Right Ventricular Research Articles

Effects of Dapagliflozin on myocardial performance in non-diabetic patients with Heart failure with reduced and mid-range ejection fraction (DAPA ECHO trial)

Abstract Background Sodium-glucose cotransporter type-2 inhibitors (SGLT2i) showed to reduced morbidity andmortality in HF patients. The aim of this study was to assess potential effects of dapagliflozin in non-diabetic patients with heart failure (HF) with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). Methods This randomized, prospective, single-center, open-label trial compared consecutive non-diabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except SGLT2i (Fig.1). Primary endpoint was the modification of left ventricular (LV) global longitudinal strain (GLS), diastolic function (as peak atrial longitudinal strain, PALS) and right ventricular (RV) function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Results Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in dapagliflozin group after 6 months, while there was a non-significant improvement in OMT group (Fig.1). Moreover, when comparing the modification of STE parameters at follow up in HFrEF and HFmrEF patients, only the main treatment effect resulted statistically significant in both groups (p<0.0001), indicating a significant difference between dapagliflozin and OMT. Conclusions This study provided randomized data on the beneficial effect of dapagliflozin in non-diabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique i.e. STE. This suggests its usefulness for LV reverse remodeling and better quality of life in patients with HFrEF and HFmrEF.

Impaired myocardial energetics and lower cardiac reserve in response to exercise stress in adults born preterm

Abstract Background/Introduction Preterm birth (<37 weeks’ gestation) affects 10% of live births globally and associates with an increased risk of heart failure, early cardiovascular-related mortality, and altered cardiac morphology. At rest, left ventricular (LV) ejection fraction (EF) is similar between adults born preterm and term, but right ventricular (RV) EF is lower in preterm-born adults. Exercise stress uncovers LVEF impairment in preterm-born adults but RVEF response to exercise stress has not been studied. The underlying cause of the impaired LVEF reserve and lower RVEF at rest in preterm-born adults remains uncertain and whether altered myocardial energetics contribute to this cardiac dysfunction is currently unknown. Purpose To measure resting myocardial energetics and ventricular function at rest and during exercise stress to determine whether reduced cardiac reserve in preterm-born adults may be explained by impaired myocardial energetics. Methods We conducted a cross-sectional, observational, case-control study of preterm (n=64; mean gestational age =31 weeks) and term-born (n=36) adults aged 34±5 years to compare myocardial energetics and ventricular function. Following maximal cardiopulmonary exercise testing (CPET), participants underwent 31-phosphorus magnetic resonance (MR) spectroscopy (31-P MRS) and cardiovascular MR imaging (CMR) on a 3-Tesla Siemens MR scanner. 31-P MRS was used to measure myocardial phosphocreatine to adenosine triphosphate ratio (PCr/ATP) as a measure of myocardial energetics. We obtained CMR-derived LVEF and RVEF at rest and during 40% peak wattage exercise (determined from CPET) using a MR compatible cardio-step module and steady-state free precession real-time cine imaging. Outcomes were analysed using unpaired Student’s t-tests and presented as mean±standard deviation. Results Age, body mass index, and sex did not differ between groups (p>0.05). PCr/ATP was 1.8±0.4 in preterm-born adults and 2.0±0.4 in term-born adults (p=0.01, Figure 1). Preterm-born adults had a similar LVEF versus term-born adults at rest (60.3±7.6 versus 62.1±4.5; p=0.19) though resting RVEF was lower in preterm-born adults (53.4±6.7 versus 55.9±4.5; p=0.05). LVEF increased by 6.5±5.5% in preterm-born adults and 10.9±6.0% in term-born adults from rest to 40% peak exercise (p<0.001), while RVEF increased by 9.2±6.3% in preterm-born adults versus 12.0±6.3% in term-born adults (p=0.06) (Figure 2). PCr/ATP associated with resting RVEF in preterm-born adults (R²=0.27, p=0.002), but was not associated with resting LVEF or the delta change in LVEF and RVEF with exercise stress. Conclusions Resting myocardial energetics is impaired in adults born preterm relative to term-born adults, with both the LV and RV demonstrating reduced functional reserve when challenged with low to moderate exercise stress. Metabolic modulators may help prevent progression to heart failure in preterm-born adults.Figure 1Figure 2

