Subclinical central hypothyroidism in patients with hypothalamic-pituitary disease: does it exist?

Central hypothyroidism (CH) is characterized by decreased thyroid hormone production due to insufficient stimulation of an otherwise normal thyroid gland by TSH. In patients with established hypothalamic-pituitary disease, a low FT4 concentration is considered highly specific, although poorly sensitive, for the diagnosis of CH. That would be comparable to diagnosing primary hypothyroidism in patients at risk only when serum FT4 concentrations are below the reference range, missing all patients with subclinical primary hypothyroidism and preventing proper therapy in patients in which thyroxine replacement is clearly beneficial. Cardiac time intervals, especially the isovolumic contraction time (ICT), have been considered the gold standard of peripheral thyroid hormone action. Using Doppler echocardiography, we have previously shown a very high proportion of prolonged ICT in patients with hypothalamic-pituitary disease and serum FT4 levels indistinguishable from controls. As ICT decreased/normalized after thyroxine-induced increases in FT4 concentrations within the normal reference range, prolonged ICT was considered a bona fide diagnostic biomarker of subclinical CH. Those findings challenge the usual interpretation that FT4 concentrations in the mid-reference range exclude hypothyroidism in patients with hypothalamic-pituitary disease. Rather, subclinical central hypothyroidism, a state analogous to subclinical primary hypothyroidism, seems to be frequent in patients with hypothalamic-pituitary disease and normal FT4 levels. They also challenge the notion that thyroid function is usually the least or the last affected in acquired hypopituitarism. The relevance of Doppler echocardiography to correctly diagnose and monitor replacement therapy in both clinical and subclinical forms of CH should improve quality of life and decrease cardiovascular risk, as already demonstrated in patients with clinical and subclinical primary hypothyroidism.

Home monitoring of fetal heart rhythm: Lived experiences of women with anti-SSA/Ro52 autoantibodies and their co-parents.

OBJECTIVE: The aim of this study was to explore the parents' experiences of home monitoring of the fetal heart rhythm. Women with anti-SSA/Ro52 autoantibodies carry a 2%-3% risk of giving birth to a child with congenital heart block (CHB), following transplacental transfer and antibody-mediated inflammation in the fetal conduction system during 18th to 24th gestational week. Early detection and subsequent treatment have been reported to decrease morbidity and mortality. Therefore, home monitoring of the fetal heart rhythm by Doppler has been offered at our fetal cardiology center. This study was undertaken to explore the lived experience of the routine. METHODS: Participants were recruited from a single fetal cardiology center. Consecutive sampling was used. The inclusion criteria were women with SSA/Ro52 antibodies who had undergone Doppler examinations within the last two and a half years at the hospital and had monitored the fetal heartbeat at home. A semi-structured questionnaire was created, and the participants were interviewed individually. The interviews were transcribed verbatim and analyzed according to qualitative content analysis. RESULTS: The overall theme was defined as "walking on thin ice," with six underlying categories: reality, different strategies, gain and loss, healthcare providers, underlying tension, and conducting the examinations again, all with a focus on how to handle the home monitoring during the risk period. CONCLUSION: Both the mother and the co-parent expressed confidence in their own abilities and that the monitoring provided them with the advantage of growing a bond with the expected child. However, all the participants described a feeling of underlying tension during the risk period. The results show that home monitoring is not experienced as complicated or a burden for the parents-to-be and should be considered a vital part of the chain of care for mothers at risk for giving birth to a child with CHB. However, explaining the teamwork between the different caregivers, for the patients involved, their areas of expertise, and how they collaborate with the patient continues to be a pedagogic challenge and should be developed further.

Non-invasive assessment of left ventricular filling pressure in aortic stenosis.

