AIMS: The aim of this study is to evaluate the usefulness of a personalized discharge checklist (PCL) based on simple baseline characteristics on mortality, readmission for heart failure (HF), and quality of care in patients hospitalized for acute HF. METHODS AND RESULTS: We designed an algorithm to generate PCL, based on 2016 HF European Society of Cardiology Guidelines and the screening of common comorbidities in elderly HF patients. We prospectively included 139 patients hospitalized for HF from May 2018 to October 2018. A PCL was fulfilled for each patient at admission and 24 to 48 hours before the planned discharge. A control cohort of 182 consecutive patients was retrospectively included from May 2017 to October 2017. The primary composite endpoint was mortality or readmission for HF at 6 months. The secondary endpoints were mortality, readmission for HF, and quality of care (evidence-based medications, management of HF comorbidities, and planned care plan). There was no difference among baseline characteristics between PCL and control cohorts; mean age was 78.1 ± 12.2 vs. 79.0 ± 12.5 years old (P = 0.46) and 61 patients (43.9%) vs. 63 (34.6%) had HF with left ventricular ejection fraction (LVEF) <40% (P = 0.24). During the 6 month follow-up period, 59 patients (42.4%) reached the primary endpoint in the PCL cohort vs. 92 patients (50.5%) in the control cohort [hazard ratio (HR): 0.79, 95% confidence interval (CI) (0.57-1.09), P = 0.15]. Subgroup analysis including only patients with either altered (<40%) or mid-range or preserved (≥40%) LVEF showed no significant difference among groups. There was a non-significant trend toward a reduction in HF readmission rate in the PCL group [38 patients (27.3%) vs. 64 patients (35.2%), HR: 0.73, 95%CI (0.49-1.09), P = 0.13]. There was no difference regarding survival or the use of evidence-based medications. A higher proportion of patients were screened and treated for iron and vitamin D deficiencies (53.2% vs. 35.7%, P < 0.01 and 73.4% vs. 29.7%, P < 0.01, respectively), as well as malnutrition supplemented in the PCL group. There was a higher referral to HF follow-up programme in the PCL group but not to telemedicine or cardiac rehabilitation programs. CONCLUSIONS: In this preliminary study, the use of a PCL did not improve outcomes at 6 months in patients hospitalized for acute HF. There was a non-significant trend towards a reduction in HF readmission rate in the PCL group. In addition, the management of HF comorbidities was significantly improved by PCL with a better referral to follow-up programme. A multicentre study is warranted to assess the usefulness of a simple costless personalized checklist in a large HF patients' population.

Analysis of inter-system variability of systolic and diastolic intraventricular pressure gradients derived from color Doppler M-mode echocardiography.

Assessment of intraventricular pressure gradients (IVPG) using color Doppler M-mode echocardiography has gained increasing interest in the evaluation of cardiac function. However, standardized analysis tools for IVPG quantification are missing. We aimed to evaluate the feasibility, the test-retest observer reproducibility, and the inter-system variability of a semi-automated IVPG quantification algorithm. The study included forty healthy volunteers (50% were men). All volunteers were examined using two ultrasound systems, the Philips Epiq 7 and the General Electric Vivid 6. Left ventricular diastolic (DIVPG) and systolic (SIVPG) intraventricular pressure gradients were measured from the spatiotemporal distribution of intraventricular propagation flow velocities using color Doppler M-mode in standard apical views. There was good feasibility for both systolic and diastolic IVPG measurements (82.5% and 85%, respectively). Intra and inter-observer test-retest variability measured with the intraclass correlation coefficient were 0.98 and 0.93 for DIVPG respectively, and 0.95 and 0.89 for SIVPG respectively. The inter-system concordance was weak to moderate with Lin's concordance correlation coefficient of 0.59 for DIVPG and 0.25 for SIVPG. In conclusion, it is feasible and reproducible to assess systolic and diastolic IVPG using color Doppler M-mode in healthy volunteers. However, the inter-system variability in IVPG analysis needs to be taken into account, especially when using displayed data.

Echocardiographic evidence of left ventricular untwisting-filling interplay.

