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The sequence Arg37-Arg38 of tyrosine hydroxylase (TH) is known to play a significant role in the feedback inhibition by the end product DA. To clarify how deeply the sequence Arg37-Arg38 and the phosphorylated Ser40 of human TH type 1 (hTH1) are involved in the regulation of this feedback inhibition in mammalian cells, we generated the following mutants: (i) RR-GG, Arg37-Arg38 replaced by Gly37-Gly38; (ii) RR-EE, Arg37-Arg38 replaced by Glu37-Glu38; (iii) S40D, Ser40 replaced by Asp40; and (iv) S40A, Ser40 replaced by Ala40. In a cell-free system, the level of the DA inhibition of the RR-EE mutant enzyme was to the same or smaller degree than that of the phosphorylation-mimicking S40D. Next, AtT-20 neuroendocrine cells were transfected with wild-type and mutated TH genes because these cells were earlier shown to be capable of fully converting L-3,4-dihydroxyphenylalanine into DA, whereby the catalytic activity of TH would be expected to be inhibited by the end product DA accumulating in the cells. The level of DA accumulation in AtT-20 cells expressing the TH gene was in the order: RR-EE > S40D > S40A = RR-GG > wild-type, which was in accordance with the observations for the cell-free system. These results suggest that the sequence Arg37-Arg38 of hTH1 is a more potent determinant of the efficient production of DA in mammalian cells than is the phosphorylated Ser40-hTH1. [ABSTRACT FROM AUTHOR]

Thallium-201 myocardial scintigraphic studies were performed on 24 patients with chronic right ventricular overload before and after surgical correction of haemodynamic overload. The ages of the patients ranged from 20 to 65 years (mean 39 years) at operation. The degree of right ventricular visualisation remained essentially unchanged in an early postoperative study (four to 60 days), though a decrease in right ventricular cavity size was noted in patients with right ventricular volume overload. On later follow-up (18 to 36 months), thallium uptake in the right ventricle was definitely less than before operation in all 13 patients studied at this time. Because thallium-201 radioactivity reflects myocardial blood flow and mass, our study indicates that right ventricular hypertrophy is largely reversible. Thus, thallium-201 myocardial scintigraphy can be used to assess non-invasively regression of right ventricular hypertrophy in patients with right ventricular overload. [ABSTRACT FROM PUBLISHER]

Coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (FFRCT) provide high diagnostic accuracy for coronary artery disease (CAD), consistent with invasive coronary angiography (ICA), the gold standard diagnostic technique. The presence of calcified components, however, complicates the interpretation of coronary stenosis severity. We present a case where there was a discrepant assessment of coronary stenosis severity between CCTA/FFRCT (indicating significant obstructive CAD) and ICA (showing no apparent obstructive CAD). CCTA/FFRCT revealed that the stenotic lesion, located in the middle segment of the left circumflex artery, was surrounded by plaque components. The proximal and distal portions of the stenotic lesion consisted of 80.9% luminal volume, 0.2% low-attenuation plaque, 13.4% intermediate-attenuation plaque, and 5.5% calcified plaque. In contrast, the stenotic lesion itself contained 50.0% luminal volume, 0.3% low-attenuation plaque, 26.7% intermediate-attenuation plaque, and 22.9% calcified plaque. Invasive coronary angiography showed no apparent obstructive CAD, implying that the lesions appearing as significant obstructive CAD on CCTA/FFRCT were likely overestimated due to the effects of extravascular calcified plaque. Advanced extravascular calcified plaque surrounding the lesion may cause several artifacts (such as blooming and/or beam hardening artifacts) and/or vasodilator dysfunction (either organic and/or functional), potentially leading to an overestimation of the severity of coronary stenosis in CCTA/FFRCT assessments.

