Comparative analysis of ventricular stiffness across species.

Investigating ventricular diastolic properties is crucial for understanding the physiological cardiac functions in organisms and unraveling the pathological mechanisms of cardiovascular disorders. Ventricular stiffness, a fundamental parameter that defines ventricular diastolic functions in chordates, is typically analyzed using the end-diastolic pressure-volume relationship (EDPVR). However, comparing ventricular stiffness accurately across chambers of varying maximum volume capacities has been a long-standing challenge. As one of the solutions to this problem, we propose calculating a relative ventricular stiffness index by applying an exponential approximation formula to the EDPVR plot data of the relationship between ventricular pressure and values of normalized ventricular volume by the ventricular weight. This article reviews the potential, utility, and limitations of using normalized EDPVR analysis in recent studies. Herein, we measured and ranked ventricular stiffness in differently sized and shaped chambers using ex vivo ventricular pressure-volume analysis data from four animals: Wistar rats, red-eared slider turtles, masu salmon, and cherry salmon. Furthermore, we have discussed the mechanical effects of intracellular and extracellular viscoelastic components, Titin (Connectin) filaments, collagens, physiological sarcomere length, and other factors that govern ventricular stiffness. Our review provides insights into the comparison of ventricular stiffness in different-sized ventricles between heterologous and homologous species, including non-model organisms.

Cardiac Function Before Sepsis and Clinical Outcomes.

This cohort study characterizes heterogeneity in cardiac function prior to sepsis and describes associations with hospitalization outcomes and mortality.

Failing with Cyanosis-Heart Failure in End-Stage Unrepaired or Partially Palliated Congenital Heart Disease.

Heart failure in cyanotic congenital heart disease (CHD) is diagnosed clinically rather than relying solely on ventricular function assessments. Patients with cyanosis often present with clinical features indicative of heart failure. Although myocardial injury and dysfunction likely contribute to cyanotic CHD, the primary concern is the reduced delivery of oxygen to tissues. Symptoms such as fatigue, lassitude, dyspnea, headaches, myalgias, and a cold sensation underscore inadequate tissue oxygen delivery, forming the basis for defining heart failure in cyanotic CHD. Thus, it is pertinent to delve into the components of oxygen delivery in this context.

PATHFINDER-CHD: prospective registry on adults with congenital heart disease, abnormal ventricular function, and/or heart failure as a foundation for establishing rehabilitative, prehabilitative, preventive, and health-promoting measures: rationale, aims, design and methods.

BACKGROUND: Adults with congenital heart defects (ACHD) globally constitute a notably medically underserved patient population. Despite therapeutic advancements, these individuals often confront substantial physical and psychosocial residua or sequelae, requiring specialized, integrative cardiological care throughout their lifespan. Heart failure (HF) is a critical challenge in this population, markedly impacting morbidity and mortality. AIMS: The primary aim of this study is to establish a comprehensive, prospective registry to enhance understanding and management of HF in ACHD. Named PATHFINDER-CHD, this registry aims to establish foundational data for treatment strategies as well as the development of rehabilitative, prehabilitative, preventive, and health-promoting interventions, ultimately aiming to mitigate the elevated morbidity and mortality rates associated with congenital heart defects (CHD). METHODS: This multicenter survey will be conducted across various German university facilities with expertise in ACHD. Data collection will encompass real-world treatment scenarios and clinical trajectories in ACHD with manifest HF or at risk for its development, including those undergoing medical or interventional cardiac therapies, cardiac surgery, inclusive of pacemaker or ICD implantation, resynchronization therapy, assist devices, and those on solid organ transplantation. DESIGN: The study adopts an observational, exploratory design, prospectively gathering data from participating centers, with a focus on patient management and outcomes. The study is non-confirmatory, aiming to accumulate a broad spectrum of data to inform future hypotheses and studies. PROCESSES: Regular follow-ups will be conducted, systematically collecting data during routine clinical visits or hospital admissions, encompassing alterations in therapy or CHD-related complications, with visit schedules tailored to individual clinical needs. ASSESSMENTS: Baseline assessments and regular follow-ups will entail comprehensive assessments of medical history, ongoing treatments, and outcomes, with a focus on HF symptoms, cardiac function, and overall health status. DISCUSSION OF THE DESIGN: The design of the PATHFINDER-CHD Registry is tailored to capture a wide range of data, prioritizing real-world HF management in ACHD. Its prospective nature facilitates longitudinal data acquisition, pivotal for comprehending for disease progression and treatment impacts. CONCLUSION: The PATHFINDER-CHD Registry is poised to offer valuable insights into HF management in ACHD, bridging current knowledge gaps, enhancing patient care, and shaping future research endeavors in this domain.

