Ventricular Outflow Tract Diameter Research Articles

Longitudinal Outcomes of Patients with Aortic Stenosis Stratified by Sex: An Asian Perspective.

Severe aortic stenosis (AS) stratified by sex has been increasingly studied in the European population. Sex-specific outcomes in Asian patients with AS remain poorly defined. Hence, we aimed to study the clinical characteristics and impact of sex in moderate-to-severe AS, undergoing both invasive and conservative interventions in an Asian cohort over 10 years. Consecutive data with echocardiographic diagnoses of AS were stratified according to gender in a tertiary academic center between 2011 and 2021. Demographics, comorbidities, and clinical outcomes were compared. Seven hundred and three (703) patients were included (56%, n = 397 were female). Calcific AS was the dominant etiology in both genders. Females had higher incidences of anemia (p < 0.001) and chronic kidney disease (p = 0.026); although, females had lower incidences of cardiovascular complications of coronary artery disease (CAD) (p = 0.002) and prior acute myocardial infarction (AMI) (p = 0.015). Echocardiographically, females had a smaller left ventricular outflow tract diameter (LVOTd) (p < 0.001), LV mass (p < 0.001), and left ventricle end diastolic volume (LVEDV) (p < 0.001). Conversely, the left atrial (LA) area (p < 0.001) and volume index (LAVI) (p < 0.001) were larger in females. Females had higher average E/e' (p = 0.010) ratios compared to males. The mean follow-up duration between genders was 4.1 ± 3.3 years. Upon univariate analysis, a greater proportion of female AS patients encountered cardiovascular (CV) hospitalization during follow-up (female: 27.5%, n = 109 vs. male: 18.3%, n = 56; p = 0.005) compared to male patients, but there were no significant differences for the outcomes of heart failure (p = 0.612), stroke (p = 0.664), and all-cause mortality (p = 0.827). Fewer females underwent aortic valve (AV) intervention compared to males (21.2% vs. 27.8%, p = 0.042), albeit with a longer duration to AV intervention (3.6 years ± 2.4 vs. 2.6 years ± 2.3, p = 0.016). In the severe AS cohort, female sex remained an independent predictor for subsequent heart failure (aHR 2.89, 95% CI 1.01-8.29, p = 0.048) and CV hospitalization (aHR 20.0, 95% CI 1.19-335, p = 0.037) after adjustments for age, ethnicity, body mass index (BMI), comorbidities, left ventricular ejection fraction (LVEF), and AV intervention. There was no difference in heart failure, stroke, and all-cause mortality outcomes between male and female Asian patients with moderate-to-severe AS. However, there were more cardiovascular hospitalizations, with fewer and longer duration to AV intervention in females compared to males in our cohort.

Assessing the repeatability, reliability, and precision of right ventricular outflow tract and mid-pulmonary artery diameters, velocity time integrals, and agreement between site-specific stroke volumes

BackgroundRight ventricular (RV) stroke volume (SV) can be calculated via Doppler echocardiography at multiple sites in the right chambers. However, the agreement between the calculated SVs at these sites is unknown. We aimed to assess the repeatability, reliability, and precision of the distal right ventricular outflow tract diameter (RVOTD), the mid-pulmonary artery diameter (MPAD), the right ventricular outflow tract velocity time integral (VTI), and the mid-pulmonary artery velocity time integral (MPAVTI). Additionally, we evaluated the agreement between RVOTSV and MPASV.MethodsFour observers each evaluated approximately 100 patients (n = 406). Basic measurements were made over three cardiac cycles, and the repeatability, reliability, and precision of the measurements were calculated. The agreement between the two methods was presented as intraclass correlation coefficients.ResultsThe repeatability coefficient ranges for RVOTD, MPAD, RVOTVTI, and MPAVTI were 2–3 mm, 2–4 mm, 2.1–2.8 cm, and 2.4–4.1 cm, respectively. The minimal detectable change ranges for these variables were 2–4 mm, 2–5 mm, 2.2–3.0 cm, and 2.6–4.3 cm, respectively. The respective precision ranges for RVOTD, MPAD, RVOTVTI, and MPAVTI were 2.7–4.7%, 2.4–5.4%, 5.0–7.4%, and 5.4–9.2%. There were significant correlations and agreements between MPASV and RVOTSV, with the Pearson correlation coefficient ranging from 0.63 to 0.89 (P < 0.001). The intraclass correlation coefficient ranged from 0.56 to 0.89 (P < 0.001), although there was a significant bias of 1.9–11.3 mL (P < 0.001).ConclusionsThe RVOTD, MPAD, RVOTVTI, and MPAVTI measurements were repeatable, reliable, and precise. The agreement between RVOTSV and MPASV ranged from fair to excellent, although significant bias, along with a wide limit of agreement, was observed. Consequently, these methods cannot be used interchangeably.