BACKGROUND: The assessment of left ventricular (LV) filling pressure (FP) is important for the management of aortic stenosis (AS) patients. Although, it is often restricted for predict LV FP in AS because of mitral annular calcification and a certain left ventricular hypertrophy. Thus, we tested the predictive ability of the algorithm for elevated LV FP in AS patients and also applied a recently-proposed echocardiographic scoring system of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score. METHODS: We enrolled consecutive 116 patients with at least moderate AS in sinus rhythm who underwent right heart catheterization and echocardiography within 7 days. Mean pulmonary artery wedge pressure (PAWP) was measured as invasive parameter of LV FP. LV diastolic dysfunction (DD) was graded according to the ASE/EACVI guidelines. The VMT score was defined as follows: time sequence of opening of mitral and tricuspid valves was scored to 0-2 (0: tricuspid valve first, 1: simultaneous, 2: mitral valve first). When the inferior vena cava was dilated, one point was added and VMT score was finally calculated as 0-3. RESULTS: Of the 116 patients, 29 patients showed elevated PAWP. Ninety patients (93%) and 67 patients (63%) showed increased values for left atrium volume index (LAVI) and E/e', respectively when the cut-off values recommended by the guidelines were applied and thus the algorism predicted elevated PAWP with a low specificity and positive predictive value (PPV). VMT ≥ 2 predicted elevated PAWP with a sensitivity of 59%, specificity of 90%, PPV of 59%, and negative predictive value of 89%. An alternative algorithm that applied tricuspid regurgitation velocity and VMT scores was tested, and its predictive ability was markedly improved. CONCLUSION: VMT score was applicable for AS patients. Alternative use of VMT score improved diagnostic accuracy of guideline-recommended algorism.

Efficacy of mitral annular velocity as an alternative marker of left ventricular global longitudinal strain to detect the risk of cancer therapy-related cardiac disorders.

PURPOSE: Left ventricular longitudinal function can be rapidly evaluated by measuring S' and mitral annular plane systolic excursion (MAPSE) using tissue Doppler imaging. Even when the image quality is poor and the left ventricular endocardium is not visible, S' and MAPSE can be measured if the mitral annulus is visible. However, the utility of S' and MAPSE in diagnosing cancer therapy-related cardiac dysfunction (CTRCD) remains unclear. This study aimed to examine the diagnostic performance of S' and MAPSE and determine appropriate cutoff values. METHODS: We retrospectively enrolled 279 breast cancer patients who underwent pre- or postoperative chemotherapy with anthracyclines and trastuzumab from April 2020 to November 2022. We compared echocardiographic data before chemotherapy, 6 months after chemotherapy initiation, and 1 year later. CTRCD was defined as a decrease in left ventricular ejection fraction below 50%, with a decrease of ≥10% from baseline or a relative decrease in left ventricular global longitudinal strain (LVGLS) of ≥15%. RESULTS: A total of 256 participants were included in this study, with a mean age of 50.2 ± 11 years. Fifty-six individuals (22%) developed CTRCD within 1 year after starting chemotherapy. The cutoff value for septal S' was 6.85 cm/s (AUC = .81, p < .001; sensitivity 74%; specificity 73%), and for MAPSE was 11.7 mm (AUC = .65, p = .02; sensitivity 79%; specificity 45%). None of the cases with septal S' exceeding 6.85 cm/s had an LVGLS of ≤15%. CONCLUSIONS: Septal S' is a useful indicator for diagnosing CTRCD. HIGHLIGHTS: Septal S' decreased at the same time or earlier than the decrease in LVGLS. The septal S' demonstrated higher diagnostic ability for CTRCD compared to LVGLS.

Acute changes in cardiac dimensions, function, and longitudinal mechanics in healthy individuals with and without high-altitude induced pulmonary hypertension at 4559 m.

BACKGROUND: High-altitude pulmonary hypertension (HAPH) has a prevalence of approximately 10%. Changes in cardiac morphology and function at high altitude, compared to a population that does not develop HAPH are scarce. METHODS: Four hundred twenty-one subjects were screened in a hypoxic chamber inspiring a FiO2  = 12% for 2 h. In 33 subjects an exaggerated increase in systolic pulmonary artery pressure (sPAP) could be confirmed in two independent measurements. Twenty nine of these, and further 24 matched subjects without sPAP increase were examined at 4559 m by Doppler echocardiography including global longitudinal strain (GLS). RESULTS: SPAP increase was higher in HAPH subjects (∆ = 10.2 vs. ∆ = 32.0 mm Hg, p < .001). LV eccentricity index (∆ = .15 vs. ∆ = .31, p = .009) increased more in HAPH. D-shaped LV (0 [0%] vs. 30 [93.8%], p = .00001) could be observed only in the HAPH group, and only in those with a sPAP ≥50 mm Hg. LV-EF (∆ = 4.5 vs. ∆ = 6.7%, p = .24) increased in both groups. LV-GLS (∆ = 1.2 vs. ∆ = 1.1 -%, p = .60) increased slightly. RV end-diastolic (∆ = 2.20 vs. ∆ = 2.7 cm2 , p = .36) and end-systolic area (∆ = 2.1 vs. ∆ = 2.7 cm2 , p = .39), as well as RA end-systolic area index (∆ = -.9 vs. ∆ = .3 cm2 /m2 , p = .01) increased, RV-FAC (∆ = -2.9 vs. ∆ = -4.7%, p = .43) decreased, this was more pronounced in HAPH, RV-GLS (∆ = 1.6 vs. ∆ = -.7 -%, p = .17) showed marginal changes. CONCLUSIONS: LV and LA dimensions decrease and left ventricular function increases at high-altitude in subjects with and without HAPH. RV and RA dimensions increase, and RV longitudinal strain increases or remains unchanged in subjects with HAPH. Changes are negligible in those without HAPH.

