Impairment Of Right Ventricular Function Research Articles

Association between right heart size and right ventricular output reserve in patients with pulmonary arterial hypertension

ObjectivesRight ventricular (RV) output reserve, defined as increase of cardiac output during exercise, is reduced in patients with pulmonary arterial hypertension (PAH). Aim of this study was to evaluate the association of right heart size measured by echocardiography and invasively measured RV function at rest and during exercise in PAH patients. MethodsAdult PAH-patients who received routine haemodynamic assessment at rest and during exercise by right heart catheterisation and echocardiographic measurement of right heart size (right atrial (RA) and RV area) were included in this study. Clinical, echocardiographic, laboratory, exercise and invasive haemodynamic parameters were retrospectively analysed. The primary endpoint was to assess the association between right heart size and right ventricular function. ResultsData from 215 PAH patients (age 58.9 ± 15.9 years, 63.3% female, 62.2% double or triple combination treatment) were analysed in this cross-sectional study. Cardiac index was significantly lower for patients with enlarged RA-area > 18 cm2 at rest, and at 25 and 50 W (all p < 0.001) and for patients with enlarged RV area > 20 cm2 at rest, 25, 50 and 75 W (all p < 0.001). Furthermore, pulmonary vascular resistance and mPAP/CO slope (all p < 0.001) were significantly higher and pulmonary arterial compliance (all p < 0.05) was significantly lower in patients with enlarged RA or RV area. RA and RV area correlated with TAPSE/sPAP (both p < 0.001, R − 0.570 and − 0.530). ConclusionThis study could underline that an enlargement of RA- and RV-area is associated with an impaired RV function at rest and during exercise in patients with PAH.

Physiological mechanisms behind respiratory variations in right atrial pressure in pulmonary hypertension

Impaired respiratory variation of right atrial pressure (RAP) in severe pulmonary hypertension (PH) suggests difficulty tolerating increased preload during inspiration. Our study explores whether this impairment links to specific factors: right ventricular (RV) diastolic function, elevated RV afterload, systolic RV function, or RV-pulmonary arterial (PA) coupling. We retrospectively evaluated respiratory RAP variation in all participants enrolled in the EXERTION study. Impaired respiratory variation was defined as end-expiratory RAP − end-inspiratory RAP ≤ 2 mm Hg. RV function and afterload were evaluated using conductance catheterization. Impaired diastolic RV function was defined as end-diastolic elastance (Eed) ≥ median (0.19 mm Hg/mL). Seventy-five patients were included; PH was diagnosed in 57 patients and invasively excluded in 18 patients. Of the 75 patients, 31 (41%) had impaired RAP variation, which was linked with impaired RV systolic function and RV-PA coupling and increased tricuspid regurgitation and Eed as compared to patients with preserved RAP variation. In backward regression, RAP variation associated only with Eed. RAP variation but not simple RAP identified impaired diastolic RV function (area under the receiver operating characteristic curve [95% confidence interval]: 0.712 [0.592, 0.832] and 0.496 [0.358, 0.634], respectively). During exercise, patients with impaired RAP variation experienced greater RV dilatation and reduced diastolic reserve and cardiac output/index compared with patients with preserved RAP variation. Preserved RAP variation was associated with a better prognosis than impaired RAP variation based on the 2022 European Society of Cardiology/European Respiratory Society risk score (chi-square P = 0.025) and survival free from clinical worsening (91% vs 71% at 1 year and 79% vs 50% at 2 years [log-rank P = 0.020]; hazard ratio: 0.397 [95% confidence interval: 0.178, 0.884]). Subgroup analyses in patients with group 1 and group 4 PH demonstrated consistent findings with those observed in the overall study cohort. Respiratory RAP variations reflect RV diastolic function, are independent of RV-PA coupling or tricuspid regurgitation, are associated with exercise-induced haemodynamic changes, and are prognostic in PH.Trial registration. NCT04663217.

Late Presentation of Pulmonary Hypertension Crisis Concurrent with Atrial Arrhythmia after Atrial Septal Defect Device Closure

Background: ASD occurs when there is a septal defect between the right and left atria, resulting in a left-to-right shunt that increases the volume of the right heart and pulmonary circulation. Increased pulmonary resistance can lead to pulmonary hypertension (PH), resulting in progressive deterioration of right ventricular function, leading to right heart failure and death. Prolonged elevation of atrial pressure induces progressive atrial dilatation and electrophysiological remodelling. Together with autonomic modulation, this leads to atrial arrhythmias (AAs). Patients with significant shunts leading to ventricular volume overload are considered for ASD closure. However, in some cases, PH occurs after ASD closure.  Case Presentation: We report a 21 yo man diagnosed with ASD Secundum Post Closure with Device (September 1th, 2023) and Pulmonary Hypertension Crisis. The left atria (LA), right atria (RA) and right ventricle (RV) were dilated. We also found moderate mitral regurgitation, severe tricuspid regurgitation, and mild to moderate pulmonary regurgitation. There was a decline in systolic function in the right ventricle, and grade III diastolic dysfunction in left ventricle. There was a well-seated device with no residual shunt on interatrial septal. The pulmonary arteries were confluence and dilated. From ECG we found atrial flutter with variable conduction. This patient was transferred to HCU. This patient treated with digoxin, furosemide, milrinon, ceftriaxone, miniaspi, sildenafil, electrophysiology, and 3D ablation.  Conclusion: Pulmonary hypertension can occur in cases of congenital heart defects, such as ASD. The operative management of ASD is closure of the ASD, but in some unique groups, this can lead to pulmonary hypertensive crisis after its closure.