Effect of stereotactic body radiation therapy on left ventricular diastole function in symptomatic patients with hypertrophic obstructive cardiomyopathy

Abstract Background We applied stereotactic body radiotherapy (SBRT) for the first time in the treatment of patients with hypertrophic obstructive cardiomyopathy (HOCM), and significant improvements in symptoms and diastolic function were observed after treatment. Objectives To evaluate the impact of SBRT on cardiac structure, function, and clinical indicators in patients with HOCM. Methods This study included 12 drug-refractory symptomatic HOCM patients (6 who underwent SBRT and 6 who received pharmacological treatment alone) and conducted a retrospective analysis of their clinical data. Transthoracic echocardiography was used to assess various ultrasound parameters, including interventricular septal thickness, left ventricular outflow tract diameter, peak pressure gradient and diastolic function before treatment and at 1, 3, and 6 months after treatment. Additionally, assessments were made for symptoms; laboratory test results (NT-proBNP, cTnT, CK-mb, and CRP); 6-minute walk test results; New York Heart Association (NYHA) functional classification; and Kansas score before and 6 months after treatment. Results HOCM patients showed significant improvement in mitral valve systolic anterior motion after SBRT. Compared to that at baseline, the interventricular septum thickness gradually decreased at 1, 3, and 6 months after treatment (-8.8%, -8.0%, -14.4%, respectively) (P&amp;lt;0.05). Compared to those in the drug group, the left ventricular diastolic function and structural parameters, including the interventricular septum thickness (mean change from baseline of -3 mm [95% CI: -5.2 to -0.8 mm] and 1.3 mm [95% CI: 0.5 to 2.2 mm]; P&amp;lt;0.05), and the LA GLS (change of 2.1% [-0.03% to 4.2%] and -0.9% [-3.1% to 1.3%]; P&amp;lt;0.05), were significantly improved in HOCM patients at 6 months posttreatment. Similarly, the clinical indicators, including KCCQ, increased from baseline (61 (range, 47.3-70) to 84 (range, 70-89.5) at 6 months posttreatment (P&amp;lt;0.05), and the 6-minute walk test score increased from 187 meters (range, 50-370) to 401 meters (range, 280-540) (P&amp;lt;0.05). Conclusion SBRT significantly improved left ventricular diastolic function and reduced interventricular septum thickness in HOCM patients. Symptoms, exercise capacity and clinical indicators improved after SBRT in HOCM patients.

Developmental nicotine exposure alters cardiovascular structure and function in neonatal and juvenile rats.

Here we test the hypothesis that continuous nicotine exposure throughout pre- and postnatal development (developmental nicotine exposure, DNE) alters the cardiovascular structure and function in neonatal and juvenile rats. Echocardiography showed that DNE reduced left ventricular mass, left ventricular outflow tract (LVOT) diameter, and posterior wall thickness, but only in females. Both male and female DNE rats had a lower end-systolic volume, higher ejection fraction, and increased fractional shortening, with unchanged stroke volume and cardiac output. Left ventricular single cardiac myocytes from male and female DNE animals exhibited increased calcium-evoked maximal tension with no effect on EC50. Tail-cuff plethysmography in awake rats showed that DNE males had lower systolic blood pressure and higher heart rate than control males. No significant changes in preload, afterload, or the in vitro renal artery response to vasodilators were observed. The results suggest that DNE enhances myocyte tension-generating capacity, possibly compensating for an unknown developmental insult, which may differ in males and females. Although this adaptation maintains normal resting cardiac function, it may lead to reduced cardiac reserve, increased energy demand, and elevated oxidative stress, potentially compromising both short- and long-term cardiovascular health in developing neonates.NEW & NOTEWORTHY Developmental nicotine exposure (DNE) induced cardiovascular changes in neonatal/juvenile rats. Relative to controls, females had reduced left ventricular mass and dimensions, while both sexes had increased ejection fraction and fractional shortening. DNE increased calcium-evoked tension in cardiac myocytes, suggesting an adaptive mechanism as resting cardiac output was preserved. Despite normal resting function, these changes may reduce cardiac reserve, potentially compromising long-term cardiovascular health. These novel findings highlight how DNE disrupts cardiovascular development and function.

Cardiac structural and functional changes in OSAHS patients with heart failure with preserved ejection fraction and atrial fibrillation

ObjectiveTo explore the cardiac structural and functional changes in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF).MethodsThis retrospective study included 336 OSAHS patients with HFpEF. They were divided into Groups A (without an AF history and no AF episodes during cardiac color ultrasound examination), B (an AF history but no AF episodes), and C (an AF history and AF episodes). They all received cardiac color ultrasound examinations. Cardiac structural and functional changes in ultrasonic cardiograms were compared between the three groups.ResultsCompared with Groups A and B, Group C showed increased left atrial diameter (LAD), left atrial volume (LAV), right ventricular diameter at end-diastole (RV-D1), right ventricular diameter at end-systole (RV-D2), right ventricular outflow tract diameter (RVOT2), right atrial diameter at end-diastole (RA-D1), right atrial diameter at end-systole (RA-D2), and right atrial area (RAA) (p < 0.05). Compared with Group A, Group C showed decreased fractional shortening (FS), left ventricular ejection fraction (LVEF), deceleration time (DT), isovolumic relaxation time (IVRT), E/E’ ratio, and peak filling velocity (FPV), as well as increased E and E’ (p < 0.01). Compared with Group B, Group C showed decreased FS and increased E and FPV (p < 0.01).ConclusionIn OSAHS patients with HFpEF and AF, cardiac remodeling and AF incidence are increased with the severity of OSAHS. OSAHS patients with HFpEF combined with AF have a significantly higher abnormality rate in right heart structural indices rather than left heart, mainly in the right atrium.