BACKGROUND: Left ventricular untwisting generates an early diastolic intraventricular pressure gradient (DIVPG) than can be quantified by echocardiography. We sought to confirm the quantitative relationship between peak untwisting rate and peak DIVPG in a large adult population. METHODS: From our echocardiographic database, we retrieved all the echocardiograms with a normal left ventricular ejection fraction, for whom color Doppler M-Mode interrogation of mitral inflow was available, and left ventricular untwisting rate was measurable using speckle tracking. Standard indices of left ventricular early diastolic function were assessed by Doppler (peaks E, e' and Vp) and speckle tracking (peak strain rate Esr). Load dependency of DIVPG and untwisting rate was evaluated using a passive leg raising maneuver. RESULTS: We included 154 subjects, aged between 18 to 77 years old, 63% were male. Test-retest reliability for color Doppler-derived DIVPG measurements was good, the intraclass correlation coefficients were 0.97 [0.91-0.99] and 0.97 [0.67-0.99] for intra- and inter-observer reproducibility, respectively. Peak DIVPG was positively correlated with peak untwisting rate (r = 0.73, P <  0.001). On multivariate analysis, peak DIVPG was the only diastolic parameter that was independently associated with untwisting rate. Age and gender were the clinical predictive factors for peak untwisting rate, whereas only age was independently associated with peak DIVPG. Untwisting rate and DIVPG were both load-dependent, without affecting their relationship. CONCLUSIONS: Color Doppler-derived peak DIVPG was quantitatively and independently associated with peak untwisting rate. It thus provides a reliable flow-based index of early left ventricular diastolic function.

Prevalence and significance of fragmented QRS complex in lead V1 on the surface electrocardiogram of healthy athletes.

AIMS: Limited data exist concerning fragmented QRS complexes (fQRSs) on the surface electrocardiogram (ECG) of apparently healthy athletes. We aimed to study the prevalence and significance of fQRS in lead V1 (fQRSV1), representing right ventricular (RV) activation, regarding training-induced RV morphological remodelling. METHODS AND RESULTS: Between January 2017 and August 2019, 434 consecutive non-sedentary subjects underwent preparticipation cardiovascular screening, including a 12-lead ECG. Three hundred and ninety-three apparently healthy subjects were included, 119 of them were athletes (defined as performing ≥8 h/week for the last 6 months) and 274 were non-athletes. All athletes underwent two-dimensional transthoracic echocardiography. Fragmented QRS complex in lead V1 pattern was defined as a narrow (<120 ms) and quadriphasic QRS complex in lead V1. Fragmented QRS complex in lead V1 was more frequent in athletes compared with non-athletes (22% vs. 5.1%, P < 0.001) and was independently associated with the athlete status [adjusted odds ratio (aOR) = 4.693, 95% confidence interval (95% CI) 2.299-9.583; P < 0.001], the endurance category (aOR = 2.522, 95% CI 1.176-5.408; P = 0.017), and age (aOR = 0.962, 95% CI 0.934-0.989; P = 0.007) in multivariate analysis. In the subgroup of athletes, fQRSV1 was independently associated with mean RV outflow tract diameter (aOR = 1.458, 95% CI 1.105-1.923; P = 0.008) and age (aOR = 0.941, 95% CI 0.894-0.989; P = 0.017) in multivariate analysis. CONCLUSION: Fragmented QRS complex in lead V1 is a newly described, frequent, ECG pattern in young and apparently healthy athletes and is associated with training-induced RV remodelling.

Synergic PDE3 and PDE4 control intracellular cAMP and cardiac excitation-contraction coupling in a porcine model.

AIMS: Cyclic AMP phosphodiesterases (PDEs) are important modulators of the cardiac response to ß-adrenergic receptor (ß-AR) stimulation. PDE3 is classically considered as the major cardiac PDE in large mammals and human, while PDE4 is preponderant in rodents. However, it remains unclear whether PDE4 also plays a functional role in large mammals. Our purpose was to understand the role of PDE4 in cAMP hydrolysis and excitation-contraction coupling (ECC) in the pig heart, a relevant pre-clinical model. METHODS AND RESULTS: Real-time cAMP variations were measured in isolated adult pig right ventricular myocytes (APVMs) using a Förster resonance energy transfer (FRET) biosensor. ECC was investigated in APVMs loaded with Fura-2 and paced at 1 Hz allowing simultaneous measurement of intracellular Ca2+ and sarcomere shortening. The expression of the different PDE4 subfamilies was assessed by Western blot in pig right ventricles and APVMs. Similarly to PDE3 inhibition with cilostamide (Cil), PDE4 inhibition with Ro 20-1724 (Ro) increased cAMP levels and inotropy under basal conditions. PDE4 inhibition enhanced the effects of the non-selective ß-AR agonist isoprenaline (Iso) and the effects of Cil, and increased spontaneous diastolic Ca2+ waves (SCWs) in these conditions. PDE3A, PDE4A, PDE4B and PDE4D subfamilies are expressed in pig ventricles. In APVMs isolated from a porcine model of repaired tetralogy of Fallot which leads to right ventricular failure, PDE4 inhibition also exerts inotropic and pro-arrhythmic effects. CONCLUSIONS: Our results show that PDE4 controls ECC in APVMs and suggest that PDE4 inhibitors exert inotropic and pro-arrhythmic effects upon PDE3 inhibition or ß-AR stimulation in our pre-clinical model. Thus, PDE4 inhibitors should be used with caution in clinics as they may lead to arrhythmogenic events upon stress.