Scoring system for early detection in pulmonary hypertension type I based on clinical presentation, electrocardiography, and chest X-ray at RSUD dr. Saiful Anwar

Background: In Indonesia, pulmonary hypertension prevalence is 1:10.000 population. Due to its atypical symptoms, often PH patients come as a late presenters thus they have a worse prognosis. The golden standard to diagnose is Right Heart Catheterization (RHC) which is not widely available. Objectives: To generate a scoring system based on clinical presentation, electrocardiogram, and chest x-ray for early detection. Methods: A hospital-based cross-sectional survey was conducted in RSUD dr. Saiful Anwar, East Java from July 2020 – November 2023 with data from the medical record in which all variables are obtained at one period. Data were analyzed using bivariate analysis, multiple logistic regression, and Area Under Curve (AUC) from Receiver Operating Characteristic (ROC). Results: A total of 244 patients who were above 18 years old were conducted RHC at RSUD dr. Saiful Anwar East Java. We found a total score of 12 consisting of Dyspnea on Effort (DOE) score 2, Palpitation score 1, Increasaed P2 score 2, Increased JVP (Jugular vein pressure) score 2, RV (Right Ventricular) Heaves score 2, Right bundle branch block (RBBB) score 1, and Cardiomegaly (CTR >50%) score 2. With a 2 x 2 table, we found that a score of ⩾5 is likely for pulmonary hypertension diagnosis. Conclusion: Our study is a predictive model with a scoring system that has good sensitivity and specificity in selected populations where one of its limitations is sampling bias thus cannot yet be applied to the general population and needs further research for validation. Keyword: congenital heart disease, pulmonary hypertension, scoring for early detection

Echocardiography in acute pulmonary embolism for the prediction of subsequent CTEPH

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a long term complication of acute pulmonary embolism (APE) with poor outcomes if untreated. Identifying already at APE diagnosis patients at risk of subsequent CTEPH can lead to earlier goal-directed management. Since standard echocardiography (TTE) is frequently performed during APE episode for short term risk stratification we aimed to asses prediction vale of echocardiography for subsequent CTEPH. Methods We analyzed retrospectively TTE performed at admission due to APE in consecutive patients, without known CTEPH who were anticoagulated for at least 3 months and were followed up for at least 24 months. After follow-up all patients underwent diagnostic workup for CTEPH according to ESC recommendations. We tried to define a set of echocardiographic parameters recorded during the acute episode predictive for CTEPH. Results The study included consecutive 625 patients with APE diagnosed at computed tomography pulmonary angiogram and managed according to ESC recommendations. During follow up 25 (4%) pts were diagnosed with CTEPH. At APE diagnosis CTEPH(+) group presented more prominent echocardiographic signs of right ventricular (RV) overload than pts without CTEPH (CTEPH(-))(table 1). However, multivariate analysis revealed that only increased TRPG and RV/LV ratio were significant CTEPH predictors with AUC 0.792 (95% CI: 0.683-0.900), p<0.001 and 0.777 (95% CI: 0.675-0.878), p<0.001 respectively (fig 1). Using Youden index in ROC analysis we defined following cut off values useful to identify patients at CTEPH risk and subjects with low probability of CTEPH development. TRPG >44mmHg and RV/LV>1.15 showed PPV for CTPEH 12.9 (95% CI: 9.8-16.7) and 13.8 (95% CI: 10.4-18.1), with high NPV of 98.4 (95% CI: 97.1-99.2) and 98.2 (95% CI: 96.8-99.0) respectively. Importantly, in the group of 61 (9.7%) patients with both signs of RV overload present in the acute phase CTEPH during follow-up was diagnosed in 14 patients (23.0%). Conclusion TRPG above 44 mmHg recorded at APE diagnosis identifies patients at risk of subsequent CTEPH especially in patients with increased RV/LV ratio.

