Predominant determinants for evaluation of right parasternal approach in transthoracic echocardiography in aortic stenosis: a study based on three-dimensional cardiac computed tomography analysis.

The maximum blood flow velocity through the aortic valve (AVmax) using Doppler transthoracic echocardiography (TTE) is important in assessing the severity of aortic stenosis (AS). The right parasternal (RP) approach has been reported to be more useful than the apical approach, but the anatomical rationale has not been studied. We aimed to clarify the influence of the angle formed by the ascending aorta and left ventricle on Doppler analysis by TTE (Sep-Ao angle) and three-dimensional multidetector computed tomography (3D-MDCT) in patients with AS. A total of 151 patients evaluated using the RP approach and 3D-MDCT were included in this study. The Sep-Ao angle determined using TTE was compared with that determined using 3D-MDCT analysis. In MDCT analysis, the left ventricular (LV) axis was measured in two ways and the calcification score was calculated simultaneously. The Sep-Ao angle on TTE was consistent with that measured using 3D-MDCT. In patients with an acute Sep-Ao angle, the Doppler angle in the apical approach was larger, potentially underestimating AVmax. Multivariate analysis revealed that an acute Sep-Ao angle, large Doppler angle in the apical approach, smaller Doppler angle in the RP approach, and low aortic valve calcification were independently associated with a higher AVmax in the RP approach than in the apical approach. The Sep-Ao angle measured using TTE reflected the 3D anatomical angle. In addition to measurements using the RP approach, technical adjustments to minimize the Doppler angle to avoid bulky calcification should always be noted for accurate assessment.

Isolated right ventricular hypoplasia associated with cyanotic atrial septal defect: a case report.

Background: Hypoxaemia in isolated right ventricular (RV) hypoplasia (IRVH) is primarily caused by a right-to-left shunt (RLS) at the atrial level, such as an atrial septal defect (ASD). When considering closure of the RLS, it should be closed only after ensuring that it will not cause right-sided heart failure (HF). Case summary: A 21-year-old woman had been experiencing shortness of breath during exertion since childhood. Transthoracic and transoesophageal echocardiography revealed an ASD with bidirectional shunting, and microbubble test revealed a marked RLS. Cardiac magnetic resonance imaging revealed a hypoplastic RV end-diastolic volume corrected for body surface area of 47 mL/m2 (70% of normal range). Right heart catheterization revealed a decreased Qp/Qs ratio of 0.89 and a pressure waveform with a clear increase in the 'A'-wave, although the mean right atrial pressure was not high (4 mmHg). Therefore, the patient was diagnosed with cyanotic ASD and IRVH. A temporary balloon occlusion test was performed to evaluate the right-sided heart response to capacitive loading prior to ASD closure. After treatment, the patient's improved markedly. The pre-operative brain natriuretic peptide (BNP) level was normal; however, 6 months after ASD closure, the BNP level was elevated, and the continuous-wave Doppler waveform of pulmonary regurgitation at the time of transthoracic echocardiography changed, suggesting an increase in diastolic RV pressure. Discussion: When ASD is complicated by hypoxaemia, the possibility of IRVH, although rare, should be considered. Another difficult point is determining whether the ASD can be closed, considering its immature RV compliance.

Clinical impact of the right ventricular impairment in patients following transcatheter aortic valve replacement.

The right ventricular (RV) impairment can predict clinical adverse events in patients following transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). Limited reports have compared impact of the left ventricular (LV) and RV disorders. This retrospective study evaluated two-year major adverse cardiac and cerebrovascular events (MACCE) in patients following TAVR for severe AS. RV sphericity index was calculated as the ratio between RV mid-ventricular and longitudinal diameters during the end-diastolic phase. Of 239 patients, 2-year MACCE were observed in 34 (14%). LV ejection fraction was 58 ± 11%. Tricuspid annular plane systolic excursion (TAPSE) and RV sphericity index were 20 ± 3 mm and 0.36 (0.31-0.39). Although the univariate Cox regression analysis demonstrated that both LV and RV parameters predicted the outcomes, LV parameters no longer predicted them after adjustment. Lower TAPSE (adjusted hazard ratio per 1 mm, 0.84; 95% confidence interval, 0.75-0.93) and higher RV sphericity index (adjusted hazard ratio per 0.1, 1.94; 95% confidence interval, 1.17-3.22) were adverse clinical predictors. In conclusion, the RV structural and functional disorders predict two-year MACCE, whereas the LV parameters do not. Impact of LV impairment can be attenuated after development of RV disorders.