Monitoring a Mystery: The Unknown Right Ventricle during Left Ventricular Unloading with Impella in Patients with Cardiogenic Shock.

Background: Right ventricular (RV) dysfunction or failure occurs in more than 30% of patients in cardiogenic shock (CS). However, the importance of timely diagnosis of prognostically relevant impairment of RV function is often underestimated. Moreover, data regarding the impact of mechanical circulatory support like the Impella on RV function are rare. Here, we investigated the effects of the left ventricular (LV) Impella on RV function. Moreover, we aimed to identify the most optimal and the earliest applicable parameter for bedside monitoring of RV function by comparing the predictive abilities of three common RV function parameters: the pulmonary artery pulsatility index (PAPi), the ratio of right atrial pressure to pulmonary capillary wedge pressure (RA/PCWP), and the right ventricular stroke work index (RVSWI). Methods: The data of 50 patients with CS complicating myocardial infarction, supported with different flow levels of LV Impella, were retrospectively analyzed. Results: Enhancing Impella flow (1.5 to 2.5 L/min ± 0.4 L/min) did not lead to a significant variation in PAPi (p = 0.717), RA/PCWP (p = 0.601), or RVSWI (p = 0.608), indicating no additional burden for the RV. PAPi revealed the best ability to connect RV function with global hemodynamic parameters, i.e., cardiac index (CI; p < 0.001, 95% CI: 0.181-0.663), pulmonary capillary wedge pressure (PCWP; p = 0.005, 95% CI: -6.721--1.26), central venous pressure (CVP; p < 0.001, 95% CI: -7.89-5.575), and indicators of tissue perfusion (central venous oxygen saturation (SvO2); p = 0.008, 95% CI: 1.096-7.196). Conclusions: LV Impella does not impair RV function. Moreover, PAPi seems to be to the most effective and valid predictor for early bedside monitoring of RV function.

Evaluation of myocardial work changes after lung resection-the significance of surgical approach: an echocardiographic comparison between VATS and thoracotomy.

Considering the controversial benefits of video-assisted thoracoscopic surgery (VATS), we intended to evaluate the impact of surgical approach on cardiac function after lung resection using myocardial work analysis. Echocardiographic data of 48 patients (25 thoracotomy vs. 23 VATS) were retrospectively analyzed. All patients underwent transthoracic echocardiography (TTE) within 2 weeks before and after surgery, including two-dimensional speckle tracking and tissue Doppler imaging. No notable changes in left ventricular (LV) function, assessed mainly using the LV global longitudinal strain (GLS), global myocardial work index (GMWI), and global work efficiency (GWE), were observed. Right ventricular (RV) TTE values, including tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TASV), right ventricular global longitudinal strain (RVGLS), and RV free-wall GLS (RVFWGLS), indicated greater RV function impairment in the thoracotomy group than in the VATS group [TAPSE(mm) 17.90 ± 3.80 vs. 21.00 ± 3.48, p = 0.006; d = 0.84; TASV(cm/s): 12.40 ± 2.90 vs. 14.70 ± 2.40, p = 0.004, d = 0.86; RVGLS(%): - 16.00 ± 4.50 vs. - 19.40 ± 2.30, p = 0.012, d = 0.20; RVFWGLS(%): - 11.50 ± 8.50 vs. - 18.31 ± 5.40, p = 0.009, d = 0.59; respectively]. Unlike RV function, LV function remained preserved after lung resection. The thoracotomy group exhibited greater RV function impairment than did the VATS group. Further studies should evaluate the long-term impact of surgical approach on cardiac function.