Cardiac resynchronization therapy in adult congenital heart disease: single center cohort study

Abstract Introduction Cardiac resynchronization therapy (CRT) is a recommended therapeutic measure for patients with heart failure. Heart failure is a major morbidity amongst patients with adult congenital heart disease (ACHD). However, the data on the efficacy and safety of CRT amongst ACHD is limited. Methods Data was analyzed from a retrospective cohort of patients with a known diagnosis of ACHD and implantation of CRT between 2015-2022. The primary outcome was echocardiographic response to CRT. This was defined as either:1) an increase in systemic ventricular ejection fraction (EF) of ≥5% in patients with EF <50% (therapeutic) or 2) maintenance of EF in patients with EF≥50% (preventative). Secondary outcomes included change in QRS duration, heart failure admissions, death and CIED (cardiovascular implantable electronic devices) infection during follow up. The outcomes were also assessed by subgroup of systemic left or right ventricle systemic ventricle. Results Our cohort included 46 patients, 96% male and average age was 54±14 years. 26 patients had a systemic left ventricle (56.6%) and 20 patients had a systemic right ventricle (44.4%). The indication for CRT implantation was 1) Reduced EF with wide QRS (n=10, 22%), 2) Reduced EF and RV (right ventricular) pacing (n=22, 49%), and 3) Normal EF with RV pacing (n=14, 33%). 25 patients (55%) had an implanted defibrillator at baseline. Primary outcome amongst patients with preserved EF at baseline was achieved in 22/32 patients (68.7%) and was achieved in 12/14 patients (85.7%) amongst patients with reduced EF at baseline. During follow up, QRS duration was shortened in 68.7%, 13 patients had heart failure admissions (30%), 4 patients underwent heart transplants/mechanical support device implantation (8.6%), death occurred in 11 patients (24%) and 3 had CIED infection (7%). There was no significant difference in complication or efficacy rates between the left systemic and right systemic group. Conclusion CRT is effective in patients with ACHD both as a therapeutic and as a preventative measure for heart failure. There was no difference in clinical response to CRT between patients with SRV compared to SLV. The percentage of patients with a safety outcome was relatively high in this subpopulation due to advanced ACHD.

Association between left atrial dysfunction and adverse outcomes after tricuspid valve surgery for atrial functional tricuspid regurgitation

Abstract Objectives To identify factors associated with clinical outcomes in patients undergoing tricuspid valve (TV) surgery for atrial functional tricuspid regurgitation (AF- TR). Methods Among 1,670 patients who underwent TV surgery between January 2000 and December 2020, we included 83 AF-TR patients (69.1±9.2 years, 50 women) who had severe TR without any cause other than atrial fibrillation. A comprehensive analysis of right ventricular (RV) and left atrial (LA) function on preoperative and postoperative echocardiography was performed. LA function was evaluated by LA emptying fraction (LAEF), LA reservoir strain, and LA stiffness index. The primary outcome was a composite of all-cause death and heart failure hospitalization during follow up after surgery. Results For a median of 39.9 (interquartile range 19.9 to 55.8) months, the primary outcome occurred in 20 (24.1%) patients. Patients with a primary outcome showed significantly lower LAEF (9.7±7.3 vs. 21.8±6.7 %, p<0.001) and LA reservoir strain, and higher LA stiffness index than those without. However, there was no difference in RV chamber size and functional parameters according to the occurrence of a primary outcome. The restricted cubic spline plot exhibited a significant relationship between LAEF and primary outcome. The low baseline LAEF (<17%) group showed a poorer outcome than the high LAEF group (log rank p<0.001). In the Cox regression analysis, the low LAEF (<17%) was independent predictor for primary outcome (adjusted hazard ratio 13.5, 95% confidence interval 3.1–58.6). Conclusion In patients undergoing TV surgery with AF-TR, preoperative LA dysfunction was independently associated with adverse outcomes.Figure1

