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Cardiac output (CO) is routinely assessed by pulsed-wave Doppler echocardiography, yet reference values in adults are lacking. We aim to establish normative values of CO and cardiac index (CI) by pulsed-wave Doppler-echocardiography and to analyze their relation with gender and age in nonobese and obese adults. We included 4,040 adults (mean age: 55 years, 53% women, 950 obese [body mass index ≥30 kg/m²]) with normal blood pressure, no history of cardiovascular disease, and normal transthoracic echocardiography. Normative reference CO and CI values for were calculated in 3,090 nonobese patients by quantile regression. CO normal limits were lower in females than in males (lower limit: 3.3 vs 3.5 L/min, upper limit: 7.3 vs 8.2 L/min). CI normal limits were identical for both genders (lower limit: 1.9 L/min/m², upper limit: 4.3 L/min/m²). Although the relation of CO to age was weak and observed only in women, CI of both genders was not influenced by age. CO of obese patients was significantly greater than that of their nonobese counterparts. CI of obese patients was not influenced by age and gender and was not significantly different than that of nonobese patients (lower limit 1.8 L/min/m², upper limit 4.1 L/min/m² for both genders). In conclusion, in a large adult population we establish normative reference values for CO and CI measured by Doppler-echocardiography. CI is a remarkably stable parameter that is not influenced by age, gender, and body size and should be used to define low- and high-output states.

Mitral valve prolapse (MVP), characterized by a displacement > 2 mm above the mitral annulus of one or both bileaflets, with or without leaflet thickening, is a common valvular heart disease, with a prevalence of approximately 2% in western countries. Although this population has a generally good overall prognosis, MVP can be associated with mitral regurgitation (MR), left ventricular (LV) remodeling leading to heart failure, ventricular arrhythmia, and, the most devastating complication, sudden cardiac death, especially in myxomatous bileaflet prolapse (Barlow's disease). Among several prognostic factors reported in the literature, LV fibrosis and mitral annular disjunction may act as an arrhythmogenic substrate in this population. Cardiac magnetic resonance (CMR) has emerged as a reliable tool for assessing MVP, MR severity, LV remodeling, and fibrosis. Indeed, CMR is the gold standard imaging modality to assess ventricular volume, function, and wall motion abnormalities; it allows accurate calculation of the regurgitant volume and regurgitant fraction in MR using a combination of LV volumetric measurement and aortic flow quantification, independent of regurgitant jet morphology and valid in cases of multiple valvulopathies. Moreover, CMR is a unique imaging modality that can assess non-invasively focal and diffuse fibrosis using late gadolinium enhancement sequences and, more recently, T1 mapping. This review describes the use of CMR in patients with MVP and its role in identifying patients at high risk of ventricular arrhythmia.

The accurate quantification of primary mitral regurgitation (MR) and its consequences on cardiac remodeling is of paramount importance to determine the best timing for surgery in these patients. The recommended echocardiographic grading of primary MR severity relies on an integrated multiparametric approach. It is expected that the large number of echocardiographic parameters collected would offer the possibility to check the measured values regarding their congruence in order to conclude reliably on MR severity. However, the use of multiple parameters to grade MR can result in potential discrepancies between one or more of them. Importantly, many factors beyond MR severity impact the values obtained for these parameters including technical settings, anatomic and hemodynamic considerations, patient's characteristics and echocardiographer' skills. Hence, clinicians involved in valvular diseases should be well aware of the respective strengths and pitfalls of each of MR grading methods by echocardiography. Recent literature highlighted the need for a reappraisal of the severity of primary MR from a hemodynamic perspective. The estimation of MR regurgitation fraction by indirect quantitative methods, whenever possible, should be central when grading the severity of these patients. The assessment of the MR effective regurgitant orifice area by the proximal flow convergence method should be used in a semi-quantitative manner. Furthermore, it is crucial to acknowledge specific clinical situations in MR at risk of misevaluation when grading severity such as late-systolic MR, bi-leaflet prolapse with multiple jets or extensive leak, wall-constrained eccentric jet or in older patients with complex MR mechanism. Finally, it is debatable whether the 4-grades classification of MR severity would be still relevant nowadays, since the indication for mitral valve (MV) surgery is discussed in clinical practice for patients with 3+ and 4+ primary MR based on symptoms, specific markers of adverse outcome and MV repair probability. Primary MR grading should be seen as a continuum integrating both quantification of MR and its consequences, even for patients with presumed “moderate” MR.