Objectives: Computed tomography (CT)-derived fractional flow reserve (FFR CT ) decreases continuously from proximal to distal segments of the vessel due to the influence of various factors even in non-obstructive coronary artery disease (NOCAD). It is known that FFR CT is dependent on vessel-length, but the relationship with other vessel morphologies remains to be explained., Purpose: To investigate morphological aspects of the vessels that influence FFR CT in NOCAD in the right coronary artery (RCA)., Methods: A total of 443 patients who underwent both FFR CT and invasive coronary angiography, with < 50% RCA stenosis, were evaluated. Enrolled RCA vessels were classified into two groups according to distal FFR CT : FFR CT  ≤ 0.80 (n = 60) and FFR CT  > 0.80 (n = 383). Vessel morphology (vessel length, lumen diameter, lumen volume, and plaque volume) and left-ventricular mass were assessed. The ratio of lumen volume and vessel length was defined as V/L ratio., Results: Whereas vessel-length was almost the same between FFR CT  ≤ 0.80 and > 0.80, lumen volume and V/L ratio were significantly lower in FFR CT  ≤ 0.80. Distal FFR CT correlated with plaque-related parameters (low-attenuation plaque, intermediate-attenuation plaque, and calcified plaque) and vessel-related parameters (proximal and distal vessel diameter, vessel length, lumen volume, and V/L ratio). Among all vessel-related parameters, V/L ratio showed the highest correlation with distal FFR CT (r = 0.61, p < 0.0001). Multivariable analysis showed that calcified plaque volume was the strongest predictor of distal FFR CT , followed by V/L ratio (β-coefficient = 0.48, p = 0.03). V/L ratio was the strongest predictor of a distal FFR CT  ≤ 0.80 (cut-off 8.1 mm 3 /mm, AUC 0.88, sensitivity 90.0%, specificity 76.7%, 95% CI 0.84-0.93, p < 0.0001)., Conclusions: Our study suggests that V/L ratio can be a measure to predict subclinical coronary perfusion disturbance., Clinical Relevance Statement: A novel marker of the ratio of lumen volume to vessel length (V/L ratio) is the strongest predictor of a distal CT-derived fractional flow reserve (FFR CT ) and may have the potential to improve the diagnostic accuracy of FFR CT ., Key Points: • Physiological FFR CT decline depends not only on vessel length but also on the lumen volume in non-obstructive coronary artery disease in the right coronary artery. • FFR CT correlates with plaque-related parameters (low-attenuation plaque, intermediate-attenuation plaque, and calcified plaque) and vessel-related parameters (proximal and distal vessel diameter, vessel length, lumen volume, and V/L ratio). • Of vessel-related parameters, V/L ratio is the strongest predictor of a distal FFR CT and an optimal cut-off value of 8.1 mm 3 /mm., (© 2023. The Author(s).)

Background: Coronary computed tomography angiography (CCTA) -derived fractional flow reserve (FFR CT ) is recommended to evaluate the functional consequences of obstructive coronary artery disease (OCAD). Real-world incremental impacts of FFR CT use still remains under debate., Methods: 1601 patients with suspected OCAD on CCTA (>50 ​% stenosis), including 808 (50.5 ​%) patients evaluated by FFR CT , were included from a 2013-2021 registry. Propensity adjusted impacts of FFR CT use on rates of invasive coronary angiography (ICA), myocardial revascularization (MR) and post MR major adverse cardiac events (MACE) were reported, including a sensitivity analysis in severe OCAD (>70 ​% stenosis) (n ​= ​450). Accuracy of numerical and comprehensive FFR CT interpretations in selection of patients requiring a MR were also compared., Results: 1160 (72,5 ​%) ICA, 559 (34.9 ​%) MR and 137 (24.5 ​%) post MR MACE occurred at 4.7 ​± ​1.9 years. FFR CT use was independently associated with decreased rate of ICA and MR (OR: 0.66; 95 ​% CI 0.53-0.83, p ​< ​0.001 and OR: 0.71; 95 ​% CI 0.58-0.88, p ​< ​0.01, respectively). Compared to the numerical interpretation, the FFR CT comprehensive assessment increased the ratio of MR per ICA (61.7 ​% vs 50.1 ​%, p ​< ​0.01) and was more accurate in selection of patients requiring MR. FFR CT reduced post MR MACE (OR: 0.64; 95 ​% CI 0.43-0.96, p ​< ​0.05). All these associations were no longer observed in severe OCAD., Conclusion: Implementing FFR CT in OCAD patients reduces ICA use, improves selection of patients requiring MR and reduces post MR MACE. However, these incremental values of FFRCT were no longer observed in severe OCAD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: The ramus artery contributes to the development of turbulence, which may influence computed tomography (CT) derived fractional flow reserve (FFR CT ) even without coronary artery disease (CAD). The relationship between ramus-induced turbulence and FFR CT is unclear., Method and Results: A total of 120 patients with <20% coronary stenosis assessed by both FFR CT and invasive coronary angiography were evaluated. The patients were divided into three groups: absent-ramus (n = 72), small-ramus that could not be analyzed by FFR CT (n = 18), and large-ramus that could be analyzed by FFR CT (n = 30). FFR CT measurements were performed at the proximal and distal segments of the left anterior descending (LAD), left circumflex (LCX), and ramus artery. With absent-ramus and small-absent ramus groups, FFR CT was measured at the distal end of the left main trunk at the same level for the proximal segments of the LAD and LCX. In absent-ramus group, proximal FFR CT showed no significant differences between three vessels (LAD = .96 ± .02; MID = .97 ± .02; LCX = .97 ± .02). However, in small and large-ramus groups, proximal FFR CT was significantly higher in the ramus artery than LAD and LCX (small-ramus, LAD = .95 ± .03, Ramus = .97 ± .02, LCX = .95 ± .03; large-ramus: LAD = .95 ± .03, Ramus = .98 ± .01; LCX = .96 ± .03; p < .05). A large ramus was associated with a higher prevalence of a distal FFR CT ≤.80 (odds ratio 7.0, 95% CI 1.2-40.1, p = .03). A proximal ramus diameter predicted distal FFR CT ≤.80 (cut-off 2.1 mm, AUC .76, sensitivity 100%, specificity 52%, 95% CI .61-.90)., Conclusions: The presence of a large-ramus artery may cause an FFR CT decline in no apparent CAD., (© 2022 Wiley Periodicals LLC.)

