Left Ventricular Structural Changes Research Articles

Short-term melatonin supplementation decreases oxidative stress but does not affect left ventricular structure and function in myxomatous mitral valve degenerative dogs

BackgroundCardiac wall stress and high oxidative stress are often found in cases of myxomatous mitral valve degenerative (MMVD) disease and can lead to myocardial injuries and cardiac dysfunction. Melatonin, an antioxidant, has been shown to exert cardioprotection in laboratory animal models. However, its effect on metabolic parameters and left ventricular (LV) adaptation in MMVD dogs has rarely been investigated. This clinical trial hypothesized that a melatonin supplement for 4 weeks would improve metabolic parameters, LV structure (diameters and wall thickness), and LV function in MMVD dogs. Blood profiles, echocardiograms, and oxidative stress levels were obtained from 18 dogs with MMVD stage B2 and C at baseline and after prescribed Melatonin (2 mg/kg) for 4 weeks. Eleven dogs with MMVD stage B2 and C, which received a placebo, were evaluated as a control group.ResultsIn this clinical trial, the baseline plasma malondialdehyde (MDA) was no different between the treatment and placebo groups. The post-treatment plasma MDA levels (4.50 ± 0.63 mg/mL) in the treatment group was significantly decreased after 4 weeks of melatonin supplementation compared to pre-treatment levels (7.51 ± 1.11 mg/mL) (P = 0.038). However, blood profiles and LV structure and function investigated using echocardiography were found not to different between pre-and post-treatment in each group. No adverse effects were observed following melatonin supplementation.ConclusionsThis clinical trial demonstrated that a melatonin supplement for 4 weeks can attenuate oxidative stress levels in MMVD dogs, especially in MMVD stage C, but does not result in LV structural changes or LV function in MMVD dogs of either stage B2 or stage C.

Triglyceride glucose index reflects the unfavorable changes of left ventricular diastolic functions and structure in uncomplicated newly diagnosed hypertensive patients

ABSTRACT Introduction Left ventricular (LV) diastolic dysfunction and structural abnormalities are common cardiac changes in hypertension (HTN), and several factors other than high blood pressure (BP) may play a role in these changes. The aim of this study was to reveal the relationship between triglyceride glucose (TyG) index, a novel parameter for insulin resistance (IR), with LV diastolic function and structure in hypertensive patients. Material and method A total of 119 newly diagnosed, untrated hypertensive patients free of diabetes and/or cardiovascular complications were included in this study. IR was estimated with the TyG index calculated from ln [fasting TG (mg/dL) × fasting blood glucose (mg/dL)/2]. Two-dimensional and Doppler echocardiographic examinations were performed to assess LV diastolic functions and structure. Results Based on median TyG index, 51 patients was assigned as group I (<8.7) and 68 patients as group II (>8.7). In patients with high TyG index, left atrial volume index (LAVi) (p < .001) LV mass index (LVMI) (p = .016), E/e’ ratio (p < .001) increased, and e’ velocity (p < .001) and E/A ratio (p = .028) decreased. There was a statistically significant correlation between TyG index and these parameters (all p > .05). Stepwise multiple regression analysis demonstrated that the relationship of TyG index with LV diastolic function and structure was independent of potential confounders (all p < .001). Conclusion This study suggest that a high TyG index is related to LV diastolic functional impairment and structure abnormality in newly diagnosed hypertensive patients in the absence of diabetes or CVD.

644 Clinical outcomes of patients with end-stage heart failure treated with left ventricular assist devices

Abstract Aims During the last decades left ventricular assist devices (LVAD) have assumed a central role in the management of patients with symptomatic end-stage heart failure (HF). The mortality rate and prognosis of these patients is poor, but the substantial progress in LVAD technologies has led to significant improvements in clinical outcomes. The third generation LVADs are small, centrifugal flow pumps, contained within the pericardium and based on full magnetic levitation, which allow to reduce the risks of pump thrombosis. The aim of our study is to evaluate the clinical outcomes and functional capacity of patients with end-stage HF before and after the implantation of a third generation LVAD, the HeartMate 3™. Methods and results We evaluated eight patients with end-stage HF, followed to Cardiology Unit of Brotzu Hospital in Cagliari and consecutively implanted with the HeartMate 3™ LVAD in the Cardiac Surgery Unit from 12 May 2017 to 24 October 2019. For each patient we collected socio-demographic and clinical features, as well as laboratory tests, therapy, echocardiographic and haemodynamics parameters and any complication. Most of our patients were male (87.5%), with mean age 65.6 ± 5.7 years and higher prevalence of cardiovascular risk factors, like smoke (87.5%), hypertension (62.5%) and hypercholesterolaemia (62.5%). The etiology of HF was mainly due to idiopatic dilated cardiomyopathy (62.5%) and ischaemic heart disease (25%); the only female patient had a history of iatrogenic dilated cardiomyopathy, post-chemo and radiotherapy. Before the implantation most of our patients experienced severe symptoms, recurrent decompensations resulting in NYHA class IV (50%) and III (37.5%); the 100% was inotrope dependant and needed short-term support devices like IABP (75%) and ECMO (25%); the 62.5% underwent mechanical ventilation. The patients had severe left ventricular (LV) dysfunction, with low LV ejection fraction (18.6 ± 1.8%), cardiac output (3.08 ± 1.2 l/min) and cardiac index (1.81 ± 0.83 l/min/m2) and increasing filling pressure (26.5 ± 9.7 mmHg), central venous pression (12.7 ± 5 mmHg) and pulmonary arteries resistance (3.81 ± 1 μW). We also found important LV structural changes, with a severe dilatation and increased volumes (EDV 140.62 ± 67.1 ml/m2; ESV 113.7 ± 55.3 ml/m2). Mild right ventricle dysfunction was present only in 50% of patients with normal diameters. We observed few complications, mainly driveline infections (42.8%) and only one case of in-hospital mortality due to multiple organ failure. The seven patients presenting at FU shown a significant improvement in everyday symptoms and functional capacity compared to pre-operative features (P = 0.029). We also found a mild improvement of systolic LV function compared to pre-operatory values, with increase of CO (3.58 ± 0.65 l/min vs. 3.08 ± 1.2) and EF (21.2 ± 9.4% vs. 18.71 ± 97) even though not statistically significant. Conclusions Our study confirms that patients with end-stage HF are mostly male, older, experience severe symptoms and require frequent hospitalizations. The survival rate reached the 87.5% and remained stable even three years after implantation. On the whole our study showed that LVADs can significally improve clinical outcomes and survival rates, confirming the role as treatment of choice for many patients with end-stage HF who cannot undergo heart transplantation, which still remains the gold standard. The complications related to LVAD were few, thanks to careful patients selection, showing a favourable risk benefit ratio.