Cardiac structure and function in patients with chronic obstructive pulmonary disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is common and strongly associated with cardiovascular disease, but the pathophysiology has not been fully elucidated. Purpose We aimed to investigate cardiac structure and function in patients with COPD compared to a matched general population. Methods In a prospective cohort study, 796 patients with COPD were included and matched 1:2 on age and sex with controls from a general population study. All participants underwent an examination program including echocardiography. Standardized linear regression coefficients were used to compare cardiac structure and function in patients with COPD vs. controls. Impaired left ventricular (LV) function was defined as a left ventricular ejection fraction (LVEF) <50%, or global longitudinal strain (GLS) <16% (numerical). Impaired right ventricular (RV) function was defined as tricuspid annular plane systolic excursion (TAPSE) <1.7 cm. Diastolic dysfunction was defined as having at least two of the following parameters: E/e’ >14, septal e’ velocity <7cm/s, or lateral e’ velocity <10 cm/s, left atrial volume index (LAVi) >34 mL/m2, or tricuspid regurgitation velocity (TRV) >2.8 m/s. Logistic regression was used to assess associations between having COPD and systolic and diastolic dysfunction. Results Mean age was 70.2 ± 8.3 years and 52% were females. COPD patients had a mean forced expiratory volume in 1 second (FEV1) of 49.4 ± 18.8% predicted. At baseline, 43% of the patients with COPD had hypertension and 10% had diabetes (DM). Additionally, 57% with COPD had cardiovascular disease at baseline, including 12% with ischemic heart disease (IHD), 15% with atrial fibrillation (AF), 6% with heart failure, and 5% with a previous ischemic stroke. Patients with COPD had impaired measures of cardiac structure and function including a lower GLS (COPD vs. controls: 16.3 vs. 19.2%), lower TAPSE (2.3 vs. 2.6 cm), larger LAVi (29.0 vs. 24.7 mL/m2), and higher TRV (2.7 vs. 2.3 m/s), p for all associations <0.001. (See figure). Patients with COPD had a significantly higher prevalence of impaired LV systolic function (OR for GLS <16%: 8.18, 95% CI(6.04; 11.1), p <0.001), impaired RV systolic function (OR for TAPSE <1.7 cm: 2.77, 95% CI(1.63; 4.69), p <0.001), and LV diastolic dysfunction (OR for diastolic dysfunction grade I or higher: 4.00, 95% CI(3.12; 5.13), p <0.001) after adjustment for age, sex, hypertension, smoking, DM, IHD, AF, and lower density lipoprotein. (See figure). Conclusion Patients with COPD had significantly impaired LV and RV systolic function as well as impaired diastolic function compared with individuals from the general population. These findings underscore the importance of recognizing and addressing cardiovascular comorbidities in COPD.