Objectives: Computed tomography (CT) derived fractional flow reserve (FFR CT ) decreases from the proximal to the distal part due to a variety of factors. The energy loss due to the bifurcation angle may potentially contribute to a progressive decline in FFR CT . However, the association of the bifurcation angle with FFR CT is still not entirely understood. This study aimed to investigate the impact of various bifurcation angles on FFR CT decline below the clinically crucial relevance of 0.80 in vessels with no apparent coronary artery disease (CAD)., Methods: A total of 83 patients who underwent both CT angiography including FFR CT and invasive coronary angiography, exhibiting no apparent CAD were evaluated. ΔFFR CT was defined as the change in FFR CT from the proximal to the distal in the left anterior descending artery (LAD) and left circumflex artery (LCX). The bifurcation angle was calculated from three-dimensional volume rendered images. Vessel morphology and plaque characteristics were also assessed., Results: ΔFFR CT significantly correlated with the bifurcation angle (LAD angle, r = 0.35, p = 0.001; LCX angle, r = 0.26, p = 0.02) and vessel length (LAD angle, r = 0.30, p = 0.005; LCX angle, r = 0.49, p < 0.0001). In LAD, vessel length was the strongest predictor for distal FFR CT of ≤ 0.80 (β-coefficient = 0.55, p = 0.0003), immediately followed by the bifurcation angle (β-coefficient = 0.24, p = 0.02). The bifurcation angle was a good predictor for a distal FFR CT ≤ 0.80 (LAD angle, cut-off 31.0°, AUC 0.70, sensitivity 74%, specificity 68%; LCX angle, cut-off 52.6°, AUC 0.86, sensitivity 88%, specificity 85%)., Conclusions: In vessels with no apparent CAD, vessel length was the most influential factor on FFR CT , directly followed by the bifurcation angle., Key Points: • Both LAD and LCX bifurcation angles are factors influencing FFR CT . • Bifurcation angle is one of the predictors of a distal FFR CT of ≤ 0.80 and an optimal cut-off value of 31.0° for the LAD and 52.6° for the LCX. • Bifurcation angle should be taken into consideration when interpreting numerical values of FFR CT ., (© 2022. The Author(s).)