Potential confounders of the obesity paradox in older patients following transcatheter aortic valve replacement.

PURPOSE: A higher body mass index (BMI) is associated with lower mortality in older patients following transcatheter aortic valve replacement (TAVR) for severe aortic valve stenosis. The current study aimed to investigate potential confounders of association between BMI and prognosis. METHODS: The retrospective single-center study included consecutive patients following TAVR and excluded those in whom subcutaneous fat accumulation (SFA), visceral fat accumulation (VFA), and major psoas muscle (MPM) volume were not assessed by computed tomography. Cachexia was defined as a combination of BMI < 20 kg/m2 and any biochemical abnormalities. RESULTS: After 2 patients were excluded, 234 (age, 86 ± 5 years; male, 77 [33%]; BMI, 22.4 ± 3.8 kg/m2; SFA, 109 (54-156) cm2; VFA, 71 (35-115) cm2; MPM, 202 (161-267) cm3; cachexia, 49 [21%]) were evaluated. SFA and VFA were strongly correlated with BMI (ρ = 0.734 and ρ = 0.712, respectively), whereas MPM was weakly correlated (ρ = 0.346). Two-year all-cause mortality was observed in 31 patients (13%). Higher BMI was associated with lower mortality (adjusted hazard ratio [aHR], 0.86; 95% confidence interval [CI], 0.77-0.95). A similar result was observed in the multivariate model including SFA (aHR in an increase of 20 cm2, 0.87; 95% CI, 0.77-0.98) instead of BMI, whereas VFA was not significant. Cachexia was a worse predictor (aHR, 2.51; 95% CI 1.11-5.65). CONCLUSIONS: Association of higher BMI with lower mortality may be confounded by SFA in older patients following TAVR. Cachexia might reflect higher mortality in patients with lower BMI.

Mechanism of Negative Thermal Expansion in Monoclinic Cu2P2O7 from First Principles.

Negative thermal expansion (NTE) materials generally have high-symmetry space groups, large average atomic volumes, and corner-sharing octahedral and tetrahedral coordination structures. By contrast, monoclinic α-Cu2P2O7, which has a small average atomic volume and edge-sharing structure, has been reported to exhibit NTE, the detailed mechanism of which is unclear. In this study, we investigate the A2B2O7 polymorphs and analyze the NTE behavior of α-Cu2P2O7 using first-principles lattice-dynamics calculations. From the polymorphism investigation in 20 A2B2O7 compounds using 6 representative crystal structures, small A and B cationic radii are found to stabilize the α-Cu2P2O7-type structure. We then analyze the NTE behavior of α-Cu2P2O7 using quasi-harmonic approximation. Our calculated thermal expansion coefficients and anisotropic atomic displacement parameters were in good agreement with those of the experimental reports at low temperatures. From the mode-Grüneisen parameter distribution plotted over the entire first-Brillouin zone, we found that the phonon contributing most significantly to NTE emerges not into the special points but between them. In this phonon mode, the O connecting two PO4 tetrahedra rotates, and the Cu and O vibrate perpendicular to the bottom of the CuO5 pyramidal unit, which folds the ac lattice plane. This vibration behavior can explain the experimentally reported anisotropic NTE behavior of α-Cu2P2O7. Our results demonstrate that the most negative mode-Grüneisen parameter contributing to NTE behavior is not always located on high-symmetry special points, indicating the importance of lattice vibration analyses for the entire first-Brillouin zone.