Accuracy of Echocardiographic Cardiac Output Assessment by Critical Care Fellows.

Advanced critical care echocardiography comprises a specific set of qualitative and quantitative point-of-care echocardiography skills, including a reliable, noninvasive method to measure cardiac output. This technique requires echocardiographic measurement of left ventricular outflow tract (LVOT) diameter and LVOT velocity time integral (VTI). Although there is a demand among critical care fellows to learn these advanced techniques, there are no data describing the acquisition of mastery in these skills. This pilot study aims to describe the accuracy of echocardiographic measurement of LVOT diameter and LVOT VTI obtained by critical care fellows after an educational intervention, as well as to enhance validation evidence for an image scoring assessment that is applicable to these measurements. We implemented a brief mastery learning intervention to teach the measurement of LVOT diameter and VTI. Fellow measurements of these parameters, along with the corresponding echocardiographic images, were compared with a gold standard of measurements obtained by professional echocardiography technicians and interpreted by cardiologists. Seven fellows performed 35 echocardiograms on 32 patients. The average fellow-reported LVOT VTI was 17.0 ± 4.37 cm, whereas the average cardiologist-reported VTI was 17.3 ± 5.19 cm. The correlation (r) between fellow and cardiologist-reported VTI was 0.73 (P < 0.001), with a mean percent difference of 19.5 ± 12.0%. The average fellow-reported LVOT diameter was 2.07 ± 0.23 cm, whereas the average cardiologist-reported LVOT diameter was 2.08 ± 0.22 cm. The correlation (r) between fellow and cardiologist-reported LVOT diameter was 0.51 (P = 0.004), with a mean percent difference of 8.05 ± 7.0%. The sensitivity for fellows to detect an abnormal LVOT VTI was 91%, with a specificity of 43%. Critical care fellow measurement of LVOT VTI and LVOT diameter demonstrated strong and moderate positive correlations with cardiologist-reported values, respectively, with acceptable clinical agreement. However, interrater reliability and percent differences showed room for improvement. Education in these advanced skills is resource intensive, and additional research is needed to determine the most effective approach to training fellows.

O59 INFLUENCE OF CIRCADIAN BLOOD PRESSURE PATTERN ON RIGHT VENTRICULAR STRUCTURE AND FUNCTION IN PATIENTS WITH ARTERIAL HYPERTENSIION

Background and Objective: It is well proven, that arterial hypertension affects left side of the heart and causes its remodeling and functional changes. Since heart works as a unit and has ventricular interdependence, aim of the study was to assess influence of hypertension and circadian blood pressure (BP) profile on a right ventricular structure and function. Methods: 75 hypertensive patients (57.13±7.27 y/o) and 25 normotensive control subjects (57.56±7.55 y/o) were involved in a study. All of them were males without history of coronary artery disease, cerebrovascular or peripheral artery disease, obstructive lung disease, significant valvular heart disease or heart failure. All of them were either lifetime nonsmokers, or stopped smoking more than 5 years. All the patients underwent to 24-hour ambulatory BP monitoring and heart ultrasound with tissue doppler imaging. Results: Hypertensive patients with dipper circadian BP profile had higher TAPSE (19±1.586 vs 17.708±2.857; P&lt;0.05), higher right ventricular ejection fraction (55.103±4.597 vs 47.829±14.605; P&lt;0,005) and lower right ventricular outflow tract diameter (29.985±3.932 vs 32.639±3.510; P&lt;0/05). None of the echo parameters were different between normotensive subjects with different circadian BP pattern. Trans tricuspid valve early diastolic (E) and late diastolic (A) peak velocities were significantly lower in hypertensive patients (1.416±0.130 vs 0.897±1.49; P&lt;0.005). Hence, non-dipper hypertensives had significantly lower tricuspid E/A ratio in comparison with dippers (0.812±0.094 vs 1.048±0.101; P&lt;0.00001). Interventricular septum and posterior wall diameters were higher in non-dipper hypertensives (1.134±0.131 vs. 1.322±0.138; P&lt;0.00001 and 1.072±0.175 vs. 1.254±0.135; P&lt;0.001; respectively). Conclusion: Study data show increased interdependence between two ventricles. Patients with arterial hypertension have systole-diastolic dysfunction, which especially well is present in patients with non-dipper circadian BP profile.

Centhaquine Increases Stroke Volume and Cardiac Output in Patients with Hypovolemic Shock.