Background: In significant obstructive coronary artery disease (SOCAD), a mismatch in assessment of severity of coronary artery stenosis may occur between invasive coronary angiography (ICA) and computed tomography (CT) derived fractional flow reserve (FFR CT ). The present study aimed to identify the factors giving an FFR CT  > 0.80 and leading to an underestimation of coronary artery severity in SOCAD vessels., Methods: A total of 141 consecutive patients who underwent both CT angiography including FFR CT and ICA, the latter showing >75% coronary artery stenosis were evaluated. Vessels were divided into two groups according to FFR CT at the distal aspect of the vessel: FFR CT  > 0.80 (n = 12) and FFR CT  ≤ 0.80 (n = 153). Vessel morphology, plaque characteristics, left-ventricular (LV) wall thickness at each site of the myocardium, and LV mass were also assessed., Results: LV myocardium-related parameters including LV wall thickness (base, middle, apex, average, and maximal), LV mass, and LV mass index were higher in FFR CT  > 0.80, whereas vessel-related parameters including, vessel morphology and plaque characteristics were not significantly different between >0.80 and < 0.80. Vessel morphology and plaque characteristics had no effect on FFR CT , whereas maximum LV wall thickness, LV mass, and LV mass index influenced FFR CT . LV mass index was the strongest predictor of distal FFR CT  > 0.80 with an area under the curve of 0.81, and an optimal cut-off value of 66.5 g/m 2 (sensitivity 77.8%, specificity 89.6%)., Conclusions: The presence of a high LV mass is a major cause for underestimation of coronary artery severity on FFR CT in SOCAD vessels. LV myocardium-related parameters should be considered when interpreting numerical values of FFR CT ., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Computed-tomography (CT) derived fractional-flow-reserve (FFR CT ) gradually may decrease from proximal to distal vessels even without apparent coronary artery disease (CAD). It may be unclear whether the decrease in FFR CT at the distal coronal artery is physiological or due to stenosis. We decided to study predictive factors of an FFR CT decline below the pathological value of 0.80 in no-apparent CAD., Methods: A total of 150 consecutive patients who had both CT angiography coupled to FFR CT analysis and invasive angiogram showing < 20% coronary stenosis were included. Vessels were divided into two groups according to FFR CT at the distal vessel: FFR CT  > 0.80 (n = 317) and FFR CT  ≤ 0.80 (n = 114). ΔFFR CT was defined as the change in FFR CT from proximal to distal vessel. Vessel morphology (vessel length and lumen volume) and plaque characteristics [low-attenuation plaque volume, intermediate-attenuation (IAP) plaque volume, and calcified plaque volume] were evaluated., Results: FFR CT decreased from proximal to distal for the three major vessels in both FFR CT  > 0.80 and FFR CT  ≤ 0.80. Compared to FFR CT  > 0.80, IAP volume was significantly higher in all three major vessels in FFR CT  ≤ 0.80. ΔFFR CT was correlated with vessel length and lumen volume in FFR CT  > 0.80, whereas ΔFFR CT was correlated with IAP volume in FFR CT  ≤ 0.80. IAP volume above 44.8 mm 3 was the strongest predictor of distal FFR CT of ≤ 0.80., Conclusions: The presence of IAP is a major predictor of gradual decrease of FFR CT below 0.80 in no-apparent CAD vessels. Vessel morphology and plaque characteristics should be considered when interpreting FFR CT ., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: The aim of this study was (a) to clarify the detailed mechanisms of structural and functional abnormalities of myocardial tissue in hypertrophic cardiomyopathy (HCM) using layer-specific strain (LSS) and compare it with healthy subjects (b) to investigate the diagnostic accuracy of LSS for HCM., Methods and Results: Forty-one patients with HCM and preserved left ventricular ejection fraction (LVEF; 66% male, 52 ± 18 years, LVEF 62.9% ± 3.7%) and 41 controls matched for age and sex (66% male, 52 ± 20 years, LVEF 63.5% ± 8.2%) underwent 2D-speckle tracking echocardiography. Absolute values of LSS were globally lower and the ratio of endocardial/epicardial layer (End/Epi ratio) was higher in HCM. LSS gradually increased from the epicardial toward the endocardial layer at all chamber views and at all levels of the LV. LSS and End/Epi ratio at the apex were higher than those at the middle or basal level of the LV. End/Epi ratio was correlated with LV maximal wall thickness both controls (r = .35, P = .03) and HCM (r = .81, P < .001). End/Epi ratio was an independent factor associated with LV maximal wall thickness (β = 0.96, P < .001). A higher End/Epi ratio (≥1.31) was associated with diagnostic criteria for HCM (sensitivity 98%, specificity 95%, area under the curve 0.99, P < .001)., Conclusion: LSS has the potential for unraveling the mechanism of impaired LV wall motion in HCM and to accurately detect HCM., (© 2021 Wiley Periodicals LLC.)

