Abnormal cardiac inflow patterns during postnatal development in a mouse model of Holt-Oram syndrome

Tbx5 del/+ mice provide a model of human Holt-Oram syndrome. In this study, the cardiac functional phenotypes of this mouse model were investigated with 30-MHz ultrasound by comparing 12 Tbx5 del/+ mice with 12 wild-type littermates at 1, 2, 4, and 8 wk of age. Cardiac dimensions were measured with two-dimensional and M-mode imaging. The flow patterns in the left and right ventricular inflow channels were evaluated with Doppler flow sampling. Compared with wild-type littermates, Tbx5 del/+ mice showed significant changes in the mitral flow pattern, including decreased peak velocity of the left ventricular (LV) early filling wave (E wave), increased peak velocity of the late filling wave (A wave), and decreased or even reversed peak E-to-A ratio. The prolongation of LV isovolumic relaxation time was detected in Tbx5 del/+ neonates as early as 1 wk of age. In Tbx5 del/+ mice, LV wall thickness appeared normal but LV chamber dimension was significantly reduced. LV systolic function did not differ from that in wild-type littermates. In contrast, the Doppler flow spectrum in the enlarged tricuspid orifice of Tbx5 del/+ mice demonstrated increased peak velocities of both E and A waves and increased total time-velocity integral but unchanged peak E/A. In another 13 mice (7 Tbx5 del/+, 6 wild-type) at 2 wk of age, significant correlation was found between Tbx5 gene expression level in ventricular myocardium and LV filling parameters. In conclusion, the LV diastolic function of Tbx5 del/+ mice is significantly deteriorated, whereas the systolic function remains normal.

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Acute recoordination rather than functional hemodynamic improvement determines reverse remodelling by cardiac resynchronisation therapy

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-021-02174-7 ◽

2021 ◽

Author(s):

Philippe C. Wouters ◽

Geert E. Leenders ◽

Maarten J. Cramer ◽

Mathias Meine ◽

Frits W. Prinzen ◽

...

Keyword(s):

Systolic Function ◽

Cardiac Resynchronisation Therapy ◽

Left Ventricular ◽

Lv Function ◽

Peak Strain ◽

Cardiac Resynchronisation ◽

Reverse Remodelling ◽

Resynchronisation Therapy ◽

Lv Systolic Function

AbstractPurpose: Cardiac resynchronisation therapy (CRT) improves left ventricular (LV) function acutely, with further improvements and reverse remodelling during chronic CRT. The current study investigated the relation between acute improvement of LV systolic function, acute mechanical recoordination, and long-term reverse remodelling after CRT. Methods: In 35 patients, LV speckle tracking longitudinal strain, LV volumes & ejection fraction (LVEF) were assessed by echocardiography before, acutely within three days, and 6 months after CRT. A subgroup of 25 patients underwent invasive assessment of the maximal rate of LV pressure rise (dP/dtmax,) during CRT-implantation. The acute change in dP/dtmax, LVEF, systolic discoordination (internal stretch fraction [ISF] and LV systolic rebound stretch [SRSlv]) and systolic dyssynchrony (standard deviation of peak strain times [2DS-SD18]) was studied, and their association with long-term reverse remodelling were determined. Results: CRT induced acute and ongoing recoordination (ISF from 45 ± 18 to 27 ± 11 and 23 ± 12%, p < 0.001; SRS from 2.27 ± 1.33 to 0.74 ± 0.50 and 0.71 ± 0.43%, p < 0.001) and improved LV function (dP/dtmax 668 ± 185 vs. 817 ± 198 mmHg/s, p < 0.001; stroke volume 46 ± 15 vs. 54 ± 20 and 52 ± 16 ml; LVEF 19 ± 7 vs. 23 ± 8 and 27 ± 10%, p < 0.001). Acute recoordination related to reverse remodelling (r = 0.601 and r = 0.765 for ISF & SRSlv, respectively, p < 0.001). Acute functional improvements of LV systolic function however, neither related to reverse remodelling nor to the extent of acute recoordination. Conclusion: Long-term reverse remodelling after CRT is likely determined by (acute) recoordination rather than by acute hemodynamic improvements. Discoordination may therefore be a more important CRT-substrate that can be assessed and, acutely restored.