Relationship Between Results of Pathological Evaluation of Endomyocardial Biopsy and Echocardiographic Indices in Patients With Non-Ischemic Cardiomyopathy.

Background: Endomyocardial biopsy (EMB) is a useful modality in diagnosing the origin of cardiomyopathy and the condition of the impaired myocardium. However, the usefulness of obtaining an EMB from the right and left ventricles (RV and LV, respectively), and its associations with echocardiographic parameters, have not been explored. Methods and Results: Ninety-five consecutive patients with non-ischemic cardiomyopathy excluding myocarditis who underwent EMB between July 2017 and May 2019 were studied. Seventy-nine RV and 93 LV biopsy specimens were pathologically analyzed. The relationships among echocardiographic data before EMB and pathologically measured cardiomyocyte diameter (CMD) and interstitial fibrosis (IF) were evaluated. CMD in both LV and RV specimens correlated with echocardiographic LV morphology, but only CMD in the LV was significantly correlated with cardiac function evaluation, including LV ejection fraction, E' and E/E'. In contrast, there were no significant correlations between IF in either the LV or RV and any echocardiographic parameters measured. Furthermore, CMD of both ventricles was significantly correlated with B-type natriuretic peptide (BNP) concentration at EMB, whereas IF of the LV was barely related and IF of the RV was not significantly correlated with BNP concentrations. Conclusions: Pathologically evaluated CMD of EMB specimens of the LV may be more related to functional parameters for heart failure status and LV geometry on echocardiographic examination, than IF.

Chemical Aspect of Displacive-Type Ferroaxial Phase Transition from Perspective of Second-Order Jahn-Teller Effect: NASICON Systems as an Example.

Ferroaxial order, characterized by a rotational arrangement of electric dipoles, attracts increasing attention in terms of a new family of ferroic orders. However, there has been no chemical guideline for exploring crystalline materials showing ferroaxial order, namely ferroaxial materials. Here, we present a chemical guideline grounded in staggered polyhedral connectivity, which we propose as a structural prerequisite for ferroaxial order, and the second-order Jahn-Teller (SOJT) theory extended from molecular orbitals to electronic band structures. Na-superionic conductors (NASICON) including NaM2(PO4)3 (M = early-transition or post-transition metal) are identified as potential ferroaxial materials because of their staggered structures composed of MO6 octahedra and PO4 tetrahedra. However, ferroaxial phase transitions hardly occur in some of the NASICON systems, which offers a platform to uncover a hidden factor playing an important role in driving this system into ferroaxial states. Our first-principles calculations demonstrate that a ferroaxial phase transition in NASICON systems occurs only when SOJT interaction is symmetrically allowed, that is, energy-lowering chemical bonds are formed as a consequence of the distortion. Our proposals would be not limited to NASICON systems but applicable to a variety of compounds and provide new insight into the exploration of displacive-type ferroaxial materials.

Transcranial Doppler for stratification of high-risk morphology of patent foramen ovale in patients with cryptogenic stroke.

Microbubble testing using transcranial Doppler (TCD) is an important screening tool for diagnosing paradoxical cerebral embolism with high-risk PFO. However, little is known about the association between the microbubble test by TCD and the features of high-risk PFO evaluated by transesophageal echocardiography (TEE). We studied 101 consecutive patients at Showa University, from April 2019 to October 2020, who underwent both TCD and TEE with a sufficient Valsalva maneuver and who were strongly suspected by neurologists as cryptogenic stroke. According to the appearance of microbubbles as high-intensity transient signals (HITS), the TCD grade was stratified into three categories based on the criteria (A: none, no HITS, B: small; 1-10 HITS, and C: large; > 10 HITS, or an uncountable number of HITS). Among patients with RLS through the PFO in TEE, high-risk morphological features of PFO for cerebral embolism were evaluated as follows: (1) tunnel height, (2) tunnel length, (3) total excursion distance of the atrial septum into the right and left atrium, (4) existence of Eustachian valve or Chiari network, (5) angle of PFO from the inferior vena cava, and (6) large shunt (20 or more microbubbles). Of 101 patients (TCD grade; Group A = 49, Group B = 26, Group C = 26), RLS through PFO was detected in 37 patients (grade A = 8, grade B = 6, grade C = 23) by TEE. Among PFO-positive patients, tunnel height, length, total excursion distance into the right and left atria, angle of PFO from the inferior vena cava, and frequency of large shunt in TEE were significantly larger in grade C than in grade A and B (p < 0.05). Additionally, grade C patients had significantly more forms of high-risk PFOs than those in grades A and B when the six features of high-risk PFO were compared. A multivariate logistic regression demonstrated that the tunnel length of PFO and the presence of large shunt in TEE were independently associated with large HITS in TCD (odds ratio: 1.18 and 49.5, 95% confidence interval 1.043-1.337 and 10.05-244.3, p = 0.0086 and p < 0.0001, respectively). In conclusion, the existence of a large HITS detected by TCD may have a screening advantage in predicting the high-risk morphologies of PFO that can cause paradoxical cerebral embolism.