Abstract 17602: Cardiac Structure and Function and Renal Outcomes in Patients With Heart Failure With Preserved Ejection Fraction: Insights From the PARAGON-HF Trial

Introduction: Chronic kidney disease is common and associated with a worse prognosis in patients with heart failure (HF). However, the association of cardiac structure and function with renal outcomes in patients with HF with preserved ejection fraction (HFpEF) is not known. Goal: Identify cardiac structural and functional correlates of renal outcomes in HFpEF. Methods: Patients enrolled in the echocardiographic sub-study of the PARAGON-HF trial were included. The endpoint of interest was a composite renal endpoint: a ≥50% decline in estimated glomerular filtration rate (eGFR) relative to baseline, development of end-stage renal disease, or death attributable to renal causes. Multivariable Cox proportional hazards models were used to identify measures of cardiac structural and functional parameters associated with the composite renal endpoint, adjusting for baseline eGFR, systolic blood pressure, NT-proBNP, treatment arm (sacubitril-valsartan or valsartan) and diabetes. Results: In 1,097 patients (53% women, mean age 74±8 years), over a median follow-up of 2.9 years (IQR 2.6-3.4 years) there were 28 composite renal events (0.9 per 100 patient-years). After multivariable adjustment, higher left ventricular (LV) posterior wall thickness and mass index, right ventricular (RV) end-diastolic and end-systolic areas as well as impaired RV function (lower fractional area change and lower absolute RV free wall longitudinal strain), but not LV systolic function (LVEF and global longitudinal strain) were each associated with a significantly higher risk for the composite renal endpoint ( Figure ). Conclusions: In the PARAGON-HF echocardiographic sub-study, evidence of cardiac biventricular remodeling and deterioration of RV function were associated with an increased risk of renal events. These results underscore the close relationship between the heart and kidneys in patients with HF even when LVEF is preserved.

Abstract 17226: Role of BMPR2 Mutation in the Development of RV Failure in Rat Experimental Pulmonary Hypertension

Introduction: BMPR2 mutations are the major genetic risk factor for pulmonary arterial hypertension (PAH) and are associated with increased disease severity and worse survival. Although worsening disease severity and prognosis in BMPR2 mutation carriers has been explained by more severe pulmonary vascular disease (PVD), recent reports suggest that BMPR2 mutations affect right ventricular (RV) myocardium and its function independently of PAH. However, mechanism of dysfunctional RV in BMPR2 mutations carriers are unknown.[Hypothesis]Rats with Bmpr2 mutation have impaired RV function independently of PVD compared to wild-type (WT) rats. Methods: Bmpr2 mutant rats were generated by CRISPR/Cas9 genome editing. Monocrotaline (MCT)-PH model was generated in mutant rats and WT littermates and changes in RV function over time with disease progression were assessed by echocardiography and catheterization in rats with (n=23) or without tadalafil treatment (n=88) Results: In untreated setting, there were no significant differences in RV systolic pressure (RVSP) and RV function between the two groups on 21 days after MCT, whereas RV-fractional area change (FAC) and cardiac index (CI), assessed at later disease stage (23 to 25 days), were significantly lower in Bmpr2 mutant rats than in WT (RV-FAC: WT 41.0±8.3 vs Bmpr2 mutant 27.5±11.5%, p&lt;.0001; CI: 413.2±114.0 vs 263.0±92.9ml/min/kg, p&lt;.0001) at comparable RVSP (64.5±11.6 vs 66.7±8.0mmHg) but higher total pulmonary resistance index (TPRI: 0.16±0.06 vs 0.27±0.09mmHg/ml/min/kg, p&lt;.0001). In rats with tadalafil treatment, Bmpr2 mutant rats had significantly lower RV-FAC (34.4±8.2 vs 23.6±5.4%, p&lt;.05) and more severe RV myocardial fibrosis compared to WT littermates despite no significant differences in RVSP (75.4±8.7 vs 71.0±8.2mmHg) and TPRI (0.19±0.06 vs 0.22±0.08mmHg/ml/min/kg) on 30 days after MCT. Conclusion: In untreated setting, RV dysfunction in Bmpr2 mutant was associated with increased afterload due to exacerbation of vascular lesions; rats treated with PDE5i and with prolonged survival had reduced RV function at comparable afterload, indicating the importance of managing RV function under treatment of PAH.

Abstract 13007: Ketone Bodies for Right Ventricular Failure: A Unique Therapeutic Opportunity

Introduction: Right ventricular failure (RVF) is the leading cause of death in pulmonary arterial hypertension (PAH), but effective therapies for RVF are lacking. Ketones exert therapeutic effects through suppression of the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome and exhibit favorable metabolic properties in LVF. However, the relationships among serum ketone bodies, RV inflammasome activation, and RV function in preclinical and human RVF are unexplored. Hypothesis: Serum ketones correlate with RV function and induction of therapeutic ketosis ameliorates RV dysfunction. Methods: 51 PAH patients were dichotomized into preserved or impaired RV function based on a cardiac index of 2.2 L/min/m 2 . Serum ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (BOHB) were quantified using ultra performance liquid chromatography and mass spectrometry. The relationships between AcAc and BOHB and clinical measures of RV function were evaluated. In rodent studies, male Sprague Dawley rats were assigned to three groups: control (saline injection), monocrotaline (MCT) standard chow diet (MCT-SD), and MCT ketogenic diet (MCT-KD). Immunoblots and confocal microscopy probed macrophage NLRP3 activation in RV extracts and sections. RV fibrosis was determined by Picrosirus Red. Echocardiography evaluated RV function. Results: Human RVF patients lacked a compensatory ketosis as serum AcAc and BOHB levels were not associated with hemodynamic or echocardiographic measures of RV function. In rodent studies, AcAc and BOHB levels were also not elevated in MCT-mediated RVF, but the ketogenic diet significantly increased AcAc and BOHB levels. MCT-KD exhibited suppressed NLRP3 activation with a reduction in NLRP3, ASC (apoptosis-associated speck-like protein), pro-caspase-1, and interleukin-1 beta on immunoblots. Moreover, the number of ASC-positive macrophage in RV sections was reduced, RV fibrosis was blunted, and RV function was augmented in MCT-KD rats. Conclusions: Our preclinical and clinical data suggests therapeutic ketosis could combat RVF, and patients with RVF are uniquely primed for ketogenic interventions due to a lack of effective ketosis.