Statistics at high-altitudes: Relevance for the interpretation of metrics that reveal cardiac morphology and performance.

Survey of four ratio-based metrics, commonly used to evaluate left ventricular performance. The numerator of each ratio is plotted against the corresponding denominator, implying that the slope of the colored line reflects the value of the ratio.9,11 Similar graphs can be constructed for the other cardiac compartments. Data sets obtained at various altitudes and defined with reference to sea level, based on Rao et al.6 Acronyms: E/A unitless ratio of the early (E) and late (A) diastolic wave peak velocities (cm/s); EDD, end-diastolic diameter (mm); EDV, end-diastolic volume (mL); EF, ejection fraction (%); ESD, end-systolic diameter (mm); ESV, end-systolic volume (mL); FS, fractional shortening (%).

Evaluation of cardiac functions in children with familial Mediterranean fever.

OBJECTIVES: Familial Mediterranean fever is an autosomal recessive autoinflammatory inherited disease. We aimed to evaluate cardiac involvement in children with familial Mediterranean fever during the attack-free period. MATERIAL AND METHODS: The prospective study included 75 familial Mediterranean fever patients during the attack-free period and 50 healthy children. Cardiac evaluation was performed using electrocardiography, 24-hour ambulatory Holter monitoring, and conventional and tissue Doppler echocardiography. Aortic stiffness indices were calculated. RESULTS: There were no differences between the groups in age, height, sex, body mass index, and arterial blood pressure parameters (p > 0.05). QT and corrected QT dispersion parameters were similar in both groups (p > 0.05). The E wave velocity and the E/A ratio of the mitral and tricuspid valves decreased, and the A wave velocity of the tricuspid and mitral valve increased in familial Mediterranean fever by the Doppler echocardiography (p < 0.05). The myocardial contraction velocities (Sd), early relaxation velocity (Ed), and Ed/late relaxation velocity (Ad) of both ventricles were decreased in familial Mediterranean fever group, whereas the Ad of both ventricles and the interventricular septum was increased in familial Mediterranean fever group. Aortic strain and distensibility were decreased, and pressure strain elastic modules (Ep), pressure strain normalised (Ep*) by diastolic pressure, and aortic stiffness ß index were increased in familial Mediterranean fever patients (p < 0.05). When time domain heart rate variability parameters were evaluated, SDNN-i, RMSSD, and PNN50 significantly decreased in familial Mediterranean fever patients (p < 0.05), whereas SDNN and SDANN were similar in both groups (p > 0.05). CONCLUSION: Our findings showed that cardiac involvement could exist in familial Mediterranean fever patients, even during nonattack periods.

Application of an automated analysis framework for pulsed-wave Doppler cardiac ultrasound measurements to generate reference data in adult zebrafish.

High-frequency cardiac ultrasound is the only well-established method to characterize in vivo cardiovascular function in adult zebrafish noninvasively. Pulsed-wave Doppler imaging allows measurements of blood flow velocities at well-defined anatomical positions, but the measurements and results obtained using this technique need to be analyzed carefully, taking into account the substantial baseline variability within one recording and the possibility for operator bias. To address these issues and to increase throughput by limiting hands-on analysis time, we have developed a fully automated processing pipeline. This framework enables the fast, unbiased analysis of all cardiac cycles in a zebrafish pulsed-wave Doppler recording of both atrioventricular valve flow as well as aortic valve flow without operator-dependent inputs. Applying this automated pipeline to a large number of recordings from wild-type zebrafish shows a strong agreement between the automated results and manual annotations performed by an experienced operator. The reference data obtained from this analysis showed that the early wave peak during ventricular inflow is lower for female compared with male zebrafish. We also found that the peaks of the ventricular inflow and outflow waves as well as the peaks of the regurgitation waves are all correlated positively with body surface area. In general, the presented reference data, as well as the automated Doppler measurement processing tools developed and validated in this study will facilitate future (high-throughput) cardiovascular phenotyping studies in adult zebrafish ultimately leading to a more comprehensive understanding of human (genetic) cardiovascular diseases.