Impact of lead position on tricuspid regurgitation, ventricular function, and heart failure exacerbation and mortality after cardiac implantable electronic device implantation. Preliminary results from the PACE-RVTR Registry.

BACKGROUND: The most frequent mechanism of lead-related tricuspid regurgitation (LRTR), which occurs in 7.2% to 44.7% of patients implanted with a cardiac implantable electronic device (CIED), is leaflet impingement or the restriction of its movement by a ventricular lead. It is unclear if the position of the lead tip - in the right ventricular apex (RVA) or other location (non-RVA) - has any influence on the development of LRTR. The study aimed to determine the impact of the CIED lead tip position on the development or progression of tricuspid regurgitation (TR) and its potential impact on heart failure exacerbation and mortality. METHODS: One hundred and two consecutive patients who received CIEDs between March 2020 and October 2021 were included in the prospective registry (PACE-RVTR). Patients were assigned to two groups depending on the lead position - the RVA group and the non-RVA group. All patients underwent echocardiographic evaluation before implantation and one year later. RESULTS: In terms of baseline clinical characteristics, the two groups did not differ. Before CIED implantation, patients in the non-RVA group had better left ventricular systolic function (P = 0.004). Pacemakers were implanted more often in the non-RVA group (P = 0.001) while implantable cardioverter-defibrillators in the RVA group (P = 0.008). Progression to severe or massive TR was more common in the non-RVA group (P = 0.005). CONCLUSION: Severe and massive TR occurred more often in patients with the non-RVA position of the lead. The right ventricular lead position did not impact heart failure progression or all-cause mortality at two-year follow-up.

Longitudinal analysis of systemic ventricular function and atrioventricular valve function after the Norwood procedure.

OBJECTIVES: To evaluate longitudinal systemic ventricular function and atrioventricular valve regurgitation in patients after the neonatal Norwood procedure. METHODS: Serial postoperative echocardiographic images before Fontan completion were assessed in neonates who underwent the Norwood procedure between 2001 and 2020. Ventricular function and atrioventricular valve regurgitation were compared between patients with modified Blalock-Taussig shunt and right ventricle to pulmonary artery conduit. RESULTS: A total of 335 patients were identified including 273 hypoplastic left heart syndrome and 62 of its variants. Median age at Norwood was 8 (7-12) days. Modified Blalock-Taussig shunt was performed in 171 patients and the right ventricle to pulmonary artery conduit in 164 patients. Longitudinal ventricular function and atrioventricular valve regurgitation were evaluated using a total of 4352 echocardiograms. After the Norwood procedure, ventricular function was initially worse (1-30 days) but thereafter better (30 days to stage II) in the right ventricle to pulmonary artery conduit group (P < 0.001). After stage II, the ventricular function was inferior in the right ventricle to the pulmonary artery conduit group (P < 0.001). Atrioventricular valve regurgitation between the Norwood procedure and stage II was more frequent in the modified Blalock-Taussig shunt group (P < 0.001). After stage II, there was no significant difference in atrioventricular valve regurgitation between the groups (P = 0.171). CONCLUSIONS: The effect of shunt type on haemodynamics after the Norwood procedure seems to vary according to the stage of palliation. After the Norwood, the modified Blalock-Taussig shunt is associated with poorer ventricular function and worse atrioventricular valve regurgitation compared to right ventricle to pulmonary artery conduit. Whereas, after stage II, modified Blalock-Taussig shunt is associated with better ventricular function and comparable atrioventricular valve regurgitation, compared to the right ventricle to pulmonary artery conduit.

Symptoms during pregnancy in primiparous women with congenital heart disease.

Background: As more women with congenital heart disease (CHD) are reaching childbearing age, it becomes more common for their symptoms to be evaluated during pregnancy. However, pregnancy-related symptoms are similar to those caused by heart disease. This study investigated the prevalence of factors associated with symptoms during pregnancy in women with CHD. Methods: The national birth register was searched for primiparous women with CHD who were registered in the national quality register for patients with CHD. Results: Symptoms during the third trimester were reported in 104 of 465 evaluated women. The most common symptom was palpitations followed by dyspnea. Factors associated with symptoms were tested in a univariable model; higher NYHA classification (>1) (OR 11.3, 95%CI 5.5-23.2), low physical activity (≤3 h/week) (OR 2.1 95%CI 1.3-3.6) and educational level ≤ 12 years (OR 1.9 95%CI 1.2-3.0) were associated with having symptoms. In multivariable analysis, low physical activity level (OR 2.4 95%CI 1.2-5.0) and higher NYHA class (OR 11.3 95%CI 5.0-25.6) remained associated with symptoms during pregnancy. There were no cases with new onset of impaired systemic ventricular function during pregnancy. Conclusion: Symptoms during pregnancy are common in women with CHD but are often already present before pregnancy. Because ordinary symptoms during pregnancy often overlap with symptoms of heart disease, it is important to know if symptoms were present before pregnancy and if they became worse during pregnancy. These results should be included in pre-pregnancy counselling and considered in the monitoring during pregnancy.

