Turbulent blood dynamics in the left heart in the presence of mitral regurgitation: a computational study based on multi-series cine-MRI

In this work, we performed a computational image-based study of blood dynamics in the whole left heart, both in a healthy subject and in a patient with mitral valve regurgitation. We elaborated multi-series cine-MRI with the aim of reconstructing the geometry and the corresponding motion of left ventricle, left atrium, mitral and aortic valves, and aortic root of the subjects. This allowed us to prescribe such motion to computational blood dynamics simulations where, for the frst time, the whole left heart motion of the subject is considered, allowing us to obtain reliable subject-specifc information. The fnal aim is to investigate and compare between the subjects the occurrence of turbulence and the risk of hemolysis and of thrombi formation. In particular, we modeled blood with the Navier–Stokes equations in the arbitrary Lagrangian–Eulerian framework, with a large eddy simulation model to describe the transition to turbulence and a resistive method to manage the valve dynamics, and we used a fnite element discretization implemented in an in-house code for the numerical solution

Left atrial strain predicts exercise capacity in heart failure independently of left ventricular ejection fraction

Aims: We hypothesized that left atrial (LA) remodelling and function are associated with poor exercise capacity as prognostic marker in chronic heart failure (CHF) across a broad range of left ventricular ejection fraction (LVEF). Methods and results: One hundred seventy-one patients with CHF were analysed [age 65 +/- 11 years, 136 males (80%); 86 heart failure with reduced ejection fraction (HFrEF), 27 heart failure with mid-range ejection fraction (HFmrEF), 58 heart failure with preserved ejection fraction (HFpEF)]. All patients underwent echocardiography and maximal cardiopulmonary exercise testing and were classified according to a prognostic cut-off of peak VO2 (pVO(2); 14 mL/kg/min). Seventy-seven (45%) patients reached pVO(2) = 14 mL/kg/min. Between the two groups, there was a considerable difference in both left atrial volume (LAVi, 53 +/- 24 vs. 44 +/- 18 mL/m(2), P = 0.005) and function (LA reservoir strain 12 +/- 5 vs. 20 +/- 10%, P < 0.0001). Receiver-operating characteristic curves identified LA reservoir strain (area under the curve: 0.73 [0.65-0.80], P < 0.0001) as strong predictor for impaired pVO(2) among all echocardiographic variables; LA reservoir strain < 23% had 37% specificity but a very high sensitivity (96%) in identifying a severely reduced pVO(2). In logistic regression analysis, LA reservoir strain < 23% was associated with a highly increased risk of pVO(2) < 14 mL/kg/min (odds ratio 16.0 [4.7-54.6]; P < 0.0001). The multivariate analysis showed that a reduced LA reservoir strain was associated with pVO(2) < 14 mL/kg/min after adjustment for age, body mass index (BMI), and clinical variables, that is, New York Heart Association class, atrial fibrillation, haemoglobin, and creatinine (b 0.22 [95% confidence interval, CI, 0.12-0.31]; P < 0.0001), and after adjustment for echocardiographic variables, that is, LVEF or left ventricular global longitudinal strain (LVGLS) and tricuspid annular plane systolic excursion (TAPSE) (b 0.16 [95% CI 0.08-0.24]; P < 0.0001). Patients with HFrEF, HFmrEF, and HFpEF were separately analysed. Among LA reservoir strain, LAVi, LVEF, LVGLS, and TAPSE, LA reservoir strain was the only one significantly associated with pVO(2) in all subgroups (after adjustment for sex and BMI, P = 0.003, 0.04, and 0.01, respectively). Conclusions: In patients with CHF, an impaired LA reservoir function is independently associated with a severely reduced pVO(2). LA dysfunction represents a marker of poor prognosis across LVEF borders in the CHF population

The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020

To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019

Clinical impact of mitral regurgitation in aortic valve stenosis: Insight from effective regurgitant orifice area

Mechanisms leading to heart failure (HF) symptoms in aortic valve stenosis (AS) are contentious. We examined the impact of secondary mitral regurgitation (MR) on the symptomatic status in patients with AS

Concomitant mitral regurgitation and aortic stenosis one step further to low-flow preserved ejection fraction aortic stenosis.