Aims: Balloon pulmonary angioplasty (BPA) improves hemodynamics and exercise tolerance in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, its diagnostic and predictive values remain unclear. We investigated the diagnostic and predictive values of BPA by assessing the mechanism of right ventricular (RV) dysfunction., Methods and Results: Hemodynamic improvement was maintained over 6 months in 99 patients with CTEPH who underwent BPA. Notably, 57 of 99 patients showed normalization of pulmonary vascular resistance (PVR) after BPA. The RV mid free wall longitudinal strain (RVMFS) was inversely correlated with the 6-min walk distance (r = -.35, P = .01) and serum levels of high-sensitivity cardiac troponin T (hs-cTNT) (r = -.39, P = .004) 6 months post-BPA in the PVR-normalized group. Among all variables analyzed, only the pre-BPA RVMFS was correlated with the post-BPA RVMFS (r = .40, P = .001), and the pre-BPA RVMFS (<-15.8%) was the strongest predictor of post-BPA normalization of RVMFS (area under the curve 0.80, P = .01, sensitivity 89%, and specificity 63%). The immediate post-BPA RVMFS showed worsening over 6 months after the procedure (-25.8% to -21.1%) in patients with high serum hs-cTNT levels (>0.0014 ng/mL). In contrast, we observed an improvement in these values in those with low serum hs-cTNT levels (-23.6% to -24.4%)., Conclusion: RVMFS of -15.8% may be a useful cutoff value to categorize the refractory and non-refractory stages of disease. Sustained serum hs-cTNT elevation post-BPA indicates subclinical RV myocardial injury, with resultant RVMFS deterioration and poor exercise tolerance., (© 2020 Wiley Periodicals LLC.)