Introduction: Centhaquine is a resuscitative agent that acts on α2B adrenergic receptors. Its effect on cardiac output in hypovolemic shock patients has not been reported. Methods: This pilot study was conducted in 12 hypovolemic shock patients treated with centhaquine who participated in an open-label phase IV study (NCT05956418). Echocardiography was utilized to measure stroke volume (SV), cardiac output (CO), left ventricular outflow tract velocity time integral (LVOT-VTI) and diameter (LVOTd), heart rate (HR), left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), and inferior vena cava (IVC) diameter before (0 min) and 60, 120, and 300 min after centhaquine (0.01 mg/kg) iv infusion for 60 min. Results: SV was significantly increased after 60, 120, and 300 min. CO increased significantly after 120 and 300 min despite a decrease in HR. IVC diameter and LVOT-VTI at these time points significantly increased, indicating the increased venous return. LVEF and LVFS did not change, while the mean arterial pressure (MAP, mmHg) increased after 120 and 300 min. Positive correlations between IVC diameter and SV (R2 = 0.9556) and between IVC diameter and MAP (R2 = 0.8928) were observed, which indicated the effects of an increase in venous return on SV, CO, and MAP. Conclusions: Centhaquine-mediated increase in venous return is critical in enhancing SV, CO, and MAP in patients with hypovolemic shock; these changes could be pivotal for reducing shock-mediated circulatory failure, promoting tissue perfusion, and improving patient outcomes. Trial Registration: CTRI/2021/01/030263 and NCT05956418.

Echocardiographic and clinical features of patients developing prosthesis‐patient mismatch after transcatheter aortic valve replacement: Insights from the Recovery-TAVR registry

The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage. 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria. 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, P = .33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 P = .46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, P = .04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, P = .02), reduced SVi (34.2 vs 38 mL/m2, P < .01) and transaortic flow rate (190.6 vs 211 mL/s, P < .01). At predischarge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, P < .01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, P = .03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs 44 IQR 35-59 in those without, P = .02)). No evidence of a significant impact of PPM on overall (P = .71) and CV (P = .70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, P = .03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, P < .001) and LVOT diameter (OR 0.79, 0.65-0.95, P = .01) had protective effect. PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk.

Right ventricular outflow tract diameter change with exercise: a prospective exercise echocardiography and invasive CPET study.

While cardiac output reserve with exercise predicts outcomes in cardiac and pulmonary vascular disease, precise quantification of exercise cardiac output requires invasive cardiopulmonary testing (iCPET). To improve the accuracy of cardiac output reserve estimation with transthoracic echocardiography (TTE), this prospective study aims to define changes in right ventricular outflow tract diameter (RVOTd) with exercise and its relationship with invasively measured haemodynamics. Twenty subjects underwent simultaneous TTE and iCPET, with data collected at rest, leg-raise, 25 W, 50 W (n = 16), 75 W (n = 14), and 100 W (n = 6). This was followed by a second exercise study with real-time RV pressure-volume loops at similar stages (except leg-raise). The overall cohort included heart failure with preserved ejection fraction (n = 12), pulmonary arterial hypertension (n = 5), and non-cardiac dyspnoea (n = 3). RVOTd was reverse engineered from the TTE-derived RVOT velocity time integral (VTI) and iCPET-derived stroke volume, using the formula: Fick stroke volume = RVOT VTI × RVOT area (wherein RVOT area = π × [RVOTd/2]2). RVOTd increased by nearly 3-4% at every 25 W increment. Using linear regression models, where each subject is treated as a categorical variable and adjusting for subject intercept, RVOTd was correlated with haemodynamic variables (cardiac output, heart rate, pulmonary artery and RV pressures). Of all the predictor haemodynamic variables, cardiac output had the highest r2 model fit (adjusted r2 = 0.68), with a unit increase in cardiac output associated with a 0.0678 increase in RVOTd (P < 0.001). Our findings indicate that RVOTd increases by 3-4% with every 25 W increment, predominantly correlated with cardiac output augmentation. These results can improve the accuracy of cardiac output reserve estimation by adjusting for RVOTd with graded exercise during non-invasive CPET and echocardiogram. However, future studies are needed to define these relationships for left ventricular outflow tract diameter.

Hemodynamic Comparison of the On-X and Top Hat Mechanical Aortic Valve Prostheses

BackgroundThere are limited data comparing hemodynamic valve function in mechanical aortic valve prostheses. This study compared the hemodynamic function of 2 commonly used mechanical aortic valve (AV) prostheses, the On-X (Artivion) and Top Hat (CarboMedics Inc) valves. MethodsThis study was a retrospective analysis of 512 patients who underwent AV replacement with the On-X (n = 252; 49%) or Top Hat (n = 260; 51%) mechanical valves between 2011 and 2019. Patients were matched on the basis of selected variables. Echocardiographic data were collected preoperatively and postoperatively over a median follow-up of 1.39 years. ResultsA total of 320 patients were matched, 160 patients in each group. Despite being matched for left ventricular outflow tract diameter, patients in the Top Hat group received a greater prevalence of smaller tissue annulus diameter valves (≤21 mm) (83% vs 38%; P < .001). Patients in the On-X group had longer aortic cross-clamp times (78 minutes vs 64 minutes; P < .001) during isolated aortic valve replacement. Discharge echocardiography showed no difference in the AV area index between both groups (1.00 cm2/m2 vs 1.02 cm2/m2; P = .377). During longer-term echocardiographic follow-up, the AV area index remained stable for both valves within their respective tissue annulus diameter groups (P = .060). ConclusionsThere was no difference between the 2 valves with respect to the AV area index at discharge, and hemodynamic function was stable during longer-term follow-up. The longer aortic cross-clamp time observed in the On-X group may indicate increased complexity of implantation compared with the Top Hat group.