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Intracoronary Injection of Autologous CD34+ Cells Improves One-Year Left Ventricular Systolic Function in Patients with Diffuse Coronary Artery Disease and Preserved Cardiac Performance—A Randomized, Open-Label, Controlled Phase II Clinical Trial

Journal of Clinical Medicine ◽

10.3390/jcm9041043 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1043 ◽

Cited By ~ 2

Author(s):

Pei-Hsun Sung ◽

Yi-Chen Li ◽

Mel S. Lee ◽

Hao-Yi Hsiao ◽

Ming-Chun Ma ◽

...

Keyword(s):

Systolic Function ◽

Coronary Intervention ◽

Left Ventricular ◽

Diffuse Coronary Artery Disease ◽

Cd34 Cells ◽

Group 2 ◽

Artery Disease ◽

One Year ◽

Lv Systolic Function ◽

Group 1

This phase II randomized controlled trial tested whether intracoronary autologous CD34+ cell therapy could further improve left ventricular (LV) systolic function in patients with diffuse coronary artery disease (CAD) with relatively preserved LV ejection fraction (defined as LVEF >40%) unsuitable for coronary intervention. Between December 2013 and November 2017, 60 consecutive patients were randomly allocated into group 1 (CD34+ cells, 3.0 × 107/vessel/n = 30) and group 2 (optimal medical therapy; n = 30). All patients were followed for one year, and preclinical and clinical parameters were compared between two groups. Three-dimensional echocardiography demonstrated no significant difference in LVEF between groups 1 and 2 (54.9% vs. 51.0%, respectively, p = 0.295) at 12 months. However, compared with baseline, 12-month LVEF was significantly increased in group 1 (p < 0.001) but not in group 2 (p = 0.297). From baseline, there were gradual increases in LVEF in group 1 compared to those in group 2 at 1-month, 3-months, 6-months and 12 months (+1.6%, +2.2%, +2.9% and +4.6% in the group 1 vs. −1.6%, −1.5%, −1.4% and −0.9% in the group 2; all p < 0.05). Additionally, one-year angiogenesis (2.8 ± 0.9 vs. 1.3 ± 1.1), angina (0.4 ± 0.8 vs. 1.8 ± 0.9) and HF (0.7 ± 0.8 vs. 1.8 ± 0.6) scores were significantly improved in group 1 compared to those in group 2 (all p < 0.001). In conclusion, autologous CD34+ cell therapy gradually and effectively improved LV systolic function in patients with diffuse CAD and preserved LVEF who were non-candidates for coronary intervention (Trial registration: ISRCTN26002902 on the website of ISRCTN registry).

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Abstract 14432: Myocardial Work in Stage I and II Hypertensive Patients

Circulation ◽

10.1161/circ.142.suppl_3.14432 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Akshar Jaglan ◽

Sarah Roemer ◽

Ana C Perez Moreno ◽

Bijoy K Khandheria

Keyword(s):

Systolic Function ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Deformation Analysis ◽

Hypertensive Patients ◽

Reduced Ejection Fraction ◽

Work Index ◽

Significant Difference ◽

Global Work ◽

Lv Systolic Function

Introduction: Myocardial work is a novel parameter that can be used in a clinic setting to assess left ventricular (LV) pressures and deformation. This study sought to distinguish patterns of global myocardial work index in hypertensive vs. non-hypertensive patients. Methods: Fifty (25 male, mean age 60±14 years) hypertensive patients and 15 (7 male, mean age 38±12 years) control patients underwent transthoracic echocardiography at rest. Hypertensive patients were divided into stage 1 (26 patients) and stage 2 (24 patients) based on the 2017 American College of Cardiology guidelines. We excluded patients with suboptimal image quality for myocardial deformation analysis, reduced ejection fraction (EF), valvular heart disease, and arrhythmia. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were estimated from LV pressure strain loops utilizing proprietary software from speckle-tracking echocardiography. LV systolic and diastolic pressures were estimated using a noninvasive brachial artery cuff. Results: Global longitudinal strain (GLS) and EF were preserved between the two groups with no statistically significant difference whereas there was a statistically significant difference in the GWI (p<0.01), GCW (p=0.03), GWW (p<0.01), and GWE (p=0.03) (Figure and Table). Conclusions: Myocardial work gives us a closer look at the relationship between LV pressure and contractility in settings of increased load dependency whereas LVEF and GLS cannot. We show how myocardial work is an advanced assessment of LV systolic function in hypertensive patients.