Automated 4D flow cardiac MRI pipeline to derive peak mitral inflow diastolic velocities using short-axis cine stack: two centre validation study against echocardiographic pulse-wave doppler.

BACKGROUND: Measurement of peak velocities is important in the evaluation of heart failure. This study compared the performance of automated 4D flow cardiac MRI (CMR) with traditional transthoracic Doppler echocardiography (TTE) for the measurement of mitral inflow peak diastolic velocities. METHODS: Patients with Doppler echocardiography and 4D flow cardiac magnetic resonance data were included retrospectively. An established automated technique was used to segment the left ventricular transvalvular flow using short-axis cine stack of images. Peak mitral E-wave and peak mitral A-wave velocities were automatically derived using in-plane velocity maps of transvalvular flow. Additionally, we checked the agreement between peak mitral E-wave velocity derived by 4D flow CMR and Doppler echocardiography in patients with sinus rhythm and atrial fibrillation (AF) separately. RESULTS: Forty-eight patients were included (median age 69 years, IQR 63 to 76; 46% female). Data were split into three groups according to heart rhythm. The median peak E-wave mitral inflow velocity by automated 4D flow CMR was comparable with Doppler echocardiography in all patients (0.90 ± 0.43 m/s vs 0.94 ± 0.48 m/s, P = 0.132), sinus rhythm-only group (0.88 ± 0.35 m/s vs 0.86 ± 0.38 m/s, P = 0.54) and in AF-only group (1.33 ± 0.56 m/s vs 1.18 ± 0.47 m/s, P = 0.06). Peak A-wave mitral inflow velocity results had no significant difference between Doppler TTE and automated 4D flow CMR (0.81 ± 0.44 m/s vs 0.81 ± 0.53 m/s, P = 0.09) in all patients and sinus rhythm-only groups. Automated 4D flow CMR showed a significant correlation with TTE for measurement of peak E-wave in all patients group (r = 0.73, P < 0.001) and peak A-wave velocities (r = 0.88, P < 0.001). Moreover, there was a significant correlation between automated 4D flow CMR and TTE for peak-E wave velocity in sinus rhythm-only patients (r = 0.68, P < 0.001) and AF-only patients (r = 0.81, P = 0.014). Excellent intra-and inter-observer variability was demonstrated for both parameters. CONCLUSION: Automated dynamic peak mitral inflow diastolic velocity tracing using 4D flow CMR is comparable to Doppler echocardiography and has excellent repeatability for clinical use. However, 4D flow CMR can potentially underestimate peak velocity in patients with AF.

Abnormal inter-ventricular diastolic mechanical delay in patients with ST-segment elevation myocardial infarction.

BACKGROUND: This study aimed to investigate the ventricular mechanical relaxation pattern and its clinical influence in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Echocardiography was performed to measure mitral and tricuspid diastolic opening times. Left ventricular diastolic mechanical delay (LVMDd) was defined as diastolic filling of the right ventricle earlier than that of the left ventricle, and right ventricular diastolic mechanical delay (RVMDd) was defined as the right ventricular diastolic filling later than left ventricular filling. RESULTS: Among 152 patients with STEMI, 100 (65.8%) had LVMDd, and 47 (30.9%) had RVMDd. In-hospital complications were significantly increased in patients with RVMDd (61.6% vs. 41.0%, P = 0.017). Those with RVMDd exhibited significantly lower left ventricular global longitudinal strain (11.7 ± 4.1% vs. 13.2 ± 4.0%, P = 0.035), global work index (913.8 ± 365.9 vs. 1098.9 ± 358.8 mmHg%, P = 0.005) and global constructive work (1218.6 ± 392.8 vs. 1393.7 ± 432.7 mmHg%, P = 0.021). Mitral deceleration time significantly decreased (127.4 ± 33.5 vs. 145.6 ± 41.7 ms, P = 0.012), and the ratio of early mitral inflow to early mitral annular velocity (E/E') significantly increased [13.0(11.0-20.0) vs. 11.9(9.3-14.3), P = 0.006] in the RVMDd group. Logistic regression analysis showed that age (odds ratio [OR]:0.920; P = 0.001), brain natriuretic peptide level (OR: 1.1002; P = 0.036) and mitral E/E' (OR: 1.187; P = 0.003) were independently associated with RVMDd. CONCLUSIONS: Delayed right ventricular filling is related to more severe left ventricular systolic and diastolic dysfunction in STEMI patients. More attention should be paid to patients with RVMDd to prevent adverse events during hospitalization.