Aims: To obtain the normal range for 2D echocardiographic (2DE) measurements of left ventricular (LV) layer-specific strain from a large group of healthy volunteers of both genders over a wide range of ages., Methods and Results: A total of 287 (109 men, mean age: 46 ± 14 years) healthy subjects were enrolled at 22 collaborating institutions of the EACVI Normal Reference Ranges for Echocardiography (NORRE) study. Layer-specific strain was analysed from the apical two-, three-, and four-chamber views using 2DE software. The lowest values of layer-specific strain calculated as ±1.96 standard deviations from the mean were -15.0% in men and -15.6% in women for epicardial strain, -16.8% and -17.7% for mid-myocardial strain, and -18.7% and -19.9% for endocardial strain, respectively. Basal-epicardial and mid-myocardial strain decreased with age in women (epicardial; P = 0.008, mid-myocardial; P = 0.003) and correlated with age (epicardial; r = -0.20, P = 0.007, mid-myocardial; r = -0.21, P = 0.006, endocardial; r = -0.23, P = 0.002), whereas apical-epicardial, mid-myocardial strain increased with the age in women (epicardial; P = 0.006, mid-myocardial; P = 0.03) and correlated with age (epicardial; r = 0.16, P = 0.04). End/Epi ratio at the apex was higher than at the middle and basal levels of LV in men (apex; 1.6 ± 0.2, middle; 1.2 ± 0.1, base 1.1 ± 0.1) and women (apex; 1.6 ± 0.1, middle; 1.1 ± 0.1, base 1.2 ± 0.1)., Conclusion: The NORRE study provides useful 2DE reference ranges for novel indices of layer-specific strain., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: The present study sought to evaluate the correlation between indices of non-invasive myocardial work (MW) and left ventricle (LV) size, traditional and advanced parameters of LV systolic and diastolic function by 2D echocardiography (2DE)., Methods and Results: A total of 226 (85 men, mean age: 45 ± 13 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. Global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE) were estimated from LV pressure-strain loops using custom software. Peak LV pressure was estimated non-invasively from brachial artery cuff pressure. LV size, parameters of systolic and diastolic function and ventricular-arterial coupling were measured by echocardiography. As advanced indices of myocardial performance, global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained. On multivariable analysis, GWI was significantly correlated with GLS (standardized beta-coefficient = -0.23, P < 0.001), ejection fraction (EF) (standardized beta-coefficient = 0.15, P = 0.02), systolic blood pressure (SBP) (standardized beta-coefficient = 0.56, P < 0.001) and GRS (standardized beta-coefficient = 0.19, P = 0.004), while GCW was correlated with GLS (standardized beta-coefficient = -0.55, P < 0.001), SBP (standardized beta-coefficient = 0.71, P < 0.001), GRS (standardized beta-coefficient = 0.11, P = 0.02), and GCS (standardized beta-coefficient = -0.10, P = 0.01). GWE was directly correlated with EF and inversely correlated with Tei index (standardized beta-coefficient = 0.18, P = 0.009 and standardized beta-coefficient = -0.20, P = 0.004, respectively), the opposite occurred for GWW (standardized beta-coefficient =--0.14, P = 0.03 and standardized beta-coefficient = 0.17, P = 0.01, respectively)., Conclusion: The non-invasive MW indices show a good correlation with traditional 2DE parameters of myocardial systolic function and myocardial strain., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: The present study sought to assess the impact of aortic stenosis (AS) on myocardial function as assessed by layer-specific longitudinal strain (LS) and its relationship with symptoms and outcome., Methods and Results: We compared 211 patients (56% males, mean age 73 ± 12 years) with severe AS and left ventricular ejection fraction (LVEF) ≥50% (114 symptomatic, 97 asymptomatic) with 50 controls matched for age and sex. LS was assessed from endocardium, mid-myocardium, and epicardium by 2D speckle-tracking echocardiography. Despite similar LVEF, multilayer strain values were significantly lower in symptomatic patients, compared to asymptomatic and controls [global LS: 17.9 ± 3.4 vs. 19.1 ± 3.1 vs. 20.7 ± 2.1%; endocardial LS: 20.1 ± 4.9 vs. 21.7 ± 4.2 vs. 23.4 ± 2.5%; epicardial LS: 15.8 ± 3.1 vs. 16.8 ± 2.8 vs. 18.3 ± 1.8%; P < 0.001 for all]. On multivariable logistic regression analysis, endocardial LS was independently associated to symptoms (P = 0.012), together with indexed left atrial volume (P = 0.006) and LV concentric remodelling (P = 0.044). During a mean follow-up of 22 months, 33 patients died of a cardiovascular event. On multivariable Cox-regression analysis, age (P = 0.029), brain natriuretic peptide values (P = 0.003), LV mass index (P = 0.0065), LV end-systolic volume (P = 0.012), and endocardial LS (P = 0.0057) emerged as independently associated with cardiovascular death. The best endocardial LS values associated with outcome was 20.6% (sensitivity 70%, specificity 52%, area under the curve = 0.626, P = 0.022). Endocardial LS (19.1 ± 3.3 vs. 20.7 ± 3.3, P = 0.02) but not epicardial LS (15.2 ± 2.8 vs. 15.9 ± 2.5, P = 0.104) also predicted the outcome in patients who were initially asymptomatic., Conclusion: In patients with severe AS, LS impairment involves all myocardial layers and is more prominent in the advanced phases of the disease, when the symptoms occur. In this setting, the endocardial LS is independently associated with symptoms and patient outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: This article will review the current guidelines for therapeutic intervention in (pulmonary hypertension) PH related to left heart disease (PH-LHD)., Recent Findings: The 6th World Symposium on Pulmonary Hypertension (WSPH) recommended that the mean pulmonary artery pressure (mPAP) should be lowered to 20 mmHg. In several randomized controlled trials performed in patients with PH-LHD, pulmonary arterial hypertension (PAH)-specific drug therapy demonstrated no evidence of beneficial effects. Furthermore, in the sildenafil for improving outcomes after valvular correction (SIOVAC) trial, the use of sildenafil in the context of PH post-valvular heart disease (VHD) intervention is associated with an increased risk of clinical deterioration and death. Therefore, medical therapy such as PAH-specific drugs is still not recommended in PH-LHD. The principle of PH-LHD therapy is the treatment of underlying VHD. It is crucial to undergo surgical intervention at an appropriate time prior the development of potentially irreversible PH. Stress echocardiography (SE) is helpful to define symptoms and can be useful to assess the systolic pulmonary artery pressure (SPAP) and stratify severity of VHD. This comprehensive review of the literature highlights the role of SE imaging to assess VHD and is needed for the asymptomatic patients with severe VHD or symptomatic patients with non-severe VHD in the context of PH-LHD. The focus of patient evaluation should be on identifying patients with significant underlying valvular heart disease and referring in a timely manner for VHD treatment per society guidelines as pharmacologic pulmonary vasodilator therapy for PH-LHD has not shown efficacy as seen in other forms of PH.

