scholarly journals Genetic Analysis of Right Heart Structure and Function in 40,000 People

2021 ◽  
Author(s):  
James P. Pirruccello ◽  
Paolo Di Achille ◽  
Victor Nauffal ◽  
Mahan Nekoui ◽  
Samuel N. Friedman ◽  
...  

The heart evolved hundreds of millions of years ago. During mammalian evolution, the cardiovascular system developed with complete separation between pulmonary and systemic circulations incorporated into a single pump with chambers dedicated to each circulation. A lower pressure right heart chamber supplies deoxygenated blood to the lungs, while a high pressure left heart chamber supplies oxygenated blood to the rest of the body. Due to the complexity of morphogenic cardiac looping and septation required to form these two chambers, congenital heart diseases often involve maldevelopment of the evolutionarily recent right heart chamber. Additionally, some diseases predominantly affect structures of the right heart, including arrhythmogenic right ventricular cardiomyopathy (ARVC) and pulmonary hypertension. To gain insight into right heart structure and function, we fine-tuned deep learning models to recognize the right atrium, the right ventricle, and the pulmonary artery, and then used those models to measure right heart structures in over 40,000 individuals from the UK Biobank with magnetic resonance imaging. We found associations between these measurements and clinical disease including pulmonary hypertension and dilated cardiomyopathy. We then conducted genome-wide association studies, identifying 104 distinct loci associated with at least one right heart measurement. Several of these loci were found near genes previously linked with congenital heart disease, such as NKX2-5, TBX3, WNT9B, and GATA4. We also observed interesting commonalities and differences in association patterns at genetic loci linked with both right and left ventricular measurements. Finally, we found that a polygenic predictor of right ventricular end systolic volume was associated with incident dilated cardiomyopathy (HR 1.28 per standard deviation; P = 2.4E-10), and remained a significant predictor of disease even after accounting for a left ventricular polygenic score. Harnessing deep learning to perform large-scale cardiac phenotyping, our results yield insights into the genetic and clinical determinants of right heart structure and function.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kanda ◽  
T Nagai ◽  
N Kondou ◽  
K Tateno ◽  
M Hirose ◽  
...  

Abstract Introduction and purpose The number of patients with right heart failure due to pulmonary hypertension has been increasing. Although several drugs have reportedly improved pulmonary hypertension, no treatments have been established for decompensated right heart failure. The heart has an innate ability to regenerate, and cardiac stem or progenitor cells (e.g., side population [SP] cells) have been reported to contribute to the regeneration process. However, their contribution to right ventricular pressure overload has not been clarified. Here, this regeneration process was evaluated using a genetic fate-mapping model. Methods and results We used Cre-LacZ mice, in which more than 99.9% of the cardiomyocytes in the left ventricular field were positive for 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-gal) staining immediately after tamoxifen injection. Then, we performed either a pulmonary binding (PAB) or sham operation on the main pulmonary tract. In the PAB-treated mice, the right ventricular cavity was significantly enlarged (right-to-left ventricular [RV/LV] ratio, 0.24±0.04 in the sham group and 0.68±0.04 in the PAB group). Increased peak flow velocity in the PAB group (1021±80 vs 1351±62 mm/sec) was confirmed by echocardiography. One month after the PAB, the PAB-treated mice had more X-gal-negative (newly generated) cells than the sham mice (94.8±34.2 cells/mm2 vs 23.1±10.5 cells/mm2; p<0.01). The regeneration was biased in the RV free wall (RV free wall, 225.5±198.7 cells/mm2; septal area, 88.9±56.5/mm2; LV lateral area, 46.8±22.0/mm2; p<0.05). To examine the direct effects of PAB on the cardiac progenitor cells, bromodeoxyuridine was administered to the mice daily until 1 week after the PAB operation. Then, the hearts were isolated and SP cells were harvested. The SP cell population increased from 0.65±0.23% in the sham mice to 1.87% ± 1.18% in the PAB-treated mice. Immunostaining analysis revealed a significant increase in the number of BrdU-positive SP cells, from 11.6±2.0% to 44.0±18%, therefore showing SP cell proliferation. Conclusions Pulmonary pressure overload stimulated cardiac stem or progenitor cell-derived regeneration with a RV bias, and SP cell proliferation may partially contribute to this process. Acknowledgement/Funding JSPS KAKENHI Grant Number JP 17K17636, GSK Japan Research Grant 2016


2022 ◽  
Author(s):  
Alexey N. Sumin ◽  
Nina S. Gomozova ◽  
Anna V. Shcheglova ◽  
Oleg G. Arkhipov