Risk score for coronary heart disease (CHD-RISK) and hemodynamically significant aortic valve stenosis.

BACKGROUND AND AIM: Multiple studies have investigated the association between coronary heart disease (CHD) risk factors and aortic valve stenosis (AS). However, limited studies have explored the relationship between CHD risk scores and AS. Whether incident risk scores for coronary heart disease (CHD-RISK) may be applied to predict AS remains unclear. We aim to investigate the association between AS and CHD-RISK. METHODS AND RESULTS: We included 4791 participants (age 54.6 ± 5.0 yrs, 58.7% women, 81% were of European origin), and CHD-RISK was estimated in 1990-1992. The participants were then followed-up until December 31, 2013. The primary outcome was hemodynamic significant AS identified by Doppler echocardiography in 2011-2013. We used multivariate-logistic regression models to assess the associations between CHD-RISK and AS. During follow-up, 963 (20.1%) cases of AS were identified. Per-standard deviation (6%) increase in CHD-RISK was associated with OR 95% Cl [1.194, 95% CI 1.068 to 1.335, p = 0.002] risk of AS in the fully adjusted models. Results were similar when stratified by quintiles of CHD-RISK, using the lowest quintiles <0.94% of CHD-RISK as the reference, 0.94%-2.26%, 2.26%-4.83%, 4.83%-9.21%, and >9.21% were; 1.33 (95% CI, 0.99-1.78, p = 0.055), 1.64 (95% CI, 1.17-2.29, p = 0.004), 2.23 (95% CI, 1.49-3.32, p = <0.001), 2.66 (95% CI, 1.65-4.31, p = <0.001) respectively. CONCLUSIONS: CHD-RISK was associated with AS. CHD-RISK and AS were high in females, age ≥55 yrs, current smokers, and BMI ≥ 30 kg/m2. This investigation suggests CHD-RISK may be applied to forecast AS risk similar to CHD. Future studies are required to detect, manage, and establish better treatment strategies in these high-risk subgroups.

Umbilical cord serum insulin-like growth factor-1 levels of infants of diabetic mothers are correlated with diastolic dysfunction detected by tissue Doppler echocardiography.

Tissue Doppler echocardiography (TDI) is a convenient method to detect cardiac dysfunction in the infants of diabetic mothers (IDMs). Umbilical cord serum insulin-like growth factor-1 (IGF-1) is known to be higher in IDMs. We aimed to determine whether there is a relation between diastolic functions examined by TDI and cord serum IGF-1 levels of IDMs. Cord serum IGF-1 levels of 32 IDMs and 22 healthy infants were measured. The cardiac functions of the infants were evaluated by M-Mode and TDI. For statistical analysis, Mann-Whitney U and Spearman correlation tests were used for continuous variables, and the chi-square test was used for categorical variables. The cord serum IGF-1 levels of the IDMs were higher (p = 0.000). The left ventricle (LV) e', LVa', LV e'/a', and LV Tei index, indicating left ventricular diastolic dysfunction in IDMs, were detected (LV e' p = 0.016; LV a' p = 0.003; LV e'/ a' p = 0.000; LV Tei index p = 0.023). IDMs' cord serum IGF-1 levels were found weakly correlated with the interventricular septum (IVS) and left ventricle posterior wall (LVPW) thicknesses in M-Mode and LV e' and LV e'/a' in TDI (IVS r = 0.357, p = 0.008; LVPW r = 0.289, p = 0.034; LV e' r = 0.297, p = 0.029; LV e'/ a' r = 0.031, p = 0.014). CONCLUSION: To our knowledge, this is the first study to examine the relationship between cord serum IGF-1 levels and diastolic functions of IDMs assessed by TDI. A weak correlation was found between IGF-1 levels and IVS and LVPW thicknesses in M-Mode and LV e' and LV e'/a' parameters in TDI, revealing diastolic dysfunction in IDMs. WHAT IS KNOWN: • The umbilical cord blood serum IGF-1 level of IDMs is higher than in infants of healthy mothers. • Diastolic dysfunction is a well-studied and frequently observed consequence in IDMs. WHAT IS NEW: • This is the first study to examine the relationship between cord serum IGF-1 levels and diastolic functions of IDMs assessed by TDI. • A weak correlation was detected between the median cord serum IGF-1 level of IDMs and the median values of IVS, LVPW, LV e', LV a', LV e'/a' ratio.