Normal-flow low-gradient severe aortic stenosis (NF-LG-SAS), defined by an aortic valve area (AVA) <1 cm², mean pressure gradient (MPG) <40 mm Hg and indexed stroke volume ≥35 ml/m², is the most prevalent form of low-gradient aortic stenosis (AS) with preserved ejection fraction (PEF). However, the true severity of AS in these patients is controversial. The aim of this Doppler echocardiographic study was to investigate changes over time in the hemodynamic severity of patients with NF-LG-SAS with PEF. We retrospectively identified 96 patients who had 2 Doppler echocardiographic examinations without an intervening event. After a median follow-up of 25 (interquartile range 15 to 52) months, progression was observed, with increased transaortic MPG (from 28 [25 to 33] to 39 [34 to 50] mm Hg; p<0.001), peak aortic jet velocity (from 3.46 [3.20 to 3.64] to 4.01 [3.70 to 4.39] m/s; p<0.001), and decreased AVA (from 0.87 [0.82 to 0.94] to 0.72 [0.62 to 0.81] cm²; p<0.001). Median annual rates of progression were 4.3 (1.7 to 8.1) mm Hg/year, 0.25 (0.08 to 0.44) m/s/year, and −0.05 (−0.10 to −0.02) cm²/year, respectively. There was no significant change in left ventricular ejection fraction over time (p = 0.74). At follow-up, 46 patients (48%) acquired the features of classical high-gradient severe AS (MPG ≥40 mm Hg). This study shows that most patients with NF-LG-SAS with PEF exhibit significant hemodynamic progression of AS severity without EF impairment. These findings suggest that NF-LG-SAS with PEF is an “intermediate” stage between moderate AS and classical high-gradient severe AS requiring close monitoring.

The clinical management of patients with low gradient severe aortic stenosis (LG-SAS) and preserved left ventricular ejection fraction (LVEF) remains challenging owing to their heterogeneity. The aim to this study was to evaluate the relation between an ejection dynamic parameter linked to AS severity and outcome, the ratio of acceleration time (AT) to ejection time (ET), in a cohort of patients with LG-SAS and preserved LVEF. Three hundred and fifty-six patients with LG-AS (defined by AVA ≤1 cm² and/or AVAi ≤0.6 cm²/m² and mean aortic pressure gradient <40 mm Hg) and preserved LVEF ≥50% were studied. The relation between AT/ET and all-cause and cardiac mortality during follow-up was studied. Median follow-up was 41 months (interquartile range, 35 to 47 months). Median AT/ET was 0.32 (interquartile range, 0.29 to 0.36). The 5-year estimates of all-cause and cardiac mortality were respectively 57 ± 7%, 36 ± 7% for patients with AT/ET >0.36 versus 43 ± 4%, 16 ± 3% for patients with AT/ET ≤0.36 (p = 0.024 and p <0.001, respectively). After adjustment on known predictors of outcome including aortic valve replacement used as a time-dependent covariate, there was a significant increase in all-cause mortality risk for patients with AT/ET >0.36 (adjusted hazard ratio 2.04 [95% confidence interval, 1.32 to 3.13]; p = 0.001) and cardiac mortality risk (adjusted hazard ratio 2.89 [95% confidence interval, 1.54 to 5.43]; p<0.001) compared with patients with AT/ET ≤0.36. The association of AT/ET >0.36 and all-cause or cardiac mortality risk was consistent in subgroups of patients with LG-SAS and preserved EF. In conclusion, an AT/ET ratio of more than 0.36 is an independent predictor of mortality in patients with LG-SAS and preserved EF.