Right ventricular assessment of the adolescent footballer’s heart

IntroductionAthletic training can result in electrical and structural changes of the right ventricle that may mimic phenotypical features of arrhythmogenic right ventricular cardiomyopathy (ARVC), such as T-wave inversion and right heart dilatation. An erroneous interpretation may have consequences ranging from false reassurance in an athlete vulnerable to cardiac arrhythmias, to unnecessary sports restriction in a healthy individual. The primary aim of this study was to define normal RV dimension reference ranges for academy adolescent footballers of different ethnicities. Secondary aims include analysis of potential overlap between this adolescent group with ARVC criteria and comparison with normal adult ranges.ResultsElectrocardiographic (ECG) and echocardiographic data of 1087 academy male footballers aged between 13 and 18 years old (mean age 16.0 ± 0.5 years), attending mandatory cardiac screening were analysed. Ethnicity was categorised as white (n = 826), black (African/Caribbean; n = 166) and mixed-race (one parent white and one parent black; n = 95). Arrhythmogenic right ventricular cardiomyopathy major criteria for T-wave inversion was seen in 3.3% of the cohort. This was more prevalent in black footballers (12%) when compared to mixed race footballers (6.3%) or white footballers (1%), P < 0.05. Up to 59% of the cohort exceeded adult reference ranges for some of the right ventricular parameters, although values were similar to those seen in adult footballers. There were no differences in right ventricular dimensions between ethnicities. In particular, the right ventricular outflow tract diameter would fulfil major criteria for ARVC dimension in 12% of footballers. Overall, 0.2% of the cohort would fulfil diagnosis for ‘definite’ arrhythmogenic right ventricular cardiomyopathy and 2.2% would fulfil diagnosis for ‘borderline’ arrhythmogenic right ventricular cardiomyopathy for RV dimensions and ECG changes. This was seen more frequently in black footballers (9.9%) than mixed race footballers (3.9%) or white footballer (0.6%), P < 0.05. Among athletes meeting definite or borderline arrhythmogenic right ventricular cardiomyopathy criteria, no cardiomyopathy was identified after comprehensive clinical assessment, including with cardiac magnetic resonance imaging, exercise testing, ambulatory electrocardiograms and familial evaluation.ConclusionRight heart sizes in excess of accepted adult ranges occurred in as many as one in two adolescent footballers. Structural adaptations in conjunction with anterior T-wave inversion may raise concern for ARVC, highlighting the need for evaluation in expert settings.

Increased cardiac output and left ventricular contractility in pigs paced with vs. without restored respiratory sinus arrhythmia - proof of principle of a newly developed pacing device

Abstract Background Heart rate variability (HRV) correlates with the severity and mortality of heart failure. Respiratory sinus arrhythmia (RSA) is defined by the dynamic increase and decrease in heart rate between breaths. Restoration of RSA might be beneficial in patients with heart failure and/or patients in need of permanent pacing. Purpose The aim of this translational, proof-of-principle study was to investigate the effect of pacing with or without RSA using a newly designed pacing device on the left ventricular contractility and cardiac output. Methods The project was initiated with the aim of designing a new pacing device capable of restoring RSA in paced hearts with the help of lung inflation sensors. Neuronal networks were designed to reconstruct the human brain using ultra-low energy-consuming technology. The lung inflation sensor fed the detected inspiration data back to the pacing device, which paced the heart via pacing leads (DDD) in the right atrium and ventricle. In total, 5 intubated but spontaneously breathing landrace pigs were paced without RSA (fixed-rate pacing) and with restored RSA. Stroke volume and cardiac output were measured by echocardiography (diameter of left ventricular outflow tract and velocity time integral measured by pulsed wave doppler averaged over three heart beats). Preload-independent cardiac contractility was measured via a pressure-volume loop catheter in the left ventricle during occlusion of the inferior vena cava. Fig. 1 indicates the setup of the trial. The trials were conducted according to the relevant rules (NIH Publication no. 85-23 revised 1985) and in accordance with national law. Results Echocardiography (n=5) showed a mean left ventricular outflow tract diameter of 21 ± 0.1 mm. The mean intrinsic heart rate was 87 ± 14 bpm, and the mean paced heart rate was 104 ± 5 bpm in the pigs (65 ± 3 kg). The main outcomes are displayed in Fig. 2: The left ventricular stroke volume increased by 11ml (+21%, p=0.036) with 100% RSA compared to pacing without RSA, while cardiac output increased by 1.14 l/min (+21%, p=0.037). The pressure volume area is proportional to the total myocardial oxygen consumption and decreased by 6234 mmHg*ml (-39%, p=0.004). Cardiac efficiency represents the relative amount of blood being pumped consuming one unit energy and increased by 0.163 (+72%, p=0.033). End-systolic pressure volume relationship demonstrated a non-significant increase by 0.183 mmHg/ml (+45%, p=0.25). Parameters of diastolic function (Tau) did not differ between the groups. Conclusion Restoration of RSA by our newly developed pacing device significantly improved the cardiac contractility/output in our proof-of-principle large animal translational model. Chronic trials will be required to definitively confirm the positive effects of RSA on cardiac remodeling.Fig. 1: Set-up of the animal trials.Fig. 2: Main results (mean/std error)