Aims: Patients with severe aortic stenosis (AS) and normal ejection fraction (EF) can paradoxically present low-transaortic flow and worse prognosis. The role of co-existing mitral regurgitation (MR) in determining this haemodynamic inconsistency has never been quantitatively explored. The hypothesis is that MR influences forward stroke volume and characterizes the low-flow AS pattern. Methods and results: Consecutive patients with indexed aortic valve area (AVA) ≤0.6 cm2/m2 and EF > 50% formed the study population. Complete echocardiographic data were collected, and mitral effective regurgitant orifice area (ERO) and regurgitant volume were obtained with proximal isovelocity surface area method. Patients were divided into subgroups according to indexed stroke volume (SV index). Included patients were 273 [age 79 ± 10 years, 53% female, EF 65 ± 7%, indexed AVA 0.47 ± 0.09 cm2/m2, mean transaortic gradient (MG) 32 ± 17 mmHg]. Mitral regurgitation was present in 89 (32%); ERO was 0.12 ± 0.08 cm2 (range 0.02–0.49 cm2). A low-flow state (SV index ≤35 mL/m2) was diagnosed in 41 (15%) patients. The prevalence of MR was higher in with low-flow vs. normal-flow group (56 vs. 28%, P = 0.03). Effective regurgitant orifice was associated to low-flow state univariately (OR: 1.75 [1.59–2.60]; P = 0.004) and after comprehensive adjustment (OR:1.76 [1.12–2.75]; P = 0.01). When MG was forced in the model, ERO remained significant (P < 0.009). On average, there was a 6 mL reduction in forward SV appeared per each 0.1 cm2 of ERO. Conclusion In patients with severely reduced AVA and preserved EF, MR is a major determinant of the low-flow condition. Furthermore, MR quantification by ERO predicts the presence of reduced flow independently of chamber volumes, systolic function, and transaortic gradient

Mitral Effective Regurgitant Orifice Area Predicts Pulmonary Artery Pressure Level in Patients with Aortic Valve Stenosis

Background: Mitral regurgitation (MR) and elevated pulmonary artery pressure are common findings in patients with aortic valve stenosis (AS). The pathophysiologic role of quantitatively defined MR as a determinant of pulmonary hypertension (PH) is incompletely characterized across the whole spectrum of AS degrees. The purpose of the study was to investigate whether the quantification of MR reveals a link to PH in patients with AS. Methods: Consecutive patients undergoing comprehensive echocardiography and presenting peak aortic velocity ≥ 2.5 m/sec were prospectively enrolled. Effective regurgitant orifice area (ERO) and regurgitant volume were obtained using the proximal isovelocity surface area method. Systolic pulmonary artery pressure was calculated by adding right atrial pressure to the tricuspid regurgitation pressure gradient. Results: A total of 642 patients were enrolled between 2008 and 2013 (mean age, 79 ± 11 years; mean ejection fraction, 62 ± 10%; mean aortic valve area, 1.09 ± 0.39 cm2); MR was present in 187 (29%). Of note, 154 of 187 patients (82%) showed ERO &lt; 0.20 cm2. ERO and regurgitant volume had the most significant associations with systolic pulmonary artery pressure (R2 = 0.30 and R2 = 0.35, respectively, P &lt;.0001). This relationship persisted after multivariate adjustment and in the subgroups of patients with severe AS or reduced ejection fraction (P &lt;.0001). For each 0.10-cm2 increase, the odds ratio for PH was 3.56 (95% CI, 2.65–4.86; P &lt;.0001). Conclusions: In patients with MR and a wide range of AS severity, ERO is independently associated with PH. Also, the role of MR quantification appears stronger than other continuous variables commonly associated with left ventricular diastolic dysfunction, such as E/e′ ratio and left atrial volume

Right Atrial Function Role in Tricuspid Regurgitation-Related Systemic Venous Congestion

: Tricuspid regurgitation (TR) is a frequent valvular pathology and when significant, may cause systemic venous congestion (SC). The right atrium (RA) is an intermediate structure between the tricuspid valve and the venous system and its role in SC is not yet defined. A total of 116 patients with a measurable TR effective regurgitant orifice area (EROA) and regurgitant volume (RVol) were selected from 2020 to 2022. SC was estimated by echocardiography using inferior vena cava diameter and estimated right atrial pressure (eRAP) and by clinical congestive features. TR grade was mild in 23 patients (20%), moderate in 53 patients (46%), and severe in 40 patients (34%). There was a significant decrease in RA function measured by strain with increasing TR severity (p&nbsp;&lt;0.001). There was a marked difference in RA strain between the groups with eRAP &gt;10 and ≤10&nbsp;mm&nbsp;Hg (25&nbsp;±&nbsp;11% vs 11&nbsp;±&nbsp;7%, p&nbsp;&lt;0.0001). Variables independently associated with inferior vena cava diameter were RA strain (β -0.532, p&nbsp;&lt;0.001), RA volume indexed (β 0.249, p&nbsp;=&nbsp;0.002), RVol (β 0.229, p&nbsp;=&nbsp;0.005) and EROA (β 0.185, p&nbsp;=&nbsp;0.016), and independently associated with eRAP &gt;10&nbsp;mm&nbsp;Hg were EROA (odds ratio [OR] 1.024, 95% confidence interval [CI] 1.002 to 1.046), RVol (OR 1.039, 95% CI 1.007 to 1.072) and RA strain (OR 0.863, 95% CI 0.794 to 0.940). The addition of RA strain to models containing EROA or RVol significantly improved the power of the model. RA strain was independently associated with the presence of 3 or more congestive features. In conclusion, echocardiographic and clinical signs of SC are frequent in higher degrees of TR, and RA function seems to play a key role in modulating the downstream effect of TR