Ketone bodies in right ventricular failure: A unique therapeutic opportunity

BackgroundKetone bodies are pleotropic metabolites that play important roles in multiple biological processes ranging from bioenergetics to inflammation regulation via suppression of the NLRP3 inflammasome, and epigenetic modifications. Ketone bodies are elevated in left ventricular failure (LVF) and multiple approaches that increase ketone concentrations exert advantageous cardiac effects in rodents and humans. However, the relationships between ketone bodies and right ventricular failure (RVF) are relatively unexplored. Methods51 PAH patients were dichotomized into preserved or impaired RV function based on a cardiac index of 2.2 L/min/m2. Impaired RV function patients were further segmented into intermediate or severe RV dysfunction based on a right atrial pressure of 8 mm Hg. Serum ketone bodies acetoacetate (AcAc) and beta-hydroxybutyrate (βOHB) were quantified using ultra performance liquid chromatography and mass spectrometry. In rodent studies, male Sprague Dawley rats were assigned to three groups: control (saline injection), monocrotaline (MCT) standard chow diet (MCT-Standard), and MCT ketogenic diet (MCT-Keto). Immunoblots and confocal microscopy probed macrophage NLRP3 activation in RV extracts and sections. RV fibrosis was determined by Picrosirus Red. Echocardiography evaluated RV function. Pulmonary arteriole remodeling was assessed from histological specimens. ResultsHuman RVF patients lacked a compensatory ketosis as serum AcAc and βOHB levels were not associated with hemodynamic, echocardiographic, or biochemical measures of RV dysfunction. In rodent studies, AcAc and βOHB levels were also not elevated in MCT-mediated RVF, but the ketogenic diet significantly increased AcAc and βOHB levels. MCT-Keto exhibited suppressed NLRP3 activation with a reduction in NLRP3, ASC (apoptosis-associated speck-like protein), pro-caspase-1, and interleukin-1 beta on immunoblots. Moreover, the number of ASC-positive macrophage in RV sections was reduced, RV fibrosis was blunted, and RV function was augmented in MCT-Keto rats. ConclusionThe ketogenic response is blunted in pulmonary arterial hypertension (PAH) patients with RVF. In the MCT rat model of PAH-mediated RVF, a dietary-induced ketosis improves RV function, suppresses NLRP3 inflammasome activation, and combats RV fibrosis. The summation of these data suggest ketogenic therapies may be particularly efficacious in RVF, and therefore future studies evaluating ketogenic interventions in human RVF are warranted.

Biventricular Dysfunction and Ventricular Interdependence in Patients With Pulmonary Hypertension: A 3.0-T Cardiac MRI Feature Tracking Study.

Pulmonary hypertension (PH) results in right ventricular (RV) dysfunction, subsequently leading to left ventricular (LV) impairment. The mechanism underlying ventricular interdependence is largely uninvestigated. To explore the biventricular dysfunction and the ventricular interdependence in PH patients. Retrospective. One hundred and seven PH patients (mean pulmonary artery pressure >20 mmHg) and 72 age- and sex-matched controls with cardiac magnetic resonance imaging (MRI) studies. 3.0 T/balanced steady-state free precession sequence. LV and RV ejection fractions (EF) and RV and LV radial, circumferential, and longitudinal strains were assessed using commercial software. Strains were compared between controls, PH patients with preserved RVEF (RVEF ≥40%, N = 48), and PH patients with reduced RVEF (RVEF <40%, N = 59). Chi-squared tests or Fisher's exact test, t tests or Mann-Whitney U test, one-way ANOVA with Bonferroni's post hoc correction or Kruskal-Wallis test, Pearson or Spearman correlation, and multivariable linear regression analysis. A two-tailed P < 0.05 was deemed statistically significant. RV strain decreased sequentially from controls, through PH with preserved RVEF, to PH with reduced RVEF. PH patients with reduced RVEF had significantly lower LV strain, especially septal strain, and LV peak diastolic strain rate compared with both controls and PH patients with preserved RVEF. Multivariable analyses showed that RVEF was independently correlated with LV strain; furthermore, independent of RVEF, RV strain was significantly correlated with LV strain (LVGRS: β = 0.416; LVGCS: β = -0.371; LVGLS: β = 0.283). Subclinical impairment of RV function was found in PH with preserved RVEF. LV strain was impaired when RV was dysfunctional, which was associated with worsening RV strain. Therefore, while focusing on improving RV function, LV dysfunction in PH patients should also be monitored and treated early in order to slow the progression of the disease. 3 TECHNICAL EFFICACY: Stage 3.