Evaluation of cardiac fibrosis and subclinical cardiac changes in children with sickle cell disease using magnetic resonance imaging, echocardiography, and serum galectin-3.

BACKGROUND: Myocardial fibrosis has recently been proposed as one of the contributing factors to the diverse pathogenicity of cardiomyopathy in sickle cell disease. OBJECTIVE: In this study, cardiac fibrosis and subclinical cardiac changes in children with sickle cell disease were evaluated using cardiac magnetic resonance imaging (MRI), tissue Doppler echocardiography and serum galectin-3. MATERIALS AND METHODS: The study included 34 children with sickle cell disease who were compared with a similar number of healthy controls. Cardiac MRI was used to evaluate late gadolinium enhancement, native T1 mapping, extracellular volume, and T2* for estimation of iron load. Cardiac function and myocardial performance index (MPI, evaluated by tissue Doppler echocardiography) and serum galectin-3 were compared to controls. RESULTS: The mean age of the included patients was 13.3 ± 3.2 years. Myocardial iron load by T2* was normal. The mean level of extracellular volume (35.41 ± 5.02%) was significantly associated with the frequency of vaso-occlusive crises (P = 0.017) and negatively correlated with hemoglobin levels (P = 0.005). Galectin-3 levels were significantly higher among cases than controls (P = 0.00), at a cutoff value on the receiver operating characteristic curve of 6.5 ng/ml, sensitivity of 82.5% and specificity of 72.8%. The extracellular volume was significantly higher in cases, with a MPI > 0.4. CONCLUSION: Diffuse interstitial myocardial fibrosis can be detected early in children with sickle cell disease using T1 mapping and is associated with a high frequency of vaso-occlusive crisis. MPI of the left ventricle and serum galectin-3 are recommended screening tools for subclinical cardiac abnormalities.

Late aortic obstruction due to ductal vasoconstriction on pulmonic end after transcatheter patent ductus arteriosus closure in an extremely low-birth-weight infant.

Device-induced aortic obstruction is a known rare complication following transcatheter closure of patent ductus arteriosus in extremely low-birth-weight infants. Various mechanisms have been proposed. We report the first description of late aortic obstruction due to ductal vasoconstriction on pulmonic end causing device to be gradually pushed out of aortic end in a 980-gram premature infant.

Impact of empagliflozin on left atrial mechanical and conduction functions in patients with type 2 diabetes mellitus.

OBJECTIVE: Empagliflozin, an oral anti-diabetic drug that inhibits the sodium-dependent glucose co-transporter 2 (SGLT2), has pleiotropic effects on the myocardium. The aim of the study is to investigate the effect of empagliflozin on atrial electromechanical delay (AEMD) and the left atrial (LA) mechanical functions in patients with type 2 diabetes mellitus (DM). METHOD: In total 62 patients (40.3% female, mean age 50.5 ± 8.6 years old) with type 2 DM were enrolled to the study. Participants were used a SGLT2 inhibitor (empagliflozin 10-25 mg/daily) for 6 months. Patients were examined initially and after 6 months with echocardiography. LA volume was recorded, atrial conduction times were measured using tissue Doppler imaging (TDI). RESULTS: No significant change was observed in LA volumes (maximal, minimal, and presystolic), total emptying and passive emptying volume at the end of 6 months; however, there was a significant decrease in active emptying volume (8.3 ± 2.9 ml/m2 vs. 7.9 ± 2.9 ml/m2 , p = 0.04). The posteroanterior lateral, septal, and tricuspid conduction times significantly decreased after the empagliflozin treatment. The decrease in right inter-AEMD was statistically significant (13.25 ± 10.21 ms vs. 10.85 ± 9.14 ms, p = 0.011). The changes in inter-AEMD were found to be correlated with the changes in LA active emptying volume (r = 0.408). CONCLUSION: Empagliflozin may enhance the structure and electrical conductions of the atrium and may prevent DM patients from DM-2-related functional disorder and arrhythmia.