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Abstract 16485: The Nitroxyl Donor 1-Nitrosocyclohexyl Acetate Limits Cardiac Superoxide Upregulation and Diastolic Dysfunction in a Mouse Model of Diabetic Cardiomyopathy

Circulation ◽

10.1161/circ.130.suppl_2.16485 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Rebecca H Ritchie ◽

Nga Cao ◽

Yung George Wong ◽

Sarah Rosli ◽

Helen Kiriazis ◽

...

Keyword(s):

Heart Failure ◽

Mouse Model ◽

Diastolic Dysfunction ◽

Diabetic Cardiomyopathy ◽

Ex Vivo ◽

Systolic Function ◽

Left Ventricular ◽

Cardiomyocyte Hypertrophy ◽

Lv Diastolic Dysfunction ◽

The Impact

Nitroxyl (HNO), a redox congener of NO•, is a novel regulator of cardiovascular function combining vasodilator and positive inotropic properties. Our previous studies have demonstrated these properties occur concomitantly in the intact heart; HNO moreover also exhibits antihypertrophic and superoxide-suppressing actions. HNO donors may thus offer favorable actions in heart failure. The impact of chronic HNO donor administration has however yet to be reported in this context. We tested the hypothesis that the HNO donor 1-nitrosocyclohexyl acetate (1-NCA) limits cardiomyocyte hypertrophy and left ventricular (LV) diastolic dysfunction in a mouse model of diabetic cardiomyopathy in vivo. Male 6 week-old FVB/N mice received either streptozotocin (55 mg/kg/day i.p. for 5 days, n=17), to induce type 1 diabetes, or citrate vehicle (n=16). After 4 weeks of hyperglycemia, mice were allocated to 1-NCA therapy (83mg/kg/day i.p.) or vehicle, and followed for a further 4 weeks. As shown in the table, blood glucose was unaffected by 1-NCA. LV diastolic dysfunction was evident in diabetic mice, measured as echocardiography-derived A wave velocity, deceleration time and E:A ratio; LV systolic function was preserved. Diabetes-induced diastolic dysfunction was accompanied by increased LV cardiomyocyte size, hypertrophic and pro-fibrotic gene expression, and upregulation of LV superoxide. These characteristics of diabetic cardiomyopathy were largely prevented by 1-NCA treatment. Selectivity of 1-NCA as a donor of HNO versus NO• was demonstrated by the sensitivity of the coronary vasodilation response of 1-NCA to the HNO scavenger L-cysteine (4mM), but not to the NO• scavenger hydroxocobalamin (50μM), in the normal rat heart ex vivo (n=3-7). Collectively, our studies provide the first evidence that HNO donors may represent a promising new strategy for the treatment of diabetic cardiomyopathy, and implies their therapeutic efficacy in settings of chronic heart failure.

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Non-Invasive Assessment of Left Ventricle Ejection Fraction: Where Do We Stand?

Journal of Personalized Medicine ◽

10.3390/jpm11111153 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1153

Author(s):

Alessandra Scatteia ◽

Angelo Silverio ◽

Roberto Padalino ◽

Francesco De Stefano ◽

Raffaella America ◽

...

Keyword(s):

Clinical Practice ◽

Ejection Fraction ◽

Systolic Function ◽

Left Ventricular ◽

Left Ventricle Ejection Fraction ◽

Advantages And Disadvantages ◽

Non Invasive ◽

Lv Ejection Fraction ◽

Lv Systolic Function ◽

Invasive Evaluation

The left ventricular (LV) ejection fraction (EF) is the preferred parameter applied for the non-invasive evaluation of LV systolic function in clinical practice. It has a well-recognized and extensive role in the clinical management of numerous cardiac conditions. Many imaging modalities are currently available for the non-invasive assessment of LVEF. The aim of this review is to describe their relative advantages and disadvantages, proposing a hierarchical application of the different imaging tests available for LVEF evaluation based on the level of accuracy/reproducibility clinically required.