Multi-omic and multispecies analysis of right ventricular dysfunction

Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Transcriptomics and proteomics analyses defined the pathways associated with cardiac magnetic resonance imaging (MRI)-derived values of RV hypertrophy, dilation, and dysfunction in control and pulmonary artery banded (PAB) pigs. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare molecular responses across species. PAB pigs displayed significant right ventricle/ventricular (RV) hypertrophy, dilation, and dysfunction as quantified by cardiac magnetic resonance imaging. Transcriptomic and proteomic analyses identified pathways associated with RV dysfunction and remodeling in PAB pigs. Surprisingly, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across the 3species. FAO and ETC proteins and transcripts were mostly downregulated in ratsbut were predominately upregulated in PAB pigs, which more closely matched the human response. All species exhibited similar dysregulation of the dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy pathways. The porcine metabolic molecular signature was more similar to human RVF than rodents. These data suggest there may be divergent molecular responses of RVF across species, and pigs may more accurately recapitulate metabolic aspects of human RVF.

Echocardiographic determination of right ventricular volumes and ejection fraction: Validation of a truncated cone and rhomboid pyramid formula.

Echocardiographic assessment of right ventricular (RV) measurements may be challenging. The aim of this study was to develop a formula for calculation of RV volumes and function based on measurements of linear dimensions by 2-dimensional (2D) transthoracic echocardiography (TTE) in comparison to cardiovascular magnetic resonance (CMR). 129 consecutive patients with standard TTE and RV analysis by CMR were included. A formula based on the geometric assumptions of a truncated cone minus a truncated rhomboid pyramid was developed for calculations of RV end-diastolic volume (EDV) and RV end-systolic volume (ESV) by using the basal diameter of the RV (Dd and Ds) and the baso-apical length (Ld and Ls) in apical 4-chamber TTE views: RV EDV = 1.21 * Dd2 * Ld, and RV ESV = 1.21 * Ds2 * Ls. Calculations of RV EDV (ΔRV EDV = 10.2±26.4 ml to CMR, r = 0.889), RV ESV (ΔRV ESV = 4.5±18.4 ml to CMR, r = 0.921) and RV EF (ΔRV EF = 0.5±4.0% to CMR, r = 0.905) with the cone-pyramid formula (CPF) highly agreed with CMR. Impaired RV function on CMR (n = 52) was identified with a trend to higher accuracy by CPF than by conventional echocardiographic parameters (tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC)). Calculations of RV volumes and RV function by 2D TTE with the newly developed CPF were in high concordance to measurements by CMR. Accuracy for detection of patients with reduced RV function were higher by the proposed 2D TTE CPF method than by conventional echocardiographic parameters of TAPSE and RV FAC.

Abstract P3205: Differential Adaptation To Mitochondrial Ca 2+ Overload In The Left And Right Ventricles

Mitochondrial Ca 2+ (mtCa 2+ ) overload has emerged as a potential contributor to heart failure (HF), possibly through inducing oxidative stress. In HF, right ventricular (RV) function is predictive of mortality, and the RV is more vulnerable to oxidative stress than the left ventricle (LV). Therefore, how the response to mtCa 2+ overload might differ in the RV and LV is critical; however, ventricle-specific mtCa 2+ handling is still poorly understood. We sought to induce cardiac mtCa 2+ overload via genetic manipulation of the mitochondrial calcium uniporter complex (mtCU) formed by the MCU pore and several regulatory subunits. mtCU stoichiometry shapes mtCa 2+ kinetics: loss of mitochondrial calcium uptake 1 (MICU1) induces mtCa 2+ overload, and reduced essential MCU regulator (EMRE) to MCU ratio decreases mtCa 2+ uptake rate. Hypothesizing that mtCa 2+ overload differentially affects LV and RV function, we generated tamoxifen (Tmx)-inducible cardiac-specific Micu1 knockout mice ( Micu1 cKO ) . After confirming that MICU1 loss at 1 week post-Tmx resulted in mtCa 2+ overload in both ventricles, we explored how the LV and RV responses diverge. In Micu1 cKO mice, LV function assessed by echocardiography declined at 4 weeks post-Tmx but recovered partially by 6 weeks. However, impaired RV function at 4 weeks post-Tmx persisted at 6 weeks and longer, without evidence of pulmonary hypertension. Interestingly, at 7-9 weeks post-Tmx, mtCa 2+ levels and oxidative stress remained elevated in the RV but returned to control levels in the LV. Concurrently, EMRE protein levels and mtCa 2+ uptake rate were reduced only in the LV, suggesting that the LV has greater capacity to adapt to mtCa 2+ overload via downregulation of EMRE. We further traced this LV-specific adaptive response to increased maturation of the mAAA-proteases that degrade EMRE. In summary, mtCa 2+ overload induced by MICU1 deletion results in greater oxidative stress and functional impairment over time in the RV than the LV due to absence of compensatory EMRE reduction in the RV.