Takotsubo cardiomyopathy (TC) is characterized by transient wall motion abnormalities most commonly involving the left ventricle (LV). Although biventricular TC had been considered uncommon condition, recently biventricular TC has been reported as a new variant observed in 19-42% of all TC presentations. Since biventricular TC has a poor prognosis as compared with isolated TC, it is important to distinguish between isolated LV TC and biventricular TC. We present a case of 70-year-old female with dyspnea persisting for 2 days. Electrocardiogram showed symmetrical T-wave inversion in leads V2-V4. Transthoracic echocardiography (TTE) revealed diffuse hypo-kinesis except for the apical inferior LV and LV ejection fraction of 32%. Hyper-kinesis of the right ventricular (RV) basal segment and dys-kinesis of the RV apical segment. 2 weeks after admission, coronary angiography showed no evidence of significant stenosis. LV ejection fraction improved to 51% and wall motion abnormalities of the RV basal and apical segments were ameliorated to normo-kinesis. Electrocardiogram revealed symmetrical and deepened T-wave inversion in leads V2-V3. The presence of a transient abnormality in biventricular wall motion beyond a single coronary artery perfusion territory with new electrocardiographic change met the diagnostic criteria of definite TC defined by Mayo Clinic criteria. 4 weeks after admission, no recurrence of wall motion abnormalities in both ventricles were found and T-wave inversion ameliorated. To our knowledge, this is the first report of biventricular TC with asymmetrical abnormities of wall motion between LV and RV.

The aortic valve (AV) is the most commonly affected site in multiple papillary fibroelastomas, but the frequency of embolism caused by the attachment side of the AV has not been elucidated. According to the review of the previous literature, 16 cases have been found attached to the AV. Of these, 6 of these have been found to be attached on the aortic side and 4 on the left ventricular side, 1 was bilateral, and 5 cases were unknown. Of the cases found on the aortic side, embolism occurred in 3 of them, and of the left ventricular side cases, embolism occurred in 2 of them. The frequency of embolism is equivalent even if papillary fibroelastoma attached to either side of the AV., (© 2019 Wiley Periodicals, Inc.)

Abiraterone is an agent effective for castration-resistant prostate cancer, but there have been no reports of cardiotoxic effects inducing cardiomyopathy, to our knowledge. We present a case of an 86-year-old man with castration-resistant prostate cancer treated with abiraterone. He had received an androgen receptor antagonist (bicalutamide) and a gonadotropin-releasing hormone antagonist (degarelix) for 3 years. These agents were changed to enzalutamide due to elevation of plasma prostate-specific antigen level of 129 ng/mL. One year later, the oral androgen receptor inhibitor (enzalutamide) caused drug-induced lung injury and was changed to abiraterone. Transthoracic echocardiography (TTE) revealed normal left ventricular systolic function, and left ventricular ejection fraction (LVEF) was 67%. Four weeks after administration of abiraterone, he complained of dyspnea on effort and bilateral leg edema, and he was diagnosed with heart failure. TTE showed hypokinesis of the diffuse LV, and LVEF decreased to 45%. The various causes of heart failure were excluded. Since a cardiotoxic effect of abiraterone was suspected, administration of abiraterone was discontinued. Two weeks after cessation of abiraterone, LVEF ameliorated to 57%, and then 5 months after cessation of abiraterone, LVEF further improved to 65%. To our knowledge, this is the first report of definite cancer therapeutics-related cardiac dysfunction due to a hormonal agent such as abiraterone diagnosed according to the American Society of Echocardiography and European Association of Cardiovascular Imaging criteria.

Balloon pulmonary angioplasty (BPA) has emerged as an effective treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Renal function has been identified as a prognostic marker in patients with pulmonary hypertension in previous studies. We, therefore, aimed to investigate the clinical parameters associated with improvements in renal function in patients with CTEPH. A total of 45 consecutive patients with inoperable CTEPH undergoing BPA (mean age 62.2 ± 15.1 years) were included in the study. We evaluated the patients' clinical characteristics at baseline and at 1-year post-BPA, and investigated the association between renal function and hemodynamic parameters, including right heart function. Hemodynamics and renal function showed sustained improvements at 1 year after BPA in 64.4% of patients. Improved estimated glomerular filtration rate (eGFR) was significantly correlated with increased cardiac index (r = 0.433, p = 0.003) and mixed venous oxygen saturation (SvO 2 ; r = 0.459, p = 0.002), and with decreased mean pulmonary arterial pressure (r = - 0.420, p = 0.004) and pulmonary vascular resistance (r = -- 0.465, p = 0.001). Multivariate analysis revealed that an increase in SvO 2 immediately after the final BPA was associated with improved eGFR after the 1st year (odds ratio 1.041; 95% confidence interval 1.004-1.078; P = 0.027). The cut-off value for predicting improved eGFR was an increase in SvO 2 after the final BPA of >125.4% over the baseline value (specificity 100%, sensitivity 24.1%). In conclusion, BPA improved symptoms, right heart function, hemodynamics, and renal function up to the chronic phase. Increasing SvO 2 by >125.4% above baseline in the acute phase is important for improving renal function at 1 year after BPA in CTEPH patients.