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CORONARY ARTERY DISEASE

The Professional Medical Journal ◽

10.29309/tpmj/2009.16.02.2894 ◽

2009 ◽

Vol 16 (02) ◽

pp. 192-197

Author(s):

FIDA MUHAMMAD ◽

Nadeem Hayat Mallick, ◽

ABDUL REHMAN ABID ◽

AJAZ AHMAD ◽

Shahid Imran

Keyword(s):

Coronary Artery Disease ◽

Risk Factor ◽

Coronary Artery ◽

Clinical Presentation ◽

Systolic Function ◽

Left Ventricular ◽

Premature Coronary Artery Disease ◽

Common Risk Factor ◽

Artery Disease ◽

Lv Systolic Function

Objectives: This study was designed to evaluate the pattern of clinical presentation, risk factors and angiographic findingsin young males presenting with acute myocardial infarction (AMI).Materials and methodsThis cross-sectional descriptive study wasconducted at the Cardiology Department, Punjab Institute of Cardiology, Lahore from May 2005 till February 2006. After fulfilling the inclusioncriteria 200 male patients <40 years with coronary artery disease (CAD) were studied. Results: Mean age of the study population was31.5±9.2 years with an age range of 31 to 40 years. Most common risk factor was smoking present in 60% patients. Family history ofischemic heart disease (IHD) was present in 44.5% patients, hyperlipidemia in 35.5% patients, hypertension in 25.5% and diabetes mellitusin 17.5% of patients.Common mode of clinical presentation was AMI 42.5% patients. Left anterior descending (LAD) was diseased in 73.5%,followed by Left Circumflex (LCx) 51% and Right Coronary Artery (RCA) in 39% patients. Left Main Stem (LMS) disease occurred in 9.5%patients. Good left ventricular (LV) systolic function was observed in 38%, moderate LV systolic function in 34% and poor LV systolic functionin 14.5% patients. Conclusion: Patients with premature coronary artery disease have unheralded acute onset of symptoms. Smoking isthe most common risk factor. Young patients have single vessel CAD with frequent involvement of LAD and commonly have good leftventricular systolic function.

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The impact of obesity on left ventricular mass and left ventricular systolic function in children

Paediatrica Indonesiana ◽

10.14238/pi45.4.2005.171-6 ◽

2016 ◽

Vol 45 (4) ◽

pp. 171

Author(s):

Ria Nova ◽

Bambang Madiyono ◽

Sudigdo Sastroasmoro ◽

Damayanti R Sjarif

Keyword(s):