Real world application of left ventricular outflow tract diameter prediction and clinical implications

Abstract Background The Left Ventricular Outflow Tract diameter (LVOTd) measured with transthoracic echocardiogram is crucial for stroke volume, flow and effective orifice area (EOA) assessment in aortic stenosis (AS), but it’s also a source of error. A formula for its prediction has been proposed (Leye’s formula), based on body surface area (BSA). However, it has never been validated externally. Purpose The aim of study is to externally validate the equation by Leye et al. in a retrospective, single-center, large cohort of consecutive non-obese patients with severe symptomatic AS undergoing surgical aortic valve replacement. Methods A population of patients with severe symptomatic AS undergoing surgical aortic valve replacement was analyzed; three different LVOTd values were obtained for each patient: measured-LVOTd (m-LVOTd, from echo database), predicted-LVOTd (p-LVOTd, using Leye’s formula) and surgical-LVOTd (s-LVOTd, obtained by surgical reports). p-LVOTd was used to reevaluate stroke volume and EOA. Results Data from 735 patients were collected; mean age was 75±8 years and 417 patients (57%) were men, mean BMI was 25.6 kg/m2 and mean BSA was 1.8 m2. m-LVOTd was significantly lower than p-LVOTd (20.2±2.4mm and 22.4±1.0mm, respectively; bias 2.1mm; p &amp;lt; 0,001). Moreover the difference between p-LVOTd and s-LVOTd (23.2±1.7mm; bias 0.8 mm) was lower than the difference between m-LVOTd and s-LVOTd (bias 3.0 mm). When the stroke volume index (SVi) was calculated through p-LVOTd, its value increased significantly compared to SVi calculated with m-LVOTd (50.0±10.9 vs 40.9±10.2 mL/m2, p&amp;lt;0.001), leading to a significant decrease in patients classified as low-flow AS, from 216 (29%) to 73 (10%) (p&amp;lt;0.001). EOA calculated with p-LVOTd was significantly wider than that calculated using m-LVOTd, and correlation was weak (0.86±0.22 vs 0.70±0.16 cm2, p&amp;lt;0.001; r=0.599, p&amp;lt;0.001). Using the p-LVOTd instead of m-LVOTd has lead to the reclassification of 188 (26%) patients from EOA≤1 cm2 to EOA&amp;gt;1cm2. Conclusion We found that in non-obese patients with severe AS, LVOTd obtained from the simple formula proposed by Leye et al correlates better with the surgical annulus diameter compared with the echocardiographic measurement of LVOT, and this has relevant consequences on AS assessment.

Abstract 14195: Right Ventricular Outflow Tract Diameter Increase With the Low-Moderate Workload: A Prospective Simultaneous Exercise Echocardiography and Invasive Cardiopulmonary Exercise Testing Study

Background: While cardiac output at rest can be estimated non-invasively with echocardiogram, change in left ventricular or right ventricular outflow tract diameter (RVOTd) with exercise makes the cardiac output estimation inaccurate. Hypothesis: RVOTd increases with exercise proportionally with an incremental workload and is determined by stroke volume augmentation. Aims: 1. Define a workload-based change in RVOTd in subjects undergoing invasive cardiopulmonary exercise test (iCPET). 2. Correlate RVOTd at exercise stages with iCPET metrics. Methods: 20 subjects undergoing simultaneous echocardiogram and iCPET were enrolled in a prospective study. Exercise datapoints were acquired at 25 W (n=20), 50W (n=16), 75W (n=14), 100W (n=6). Three hemodynamic groups included: HFpEF (n=12), PAH (n=5), controls (n=3). Utilizing iCPET-based direct Fick cardiac output and stroke volume, RVOTd was reverse engineered with RVOT velocity time integral, per ASE guidelines. Pearson correlation was used to assess correlation of RVOTd with hemodynamic metrics. p&lt;0.05* Results: In overall cohort, age was 64±12 years, BMI 31.2±4.9 Kg/m 2 , female 60%, peak VO 2 13.7±5.7 mL/Kg.min -1 and V E /VCO 2 37±8. Increase in RVOTd with exercise is represented in the Figure. In comparison to rest, RVOTd increased significantly even at low-25W (+4.1±13.6%*) and moderate-50W (+7.6±17.2%*) workloads. Overall, RVOTd increased by 4-5% every 25W. At high workload (100W), the diameter increased by 24% (n=6). There were no differences in RVOT diameter between subgroups. RVOTd at four exercise stages (25W, 50W, 75W, 100W) correlated significantly with stroke volume index (r=0.68*, 0.80*, 0.23, 0.64) and cardiac output (r=0.50*, 0.80*, 0.08, 0.68), but non-significantly with heart rate (r=-0.15, 0.19, -0.10, 0.68). Conclusion: RVOTd increases by 4-5% every 25W on an incremental workload protocol. This behavior is predominantly associated with an increase in stroke volume index with exercise.