Abstract 10069: Effect of Renin-Angiotensin-Aldosterone System Inhibitors on Left Ventricular Structure and Function in Duchenne Muscular Dystrophy Carriers

Introduction: Duchenne muscular dystrophy (DMD) is a rare X-linked neuromuscular disorder affecting 1:5,000 males that results in terminal injury to the skeletal muscle and the heart. Recent evidence suggests that DMD female carriers are also at increased risk of developing cardiomyopathy. Renin-angiotensin-aldosterone system (RAAS) antagonists reduce morbidity and mortality and inhibit adverse left ventricular remodeling in patients with heart failure with reduced ejection fraction. The benefit of RAAS inhibition in DMD carriers has not been studied to date. Hypothesis: We hypothesize that RAAS inhibition will improve left ventricular function and induce favorable left ventricular structural changes in DMD carriers over time. Methods: A retrospective, single-center cohort study was undertaken to compare cardiac magnetic resonance imaging (cMRI) parameters in DMD carriers at the time of RAAS inhibitor initiation and after treatment with RAAS inhibitors for at least 12 months. RAAS inhibitors included angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor neprilysin inhibitors. Through EMR review, demographic data and cMRI parameters were collected retrospectively on 20 consecutive DMD carriers. Results: The average time elapsed between cMRIs was 39 months. Overall, left ventricular ejection fraction (LVEF) increased in DMD carriers over time, though the improvement in LVEF did not reach significance (57% + 8 vs 59% + 6, p=0.2). However, subgroup analysis of 16 DMD carriers with reduced LVEF (defined as LVEF &lt;62%) demonstrated significant improvement in LVEF following RAAS inhibition (54% + 6 vs 58% + 7; p= 0.004). DMD carriers with reduced LVEF additionally demonstrated a significant decrease in left ventricular end systolic volume index (LVESVi) after RAAS inhibition (38 + 10 vs 32 + 10 ml/m2; p= 0.013). Conclusions: DMD carriers with reduced LVEF showed significant improvement in LVEF and LVESVi following RAAS inhibition. Collectively, the data suggest that RAAS inhibition significantly improves left ventricular systolic function and significantly reduces maladaptive left ventricular remodeling and dilation in this population.

Abstract 10437: “Explainable Artificial Intelligence (ai) in Cardiology”: A Tool to Provide Personalized Predictions on Cardiac Health States Among Older Adults Engaged in Physical Activity

Introduction: As a prevention strategy, the effect of physical activity on older adults is likely heterogeneous against a background of individual ageing trajectories. While machine learning models that combine various systemic signals may aid in predictive modeling, the inability to rationalize predictions at a patient personalized level is a major shortcoming in AI. Methods: We applied a novel approach using Shapley Additive Explanations (SHAP) methodology on a dataset of older adults whose physical activity levels were studied in conjunction with changes in left ventricular (LV) structure. The SHAP approach provided intelligible visualization on the magnitude of the impact of the features in their physical activity levels on their LV structure. Results: As proof of concept, we studied n = 86 older adults (mean age 72±4 years). Using repeated K-cross validation on the train set (n = 68), we found the Random Forest Regressor with the most optimal hyperparameters, which achieved the lowest mean squared error. With the trained model, we evaluated its performance by reporting its mean absolute error and plotting the correlation on the test set (n = 18) (Fig 1). A collective force plot for individually numbered patients (horizontal axis) showing magnitude (i.e., effect) of physical parameters (higher in red; lower in blue) towards prediction of LV structure (Fig 2). For example, for patient number 6, basal metabolic rate was the predominant positive factor on LV structure, outweighing other weaker positive factors and negative factor contributed by body fat mass (Figure 3). In contrast, LV structure in patient number 11 was predicted jointly by several weaker positive factors without any single predominant factor (Figure 4). Conclusions: As a tool that identified specific features in physical activity that predicted cardiac structure on a per patient level, our findings support a role for explainable AI to be incorporated into personalized cardiology strategies.