Investigating the role of WT1 in Brugada syndrome pathophysiology

Abstract Background Brugada syndrome (BrS) is a heritable arrhythmic disorder presumably caused by conduction slowing in the right ventricular (RV) outflow tract (RVOT). A recent genome-wide association study found an association between common variants on chromosome 11 near WT1, tagged by the SNP rs72905083, and BrS susceptibility. Purpose To study whether WT1 affects cardiac conduction and could therefore represents the underlying association of the chr11 locus with BrS susceptibility. Methods We conducted in silico analyses of omics datasets to identify the likely causal gene at the chr11 BrS locus. Next, we conducted electrophysiological studies in heterozygous young adult (4 months old) Wt1-deficient (Wt1+/-) mice and wild-type littermates to explore the effect of Wt1 on cardiac conduction. To study the potential role of Wt1 in the setting of reduced conduction reserve, we compared aged Scn5a haploinsufficient mice (Scn5a+/-;Wt1+/+, 17 months) with littermates haploinsufficient for both Wt1 and Scn5a (Scn5a+/-;Wt1+/-). Optical mapping was performed in Langendorff-perfused hearts, where conduction was further challenged by acute ajmaline administration or by pacing at the effective refractory period (ERP). Transcriptomic analyses were conducted in Wt1+/- and wild-type mice by RNAseq of PCM1-sorted cardiomyocytes. Results Analysis of omics datasets uncovered WT1 as the likely causal gene since WT1 was the closest gene to, and in fact overlapped, the BrS-associated region; promoter capture Hi-C data in human tissue showed chromatin contact between the promoter of WT1 and the associated region; and H3K27ac ChIP-seq signals (i.e. enhancer activity) of putative cardiac enhancers located within the associated region were correlated with WT1 transcript abundance across multiple tissues (Z-score = 4.32, p=1.57e-05). No differences were observed in ECG parameters or optically mapped epicardial conduction between Wt1+/- mice and wild-type littermates. However, comparison of aged Scn5a+/-;Wt1+/- and Scn5a+/-; Wt1+/+ hearts, in the setting of acute ajmaline challenge or pacing at the ERP, showed faster conduction in RV/RVOT in the presence of Wt1 haploinsufficiency (genotype effect: p=0.057 and p=0.041 for RV and RVOT epicardial conduction, respectively, during ajmaline challenge; p=0.034 for RV epicardial conduction during pacing at ERP). RNAseq of RV/RVOT cardiomyocytes revealed higher Scn5a expression in Wt1+/- vs wild-type (p=0.006). Conclusion We identified WT1 as the gene that most likely underlies the effect of the chr11 BrS susceptibility locus. Functional data revealed protective effects of reduced Wt1 expression in the setting of reduced conduction reserve. Transcriptomic data suggest that this occurs through a transcriptional effect on Scn5a expression.

Association between current of injury and intraoperative R wave amplitude fluctuation immediately after active fixation pacing lead implantation

Abstract Background Active fixation lead stability and pacing threshold adequacy are predictable from assessment of current of injury (COI) prevalence. However, time courses of R wave amplitude value immediately after implantation varies despite of COI prevalence. Objective This study aims to clarify whether intraoperative R wave amplitude fluctuation is associated with COI, and the adequacy assessment is possible. Methods Consecutive recipients of active fixation lead implanted to right ventricular (RV) septum from April to November 2023 were enrolled. R wave amplitude values automatically measured by programmer were continuously recorded from immediately after implantation to generator connection. The final R wave amplitude value greater than 4 mV was determined as implantation success. The successful implantation time courses of R wave amplitude value classified into following three types (Figure 1): (1) the Dipper type; R wave amplitude transiently decreases to the bottom value and then increases, (2) the Riser type; R wave amplitude shows a upward trend (no decline) for the first 5 minutes after active fixation, and (3) the other type. The primary outcome was prevalence of favorable amplitude increase defined as the final R wave amplitude value exceeding that of immediately after the active fixation. Results Among 106 of RV lead implantations in 78 consecutive pacemaker recipients, 73 successful implantation records were evaluated (5 missing data and 28 unsuccess implantations). According to the continuous R wave amplitude records, 51 and 19 successful implantation time courses could be classified into the Dipper and Riser types, respectively. In the Dipper type, the median screw-in to bottom time (SBT) was 5 (interquartile range: 5–12) minutes, and then R wave amplitude improved to mean of 1.7 ± 0.6 times higher than the bottom value. The electrogram (EGM) immediately after active fixation showed R wave < COI pattern, and gradually changed to R wave > COI pattern by the withdrawal of COI over time. Among them, 26 implantations showed favorable amplitude increases and significantly shorter SBT than the remaining implantations (6 ± 4 minutes vs. 10 ± 5 minutes, P=0.03). The ROC analysis showed the predictive cut-off value of SBT for favorable amplitude increase was 6 minutes (AUC:0.73, sensitivity:0.81, specificity:0.60). In the Riser type, acceptable R wave amplitude and R wave > COI pattern EGM were consistently recorded, and finally obtained the favorable amplitude increase in all implantations. Conclusion More than 95% of R wave amplitude fluctuation patterns immediately after successful lead implantation could be classified as the Dipper or Riser types. The mechanism might be associated with a competition among R wave amplitude and COI magnitude, and the prediction of favorable R wave amplitude increase might be possible by the EGM patterns obtained immediately after active lead fixation and the subsequent 5–6 minutes of observation.Success implantation time coursesClinical implication