Wall Thickness ◽

Systolic Function ◽

Posterior Wall ◽

Left Ventricular ◽

Internal Diameter ◽

Obese Children ◽

Normal Children ◽

Posterior Wall Thickness ◽

Lv Mass ◽

Lv Systolic Function

Background Obesity causes cardiovascular disturbances. Theincidence of cardiovascular disease is higher even in mildly obesepatients than in lean subjects.Objectives The purpose of this study was to compare left ven-tricular (LV) mass, LV internal dimensions, and LV systolic func-tion between obese and normal children; and to determine the as-sociation of the degree of obesity with LV mass and LV systolicfunction.Methods This cross-sectional study was conducted on elemen-tary school students in Jakarta from February to April 2003. Wemeasured the subjects’ body weight and height, and performedlipid profile and echocardiography examinations. Measurementsof LV mass, LV internal dimensions with regard to septum thick-ness, LV internal diameter, and LV posterior wall thickness; andLV systolic function as indicated by shortening fraction and ejec-tion fraction, were performed echocardiographically. The differ-ences in measurements between obese and normal children aswell as between obese children with and without lipid abnormalitywere analyzed. The correlation between the degree of obesity withLV size and systolic function was determined.Results Twenty-eight normal children and 62 obese children wereenrolled in the study. Mean LV mass was 35.7 (SD 5.16) g/cm 3 inobese children versus 24.0 (SD 3.80) g/cm 3 in normal children(P<0.0001). Mean septum thickness was 0.8 (SD 0.14) mm inobese children versus 0.6 (SD 7.90) mm in normal children (P<0.0001). Mean posterior wall thickness was 0.9 (SD 0.14) mm inobese children versus 0.6 (SD 9.97) mm in normal children(P<0.0001). Mean LV internal diameter was 4.0 (SD 0.34) mm inobese children versus 3.9 (SD 0.29) mm in normal children(P=0.300). There was strong correlation between the degree ofobesity and LV mass (r=0.838, P<0.0001). LV systolic function(shortening fraction) was 37.1 (SD 4.20) percent in obese childrenversus 35.8 (SD 4.99) percent in normal children (P=0.19). Ejec-tion fraction was 67.4 (SD 5.32) percent in obese children versus65.5 (SD 6.29) percent in normal children (P=0.13). There wasweak correlation between LV systolic function and the degree ofobesity (shortening fraction r=0.219, P=0.038; ejection fractionr=0.239, P=0.023).Conclusions Obese children had significantly greater LV mass,septum thickness, and posterior wall thickness than normal chil-Backgrounddren. Such significant difference was absent for LV internal diam-eter and measures of LV systolic function. There was no signifi-cant difference in LV mass and LV systolic function between obesechildren with or without abnormality of lipid profile. A strong corre-lation exists between the degree of obesity and LV mass, but thecorrelation between degree of obesity and LV systolic function wasweak

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Correlation between hemoglobin level and left ventricular systolic functions and dimensions in children with chronic severe anemia

Paediatrica Indonesiana ◽

10.14238/pi51.2.2011.79-83 ◽

2011 ◽

Vol 51 (2) ◽

pp. 79

Author(s):

Erlina Masniari Napitupulu ◽

Fera Wahyuni ◽

Tina Christina L. Tobing ◽

Muhammad Ali ◽

Bidasari Lubis

Keyword(s):

Systolic Function ◽

Pearson Correlation ◽

Systolic Dysfunction ◽

Univariate Analysis ◽

Left Ventricular Systolic Function ◽

Left Ventricular ◽

Lv Function ◽

Severe Anemia ◽

Cross Sectional ◽

Lv Systolic Function

Background Chronic severe anemia is a connnon disease. Cardiac output may increase when the hemoglobin (Hb) level decreases to < 7 g/dL for 3 months or more. Alteration of left ventricular (LV) function occurs frequently in children 'With chronic severe anemia, in the {onn of concentric LV hypertrophy, LV dilatation with or v.ithout LV hypertrophy, or systolic dysfunction. Objective To examine the correlation between Hb level and alteration of LV systolic function in children with chronic severe anemia. Methods We conducted a cross-sectional study in Adam Malik Hospital from October to December 2009. Subjects were chronic severely anemic children. Left ventricular systolic function (ejection fraction/EF, fractional shortening/FS) and dimensions (left ventricular end diastolic diameter/LVEDD and left ventricular end systolic diameter/LVESD) were measured using Hitachi EUB 5500 echocardiography unit. Univariate analysis and Pearson correlation were performed.Results Thirty children were enrolled in the study. The mean of age was 113.5 months (SD 53.24). Hb values ranged from 2.1 to 6.9 g/dL with mean value of 4.6 g/dL (SD 1.44). Mean duration of anemia was 3.9 months (SD 0.70). Chronic severe anemia was not associated \\lith decreased LV systolic function [EF 62.2% (SD 9.16), r =0.296, P=0.112; FS 33.8% (SD 7.26), r =0.115, P=0.545], nor LV dimension changes [LVEDD 40.2 mm (SD 6.85), r = -0.192, P=0.308; LVESD 26.2 mm (SD 4.98), r=-0.266, P=0.156]. Conclusion There was no correlation between Hb level in chronically anemic children and changes in LV systolic function or dimension.