Assessment of Cardiovascular Health of Children Ages 6 to 10 Years Conceived by Assisted Reproductive Technology

Assisted reproductive technology (ART) has been widely used for treatment of infertility and has brought millions of births worldwide. The health of offspring conceived by ART has been of much concern, and adverse cardiovascular health outcomes have been reported by previous studies. To assess the cardiovascular health of children conceived by ART. This cohort study was conducted among participants recruited from November 2017 to February 2019. Participants were 382 children conceived by ART who were selected from a single reproductive center and 382 children who were naturally conceived, randomly selected from a primary school, and matched by sex, age, and maternal age at the child's birth (2 years older or younger). Data were analyzed from March 2019 through December 2019. Conception by ART. Blood pressure was measured, and echocardiography was performed to determine left ventricular structural and functional parameters. Adjusted relative wall thickness (aRWT) was found for age, with high RWT defined as an aRWT of 0.375 or more. Among 764 children aged 6 to 10 years, 382 children were conceived by ART (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys) and 382 children were naturally conceived (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys). Children conceived by ART had statistically significantly increased mean (SD) height (130.2 [9.5] cm vs 128.5 [8.1] cm; P = .007) and body mass index (17.6 [3.6] vs 17.1 [2.7]; P = .03). Those conceived by ART, compared with children in the matched control group, had statistically significantly increased blood pressure (mean [SD] systolic blood pressure, 105.5 [6.9] mm Hg vs 103.5 [8.4] mm Hg; adjusted P < .001; mean [SD] diastolic blood pressure, 67.2 [5.6] mm Hg vs 62.2 [6.3] mm Hg ; adjusted P < .001), left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 64.61% [3.20%] vs 66.70% [3.89%]; adjusted P < .001), and diastolic dysfunction (mean [SD] early/late mitral/tricuspid diastolic velocities ratio, 1.66 [0.28] vs 2.21 [0.36]; adjusted P < .001). They also had statistically significantly increased parameters of left ventricular structure, including mean (SD) left ventricular mass index (31.97 [5.04] g/m2.7 vs 28.28 [3.54] g/m2.7; adjusted P < .001) and RWT (3.30 [0.41] mm vs 2.98 [0.14] mm; adjusted P < .001). Additionally, children conceived by ART had statistically significantly increased prevalence of left ventricular hypertrophy (9 children [2.4%] vs 2 children [0.5%]; P = .03), high RWT (61 children [16.0%] vs 0 children; P < .001), and left ventricle remodeling patterns, including concentric remodeling (60 children [15.7%] vs 0 children), eccentric hypertrophy (8 children [2.1%] vs 2 children [0.5%]), and concentric hypertrophy (1 child [0.3%] vs 0 children) (P for left ventricle remodeling < .001). This study found that children conceived by ART had increased blood pressure and unfavorable changes in left ventricular structure and function compared with children who were naturally conceived. These findings suggest that further studies are needed to investigate the potential mechanisms and long-term outcomes associated with these differences.

Choline or CDP-choline restores hypotension and improves myocardial and respiratory functions in dogs with experimentally – Induced endotoxic shock

Endotoxin shock is associated with severe impairments in cardiovascular and respiratory functions. We showed previously that choline or cytidine-5′-diphosphocholine (CDP-choline) provides beneficial effects in experimental endotoxin shock in dogs. The objective of the present study was to determine the effects of choline or CDP-choline on endotoxin-induced cardiovascular and respiratory dysfunctions.Dogs were treated intravenously (i.v.) with saline or endotoxin (LPS, 0.1 mg/kg) 5 min before i.v. infusion of saline, choline (20 mg/kg) or CDP-choline (70 mg/kg). Blood pressure, cardiac rate, myocardial and left ventricular functions, respiratory rate, blood gases, serum electrolytes and cardiac injury markers were determined before and at 0.5-48 h after endotoxin. Plasma tumor necrosis factor alpha (TNF-α), high mobility group box-1 (HMGB1), catecholamine and nitric oxide (NO) levels were measured 2 h and 24 h after the treatments.Endotoxin caused immediate and sustained reductions in blood pressure, cardiac output, pO2 and pH; changes in left ventricular functions, structure and volume parameters; and elevations in heart rate, respiratory rate, pCO2 and serum electrolytes (Na, K, Cl, Ca and P). Endotoxin also resulted in elevations in blood levels of cardiac injury markers, TNF-α, HMGB1, catecholamine and NO. In choline- or CDP-choline-treated dogs, all endotoxin effects were much smaller in magnitude and shorter in duration than observed values in controls.These data show that treatment with choline or CDP-choline improves functions of cardiovascular and respiratory systems in experimental endotoxemia and suggest that they may be useful in treatment of endotoxin shock in clinical setting.