ECG-free cine MRI with data-driven clustering of cardiac motion for quantification of ventricular function.

BACKGROUND: Despite the widespread use of cine MRI for evaluation of cardiac function, existing real-time methods do not easily enable quantification of ventricular function. Moreover, segmented cine MRI assumes periodicity of cardiac motion. We aim to develop a self-gated, cine MRI acquisition scheme with data-driven cluster-based binning of cardiac motion. METHODS: A Cartesian golden-step balanced steady-state free precession sequence with sorted k-space ordering was designed. Image data were acquired with breath-holding. Principal component analysis and k-means clustering were used for binning of cardiac phases. Cluster compactness in the time dimension was assessed using temporal variability, and dispersion in the spatial dimension was assessed using the Calinski-Harabasz index. The proposed and the reference electrocardiogram (ECG)-gated cine methods were compared using a four-point image quality score, SNR and CNR values, and Bland-Altman analyses of ventricular function. RESULTS: A total of 10 subjects with sinus rhythm and 8 subjects with arrhythmias underwent cardiac MRI at 3.0 T. The temporal variability was 45.6 ms (cluster) versus 24.6 ms (ECG-based) (p < 0.001), and the Calinski-Harabasz index was 59.1 ± 9.1 (cluster) versus 22.0 ± 7.1 (ECG based) (p < 0.001). In subjects with sinus rhythm, 100% of the end-systolic and end-diastolic images from both the cluster and reference approach received the highest image quality score of 4. Relative to the reference cine images, the cluster-based multiphase (cine) image quality consistently received a one-point lower score (p < 0.05), whereas the SNR and CNR values were not significantly different (p = 0.20). In cases with arrhythmias, 97.9% of the end-systolic and end-diastolic images from the cluster approach received an image quality score of 3 or more. The mean bias values for biventricular ejection fraction and volumes derived from the cluster approach versus reference cine were negligible. CONCLUSION: ECG-free cine cardiac MRI with data-driven clustering for binning of cardiac motion is feasible and enables quantification of cardiac function.

Longitudinal Strain vs. Conventional Echocardiographic Parameters in the First Week of Life in Healthy Term Newborns.

The first week of life is characterized by substantial alterations in hemodynamic conditions. Changes in myocardial contractility will reflect these changes. We aimed to assess right and left ventricular function on the third and seventh days of life in 50 healthy term newborns. To assess myocardial function, we used speckle tracking echocardiography. Pulsed-wave tissue Doppler imaging, M-mode, Doppler and pulsed-wave Doppler were also used to assess ventricular function. We found a significant increase in both right and left longitudinal strain and an increase in systolic and diastolic tissue Doppler velocities, whereas most other parameters remained unchanged. At both time points, the measured parameters were significantly greater for the right ventricle, but the changes with time were similar for both ventricles. We also found an increase in right ventricular outflow tract acceleration time as an indirect sign of decreasing pulmonary vascular resistance and an increase in systolic blood pressure, pointing to increasing systemic vascular resistance. Together with a decreasing proportion of patients with patent ductus arteriosus, the estimated left ventricular cardiac output decreased and right ventricular cardiac output increased but not to a statistically significant degree. In conclusion, the results of our study show how different echocardiographic techniques capture hemodynamic changes and changes in myocardial contractility and compliance. Both longitudinal strain and tissue Doppler imaging parameters seem to offer greater sensitivity in comparison with conventional echocardiographic parameters.

Serum neuregulin 1 in relation to ventricular function and subclinical atherosclerosis in type 2 diabetes patients.