Cardiovascular magnetic resonance to differentiate veteran athlete's heart with cavity dilatation and mild dilated cardiomyopathy

Abstract Introduction Endurance athletic training may lead to left ventricular (LV) dilatation and mildly reduced resting LV function which can be difficult to differentiate from dilated cardiomyopathy (DCM). Myocardial fibrosis is increasingly recognised in lifelong athletes and is also prevalent in DCM where it confers adverse prognosis.(1,2) However, it is unknown whether the pattern and prevalence of fibrosis in athletes with cavity dilatation differs from DCM. In this study, we compared the CMR fibrosis distribution and tissue characteristics between athletic LV dilatation and mild DCM patients. Methods We prospectively recruited 113 males; 64 endurance athletes and 49 mild DCM patients. Inclusion criteria Age 50-80 years, LVEF 45-54% and LV end-diastolic volume indexed to body surface area (LVEDVi)≥110ml/m2. Athletes trained≥10 weekly hrs for≥15 yrs. Exclusion criteria; Chest pain, prior coronary revascularisation, severe valvular disease, myocarditis, hypertrophic cardiomyopathy, inducible ischaemia or myocardial infarction on CMR. CMR protocol included volumetric assessment, T1 mapping, quantitative stress perfusion and quantitative late gadolinium enhancement. Statistical analysis between groups was performed using unpaired t-test and receiver-operator curve (ROC) analysis. Results LVEDVi was not significantly different between athletes and mild DCM patients (123.3±12.6 vs 129.8±23.1ml/m2, P=0.057). However, LVEF (52.0±6.1 vs 47.6±5.2%, P<0.001) and right ventricular (RV) EDVi (121.0±14.3 vs 97.6±25.2ml/m2, P<0.001) were both greater in athletes. There was no difference in non-ischaemic fibrosis prevalence between both groups (50.0 vs 49.0%, P=0.915) nor the burden of fibrosis (3.5±2.9 vs 7.4±12.0g, P=0.087). However, the distribution of fibrosis varied with a significantly greater prevalence of basal mid-myocardial inferolateral fibrosis amongst athletes (87.5 vs 50.0%, P=0.002) whereas basal mid-myocardial inferoseptal fibrosis was significantly more common in mild DCM (45.8 vs 9.4%, P=0.002). Native T1 (1249.0±38.1 vs 1308.3±47.1ms, P<0.001) and extracellular volume (ECV) (22.0±2.1 vs 25.9±3.5%, P<0.001) were both lower in athletes than mild DCM patients. Furthermore, athletes had higher myocardial perfusion reserve (MPR) (3.65±1.30 vs 2.76±0.92, P<0.001) and stress myocardial blood flow (MBF) (2.09±0.70 vs 1.62±0.66, P<0.001). On ROC analysis, native T1 (area under curve (AUC) 0.89, P<0.001), ECV (AUC 0.85, P<0.001) and stress MBF (AUC 0.68, P<0.001) were able to differentiate athletes and mild DCM. Native T1 and ECV were significantly better at discriminating than MPR (P<0.001). Conclusion Myocardial fibrosis was highly prevalent in both veteran endurance athlete's heart and mild DCM whilst its distribution was distinctive between the groups. Native T1 and ECV were the best discriminators. Recognition of fibrosis patterns and associated tissue characteristics may be clinically useful to differentiate these two overlapping phenotypes.Figure 1; LGE distribution in athletes cFigure 2; CMR tissue characteristics to

Higher product of right ventricle to left ventricle diameter ratio and septal wall thickness is associated with increased risk of cardiovascular death in patients post TAVI