Abstract 16873: Takotsubo Variant is Associated With Worse Right and Left Ventricular Systolic Function Than Other Stress Cardiomyopathy Variants

Introduction: Stress cardiomyopathy (SCM) is usually associated with reduced systolic function on echocardiogram. However, the prevalence of systolic dysfunction between different variables of SCM has not been established. Hypothesis: Whether Takotsubo variant SCM is associated with worse systolic function compared to other SCM variants. Methods: We conducted a retrospective cohort study evaluating echocardiograms of all patients with SCM between 2010 and 2022 at Hennepin Healthcare, MN, USA. The diagnosis of SCM was made based on the International Takotsubo (InterTak) diagnostic criteria. Results: Between January 2010 and December 2022, 296 patients presented with SCM. The majority of patients (N= 173, 58.4%) had the apical (Takotsubo) variant, compared to 78 (26.3%) patients with the midventricular variant and 45 (15.2%) with the basal variant. The three groups had no significant difference in the left ventricular outflow tract and septal diameters. Patients with the apical variant had a lower ejection fraction on presentation compared to mid-ventricular and basal variants (28.1% vs. 36.8% and 35.7%, respectively, p&lt;0.001). Patients with Takotsubo CM had the lowest cardiac output and cardiac index among the three groups ( table 1 ). Right ventricular systolic function, evaluated by Tricuspid Annular Plane Systolic Excursion (TAPSE), was lowest in patients with apical SCM (mean TASPE 1.58 cm, p=0.027). All patients had similar ejection fraction recovery at follow-up (mean EF &gt; 55%, p=0.793, mean follow-up time &lt; 4 weeks, p=0.913). Conclusion: Takotsubo variant is associated with worse right and left ventricular systolic function compared to other SCM variants, with similar systolic function recovery at follow-up.

Deep learning for automated left ventricular outflow tract diameter measurements in 2D echocardiography

BackgroundMeasurement of the left ventricular outflow tract diameter (LVOTd) in echocardiography is a common source of error when used to calculate the stroke volume. The aim of this study is to assess whether a deep learning (DL) model, trained on a clinical echocardiographic dataset, can perform automatic LVOTd measurements on par with expert cardiologists.MethodsData consisted of 649 consecutive transthoracic echocardiographic examinations of patients with coronary artery disease admitted to a university hospital. 1304 LVOTd measurements in the parasternal long axis (PLAX) and zoomed parasternal long axis views (ZPLAX) were collected, with each patient having 1–6 measurements per examination. Data quality control was performed by an expert cardiologist, and spatial geometry data was preserved for each LVOTd measurement to convert DL predictions into metric units. A convolutional neural network based on the U-Net was used as the DL model.ResultsThe mean absolute LVOTd error was 1.04 (95% confidence interval [CI] 0.90–1.19) mm for DL predictions on the test set. The mean relative LVOTd errors across all data subgroups ranged from 3.8 to 5.1% for the test set. Generally, the DL model had superior performance on the ZPLAX view compared to the PLAX view. DL model precision for patients with repeated LVOTd measurements had a mean coefficient of variation of 2.2 (95% CI 1.6–2.7) %, which was comparable to the clinicians for the test set.ConclusionDL for automatic LVOTd measurements in PLAX and ZPLAX views is feasible when trained on a limited clinical dataset. While the DL predicted LVOTd measurements were within the expected range of clinical inter-observer variability, the robustness of the DL model requires validation on independent datasets. Future experiments using temporal information and anatomical constraints could improve valvular identification and reduce outliers, which are challenges that must be addressed before clinical utilization.Graphical

Incremental Value of Right Ventricular Outflow Tract Diameter in Risk Assessment of Chronic Heart Failure Patients with Implantable Cardioverter Defibrillators: Development of RVOTD-ICD Benefit Score in Real-World Setting.

Left ventricular ejection fraction (LVEF) remains the basic reference for the prevention of sudden cardiac death (SCD) patients, while right ventricular (RV) abnormalities have now been associated with SCD risk. A modified benefit assessment tool incorporating RV function parameters in consideration of implantable cardioverter defibrillators (ICD) insertion should be taken into account. We enrolled 954 chronic heart failure (CHF) patients (age 58.8 13.1 years; 79.0% male) with quantitative measurements of right ventricular outflow tract diameter (RVOTD) before ICD implantation and then divided them according to the median level of RVOTD. The predictive value of RVOTD in life-threatening ventricular tachycardia (VT)/ventricular fibrillation (VF) vs. non-arrhythmic mortality (defined as death without prior sustained VT/VF), was evaluated respectively. Based on RVOTD and other identified risk factors, a simple risk assessment tool, RVOTD-ICD benefit score, was developed. A higher RVOTD level was significantly associated with an increased risk of VT/VF (per 1 standard deviation (SD) increase, hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.11-1.33; p = 0.002) but not non-arrhythmic mortality (per 1 SD increase, hazard ratio, 0.93; 95% CI, 0.66-1.33; p = 0.709) after multivariable adjustment. Three benefit groups were created based on RVOTD-ICD benefit score, which was calculated from VT/VF score (younger age, higher RVOTD, diuretic use, prior non-sustainable VT, prior sustainable VT/VF) and non-arrhythmic mortality scores (older age, renin-angiotensin-aldosterone system inhibitors use, diabetes, higher left ventricular end-diastolic diameter, New York Heart Association III/IV, higher N-terminal pro-B-type natriuretic peptide levels). In the highest RVOTD-ICD benefit group, the 3-year risk of VT/VF was nearly 8-fold higher than the corresponding risk of non-arrhythmic mortality (39.2% vs. 4.8%, p 0.001). On the contrary, the 3-year risk of VT/VF was similar to the risk of non-arrhythmic mortality (21.9% vs. 21.3%, p = 0.405) in the lowest benefit group. RVOTD-ICD benefit score system yielded improvement in discrimination for VT/VF, non-arrhythmic mortality, and all-cause mortality than Multicenter Automatic Defibrillator Implantation Trial (MADIT)-ICD benefit score in this cohort. Higher RVOTD was associated with significantly increased risk of sustained VT/VF in CHF patients. A simple risk assessment tool incorporating RVOTD (RVOTD-ICD benefit score) could be generalized to ICD populations, and optimize the decision-making process of ICD implantation.