Type I Diabetes Mellitus Increases the Cardiovascular Complications of Influenza Virus Infection

People with diabetes mellitus are susceptible to both cardiovascular disease and severe influenza A virus infection. We hypothesized that diabetes also increases risks of influenza-associated cardiac complications. A murine type 1 (streptozotocin-induced) diabetes model was employed to investigate influenza-induced cardiac distress. Lung histopathology and viral titres revealed no difference in respiratory severity between infected control and diabetic mice. However, compared with infected control mice, infected diabetic mice had increased serum cardiac troponin I and creatine-kinase MB, left ventricular structural changes and right ventricular functional alterations, providing the first experimental evidence of type I diabetes increasing risks of influenza-induced cardiovascular complications.

Treating symptoms and reversing remodelling: clinical and echocardiographic 1-year outcomes with percutaneous mitral annuloplasty for mild to moderate secondary mitral regurgitation.

To determine the effects of percutaneous mitral annuloplasty on symptoms, walk distance and left ventricular (LV) structure and function in patients with mild or moderate secondary mitral regurgitation (SMR). This was a pooled analysis of patients (n= 68) who, despite guideline-directed medical therapy had symptomatic heart failure (HF) with mild (n= 25) or moderate (n= 43) SMR treated with percutaneous mitral annuloplasty as part of the TITAN, TITAN II, or REDUCE-FMR trials. Primary outcomes were changes in symptoms, 6-min walk distance, and quality of life assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) after 1year. Secondary analyses included changes in LV structure and function. At 1 year, New York Heart Association class status was maintained (48%) or improved (46%) in most patients, mean KCCQ scores increased from baseline by 10units [95% confidence interval (CI) 3 to17; P< 0.01] and mean 6-min walk test distance increased by 34 m (95% CI 12 to 57; P< 0.01). SMR grade improved in 25% of patients and was maintained in 58% of patients with changes in mean regurgitant volume of -7mL (95% CI -11 to -3; P< 0.001), vena contracta -0.11 cm (95% CI -0.20 to -0.02; P< 0.05), and effective regurgitant orifice area -0.03 cm2 (95% CI -0.06 to -0.01; P< 0.05). There were non-significant improvements in LV ejection fraction and volumes. Survival over 1year was 89% with no difference between mild (96%) and moderate (86%) SMR (log-rank P= 0.22). Progression-free survival was 70% (82% in mild vs. 63% in moderate SMR; P= 0.16). Freedom from HF hospitalization was 73% (87% in mild SMR vs. 66% in moderate SMR; P= 0.07). Among patients with symptomatic HF and mild or moderate SMR on guideline-directed medical therapy, percutaneous mitral annuloplasty was associated with improvements in symptoms, SMR, a stabilization of LV structure and function, and high survival rates.

Cardiac natriuretic peptide deficiency sensitizes the heart to stress-induced ventricular arrhythmias via impaired CREB signalling

The cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are important regulators of cardiovascular physiology, with reduced natriuretic peptide (NP) activity linked to multiple human cardiovascular diseases. We hypothesized that deficiency of either ANP or BNP would lead to similar changes in left ventricular structure and function given their shared receptor affinities. We directly compared murine models deficient of ANP or BNP in the same genetic backgrounds (C57BL6/J) and environments. We evaluated control, ANP-deficient (Nppa-/-) or BNP-deficient (Nppb-/-) mice under unstressed conditions and multiple forms of pathological myocardial stress. Survival, myocardial structure, function and electrophysiology, tissue histology, and biochemical analyses were evaluated in the groups. In vitro validation of our findings was performed using human-derived induced pluripotent stem cell cardiomyocytes (iPS-CMs). In the unstressed state, both ANP- and BNP-deficient mice displayed mild ventricular hypertrophy which did not increase up to 1 year of life. NP-deficient mice exposed to acute myocardial stress secondary to thoracic aortic constriction (TAC) had similar pathological myocardial remodelling but a significant increase in sudden death. We discovered that the NP-deficient mice are more susceptible to stress-induced ventricular arrhythmias using both in vivo and ex vivo models. Mechanistically, deficiency of either ANP or BNP led to reduced myocardial cGMP levels and reduced phosphorylation of the cAMP response element-binding protein (CREBS133) transcriptional regulator. Selective CREB inhibition sensitized wild-type hearts to stress-induced ventricular arrhythmias. ANP and BNP regulate cardiomyocyte CREBS133 phosphorylation through a cGMP-dependent protein kinase 1 (PKG1) and p38 mitogen-activated protein kinase (p38 MAPK) signalling cascade. Our data show that ANP and BNP act in a non-redundant fashion to maintain myocardial cGMP levels to regulate cardiomyocyte p38 MAPK and CREB activity. Cardiac natriuretic peptide deficiency leads to a reduction in CREB signalling which sensitizes the heart to stress-induced ventricular arrhythmias.

Extent and determinants of left ventricular reverse remodeling in patients with secondary mitral regurgitation undergoing MitraClip implantation.