Quadricuspid aortic valve has been classified based on leaflet size. However, no association is seen between classification and severity of aortic regurgitation (AR). Bicuspid aortic valve is classified according to the number of cusps, with significantly higher prevalence of AR in cases with a raphe. We classified cases according to raphe number. In 1 patient with no raphe, AR severity did not change into the eighth decade. However, AR severity worsened in patients with a raphe, in 1 case requiring aortic valve replacement in the fifth decade. Unequal shear stress may lead to leaflet fibrosis and progressive AR., (© 2019 Wiley Periodicals, Inc.)

Background: There is no consensus on the length of hospital stay (LOHS) and post-interventional management after balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We examined temporal trends with respect to LOHS and requirement for intensive care for BPA and their relationship with the incidence of BPA-related complications., Methods: From November 2012 to September 2017, a total of 123 consecutive patients with CTEPH who underwent BPA were enrolled (age: 66.0 [54.0 to 74.0], World Health Organization [WHO] functional class II/III/IV; 27/88/8). Patients were divided for analysis into 3 groups according to the date of their first BPA: early-, middle-, and late-phase groups., Results: Mean pulmonary arterial pressure decreased from 36.0 (29.0 to 45.0) to 20.0 (16.0 to 22.0) mm Hg after BPA (P < 0.001). The LOHS was 41.0 (31.0 to 54.0) days in total including all sessions and 6.6 (6.0 to 7.9) days/session. Despite no significant differences in age, baseline hemodynamics, and laboratory data among the 3 groups, there was a significant reduction in LOHS (7.9 [7.0 to 9.5], 6.5 [6.1 to 7.3], 6.0 [5.3 to 6.5] days/session, P < 0.001) and use of intensive/high care unit (100%, 93%, 46%, P < 0.001). The reduction in LOHS and intensive/high care unit use did not affect the occurrence of BPA-related complications., Conclusions: Increasing experience with BPA was associated with a reduction in LOHS and the use of intensive/high care unit, but no change was noted in the rate of BPA-related complications. These findings suggest that the reduction in both LOHS and use of the intensive care unit for BPA is feasible and does not jeopardize the safety of the procedure., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

To our knowledge, only 15 cases of delayed traumatic hemopericardium resulting from non-penetrating chest trauma have been reported. We present the case of a 63-year-old man with delayed hemopericardium, 2 months after striking the anterior chest on a mailbox when he fell down three steps during a postal delivery. Our case and review of the previously reported cases suggest that some cases might show quite slow progression of blood accumulation. Therefore, careful observation of patients who have experienced blunt trauma of the anterior chest is necessary.

Chronic thromboembolic pulmonary hypertension (CTEPH) has a poor prognosis because of the associated progressive right heart failure. Accurate evaluation of right ventricular (RV) function would thus be useful to predict prognosis. However, the significance of RV diastolic function remains unclear. We aimed to identify which echocardiographic measures are most accurate, and potentially useful, in assessing RV diastolic function in patients with CTEPH, and to study the effects of balloon pulmonary angioplasty (BPA) on them. We enrolled 53 CTEPH patients who underwent BPA. Echocardiographic parameters, including two-dimensional speckle-tracking echocardiography, were compared to the hemodynamic parameters measured by right heart catheterization before and after BPA. RV strain rate during early diastole (SR&#95;E), tricuspid e' and right atrial area (RAA) were ameliorated after BPA, concomitant with a decrease in the time constant of the RV pressure curve during diastole (tau), indicating the improvement of RV diastolic function. Among them, SR&#95;E had the strongest correlation with tau (r = - 0.39, p < 0.001). Furthermore, the receiver operating characteristic analyses revealed that E/SR&#95;E (AUC 0.704) and inferior vena cava diameter (AUC 0.726) had a stronger association with higher mean right atrial pressure than RAA (AUC 0.632). In contrast, RAA had a stronger correlation with 6 min-walk distances than SR&#95;E (r = - 0.39, p < 0.001 vs. r = 0.30, p = 0.005). Taken together, echocardiographic assessment of RV diastolic function might be associated with hemodynamics as well as exercise tolerance in patients with CTEPH, indicating its benefits in evaluating the therapeutic effects of BPA.