Protocol for rheumatoid arthritis complicated with cardiovascular damage treated with Guanxining tablet with a randomized controlled trial

BackgroundCardiovascular disease (CVD) is the main cause of death in patients with rheumatoid arthritis (RA). Apart from traditional cardiovascular risk factors, immune dysfunction and chronic inflammation of RA are also risk factors for complex cardiovascular damage. Although methotrexate (MTX) is beneficial to CVD in RA patients by inhibiting inflammation, its adverse effects limit its clinical application. Therefore, it is essential to seek safer and more effective drugs. ObjectiveWe aimed to assess the efficacy of Guanxining Tablet (GXNT) for rheumatoid arthritis complicated with cardiovascular damage. MethodsWe will conduct a prospective single-center randomized trial. We will randomly divide 56 eligible patients into two groups. The treatment group will take GXNT and MTX treatment, and the control group will receive MTX and the placebo. The primary outcome measure will be aortic distensibility (AD). Secondary outcome measures will be Cardiac function which will contain right ventricular outflow tract diameter (RVOTD), aortic diameter (AOD), left atrium diameter (LAD), right ventricular end diastolic diameter (RVDD), left ventricular end diastolic diameter (LVDD), ejection fraction (EF%), fractional shortening (FS%), stroke volume (SV). Adverse events will be closely monitored during the entire trial period. DiscussionThis trial is intended to determine whether the addition of GXNT will improve the prognosis of patients with rheumatoid arthritis and cardiovascular damage without severe adverse reactions. Completing this clinical trial might provide these patients with a novel and effective drug while avoiding adverse reactions similar to methotrexate. Trial registrationChiCTR2000030247.

Tidal volume challenge-induced hemodynamic changes can predict fluid responsiveness during one-lung ventilation: an observational study.

To evaluate the ability of tidal volume challenge (VTC)-induced hemodynamic changes to predict fluid responsiveness in patients during one-lung ventilation (OLV). 80 patients scheduled for elective thoracoscopic surgery with OLV were enrolled. The inclusion criteria were: age ≥ 18 years, American Society of Anesthesiologists physical status I-III, normal right ventricular function, normal left ventricular systolic function (ejection fraction ≥55%), and normal or slightly impaired diastolic function. The study protocol was implemented 15 min after starting OLV. Simultaneous recordings were performed for hemodynamic variables of diameter of left ventricular outflow tract, velocity time integral (VTI) of aortic valve, and stroke volume (SV), and ΔSV-VTC, ΔVTI-VTC, and ΔMAP-VTC were calculated at four time points: with VT 5 mL/kg (T1); after VT increased from 5 mL/kg to 8 mL/kg and maintained at this level for 2 min (T2); after VT was adjusted back to 5 mL/kg for 2 min (T3); and after volume expansion (250 mL of 0.9% saline infused over 10-15 min) (T4). Patients were considered as responders to fluid administration if SV increased by ≥10%. Receiver operating characteristic (ROC) curves for percent decrease in SV, VTI, and MAP by VTC were generated to evaluate their ability to discriminate fluid responders from nonresponders. Of the 58 patients analyzed, there were 32 responders (55%) and 26 nonresponders (45%). The basic characteristics were comparable between the two groups (p > 0.05). The area under the curve (AUC) for ΔSV-VTC, ΔVTI-VTC, and ΔMAP-VTC to discriminate responders from nonresponders were 0.81 (95% CI: 0.68-0.90), 0.79 (95% CI: 0.66-0.89), and 0.56 (95% CI: 0.42-0.69). The best threshold for ΔSV-VTC was -16.1% (sensitivity, 78.1%; specificity, 84.6%); the best threshold for ΔVTI-VTC was -14.5% (sensitivity, 78.1%; specificity, 80.8%). Tidal volume challenge-induced relative change of stroke volume and velocity time integral can predict fluid responsiveness in patients during one-lung ventilation.Clinical Trial Registration: Chinese Clinical Trial Registry, No: chictr210051310.