BackgroundIn secondary MR, data on left ventricular (LV) remodeling after MitraClip procedure are rare, even this information may impact patient selection. This study investigated changes in LV structure and function by cardiovascular magnetic resonance (CMR) following MitraClip implantation for secondary mitral regurgitation (MR) in order to assess extent and predictors of LV reverse remodeling (LVRR).Methods and ResultsTwenty-nine patients underwent CMR imaging prior to and six months after MitraClip procedure. LVRR was defined by a decrease of LV end-diastolic volume index (LVEDVi) > 15% compared to baseline. According to the definition of LVRR, 34% of patients displayed LVRR at follow-up CMR. Baseline LV stroke volume index (LVSVi), LV ejection fraction (LVEF), LV circumferential strain and MR volume at baseline were predictors of LVRR at follow-up. At second CMR, we detected an improvement in hemodynamic status as illustrated by an increase in effective LVSVi (28 ± 8 ml/m2 vs. 33 ± 8 ml/m2; p = 0.053) and cardiac index (2.0 ± 0.5 vs. 2.3 ± 0.5 l/min; p = 0.016), while LVEF and LV strain parameters did not change (p > 0.05). Improvements in effective LVSVi were associated with the decrease of MR volume (r = 0.509; p = 0.018) and MR fraction (r = 0.629; p = 0.002) by MitraClip.ConclusionsTogether, MitraClip implantation is associated with LVRR in one third of patients. Baseline LV function and magnitude of MR are important predictors of LVRR. Improvement of hemodynamic status may be assessed by effective stroke volume index and correlates with the reduction of MR by MitraClip implantation, rather than an increase in LV contractility.

Comparison of Cardiac Reverse Remodeling between Older and Newer Generation Continuous-Flow LVAD

<h3>Purpose</h3> The purpose of our study is to compare the left ventricular (LV) functional and structural changes following mechanical circulatory support (MCS) between continuous-flow left ventricular assist devices (CF-LVADs) that provide mechanical unloading characterized by specific bioengineering differences. <h3>Methods</h3> The study enrolled 311 chronic HF patients undergoing MCS with HVAD (HW, hybrid levitation centrifugal pump, n=95), HeartMate 3 (HM3, full magnetic levitation centrifugal pump, n=140), and HeartMate II (HM2, axial flow pump, n=76) at four sites across the US. Echocardiographic parameters of LV structure and function were obtained pre-implant and at 1, 3, 6, and 12 months of CF-LVAD support. <h3>Results</h3> There were no significant differences in baseline characteristics between groups. At 3 months post-LVAD support the LV ejection fraction (LVEF) was higher (p=0.03, Figure 1A) and left ventricular end diastolic diameter (LVEDD) was lower (p=0.04, Figure 1B) in HMII patients, but there were no significant difference in LVEF and LVEDD between devices at 6 or 12 months. The proportion of patients achieving "cardiac reverse remodeling responder" status (defined as improvement of LVEF to ≥40% and LVEDD <6.0cm) was 9.32%, and comparable between the CF-LVADs. <h3>Conclusion</h3> The newest generation full magnetically levitated CF-LVAD results in similar cardiac reverse remodeling as older generation CF-LVADs. These findings suggest that the fully magnetically levitated device technology could provide an adequate platform to further study and promote reverse cardiac remodeling clinically.

Changes in left ventricular structure and function associated with renal transplantation: a systematic review and meta-analysis.

AimsThis study aimed to examine if the cardiac changes associated with uraemic cardiomyopathy are reversed by renal transplantation.Methods and resultsMEDLINE, Embase, OpenGrey, and the Cochrane Library databases were searched from 1950 to March 2020. The primary outcome measure was left ventricular mass index. Secondary outcome measures included left ventricular dimensions and measures of diastolic and systolic function. Studies were included if they used any imaging modality both before and after successful renal transplantation. Data were analysed through meta‐analysis approaches. Weight of evidence was assessed through the Grading of Recommendations Assessment, Development and Evaluation system. Twenty‐three studies used echocardiography, and three used cardiac magnetic resonance imaging as their imaging modality. The methodological quality of the evidence was generally poor. Four studies followed up control groups, two using cardiac magnetic resonance imaging and two using echocardiography. Meta‐analysis of these studies indicated that there was no difference in left ventricular mass index between groups following transplantation {standardized mean difference −0.07 [95% confidence interval (CI) −0.41 to 0.26]; P = 0.67}. There was also no difference observed in left ventricular ejection fraction [mean difference 0.39% (95% CI −4.09% to 4.87%); P = 0.86] or left ventricular end‐diastolic volume [standardized mean difference −0.24 (95% CI −0.94 to 0.45); P = 0.49]. Inconsistent reporting of changes in diastolic dysfunction did not allow for any meaningful analysis or interpretation.ConclusionsThe evidence does not support the notion that uraemic cardiomyopathy is reversible by renal transplantation. However, the evidence is limited by methodological weaknesses, which should be considered when interpreting these findings.

Genetic ablation of fibroblast activation protein alpha attenuates left ventricular dilation after myocardial infarction.