Abstract Objective of this study was to compare right ventricular echocardiography parameters in urbanized hypertensive patients of the Shor and non-indigenous ethnic groups in the Mountain Shoria region. Methods The study included patients with arterial hypertension: 58 Shors and 50 non-indigenous urbanized residents, comparable in age, and divided by ethnicity and gender into 4 groups: Shors men (n = 20), Shors women (n = 38), non-indigenous men (n = 15) and non-indigenous women (n = 35). All underwent echocardiographic examination, and the right heart parameters were studied. Results Shor men with arterial hypertension had the lowest values ​​of the pulmonary artery index, the right atrium dimensions, and the highest values ​​of the blood flow velocity in the right ventricle, et' and st' in comparison with non-indigenous men. Shor women have the lowest values Et and Et/At ratios. RV diastolic dysfunction was detected mainly in women, somewhat more often in Shors. Ethnicity was one of the factors associated with the right ventricular diastolic dysfunction presence. Among the factors associated with the RV diastolic dysfunction were risk factors (smoking, obesity), blood pressure, gender, ethnicity, and left ventricular parameters (diastolic dysfunction and the myocardial mass increase). Conclusion Our study established the influence of ethnic differences on the right heart echocardiographic parameters in Shors and Caucasians with arterial hypertension. The revealed differences should improve the assessment of the right heart structure and function in patients with arterial hypertension from small ethnic groups, which will help to improve the diagnosis and treatment of such patients.


2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
B Alushi ◽  
O Bisht ◽  
N Menck ◽  
V Mattea ◽  
Y Primet ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): Helios Clinical Research Institute Background/Introduction Patients with severe tricuspid regurgitation (TR) are characterized from severe dilatation and negative remodeling of the right heart chambers causing functional right ventricular (RV) failure and increased mortality and morbidity. The transcatheter tricuspid edge-to-edge repair (TTVR) is a new treatment option associated with symptom improvement and reduced hospitalization. The cardiac magnetic resonance imaging (CMRI) remains the gold standard for evaluating the right ventricular morphology and function and could be a useful in assessing the RV reverse remodeling after TTVR.  The Tricuspid Regurgitation REgistry (TRuE) is an ongoing national prospective register of patients with severe TR that aims to identify morphofunctional parameters of the right heart chambers related to improve outcomes after TTVR. Purpose The present is a subanalysis of patients with serial CMRI examinations recruited in the ongoing prospective TRuE registry. Methods After excluding patients with intracardiac RV leads, seven patients (age 70 ±12 years) with completed thirty-day follow up were included in the present analysis. Retrospective gated steady state free precession cine images were acquired in the long and short-axis views covering the entirety of both ventricles. Aortic and pulmonary flow data were acquired with a flow-sensitive gradient echo sequence. Assessment of left ventricular (LV) and RV volumes was performed manually in the short-axis cine images (Circle Cardiovascular Imaging, Calgary, Alberta, Canada). The TR fraction was calculated as: ({total RV stroke volume (SV) – total pulmonary forward flow}/total RVSV) × 100. All volumes and flow measurements were indexed for body surface area and expressed in ml/m2. The ratio between the diameter of pulmonary artery (PA) and ascending aorta (AA) was used as indirect measurement of pulmonary arterial hypertension (PAH). CMRI parameters assessing TR quantification, RV morphology and function were analyzed at baseline and follow-up with Fisher´s test or paired t-test. Results At thirty days there was a significant reduction of the TR fraction (45% to 20%, p &lt; 0.001), RV dilatation (RV-end diastolic volume (EDV): 106 ± 12ml/m2 to 86 ± 9.4ml/m2, p = 0.002, RV- end sistolic volume (ESV):55 ± 6.5 to 43 ± 6.6ml, p = 0.003) and improvement of function (RVEF: 47 ± 3.6 to 53 ± 2.4 %, p = 0.006). On the left heart side, there was an improvement of LV filling, with increased LVEDV and LVESV and of the LVSV (36 ± 5.3 to 41 ± 3.7ml/m2, p = 0.040), causing an improvement of the cardiac index (2.2 ± 0.9 l/min/m2 to 2.9 ± 0.7 l/min/m2; p = 0.019. Furthermore, the PA/AA ratio improved significantly (0.91 ± 0.15 to 0.81 ± 0.14, p = 0.006). Conclusion TTVR is associated with positive reverse remodeling of the RV with reduction of dilatation, PAH and function improvement.


2021 ◽  
pp. 204589402110136
Author(s):  
Tailong Zhang ◽  
Weitao Liang ◽  
Longrong Bian ◽  
Zhong Wu

Right heart thrombus (RHT) accompanied by chronic thromboembolic pulmonary hypertension (CTEPH) is a rare entity. RHT may develop in the peripheral veins or in situ within the right heart chambers. The diagnosis of RHT is challenging, since its symptoms are typically non-specific and its imaging features resemble those of cardiac masses. Here, we report two cases of RHT with CTEPH that presented as right ventricular masses initially. Both patients underwent simultaneous pulmonary endarterectomy (PEA) and resection of the ventricular thrombi. Thus, when mass-like features are confirmed by imaging, RHT should be suspected in patients with CTEPH, and simultaneous RHT resection is required along with PEA.