Morphological and functional types of tricuspid regurgitation: prognostic value in patients undergoing tricuspid annuloplasty during left-sided valvular surgery.

The nonuniform benefit of tricuspid annuloplasty may be explained by the proportionality of tricuspid regurgitation (TR) severity to right ventricular (RV) area. The purpose of this study was to delineate distinct morphological phenotypes of functional TR and investigate their prognostic implications in patients undergoing tricuspid annuloplasty during left-sided valvular surgery. The ratios of pre-procedural effective regurgitant orifice area (EROA) with right ventricular end-diastolic area (RVDA) were retrospectively assessed in 290 patients undergoing tricuspid annuloplasty. Based on optimal thresholds derived from penalized splines and maximally selected rank statistics, patients were stratified into proportionate (EROA/RVDA ratio ≤ 1.74) and disproportionate TR (EROA/RVDA ratio > 1.74). Overall, 59 (20%) and 231 (80%) patients had proportionate and disproportionate TR, respectively. Compared to those with proportionate TR, patients with disproportionate TR were older, had a higher prevalence of atrial fibrillation, lower pulmonary pressures, more impaired RV function, and larger tricuspid leaflet tenting area. Over a median follow-up of 4.1years, 79 adverse events (47 heart failure hospitalizations and 32 deaths) occurred. Patients with disproportionate TR had higher rates of adverse events than those with proportionate TR (32% vs 10%; P = 0.001) and were independently associated with poor outcomes on multivariate analysis. TR proportionality outperformed guideline-based classification of TR severity in outcome prediction and provided incremental prognostic value to both the EuroSCORE II and STS score (incremental χ2 = 6.757 and 9.094 respectively; both P < 0.05). Disproportionate TR is strongly associated with adverse prognosis and may aid patient selection and risk stratification for tricuspid annuloplasty with left-sided valvular surgery.

Disease progression in exercise-induced compared to desmosomal arrhythmogenic cardiomyopathy - a longitudinal cohort study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Oslo University Hospital, Procardio Center for Innovation Introduction Arrhythmogenic cardiomyopathy (AC) is an inheritable heart disease caused by mutations in genes encoding the cardiac desmosomes, while exercise-induced AC (EiAC) has been proposed as an acquired similar phenotype in athletes. Little is known about the progression of EiAC compared to AC. Purpose To assess functional and structural disease progression in EiAC compared to desmosomal AC during long-term follow-up. Methods We consecutively included probands with definite AC diagnosis according to the 2010 Task Force Criteria and patients with EiAC in a longitudinal cohort study. EiAC was diagnosed in competitive endurance athletes (&amp;gt;24 MET-hours/week for &amp;gt;6 consecutive years) referred with symptomatic ventricular arrhythmias who had no family history, no genetic mutations associated with heart disease, and no other identified etiology after through clinical work-up. All patients in both groups were recommended to avoid high intensity exercise. Progression of the structural phenotype was assessed by regular repeated echocardiographic examinations during long-term follow-up. Right ventricular (RV) function and size were assessed by RV fractional area change (FAC), RV basal diameter (RVD) and RV outflow tract (RVOT) diameter. Disease progression was evaluated and compared using linear mixed model regression. Results Forty-one EiAC patients (15% women, age 45±13 years) and 84 AC probands (51% mutation positive, 35% women, age 43±15) were followed for 6.6 (IQR 3.7-10.5) and 7.9 (IQR 5.2-10.8) years, respectively. Key parameters from 570 echocardiographic examinations (184 EiAC and 386 AC) were assessed. There was no deterioration of RV function during follow-up in EiAC patients, in contrast to AC patients (FAC yearly progression rate: EiAC +0.02% [95% CI -0.27 to 0.31] vs AC -0.60% [95% CI -0.71 to -0.50] per year, p=0.001, Figure left panel). RV size did not increase in EiAC patients in contrast to AC patients (RVD: EiAC +0.01 mm [95% CI -0.00 to 0.03] vs AC +0.78 mm [95% CI 0.68 to 0.89] per year, p&amp;lt;0.001, Figure mid panel, and RVOT: EiAC +0.01 mm [95% CI -0.01 to 0.02] vs AC +0.47 mm [95% CI 0.38 to 0.56] per year, p&amp;lt;0.001, Figure right panel). Conclusion Patients with exercise-induced AC had no evidence of disease progression during long-term follow-up. These patients had a more benign disease trajectory than patients with desmosomal AC. Despite the limited sample size, these results seem reassuring for patients diagnosed with exercise-induced AC.