Potential drug-drug interaction between tolvaptan and warfarin in a geriatric patient with heart failure.

Tolvaptan is a key drug for patients with heart failure. Here, we present a 92-year-old woman, whose PT-INR/dose increased from 1.74 to 3.30 after warfarin and tolvaptan co-administration, and resulted in a large cerebral infarction after warfarin dose down. Therefore, the interaction between these two drugs may be clinically significant.

A case report of platypnea-orthodeoxia syndrome: A rare condition found during diagnostic workup of a patient with embolic stroke of undetermined sources.

Platypnea-orthodeoxia syndrome (POS) is a rare condition wherein the magnitude of the interatrial shunt changes between the sitting and supine positions. We diagnosed POS in a case initially considered to be of embolic stroke of undetermined source and performed emergency foramen ovale closure as definitive management for the patient. In this case, additional risk factors for POS include spinal deformity, meandering of the aorta, and exclusion of the right atrium due to overextension. Transcranial color flow imaging is recommended for the diagnosis of POS because of its sensitivity, specificity, and non-invasiveness. Although POS is an important barrier to effective rehabilitation, early diagnosis and definitive management lead to dramatic clinical improvement.

Right ventricular contractility affects the clinical efficacy of add-on tolvaptan following hospitalization for heart failure in patients with significant tricuspid regurgitation.

Tricuspid regurgitation (TR) is a common condition that is independently associated with high mortality rates in patients with heart failure (HF). Several studies have demonstrated the clinical efficacy of add-on tolvaptan in patients hospitalized for HF. However, the effects of add-on tolvaptan in patients with significant TR are less well understood. Among the patients with moderate-to-severe TR assessed by transthoracic echocardiography during hospitalization for congestive HF, 39 patients who could complete the clinical course after starting add-on tolvaptan were included in the study. Rehospitalization due to HF and cardiac death were defined as adverse cardiac events in this study. We investigated the presence or absence of cardiac events within 2 years following the introduction of tolvaptan and evaluated echocardiographic functional parameters associated with cardiac events. The average patient age was 75 ± 14 years, and 23 patients (59%) experienced adverse cardiac events within 2 years after add-on tolvaptan administration. Serum creatinine (mg/dL) and brain natriuretic peptide (pg/mL) concentrations at discharge were significantly higher in patients with cardiac events than in those without cardiac events {1.48 [1.02-1.58] vs. 1.07 [0.79-1.41], p = 0.03; 526 [414-1044] vs. 185 [104-476], p = 0.01, respectively}. The presence or absence of past hospitalization for HF was also significantly higher in the event-positive group compared to event-free group (78 vs. 44%, p = 0.04). Comparison of echocardiographic parameters revealed that patients with cardiac events had a significantly lower left ventricular ejection fraction (40 ± 16 vs. 49 ± 15%, p = 0.049) and lower right ventricular fractional area change (RVFAC) (35 ± 12 vs. 45 ± 10%, p = 0.008) than those without cardiac events. Multiple logistic regression analysis revealed that RVFAC and past hospitalization for HF were independently associated with cardiac events following the introduction of tolvaptan (odds ratio, 0.934 and 4.992; p = 0.048 and 0.04, respectively). Right ventricular contractility as well as past history of admission for HF, left ventricular ejection fraction, renal function, and brain natriuretic peptide level at discharge may reflect the clinical outcomes after HF hospitalization in patients with significant TR who were treated with tolvaptan.