2012 ◽  
Vol 39 (3) ◽  
pp. 685-701 ◽  
Author(s):  
Gautam K. Singh ◽  
Philip T. Levy ◽  
Mark R. Holland ◽  
Aaron Hamvas

2021 ◽  
Author(s):  
Janus Adler Hyldebrandt ◽  
Nikolaj Bøgh ◽  
Camilla Omann Christensen ◽  
Peter Agger

Abstract Background: Pulmonary hypertension is a significant risk factor in patients undergoing surgery. The combined effects of general anaesthesia and positive pressure ventilation can aggravate this condition and cause increased pulmonary blood pressures, reduced systemic blood pressures and ventricular contractility. Although perioperative use of inotropic support or vasopressors is almost mandatory for these patients, preference is disputed. In this study, we investigated the effects of norepinephrine and dobutamine and their ability to improve the arterio-ventricular relationship and haemodynamics in pigs suffering from chronic pulmonary hypertension.Method: Pulmonary hypertension was induced in five pigs by banding the pulmonary artery at 2–3 weeks of age. Six pigs served as controls. After 16 weeks of pulmonary artery banding, the animals were re-examined under general anaesthesia using biventricular conductance catheters and a pulmonary artery catheter. After baseline measurements, the animals were exposed to both norepinephrine and dobutamine infusions in incremental doses, with a stabilizing period in between the infusions. The hypothesis of differences between norepinephrine and dobutamine with incremental doses was tested using repeated two-way ANOVA and Bonferroni multiple comparisons post-test. Results: At baseline, pulmonary artery banded animals had increased right ventricular pressure (+39%, p=0.04), lower cardiac index (-23% p=0.04), lower systolic blood pressure (-13%, p=0.02) and reduced left ventricular end-diastolic volume (-33%, p=0.02). When incremental doses of norepinephrine and dobutamine were administered, the right ventricular arterio-ventricular coupling was improved only by dobutamine (p<0.05). Norepinephrine increased both left ventricular end-diastolic volume and left ventricular contractility to a greater extent (p<0.05) in pulmonary artery banded animals. While the cardiac index was improved equally by norepinephrine and dobutamine treatments in pulmonary artery banded animals, norepinephrine had a significantly greater effect on mean arterial pressure (p<0.05) and diastolic arterial pressure (p<0.05).Conclusion: While norepinephrine and dobutamine improved cardiac index equally, it was obtained in different manners. Dobutamine significantly improved the right ventricular function and the arterio-ventricular coupling. Norepinephrine increased systemic resistance, thereby improving arterial pressures and left ventricular systolic function by maintaining left ventricular end-diastolic volume.


1994 ◽  
Vol 17 (4) ◽  
pp. 224-229 ◽  
Author(s):  
Y. Abe ◽  
K. Kotoh ◽  
P.H. Deleuze ◽  
M. Miyama ◽  
G.J. Cooper ◽  
...  

Changes in the right ventricular function measured with a thermodilution ejection fraction catheter have been recorded in open-chest normal pigs and pigs with acute right heart failure (RVF) undergoing left ventricular assistance with a pneumatic-sactype device (LVAD). To produce acute right heart failure, 5 pigs underwent ligation of the right ventricular free wall coronary arteries. Compared with normal pigs, cardiac output in ligated pigs fell by 21% (7.5 ± 0.5 vs 9.5 ± 1.2 L/min; p < 0.05) and the right ventricular end diastolic pressure rose (11.4 ± 2.6 vs 5.7 ± 3.6 vs mmHg: p <0.05). With the left ventricular assist device connected, the right atrial pressure was increased to 3, 5, 7, 10 and 12 mmHg by volume loading while maintaining the haematocrit at 35 ± 6%. The right ventricular stroke work index (RVSWI) increased with volume loading in normal pigs. In RVF pigs, RVSWI increased significantly with the LVAD (59.2 ± 5.8 vs 23.5 ± 7.8 mmHg ml/min/kg, p<0.01), approaching that of normal pigs (62.3 ± 4.8 mmHg ml/min/kg). Similar changes were observed in the cardiac output and right ventricular stroke volume. These results show that, in this model of open-chest, mild, acute right heart failure, left ventricular assistance allows right ventricular function to return to normal, despite volume overloading, by decreasing right ventricular after load and increasing right ventricular compliance


2019 ◽  
Vol 316 (1) ◽  
pp. H113-H122 ◽  
Author(s):  
Yin Kang ◽  
Sheng Wang ◽  
Jiapeng Huang ◽  
Lu Cai ◽  
Bradley B. Keller

The increasing prevalence of diabetic cardiomyopathy (DCM) is an important threat to health worldwide. While left ventricular (LV) dysfunction in DCM is well recognized, the accurate detection, diagnosis, and treatment of changes in right ventricular (RV) structure and function have not been well characterized. The pathophysiology of RV dysfunction in DCM may share features with LV diastolic and systolic dysfunction, including pathways related to insulin resistance and oxidant injury, although the RV has a unique cellular origin and composition and unique biomechanical properties and is coupled to the lower-impedance pulmonary vascular bed. In this review, we discuss potential mechanisms responsible for RV dysfunction in DCM and review the imaging approaches useful for early detection, protection, and intervention strategies. Additional data are required from animal models and clinical trials to better identify the onset and features of altered RV and pulmonary vascular structure and function during the onset and progression of DCM and to determine the efficacy of early detection and treatment of RV dysfunction on clinical symptoms and outcomes.


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