IntroductionRegulating excessive activation of fibroblasts may be a promising target to optimize extracellular matrix deposition and myocardial stiffness. Fibroblast activation protein alpha (FAP) is upregulated in activated fibroblasts after myocardial infarction (MI), and alters fibroblast migration in vitro. We hypothesized that FAP depletion may have a protective effect on left ventricular (LV) remodeling after MI.Materials and methodsWe used the model of chronic MI in homozygous FAP deficient mice (FAP-KO, n = 51) and wild type mice (WT, n = 55) to analyze wound healing by monocyte and myofibroblast infiltration. Heart function and remodeling was studied by echocardiography, morphometric analyses including capillary density and myocyte size, collagen content and in vivo cell-proliferation. In non-operated healthy mice up to 6 months of age, morphometric analyses and collagen content was assessed (WT n = 10, FAP-KO n = 19).ResultsHealthy FAP-deficient mice did not show changes in LV structure or differences in collagen content or cardiac morphology. Infarct size, survival and cardiac function were not different between FAP-KO and wildtype mice. FAP-KO animals showed less LV-dilation and a thicker scar, accompanied by a trend towards lower collagen content. Wound healing, assessed by infiltration with inflammatory cells and myofibroblasts were not different between groups.ConclusionWe show that genetic ablation of FAP does not impair cardiac wound healing, and attenuates LV dilation after MI in mice. FAP seems dispensable for normal cardiac function and homeostasis.

Surgical treatment of congenital left ventricular diverticulum.

BackgroundCongenital left ventricular diverticulum (LVD) is a rare cardiac malformation. Its prevalence rate is less than 0.1% of the congenital heart diseases requiring surgery. Some scholars suggest that all LVD should be actively removed to prevent possible risks, including diverticulum rupture, arterial embolism, and malignant arrhythmia. However, others believe that asymptomatic LVD can be followed up without immediate surgery. We reviewed and reported the diagnosis, clinical features, and surgical treatment of four cases of congenital LVD to provide clinical experience and a reference for the treatment of such patients.MethodsFour patients (aged 3–32 years old) were diagnosed with congenital LVD and received surgical treatment at the Department of Cardiovascular Surgery of PLA General Hospital, Beijing, China from September 2009 to July 2019. All four patients had complete long-term postoperative follow-up data, including echocardiogram, enhanced cardiac computed tomography (CT), and electrocardiogram to monitor changes in left ventricular structure, heart function, and heart rhythm.ResultsIn the first case, the fibrodiverticulum under the aortic valve squeezed the right ventricular outflow tract and the right main coronary artery; the morphology of the right ventricle and coronary artery returned to normal after surgery. The second patient was complicated with a huge lipoma in the apex of the left ventricle and underwent lipoma resection during LVD resection surgery. The third and fourth cases had muscular diverticula in the left ventricular apexes and received LVD removal surgery. All four patients recovered well after surgery and their left ventricular morphology and cardiac function were normal without adverse complications, such as atrial fibrillation, ventricular arrhythmia, and cerebrovascular accident.ConclusionsAlthough the morphology and character of congenital LVD were different in each case, the use of effective diagnostic and follow-up tools, including echocardiogram, enhanced CT, and magnetic resonance imaging (MRI), allowed for successful surgical treatment of the left ventricular diverticula and symptoms or other malformations. We propose that congenital LVD should be actively treated with surgery, especially considering effectiveness and low risk associated with this therapeutic option.

December 2020 at a glance: focus on COVID-19, comorbidities and palliative care.