Association between diabetic nephropathy and left ventricular longitudinal myocardial function in type 1 diabetes mellitus patients with preserved ejection fraction.

Left ventricular (LV) longitudinal myocardial dysfunction can be observed even in type 2 diabetes mellitus (DM) (T2DM) patients with preserved LV ejection fraction (LVEF), and is considered the earliest marker of DM-related cardiac dysfunction. Furthermore, diabetic nephropathy (DN), a common complication in DM, is strongly associated with LV longitudinal myocardial function in T2DM patients, but its association with type 1 DM (T1DM) has not been fully investigated. We studied 125 asymptomatic T1DM patients with preserved LVEF, and 75 age-, gender-, LVEF-matched non-diabetic healthy controls. Two-dimensional speckle-tracking strain LV was used to assess longitudinal myocardial function as global longitudinal strain (GLS). GLS of T1DM patients was significantly lower than that of normal controls (19.7 ± 3.6% vs. 20.6 ± 1.8%, P = 0.049). GLS of T1DM patients with DN was significantly lower that of T1DM patients without DN (17.3 ± 3.7% vs. 20.2 ± 3.5%, P < 0.001), but that of T1DM patients without DN was similar compared to normal controls (20.6 ± 1.8% vs. 20.2 ± 3.5%, P = 0.37). Moreover, multiple regression analysis identified DN the independent determinant parameters for GLS of T1DM patients also correlated significantly with duration of T1DM. Impaired LV longitudinal myocardial function was observed in asymptomatic T1DM patients with preserved LVEF, and DN was associated with LV longitudinal myocardial dysfunction. These findings are clinically useful for better management of T1DM patients to prevent impending development of cardiovascular disease.

Association of left ventricular longitudinal myocardial function with subclinical right ventricular dysfunction in type 2 diabetes mellitus.

BACKGROUND: Left ventricular (LV) involvement in diabetic cardiomyopathy has been reported; however, only limited data exist on right ventricular (RV) involvement. Therefore, our purpose was to investigate RV systolic dysfunction and its association with LV longitudinal myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) and preserved LV ejection fraction (LVEF). METHODS: We studied 177 T2DM patients with preserved LVEF and 79 age-, sex-, and LVEF-matched healthy volunteers. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), and RV systolic function was assessed as RV free-wall strain, and predefined cutoff values for subclinical dysfunction were set at GLS < 18% and RV free-wall strain < 20%, respectively. RESULTS: RV free-wall strain in T2DM patients was significantly lower than that in normal controls (19.3% ± 4.8% vs. 24.4% ± 5.1%; P < 0.0001). RV free-wall strain in T2DM patients and LV longitudinal dysfunction was similar compared to that in T2DM patients without (19.0 ± 4.5% vs. 19.6 ± 5.0%, P = 0.40). Furthermore, multivariate logistic regression analyses showed that GLS was independently associated with RV systolic dysfunction as well as mitral inflow E and mitral e' annular velocities ratio (odds ratio, 1.16; 95% confidence interval: 1.03-1.31; P < 0.05). Sequential logistic models evaluating the association of RV systolic dysfunction in T2DM patients showed an improvement in clinical variables (χ2 = 6.2) with the addition of conventional echocardiographic parameters (χ2 = 13.4, P < 0.001) and a further improvement with the addition of GLS (χ2 = 20.8, P < 0.001). CONCLUSION: RV subclinical systolic dysfunction was observed in T2DM patients with preserved LVEF and was associated with LV longitudinal myocardial dysfunction. Our findings may provide additional findings for the management of T2DM patients.