Accuracy of speckle tracking in the context of stress echocardiography in short axis view: An in vitro validation study.

AIM: This study aimed to test the accuracy of a speckle tracking algorithm to assess myocardial deformation in a large range of heart rates and strain magnitudes compared to sonomicrometry. METHODS AND RESULTS: Using a tissue-mimicking phantom with cyclic radial deformation, radial strain derived from speckle tracking (RS-SpT) of the upper segment was assessed in short axis view by conventional echocardiography (Vivid q, GE) and post-processed with clinical software (EchoPAC, GE). RS-SpT was compared with radial strain measured simultaneously by sonomicrometers (RS-SN). Radial strain was assessed with increasing deformation rates (60 to 160 beats/min) and increasing pulsed volumes (50 to 100 ml/beat) to simulate physiological changes occurring during stress echocardiography. There was a significant correlation (R2 = 0.978, P <0.001) and a close agreement (bias ± 2SD, 0.39 ± 1.5%) between RS-SpT and RS-SN. For low strain values (<15%), speckle tracking showed a small but significant overestimation of radial strain compared to sonomicrometers. Two-way analysis of variance did not show any significant effect of the deformation rate. For RS-SpT, the feasibility was excellent and the intra- and inter-observer variability were low (the intraclass correlation coefficients were 0.96 and 0.97, respectively). CONCLUSIONS: Speckle tracking demonstrated a good correlation with sonomicrometry for the assessment of radial strain independently of the heart rate and strain magnitude in a physiological range of values. Though speckle tracking seems to be a reliable and reproducible technique to assess myocardial deformation variations during stress echocardiography, further studies are mandated to analyze the impact of angulated and artefactual out-of-plane motions and inter-vendor variability.

Standard and Strain Measurements by Echocardiography Detect Early Overloaded Right Ventricular Dysfunction: Validation against Hemodynamic and Myocyte Contractility Changes in a Large Animal Model.

BACKGROUND: Early detection of right ventricular (RV) failure is required to improve the management of patients with congenital heart diseases. The aim of this study was to validate echocardiography for the early detection of overloaded RV dysfunction, compared with hemodynamic and myocyte contractility assessment. METHODS: Using a porcine model reproducing repaired tetralogy of Fallot, RV function was evaluated over 4 months using standard echocardiography and speckle-tracking compared with hemodynamic parameters (conductance catheter). Sarcomere shortening and calcium transients were recorded in RV isolated myocytes. Contractile reserve (ΔEmax) was assessed by ß-adrenergic stimulation in vivo (dobutamine 5 µg/kg) and ex vivo (isoproterenol 100 nM). RESULTS: Six operated animals were compared with four age- and sex-matched controls. In the operated group, hemodynamic RV efficient ejection fraction was significantly decreased (29.7% [26.2%-34%] vs 42.9% [40.7%-48.6%], P < .01), and inotropic responses to dobutamine were attenuated (ΔEmax was 51% vs 193%, P < .05). Echocardiographic measurements of fraction of area change, tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity (S') and RV free wall longitudinal systolic strain and strain rate were significantly decreased. Strain rate, S', and tricuspid annular plane systolic excursion were correlated with ΔEmax (r = 0.75, r = 0.78, and r = 0.65, respectively, P < .05). These alterations were associated in RV isolated myocytes with the decrease of sarcomere shortening in response to isoproterenol and perturbations of calcium homeostasis assessed by the increase of spontaneous calcium waves. CONCLUSIONS: In this porcine model, both standard and strain echocardiographic parameters detected early impairments of RV function and cardiac reserve, which were associated with cardiomyocyte excitation-contraction coupling alterations.