The coronavirus disease 2019 (COVID-19) pandemic had a catastrophic impact on health systems worldwide. In Germany, hospitalizations due to acute heart failure (HF) had a reduction in the first pandemic period (13 March–21 May 2020) compared to control intervals in 2020 (1 January–12 March) and 2019 (13 March–21 May), with an increase in case severity and in-hospital mortality.1 Similarly, a study conducted in London showed a reduction in HF hospitalizations during the pandemic period, compared to the previous year. Although patients had similar characteristics to those of the patients hospitalized in 2019, in-hospital mortality was significantly higher in 2020 than in 2019 (P = 0.015) and hospitalization in 2020 was independently associated with increased in-hospital mortality.2 In a study conducted in Madrid, Spain, including 3080 COVID-19 patients, those with a previous history of chronic HF were more likely to develop acute HF (11.2% vs. 2.1%; P < 0.001) and had higher mortality rates (48.7% vs. 19.0%; P < 0.001).3 In an Italian study including 13 centres and 692 patients, history of HF was an independent predictor of increased in-hospital mortality [adjusted hazard ratio (HR) 2.25, 95% confidence interval (CI) 1.26–4.02; P = 0.006), along with age, sex, oxygen saturation and oxygen partial pressure/fraction of inspired oxygen (PaO2/FiO2) ratio.4 Concerns were raised that angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) may enhance the susceptibility to COVID-19 through an increased expression of ACE2.5 Lebek et al.6 measured ACE2 mRNA expression using real-time quantitative polymerase chain reaction in atrial biopsies of 81 patients undergoing coronary artery bypass grafting. ACE2 mRNA expression was higher in patients treated with ACEi/ARBs compared to those not treated. Furthermore, ACEi/ARB treatment was associated with an independent increase in ACE2 expression in ventricle biopsies of patients with end-stage HF, while left ventricular (LV) assist device implantation led to a decline in mRNA expression. Although these data may show that ACE2 expression is increased by ACEi/ARB treatment, they do not imply that this may increase susceptibility to COVID-19 as ACE2 may actually have a protective role after infection has developed.5 A reduction of cardiac remodelling may be a therapeutic goal in HF with preserved ejection fraction (HFpEF).7 Yamanaka et al.8 investigated the prognostic impact of LV structural changes in patients with HFpEF from the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) study. Patients who presented LV hypertrophy and enlargement at baseline and those with LV hypertrophy who developed LV enlargement had a worse subsequent prognosis (HR 4.65, 95% CI 3.09–6.99, P < 0.001; HR 4.01, 95% CI 2.85–5.65, P < 0.001, respectively), compared with those without LV hypertrophy and enlargement. Cancer and HF have a close and complex relationship.9, 10 Common mechanistic pathways in cancer and HF, including inflammation, cellular metabolic changes, genetic predisposition, clonal haematopoiesis, angiogenesis, are summarized in this issue of the journal.11 Cooperation between cardiologists and oncologists is key to manage properly these patients.12 Zamorano et al.13 provided an overview of the main cardiovascular adverse events of cancer therapy and proposed strategies for risk assessment, prevention, early diagnosis, medical management and long-term follow-up of cardiotoxicity. Frailty is frequent among HF patients and is associated with poor outcome.14, 15 Available knowledge of cachexia, muscle wasting and physical frailty in patients with cardiovascular illness is reviewed by Bielecka-Dabrowa et al.16 Management of end-stage HF needs to include palliative care.17, 18 A position paper provides day-to-day practical clinical guidance on palliation strategies.19 Sahlollbey et al.20 provided a meta-analysis from 10 randomized trials showing that palliative care, compared with usual care, was associated with a reduction in HF hospitalization, and a modest, though significant, improvement of quality of life and symptoms in patients with advanced HF. Cardiac resynchronization therapy (CRT) in HF with reduced ejection fraction (HFrEF) is less used than indicated by guidelines and several studies tried to identify patients with major benefits from CRT.21-23 A position statement in this issue is aimed at overcoming CRT under-utilization, improving patient selection and implementing dedicated post-implant CRT care pathways.24 Kristensen et al.25 studied the prognostic role of intra-ventricular conduction delay in HFrEF patients without a cardiac device enrolled in two recent major clinical trials. They found that a wide QRS was associated with an increased risk of the primary composite outcome of cardiovascular death or HF hospitalization, irrespective of morphology. New-onset left bundle branch block occurred with an incidence of about 2.5% per year, leading to a greater risk of adverse outcomes.

Effect of Adenotonsillectomy on Cardiac Function in Children Age 5-13 Years With Obstructive Sleep Apnea

Changes in left ventricular structure and function have been previously described in children with obstructive sleep apnea (OSA). We aimed to determine if these structural and functional cardiac changes are reversible after treatment of OSA with adenotonsillectomy. Children aged 5 to 13 years with OSA and matched healthy controls were recruited. Adenotonsillectomy occurred within 1 month after diagnosis. Echocardiography and polysomnography were repeated postoperatively. Linear mixed models were fitted to echocardiography measures at baseline and follow-up to assess the effect of OSA on cardiac structure and function. These adjusted for age, gender, race, body mass index, systolic, and diastolic blood pressure. The study sample included 373 children, 199 with OSA and 174 healthy controls. In the control group, 114 children completed the study and 112 completed the study in the OSA group. Children with OSA had reduced diastolic function, lower systolic function, and greater left ventricular mass index at baseline compared with healthy controls (all p < 0.05). Measures of active relaxation, elastic recoil and lengthening of the left ventricle impacted overall diastolic function; each of these worsened with increasing OSA severity. Postoperatively, diastolic function improved in children with OSA compared with controls. There were not significant changes in LV mass index or geometry. In conclusion, children with OSA have impaired left ventricular relaxation during diastole indicating early stage diastolic dysfunction. Adenotonsillectomy for OSA signficantly improved diastolic function. Left ventricular remodeling did not change with improvement of OSA.

Abstract 13300: Hepatocyte Growth Factor and 10-year Change in Left Ventricular Structure: The Multi-Ethnic Study of Atherosclerosis

Introduction: Hepatocyte Growth Factor (HGF) is a mesenchymal cytokine linked to incident heart failure (HF), with recent data from our group showing a strong and independent association with HF with preserved ejection fraction (HFpEF). Cardiac MRI (cMRI) allows for precise analysis of morphologic changes in left ventricular (LV) structure. Increasing LV mass and concentric remodeling (defined by an increasing mass:volume ratio) are imaging markers of HFpEF risk. Whether HGF is associated with adverse LV remodeling over time is unknown. Hypothesis: Higher HGF will be associated with increasing LV mass, decreasing LV volume and increasing mass:volume ratio over 10 yrs. Methods: We studied 4762 participants of the MESA cohort, free of cardiovascular disease (CVD) and HF at baseline, who completed both HGF measurement and cMRI at baseline. Participants with LV EF&lt;50% were excluded. Of these, 2855 completed a 2 nd cMRI at 10 yrs. We examined the cross-sectional and longitudinal associations of HGF and LV parameters using multivariable-adjusted linear mixed effect models. Results: The mean (SD) for age was 61 (10) yrs. Median (IQR) for HGF level was 888 pg/mL (745-1066); 53% women. At baseline, the 3 rd HGF tertile, compared to the 1 st , was associated with greater mass:volume ratio [relative difference 1.66 (0.43, 2.89)] and lower LV end diastolic volume [-1.87 mL (-3.45, -0.28)], after adjustment for CVD risk factors and NT- proBNP (model 2) [Table] . In longitudinal analysis, the 3 rd HGF tertile was also associated with increasing mass:volume ratio [difference in 10-yr change: 4.79 (2.73, 6.85)] and decreasing LV end diastolic volume [-4.97 (-7.10, -2.85)]. Conclusions: In a community cohort, higher HGF levels were independently associated with a concentric LV remodeling pattern of increasing mass:volume ratio and decreasing LV end diastolic volume over 10 yrs. This association may suggest an intermediate phenotype explaining the association of HGF with HFpEF risk.