Multiparametric analysis of coronary flow in psoriasis using a coronary flow reserve companion.

BACKGROUND: Coronary microvascular dysfunction (CMD) is usually evaluated measuring coronary flow velocity reserve (CFVR). A more comprehensive analysis of CFVR including additional consideration of the associated logical companion-CFVR, where hyperemic diastolic coronary flow velocity may act as surrogate, was applied in this study to elucidate the mechanism of CMD in psoriasis. METHODS AND RESULTS: Coronary flow velocity reserve was analysed using transthoracic echocardiographs of 127 psoriasis patients (age 36 ± 8 years; 104 males) and of 52 sex- and age-matched healthy controls. CFVR determination was repeated in the patient subgroup (n = 78) receiving anti-inflammatory therapy. Baseline and hyperemic microvascular resistance (MR) were calculated. CMD was defined as CFVR ≤ 2.5. Four endotypes of CMD were identified referring to concordant or discordant impairments of hyperemic flow or CFVR. We evaluated the companion-CFVR, as derived from the quadratic mean of hyperemic and diastolic flow velocity at rest. Coronary flow parameters, including CFVR (p = 0.01), were different among the two endotypes having CFVR > 2.5. Specifically, all 11 (14%) patients with CFVR deterioration despite therapy, belonged to endotype 1, and had higher baseline and hyperemic MR (p < 0.0001, both). Interestingly, while CFVR was comparable in patients with worsened versus those with improved CFVR, the companion-CFVR could discriminate by being lower in patients with worsened CFVR (p = 0.01). CONCLUSIONS: The reduced CFVR in psoriasis is driven by decreased companion-CFVR, combined with increased hyperemic MR. Adoption of the mandatory companion-CFVR enables a personalized characterization superior to that achieved by exclusive consideration of CFVR.

In vitro Doppler versus catheter transvalvular pressure gradients in balloon-expandable versus self-expanding transcatheter aortic valves.

OBJECTIVES: The objective of this in vitro study was to compare Doppler versus catheter transvalvular pressure gradients (TPG) in third generations balloon-expandable (BE) versus self-expanding (SE) transcatheter heart valves (THV). BACKGROUND: TPG is a key parameter to assess and follow valve hemodynamic function following transcatheter aortic valve implantation (TAVI). It remains uncertain and debated whether, and to which extent, TPGs differ according to the type of THV, that is, BE versus SE and to the method used for TPG measurement, that is, Doppler echocardiography versus cardiac catheterization. METHODS: The CoreValve EVOLUT PRO 26 mm and the SAPIEN 3 23 mm THVs were tested in a left heart simulator using a 21 mm aortic annulus under following conditions: heart rate: 70 bpm, mean aortic pressure: 100 mmHg, stroke volume: 30, 70 and 100 ml. Mean TPGs were measured by continuous-wave Doppler and by micro-tip pressure catheters positioned in the left ventricle and at 50 mm downstream to the tip of the THV leaflets. RESULTS: Doppler TPGs (9.5 ± 3.9 mmHg) were on average 40.5 ± 13.9% higher (p < 0.001) than catheter TPGs (6.3 ± 3.4 mmHg). Both Doppler and catheter TPGs were lower (p = 0.003) in the SE versus BE THVs (Doppler: 8.7 ± 3.5 vs. 10.7 ± 4.6; catheter: 5.0 ± 1.7 mmHg vs. 7.1 ± 2.2). The Doppler versus catheter difference in TPG increased with the higher flow conditions. The Doppler versus catheter difference in TPG was similar in BE versus SE THVs (3.6 ± 1.1 vs. 3.7 ± 1.4 mmHg or 42 ± 9 vs. 47 ± 9%; p = 0.58) overall and in each flow conditions. CONCLUSION: The Doppler TPGs are, on average, 40% higher than the catheter TPGs for both BE and SE THVs. The SE THV had lower Doppler and catheter TPGs compared to the BE THV, at normal and high flow states. The absolute and percent differences between Doppler versus catheter TPGs were similar in BE versus SE THVs.