Right Ventricular Function and Pulmonary Coupling in Patients With Heart Failure and Preserved Ejection Fraction

BackgroundLimited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction (HFpEF). ObjectivesThis study sought to assess the clinical implications of RV function, the association with N-terminal pro–B-type natriuretic peptide, and the risk for adverse events among patients with HFpEF. MethodsThis study analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (PASP) (RVFWLS/PASP ratio) in 528 patients (mean age 74 ± 8 years, 56% female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline N-terminal pro–B-type natriuretic peptide and with total HF hospitalizations and cardiovascular death were assessed, after accounting for confounders. ResultsOverall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion and RV fractional area change, more than one-half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating N-terminal pro–B-type natriuretic peptide. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and cardiovascular deaths. Both absolute RVFWLS (HR: 1.39; 95% CI: 1.05-1.83; P = 0.018) and RVFWLS/PASP ratio (HR: 1.43; 95% CI: 1.13-1.80; P = 0.002) were significantly associated with the composite outcome. Treatment effect of sacubitril/valsartan was not modified by measures of RV function. ConclusionsWorsening RV function and its ratio to pulmonary pressure is common and significantly associated with an increased risk of HF hospitalizations and cardiovascular death in patients with HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)

Right ventricular function is a predictor for sustained ventricular tachycardia requiring anti-tachycardic pacing in arrhythmogenic ventricular cardiomyopathy: insight into transvenous vs. subcutaneous implantable cardioverter defibrillator insertion.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients develop ventricular arrhythmias (VAs) responsive to anti-tachycardia pacing (ATP). However, VA episodes have not been characterized in accordance with the device therapy, and with the emergence of the subcutaneous implantable cardioverter defibrillator (S-ICD), the appropriate device prescription in ARVC remains unclear. Study aim was to characterize VA events in ARVC patients during follow-up in accordance with device therapy and elicit if certain parameters are predictive of specific VA events. This was a retrospective single-centre study utilizing prospectively collated registry data of ARVC patients with ICDs. Forty-six patients were included [54.0 ± 12.1 years old and 20 (43.5%) secondary prevention devices]. During a follow-up of 12.1 ± 6.9 years, 31 (67.4%) patients had VA events [n = 2, 6.5% ventricular fibrillation (VF), n = 14], 45.2% VT falling in VF zone resulting in ICD shock(s), n = 10, 32.3% VT resulting in ATP, and n = 5, 16.1% patients had both VT resulting in ATP and ICD shock(s). Lead failure rates were high (11/46, 23.9%). ATP was successful in 34.5% of patients. Severely impaired right ventricular (RV) function was an independent predictor of VT resulting in ATP (hazard ratio 16.80, 95% confidence interval 3.74-75.2; P < 0.001) with a high predictive accuracy (area under the curve 0.88, 95%CI 0.76-1.00; P < 0.001). VA event rates are high in ARVC patients with a majority having VT falling in the VF zone resulting in ICD shock(s). S-ICDs could be of benefit in most patients with ARVC with the absence of severely impaired RV function which has the potential to avoid consequences of the high burden of lead failure.

Evaluation of cardiac function in asthmatic children by Tissue Doppler Echocardiography

BackgroundBronchial asthma is a global health problem with rising prevalence in developing countries. Children with severe asthma can experience cor pulmonale later in life, but little is known about the cardiac changes that might be present earlier in mild or moderate severity of disease. This study aimed to evaluate biventricular function among children suffering from persistent asthma by Tissue Doppler Echocardiography (TDE).ResultsThirty-five asthmatic children enrolled from Alexandria Children’s Hospital between September 2021 to May 2022; they were compared to 35 healthy matched children. Chronic respiratory disease, cardiac disease, or other comorbidities were excluded. The mean age of cases was 8.87 ± 2.03 years with a male/female ratio of 54.3%:45.7%. There were 28.3% mild cases, 45.7% moderate, and 25.7% severe. Conventional echocardiographic variables of cardiac function were normal for both ventricles. The TDE indices of medial mitral annulus (S’ velocity and peak E’) were significantly reduced (14.55 ± 2.30 and 14.69 ± 2.30) versus controls (15.68 ± 1.96, 15.69 ± 1.76, P; 0.044, P < 0.0045) but with preserved LV function. The lateral tricuspid annulus (S’ velocity and peak E’) was significantly reduced (11.53 ± 3.24 and 11.56 ± 3.18) versus controls (15.71 ± 0.98, 16.02 ± 1.75, < 0.001*), while E/A and IVRT were significantly increased (1.49 ± 0.06 versus 1.70 ± 0.18 and 102.39 ± 5.37 versus 140.10 ± 34.35, respectively, P < 0.001*) with impaired RV function. Peak expiratory flow rate (PEFR) was negatively correlated with the IVRT of the tricuspid annulus (P = 0.002, r = −0.503*) and to the E'/A' (P = 0.036, r =−0.355*). All TDE variables of lateral tricuspid annulus of severe subgroups were significantly changed versus moderate or mild subgroups.ConclusionsTissue Doppler echocardiography is the recommended modality for early detection of biventricular cardiac dysfunction among children with different levels of asthma severity. Periodic screening is advised through the use of IVRT especially for RV.