The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains controversial. We aimed at evaluating the relation between left ventricular ejection time (LVET) and outcome in patients with moderate or severe chronic primary MR because of prolapse. Clinical, Doppler echocardiographic, and outcome data prospectively collected from 302 patients (median age 61 [54 to 74] years, 34% women) with moderate or severe primary MR were analyzed. Patients were retrospectively stratified by quartiles of LVET. The primary end point of the study was the composite of need for MV surgery or all-cause mortality. During a median follow-up time of 66 (25th to 75th percentile, 33 to 95) months, 178 patients reached the primary end point. Patients in the lowest quartile of LVET (<260 ms) were at high risk for adverse events compared with those in the other quartiles of LVET (global p = 0.005), whereas the rate of events was similar for the other quartiles (p = NS for all). After adjustment for clinical predictors of outcome, including age, gender, history of atrial fibrillation, MR severity, and current recommended triggers for MV surgery in asymptomatic primary MR, LVET <260 ms was associated with an increased risk of events (adjusted hazard ratio 1.49, 95% confidence interval 1.03 to 2.16, p = 0.033). In conclusion, we observed that shorter LVET is associated with increased risk of adverse events in patients with moderate or severe primary MR because of prolapse. Further studies are required to investigate whether shorter LVET has a direct effect on outcomes or is solely a risk marker in primary MR.

The ability to visualize the right atrium (RA) by echocardiography allows a quantitative, highly reproducible assessment of the RA volume (RAV). The aim of this study is to evaluate the relation between RAV and long-term mortality in a prospective cohort of heart failure and reduced ejection fraction patients in sinus rhythm receiving cardiac resynchronization therapy. 172 patients were included. The right atrium volume index (RAVI) was calculated using Simpson's method from the apical four-chamber view and indexed to body surface area. The relation between RAVI and mortality during follow up was studied. Median follow up was 68 months (interquartile range 62 to 73 months). Mean RAVI was 27 ± 14 mL/m² (IQR 22 to 33 mL/m²). Cumulative 5-year all-cause mortality was 22 ± 6% in patients with RAVI ≤ 19 mL/m², 24 ± 6% for RAVI 19 to 29 mL/m² and 58 ± 7% for RAVI >29 mL/m² (p for trend <0.001). After adjustment on clinical and echocardiographic predictors of outcome including indices of right ventricular function, there was a significant increase in overall mortality risk with increasing RAVI (adjusted hazard ratio 1.02 [95% confidence interval, 1.00 to 1.03], per 1 mL/m2 increment; p = 0.042). Patients in the highest tertile (RAVI >29 mL/m²) had significantly greater risk of death compared with those with RAVI ≤29 mL/m² (adjusted hazard ratio 2.01 [95% confidence interval, 1.15 to 3.50]; p = 0.014). In conclusion, RA enlargement is a powerful and highly reproducible independent predictor of long-term mortality in patients with heart failure and reduced ejection fraction in sinus rhythm receiving cardiac resynchronization therapy.

Age-related health, brain, and cognitive impairment is a great challenge in current society. Cognitive training, aerobic exercise and their combination have been shown to benefit health, brain, cognition and psychological status in healthy older adults. Inconsistent results across studies may be related to several variables. We need to better identify cognitive changes, individual variables that may predict the effect of these interventions, and changes in structural and functional brain outcomes as well as physiological molecular correlates that may be mediating these effects. Projecte Moviment is a multi-domain randomized trial examining the effect of these interventions applied 5 days per week for 3 months compared to a passive control group. The aim of this paper is to describe the sample, procedures and planned analyses. One hundred and forty healthy physically inactive older adults will be randomly assigned to computerized cognitive training (CCT), aerobic exercise (AE), combined training (COMB), or a control group. The intervention consists of a 3 month home-based program 5 days per week in sessions of 45 min. Data from cognitive, physical, and psychological tests, cardiovascular risk factors, structural and functional brain scans, and blood samples will be obtained before and after the intervention. Effects of the interventions on cognitive outcomes will be described in intention-to-treat and per protocol analyses. We will also analyze potential genetic, demographic, brain, and physiological molecular correlates that may predict the effects of intervention, as well as the association between cognitive effects and changes in these variables using the per protocol sample. Projecte Moviment is a multi-domain intervention trial based on prior evidence that aims to understand the effects of CCT, AE, and COMB on cognitive and psychological outcomes compared to a passive control group, and to determine related biological correlates and predictors of the intervention effects. www.ClinicalTrials.gov, identifier NCT03123900.