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.

Application of the proximal isovelocity surface area method for estimation of the effective orifice area in aortic stenosis.

Although the echocardiographic effective orifice area (EOA) calculated using the continuity equation is widely used for the assessment of severity in aortic stenosis (AS), the existence of high flow velocity at the left ventricular outflow tract (LVOT) potentially causes its overestimation. The proximal isovelocity surface area (PISA) method could be an alternative tool for the estimation of EOA that limits the influence of upstream flow velocity. EOA was calculated using the continuity equation (EOACont) and PISA method (EOAPISA), respectively, in 114 patients with at least moderate AS. The geometric orifice area (GOA) was also measured using the planimetry method in 51 patients who also underwent three-dimensional transesophageal echocardiography. Patients were divided into two groups according to the median LVOT flow velocity. EOAPISA could be obtained in 108 of the 114 patients (95%). Although there was a strong correlation between EOACont and EOAPISA (r = 0.78, P < 0.001), EOACont was statistically significantly larger than EOAPISA (0.86 ± 0.33 vs 0.75 ± 0.29 cm2, P < 0.001). Both EOACont and EOAPISA similarly correlated with GOA (r = 0.70, P < 0.001 and r = 0.77, P < 0.001, respectively). However, a fixed bias, which is hydrodynamically supposed to exist between EOA and GOA, was not observed between EOACont and GOA. In contrast, there was a negative fixed bias between EOAPISA and GOA with smaller EOAPISA than GOA. The difference between EOACont and GOA was significantly greater with a larger EOACont relative to GOA in patients with high LVOT flow velocity than in those without (0.16 ± 0.25 vs - 0.07 ± 0.10 cm2, P < 0.001). In contrast, the difference between EOAPISA and GOA was consistent regardless of the LVOT flow velocity (- 0.07 ± 0.12 vs - 0.07 ± 0.15 cm2, P = 0.936). The PISA method was applied to estimate EOA in patients with AS. EOAPISA could be an alternative parameter for AS severity grading in patients with high LVOT flow velocity in whom EOACont would potentially overestimate the orifice area.

Stress exercise haemodynamic performance and opening reserve of a stented bovine pericardial aortic valve bioprosthesis.

OBJECTIVES: Despite unusual high rates of patient-prosthesis mismatch (PPM), excellent midterm clinical outcomes have been reported after surgical aortic valve replacement (SAVR) with the Avalus™ bioprosthetic valve (Medtronic). To elucidate this "PPM conundrum," the Avalus valve haemodynamics were assessed during exercise testing. METHODS: Of the 148 patients who had undergone SAVR with the Avalus valve at our institution, 30 were randomly selected among those in whom stress test was deemed feasible and underwent a resting transthoracic echocardiography immediately followed by exercise echocardiography. Severe PPM was defined as indexed effective orifice area (iEOA) ≤ 0.65 cm2 /m2 and moderate PPM as iEOA > 0.65 and ≤ 0.85 cm2 /m2 . Measured PPM was determined with the use of the measured iEOA at rest or stress, while the estimated PPM was based on the estimated iEOA, derived from the mean EOA reported for each valve size in the manufacturer chart. RESULTS: Measured EOA significantly increased from rest to peak exercise in all PPM groups (p < .05) and the rates of moderate and severe measured PPM decreased from 40% and 20% to 27% and 0%, respectively. The patients with low-flow state (flow < 250 ml/s) had significantly lower measured rest EOA (p = .03). On the basis of the estimated iEOA, there was no severe PPM and 19 patients had moderate PPM (63.3%), with a significantly lower opening reserve than the patients without estimated PPM (p = .04). The estimated iEOA was more reliably correlated to the measured iEOA at maximal stress than the measured iEOA at rest, especially in patients with a low-flow state. CONCLUSIONS: This study supports the concept of an opening reserve of the Avalus valve to explain the PPM conundrum and promotes the use of exercise Doppler-echocardiography to complete the assessment of mismatch, especially in patients with a low-flow state. Published estimated EOA seems reliable to predict the haemodynamic performance of the Avalus valve, whether the flow conditions at rest.