Oral Microbiota in Children and Adolescents with Type 1 Diabetes Mellitus: Novel Insights into the Pathogenesis of Dental and Periodontal Disease

: The oral microbiota can be influenced by multiple factors, but only a few studies have focused on the role of glycemic control in determining early alterations of oral microbiota and their association with pathogenesis of both periodontitis and caries. The aim of this study is to evaluate the interplay between bacteria composition, oral hygiene, and glycemic control in a cohort of children with T1D. A total of 89 T1D children were enrolled (62% males, mean age: 12.6 ± 2.2 years). Physical and clinical characteristics, glucometabolic parameters, insulin treatment, and oral hygiene habits data were collected. Microbiological analysis was performed from saliva samples. A high prevalence of cariogenic and periodontopathogens bacteria in our cohort was detected. In particular, in all subjects Actinomyces spp., Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Lactobacillus spp. were isolated. S. mutans was found in about half of the analyzed sample (49.4%), in particular in patients with imbalance values of glycemic control. Moreover, a higher presence of both S. mutans and Veillonella spp. was detected in subjects with poorer glycemic control, in terms of HbA1c, %TIR and %TAR, even adjusting for age, sex, and hygiene habits as covariates. Virtuous oral hygiene habits, such as frequency of toothbrush changes and professional oral hygiene, negatively correlated with the simultaneous presence of Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis, red complex bacteria. Our study shows it is crucial to pay attention to glycemic control and regular oral hygiene to prevent the establishment of an oral microbiota predisposing to dental and periodontal pathology in subjects with T1D since childhood

Relevance of Functional Mitral Regurgitation in Aortic Valve Stenosis

The clinical relevance of functional-mitral-regurgitation (FMR) in patients with aortic valve stenosis (AS) has been poorly studied using a quantitative approach. In addition, FMR prognostic value has mostly been analyzed after aortic valve replacement. Between 2010 and 2014 the echocardiograms of consecutive AS patients were retrospectively reviewed. Inclusion criteria were calcified aortic valve with transaortic-velocity &gt;2.5 m/s and calculated mitral effective regurgitant orifice area (ERO) in the presence of mitral regurgitation. Organic mitral valve disease was an exclusion-criteria. Primary endpoint was heart failure or death under medical management. Secondary endpoint was heart failure or death. Eligible patients were 189, age 79 \ub1 8\u2009years, 61% NYHA I/II, indexed aortic valve area (AVA) 0.55 \ub1 0.17 cm2/m2. Mitral ERO was 7.6 \ub1 4.2 mm2 (&gt;10 mm2 in 30% of patients). Longitudinal function (by S'-TDI) was associated with mitral ERO independently of ejection fraction and ventricular volumes (p\u202f=\u202f0.01). Mitral ERO greater than 10 mm2 (threshold identified by spline survival-modeling) was associated with severe symptoms (Odds ratio [OR] 3.1 [1.6 to 6.0]; p\u202f=\u202f0.0006) and higher pulmonary-arterial-pressure (OR 3.0 [1.4 to 5.9]; p\u202f=\u202f0.002). Follow-up was completed for 175 patients. After 4.7 [1.4 to 7.2] years, 87 (50%) patients underwent AVR, 66 (38%) had heart-failure, 64 (37%) died. No procedure on FMR was required. Mitral ERO was independently associated with primary and secondary endpoints both as continuous variable (Hazard ratio [HR] 1.15 [1.00 to 1.30]; p\u202f=\u202f0.04 and HR 1.23 [1.05 to 1.43]; p\u202f=\u202f0.01 per 5 mm2 ERO increase) or as ERO&gt; versus 6410 mm2. Adjustment for S'-TDI or subgroup-analysis did not affect results. The analysis by AVA revealed the incremental prognostic role of mitral ERO over AS severity. In conclusion, AS patients with concomitant FMR &gt;10 mm2 holds a higher risk during medical follow-up. FMR quantitation, even for volumetrically modest regurgitation, provides incremental prognostic information over AS severity