Phosphodiesterase-5 inhibitors for left ventricular assist device implantation complicated by right ventricular failure.

Phosphodiesterase-5 inhibitors (PDE5I) are frequently implemented after left ventricular assist device (LVAD) implantation to improve haemodynamics in patients with early postoperative right ventricular (RV) failure. It is unknown if long-term PED5I therapy beyond the early post-operative period provides any clinical benefit in stable outpatients, who have recovered from post-operative RV failure under univentricular device support. This study aimed to investigate the impact of PDE5I discontinuation on RV function and cardiopulmonary exercise capacity in patients on durable LVAD support. We enrolled 31 clinically stable LVAD recipients on long-term oral PDE5I therapy. The mean age was 53years, and 90% were male. Patients discontinued PDE5I and underwent cardiopulmonary exercise testing, echocardiography, LVAD interrogation, and biomarker analysis at baseline and 4weeks after PDE5I withdrawal. At 4weeks, no significant changes were observed in echocardiographic indices of RV morphology and function but an increase in peak tricuspid regurgitation velocity (2.1 vs. 2.4m/s, P=0.01). Peak oxygen consumption (11.4 vs. 11.8mL/min/kg, P=0.52), minute ventilation/carbon dioxide production slope (33 vs. 35, P=0.56), N-terminal pro-brain natriuretic peptide (1455 vs. 1399pg/mL, P=0.55), flow and power readings of the device, and quality of life (Kansas City Cardiomyopathy Questionnaire score 78.3% vs. 77.5%, P=0.62) exhibited no significant changes. We observed an increase in 6-min walking distance (346 vs. 364m, P=0.03). Two patients were hospitalized for non-cardiac reasons (subtherapeutic INR, driveline infection). No patient was hospitalized for cardiac decompensation. In LVAD patients with a history of early post-operative RV failure, discontinuation of long-term PDE5I therapy was not associated with deterioration of RV function, exercise capacity, and quality of life. PDE5I should be critically evaluated until more evidence regarding the net clinical benefit of this pharmacologic intervention becomes available.

Cardiovascular indicators associated with ventricular remodeling in chronic high-altitude disease: a cardiovascular MRI study.

This study aimed to assess biventricular function and mechanics in patients with the chronic high-altitude disease (CHAD) using cardiovascular MRI and explore the possible risk factors associated with ventricular remodeling. In this prospective study, consecutive CHAD patients and healthy controls at high-altitude (HA) and at sea level (SL) underwent cardiovascular MRI. Right ventricular (RV) and left ventricular (LV) function and global strain parameters were compared. To identify risk factors associated with ventricular remodeling, multiple linear regression analyses were used. A total of 33 patients with CHAD (42.97years ± 11.80; 23 men), 33 HA (41.18years ± 8.58; 21 men), and 33 SL healthy controls (43.48years ± 13.40; 21 men) were included. A Significantly decreased biventricular ejection fraction was observed in patients (all p < 0.05). Additionally, the HA group displayed lower magnitudes of biventricular longitudinal peak strain (PS) (RV, - 13.67% ± 4.05 vs. - 16.22% ± 3.03; LV, - 14.68% ± 2.20 vs. - 16.19% ± 2.51; both p < 0.05), but a higher LV circumferential PS (- 20.74% ± 2.02 vs. - 19.17% ± 2.34, p < 0.05) than the SL group. Moreover, multiple linear regression analyses revealed that HGB (β = 0.548) was related to the LV remodeling index, whereas BUN (β = 0.570) was associated with the RV remodeling index. With the deterioration of RV function in patients with CHAD, LV function was also impaired concomitantly. Hypoxia-induced erythrocytosis may contribute to LV impairment, while BUN was considered an independent risk factor for RV remodeling. • A significantly lower biventricular ejection fraction was observed in patients, with a decreased magnitude of left ventricular (LV) peak systolic strain rate (radial and circumferential) and peak diastolic strain rate (all p < 0.05). • High-altitude healthy natives showed a lower biventricular longitudinal peak strain (all p < 0.05). • Hemoglobin was related to LV remodeling (β = 0.548), while BUN (β = 0.570) was independently associated with RV remodeling in CHAD patients.