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Remodeling of the heart and main vessels in patients with marfanoid habitus

Pediatrician (St Petersburg) ◽

10.17816/ped10527-34 ◽

2020 ◽

Vol 10 (5) ◽

pp. 27-34

Author(s):

Eugene V. Timofeev ◽

Eduard G. Malev ◽

Nina N. Parfenova ◽

Eduard V. Zemtsovsky

Keyword(s):

Marfan Syndrome ◽

Aortic Root ◽

Structural Changes ◽

Systolic Function ◽

Interventricular Septum ◽

Age Groups ◽

Ventricular Myocardium ◽

Left Ventricular ◽

Control Group ◽

Left Ventricular Myocardium

For many hereditary connective tissue disorders (HCTD), especially Marfan syndrome, remodeling of the heart and main vessels is described, which is manifested by a decrease in the systolic function of the left ventricle and expansion of the thoracic aorta. Evaluation of morphometric characteristics of the heart and main vessels in patients with other HCTD, in particular marfanoid habitus (MH) has not been previously carried out. Materials and methods. Weexamined 90 young men and 74 young women between the ages of 18 to 25 years, 111 patients older age groups with stable over coronary heart disease (mean age 64.66.2 years) and 9 patients with verified Marfan syndrome (mean age 27.99.3years). All survey phenotypic and performed anthropometric survey identifying bone signs of dysembryogenesis as well as Echocardiography study on standard protocol. The results.Patients with MH as compared with control group revealed a relatively larger diameter of aortic root (30.44.7 vs 28.03.6 mm,p= 0.03) and the ascending aorta (26.64.9 vs 24.63.2 mm,p= 0.05). Also young with MH turned out to be significantly thicker myocardium of left ventricular posterior wall (8.30.8 vs 7.71.1 mm,p= 0.02) and interventricular septum (8.81.2vs 8.21.1mm,p= 0.04). When performing correlation analysis identified reliable positive correlation between such highly specialized bone signs as high palate (r= 0.31), infundibular deformation of the chest (r= 0.43), arachnodactyly (r= 0.45) andZ-test (p 0.05 for all). Expansion of the aorta (Z-criterion 2.0) have found 24% of older patients with MH. Conclusion.Inpatients with MH revealed significant structural changes of heart and main vessels which are progredient character thickening of the left ventricular myocardium and expansion of the aortic root.

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Tachycardia-induced myocardial ischemia and diastolic dysfunction potentiate secretion of ANP, not BNP, in hypertrophic cardiomyopathy

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00110.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. H1064-H1070 ◽

Cited By ~ 2

Author(s):

Shinsuke Kido ◽

Naoyuki Hasebe ◽

Yoshinao Ishii ◽

Kenjiro Kikuchi

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Myocardial Ischemia ◽

Diastolic Dysfunction ◽

Diastolic Pressure ◽

Systolic Function ◽

Left Ventricular ◽

Atrial Pacing ◽

Catheter Tip ◽

Lv Systolic Function ◽

Lv Diastolic Dysfunction

The aim of this study was to investigate what factor determines tachycardia-induced secretion of atrial and brain natriuretic peptides (ANP and BNP, respectively) in patients with hypertrophic cardiomyopathy (HCM). HCM patients with normal left ventricular (LV) systolic function and intact coronary artery ( n = 22) underwent rapid atrial pacing test. The cardiac secretion of ANP and BNP and the lactate extraction ratio (LER) were evaluated by using blood samples from the coronary sinus and aorta. LV end-diastolic pressure (LVEDP) and the time constant of LV relaxation of tau were measured by a catheter-tip transducer. These parameters were compared with normal controls ( n = 8). HCM patients were divided into obstructive (HOCM) and nonobstructive (HNCM) groups. The cardiac secretion of ANP was significantly increased by rapid pacing in HOCM from 384 ± 101 to 1,268 ± 334 pg/ml ( P < 0.05); however, it was not significant in control and HNCM groups. In contrast, the cardiac secretion of BNP was fairly constant and rather significantly decreased in HCM ( P < 0.01). The cardiac ANP secretion was significantly correlated with changes in LER ( r = −0.57, P < 0.01) and tau ( r = 0.73, P < 0.001) in HCM patients. Tachycardia potentiates the cardiac secretion of ANP, not BNP, in patients with HCM, particularly when it induces myocardial ischemia and LV diastolic dysfunction.

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