BACKGROUND AND AIMS: Neuregulin 1 (NRG-1) is one of the members of the epidermal growth factors proteins. The present study provides novel insights into the relationship between serum levels of NRG-1 and insulin resistance, subclinical atherosclerosis and cardiac dysfunction that occur in type 2 diabetes (T2D). METHODS: The study included 50 patients with T2D and 40 healthy age- and gender-matched controls. Serum NRG-1 was measured using ELISA. Glycemic parameters, lipid profile and insulin resistance were assessed. Trans-thoracic echocardiography and carotid intima media thickness (CIMT) were studied for all study subjects. RESULTS: T2D patients had significantly lower serum NRG-1 levels than controls. Serum NRG-1 was negatively correlated with age, fasting blood glucose, HbA1c, insulin resistance, blood urea, serum creatinine and LDL-C, and positively correlated with HDL-C, eGFR and CIMT. Regarding echocardiographic variables, serum NRG-1 was found to correlate positively with left ventricular global longitudinal strain and negatively with E/Ea ratio. NRG-1 was found to predict subclinical atherosclerosis in type 2 diabetes patients at a cut-off value<108.5pg/ml with 78% sensitivity and 80% specificity. CONCLUSIONS: A robust relationship was found between serum NRG-1 levels and hyperglycemia, insulin resistance, subclinical atherosclerosis, and cardiac dysfunction in patients with type 2 diabetes. These results shed light on a possible role of NRG-1 as a potential noninvasive biomarker for detection of cardiometabolic risk in T2D.

Ventricular Ejection Fraction and Global Strains in Connection with the Volume Regulation Graph.

Ejection fraction (EF) is traditionally considered useful to infer ventricular function. Newer metrics such as global function index (GFI) and various strains add supplemental diagnostic or prognostic value. All these candidates refer to dimensionless ratios, rather than to the characteristics of the underlying components. Therefore, we introduced the volume regulation graph (VRG), relating end-systolic volume (ESV) to end-diastolic volume (EDV). An individual patient is then uniquely defined by the prevailing working point in the volume domain. Alternatively, the combination of EF=(1-ESV/EDV) and any suitable companion (denoted as C) metric (e.g. the Pythagorean mean) specifies this working point.An expression relates EF to global longitudinal (GLS) and circumferential strain (GCS): ESV/EDV = (GLS+1) (GCS+1)2, resembling the empirical regression equation for the VRG. However, the latter has a non-zero intercept (mL). The discrepancy can be solved by the introduction of one or more pertinent companion metrics.We studied 96 patients by cardiac magnetic resonance imaging and calculated EF, EFC, GFI, GLS and GCS. The GFI is inversely related to GLS (R2=0.26). For regression we found: ESV=0.74 EDV-27.0 with R2=0.81 for N=96. Similar results were obtained for echocardiography data (N=25). Graphs relating EF to GLS and GCS indicate that EFC can distinguish patients with nearly identical values for these 3 metrics.Thus, the VRG offers a unifying framework that visualizes the association between ESV and EDV, while documenting iso-EF and iso-EFC trajectories. Newer metrics including GFI, GLS and GCS require consideration of a companion variable such as EFC to permit a comprehensive analysis.Clinical Relevance- The VRG allows insight into ventricular functioning and illustrates the working point concept. Companion metrics (having a physical dimension) should be considered in conjunction with any traditional ratio-based index.

Outcomes of coronary artery bypass surgery using modified del Nido cardioplegia in patients with poor ventricular function.

BACKGROUND: del Nido cardioplegia (DN) has been shown to be safe in adult patients undergoing isolated coronary artery bypass grafting with normal left ventricular ejection fraction. We sought to determine whether it was also safe in adult patients with diminished left ventricular function. METHODS: All patients with preoperative left ventricular ejection fraction ≤ 40% undergoing isolated coronary artery bypass grafting between 1/1/2019 and 7/10/2022 were retrospectively analyzed. Off-pump and beating heart cases were excluded. Patients were divided by surgeon preference between conventional cardioplegia (CCP) and DN. Baseline and intraoperative characteristics and short-term postoperative outcomes were compared. RESULTS: Six surgeons performed 829 isolated coronary artery bypass operations during the study. Two-hundred seventy-two met study criteria. Three surgeons used exclusively CCP for the duration of the study, two used exclusively DN and one switched from CCP to DN mid-way through. Group totals were: CCP n = 181 and DN n = 91. There were no significant differences in baseline characteristics including mean left ventricular ejection fraction (CCP 32.5 ± 7.4% vs. DN 33.4 ± 7.29%, p = 0.939). Other than a significant decrease in bypass time for DN (113.20 ± 37.2 vs. 122.43 ± 34.3 min, p = 0.043) there were no intergroup differences in urgency, number of grafts, ischemic time or incidence of blood transfusion. Postoperative outcomes between CCP and DN were similar including incidence of atrial fibrillation (12.2% vs. 8.8%, p = 0.403), intensive care length of stay (3.7 ± 2.3 vs. 4.3 ± 3.7 days, p = 0.886), total length of stay (5.7 ± 3.7 vs. 6.3 ± 4.4 days, p = 0.922) and 30-day mortality (3.85% vs. 1.10%, p = 0.205). CONCLUSION: Compared to conventional cardioplegia, del Nido cardioplegia provides equivalent short-term outcomes in patients with low left ventricular ejection fraction undergoing isolated coronary artery bypass grafting.

Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.

BACKGROUND: Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling. METHODS: In three independent murine heart failure models, including models of metabolic stress, ischemia, and pressure overload, mice underwent 5 Gy cardiac radiation or sham treatment followed by echocardiography. Immunofluorescence, flow cytometry, and non-invasive PET imaging were employed to evaluate cardiac macrophages and fibroblasts. Serial cardiac magnetic resonance imaging (cMRI) from patients with cardiomyopathy treated with 25 Gy cardiac RT for ventricular tachycardia (VT) was evaluated to determine changes in cardiac function. FINDINGS: In murine heart failure models, cardiac radiation significantly increased LV ejection fraction and reduced end-diastolic volume vs. sham. Radiation resulted in reduced mRNA abundance of B-type natriuretic peptide and fibrotic genes, and histological assessment of the LV showed reduced fibrosis. PET and flow cytometry demonstrated reductions in pro-inflammatory macrophages, and immunofluorescence demonstrated reduced proliferation of macrophages and fibroblasts with RT. In patients who were treated with RT for VT, cMRI demonstrated decreases in LV end-diastolic volume and improvements in LV ejection fraction early after treatment. CONCLUSIONS: These results suggest that 5 Gy cardiac radiation attenuates cardiac remodeling in mice and humans with heart failure. FUNDING: NIH, ASTRO, AHA, Longer Life Foundation.

Evaluation of right-ventricular function by two-dimensional echocardiography and two-dimensional speckle-tracking echocardiography in patients with successful RCA CTO recanalization.

OBJECTIVES: Chronic total occlusion (CTO) of the right coronary artery (RCA) is common in patients with coronary artery disease. Although revascularization techniques and success rates have improved significantly in recent years, there are still no studies investigating possible effects of successful recanalization of RCA CTO on the right-ventricular (RV) function. With this study, we aimed to evaluate RV function after recanalization of the RCA by two-dimensional transthoracic echocardiography (2DE) and additional two-dimensional speckle-tracking echocardiography (2DSTE). METHODS AND RESULTS: Our analysis included 102 patients undergoing successful RCA CTO recanalization at the University Medical Center of Mainz. All patients underwent 2DE and 2DSTE to assess RV function before PCI procedure and 6 months after successful revascularization. We found an altered RV function in our collective at baseline assessed by 2DSTE with a significant improvement at 6 month follow-up (baseline RV free wall strain: - 20.7 [- 6.3 to - 32.0] % vs. - 23.4 [- 8.3 to - 39.3] % at follow-up, p < 0.001 and baseline RV global strain - 15.9 [- 6.0 to - 25.7] % vs. - 17.9 [- 7.0 to - 29.5] % at follow-up, p < 0.001). CONCLUSION: RV function was altered in patients with RCA CTO and showed significant improvement after successful recanalization. We also noticed an improvement in patient-reported clinical symptoms. Our study suggests that CTO procedure is a beneficial treatment option in symptomatic patients with RCA CTO.

Autonomic control of ventricular function in health and disease: current state of the art.

PURPOSE: Cardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of the art on the pathological remodeling that occurs within the autonomic nervous system with cardiac injury and available neuromodulatory therapies for autonomic dysfunction in heart failure. METHODS: Data from peer-reviewed publications on autonomic function in health and after cardiac injury are reviewed. The role of and evidence behind various neuromodulatory therapies both in preclinical investigation and in-use in clinical practice are summarized. RESULTS: A harmonic interplay between the heart and the autonomic nervous system exists at multiple levels of the neuraxis. This interplay becomes disrupted in the setting of cardiovascular disease, resulting in pathological changes at multiple levels, from subcellular cardiac signaling of neurotransmitters to extra-cardiac, extra-thoracic remodeling. The subsequent detrimental cycle of sympathovagal imbalance, characterized by sympathoexcitation and parasympathetic withdrawal, predisposes to ventricular arrhythmias, progression of heart failure, and cardiac mortality. Knowledge on the etiology and pathophysiology of this condition has increased exponentially over the past few decades, resulting in a number of different neuromodulatory approaches. However, significant knowledge gaps in both sympathetic and parasympathetic interactions and causal factors that mediate progressive sympathoexcitation and parasympathetic dysfunction remain. CONCLUSIONS: Although our understanding of autonomic imbalance in cardiovascular diseases has significantly increased, specific, pivotal mediators of this imbalance and the recognition and implementation of available autonomic parameters and neuromodulatory therapies are still lagging.