Abstract 16416: Associations of NT-proBNP and High Sensitivity Cardiac Troponin T Concentrations With 6-year Changes in Left Ventricular Structure and Function in Older Adults: The Atherosclerosis Risk in Community (ARIC) Study

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT) improve prediction of incident heart failure (HF) and are cross-sectionally associated with left ventricular (LV) remodeling, but their associations with changes in cardiac structure and function are unclear. Hypothesis: Concentrations of NT-proBNP and hs-cTnT associate with 6-year change in cardiac structure in older adults. Methods: We studied 1,916 participants aged 67-88 in the ARIC Study free of overt cardiovascular disease at baseline (study Visit 5; 2011-13). We quantified the associations of baseline NT-proBNP and hs-cTnT with subsequent changes in LV structure and systolic and diastolic function assessed by echocardiography over a median of 6.6 (IQR 6.1-7.0) years using multivariable linear regression and restricted cubic spline models. Models adjusted for demographics, systolic blood pressure, heart rate, body mass index, diabetes, hypertension, kidney function, and the baseline echocardiographic value of interest at Visit 5. Results: Mean age was 75±4 years, 60% were female, 23% were black, median hs-cTnT was 9 (IQR 6-13) ng/L and NT-proBNP was 88 (50-157) ng/L at Visit 5. In adjusted models, higher hs-cTnT was modestly associated with 6-year increase in LV wall thickness (p=0.02) but not with changes in LV function. In contrast, higher NT-proBNP at Visit 5 was associated with 6-year increase in LV mass, decline in LV systolic function (ejection fraction, longitudinal and circumferential strain), and worsening of diastolic function (left atrium volume, E/e’, tricuspid regurgitation peak velocity) (all p&lt;0.01, Figure ). These associations were non-linear. Conclusions: Higher NT-proBNP, but not hs-cTnT, concentrations are associated with greater declines in LV systolic and diastolic function over ~6 years in late life.

Association between maternal diabetes and cardiac left ventricular structure and function in the neonate: a study from the Copenhagen Baby Heart Study

Abstract Background Prenatal exposure to maternal diabetes has been associated with increased risk of congenital heart defects. Purpose To evaluate whether maternal diabetes is associated with more subtle morphological and functional cardiac changes in neonates without congenital heart defects. Methods We included 17,869 newborns sampled from the Copenhagen Baby Heart Study, all of whom underwent transthoracic echocardiography within 30 days of delivery. We investigated the association between exposure to maternal diabetes (pre-existing diabetes [type 1 or type 2 diabetes] or gestational diabetes [GDM]) and the neonates' echocardiographic indices of left ventricular structure (left posterior wall thickness in end-diastole [LVPWd], interventricular septum thickness in end-diastole [IVSd], left ventricular internal diameter in end-systole [LVIDs] and end-diastole [LVIDd]), systolic function (fractional shortening [FS], stroke volume [SV]) and diastolic function (mitral valve peak early and atrial filling velocities, deceleration time of early filling, and E/A-ratio), using linear and logistic regression. Models were adjusted for maternal age, infant sex, infant birth weight for gestational age and gestational age in days. In additional analyses, we evaluated the relationship between HbA1C levels in first and third trimester and left ventricular structure and function. Results We found that infants exposed to pre-existing maternal diabetes (n=x) had, on average, a thicker LVPWd (mean difference 0.12 mm [95% CI: 0.06–0.19]), a smaller LVIDs (−0.27 mm [95% CI: −0.46, −0.07]) and LVIDd (−0.43 mm [95% CI: −0.66, −0.19]), and decreased SV (−0.50 ml [95% CI: −0.77, −0.23]). We found no significant differences in IVSd, FS, and measures of diastolic function for infants exposed to pre-existing maternal diabetes compared with infants not exposed to diabetes. Infants exposed to GDM (n=) also had thicker LVPWd (0.06 mm [95% CI: −0.28, −0.01]) and smaller LVIDs (−0.15 mm [95% CI: −0.28, −0.01]); however, on average, IVSd, LVIDd, and measures of systolic and diastolic function did not differ for infants born to mothers with and without GDM. We observed no consistent association between HbA1C levels measured early and late in pregnancy in mothers with diabetes and indices of left ventricular structure and function. Conclusion In conclusion, we found that exposure to maternal pre-existing diabetes, and to a lesser degree GDM, was associated with changes in neonatal left ventricular structure and function, including a thicker left ventricular posterior wall, smaller left ventricular internal diameters, and lower stroke volumes. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Rigsbospitalet Research Foundation