Abstract Background Right ventricular (RV) dilatation is a significant predictor for mortality in various cardiovascular diseases. Hypertrophy is common in patients undergoing transcatheter aortic valve implantation (TAVI). We tested the hypothesis that the product of right ventricle to left ventricle diameter (RV/LV) ratio and septal wall thickness (SWT) might be a determinant of cardiovascular death in TAVI patients. Methods This retrospective study enrolled 1123 patients undergoing TAVI in our department between 2009 and 2021 (mean age 81.4±5.6 year, male 51.2%). We assessed standard echocardiographic measures prior to the TAVI procedure. End-diastolic basal biventricular dimensions were measured from a standard apical 4-chamber view, and the ratio of RV dimension (RVD) to LV dimension (LVD) was calculated as the RV/LV ratio. We tested the prognostic performance of the product of RV/LV ratio and septal wall thickness (RV/LV ratio*SWT). The primary endpoint was cardiovascular (CV) death up to 2 years after TAVI. Results CV mortality was 11.8% (132/1123) at 2 years after TAVI. SWT was similar between the groups with and without CV death (11.9±1.9 vs. 11.6±1.8 mm, P=0.188). However, the RV/LV ratio (0.84±0.15 vs. 0.80±0.13, P=0.002) and RV/LV ratio*SWT (10.0±2.7 vs. 9.3±3.1 mm, P=0.005) were notably higher in the CV-death group compared to the no CV-death group. Higher RV/LV ratio*SWT remained independently associated with elevated 2-year CV mortality after TAVI (HR=1.09, 95% CI 1.01-1.17, P=0.024), while the RV/LV ratio was no longer significantly linked with CV mortality (HR=2.83, 95% CI 0.87-9.19, P=0.082) after adjusting for potential confounding factors including age, sex, and atrial fibrillation. RV/LV ratio*SWT >12.7 mm was associated with a twofold increased risk of 2-year CV mortality compared to patients with RV/LV ratio*SWT ≤12.7 mm (2-year mortality 14.4% vs. 6.0%, P<0.001; HR=2.04, 95% CI 1.25-3.32, P=0.004), regardless of age, sex, and atrial fibrillation. Conclusions Combined assessment of biventricular remodelling and left ventricular hypertrophy by calculating RV/LV ratio*SWT is of clinical importance for risk stratification of cardiovascular death among TAVI patients.

Cardiac MRI traits linked to cardiomyopathy mutations in phenotype naive carriers

Abstract Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are prevalent forms of cardiomyopathies, characterised by changes in cardiac structure and function, associated with an increased risk of atrial fibrillation (AF), heart failure (HF), and sudden cardiac death (SCD). Due to these potential life-threatening consequences close monitoring of genetic mutation carriers of HCM and DCM, is important. However, disease onset in these subjects is highly variable, with a substantial subset of people only developing disease late-in-life, or not at all, making risk stratification challenging. We set out to identify cardiac MRI (CMR) based imaging biomarkers of HCM and DCM carriership in phenotype naïve individuals, which were benchmarked against associations with AF and HF. CMR and whole genome sequencing (n: 42,723) data were sourced from a UK biobank sample free of heart failure at the time of CMR measurements. A previously validated deep learning(DL) network was used to derive 22 CMR traits(1). Adjusted cox regression models were used to determine the CMR associations with the onset of heart failure and atrial fibrillation, providing empirical validation of the DL CMR network. Univariable and multivariable generalised linear models were employed to identify associations with genetic carriership conditional on cardiac risk factors. 14 and 19 CMR measurements were associated with the time until HF (274 cases), AF (704 cases), respectively. These variables included left-ventricle (LV) ejection fraction (EF), LV end systolic volume (ESV), Right-ventricular (RV) EF and right atrial (RA) EF. Using WGS data we identified 154 people with an HCM mutation and 220 with a DCM mutation, where HCM carriership associated with five and DCM with four CMR traits. This included RA-EF (OR 1.26 95%CI 1.10; 1.45), and RV-EF (OR 1.41 95%CI 1.23;1,63) for HCM, and LV-EF (OR 0.72 95%CI 0.62; 0.84), and RV stroke volume (OR 0.75 95CI 0.62; 0.91) for DCM. By combining deep learning of CMR with large sample size WGS we were able to identify cardiac imaging biomarkers of HCM and DCM carriership in apparently healthy subjects. This could prove relevant for early identification and monitoring of phenotype naïve people.

Evaluation of right ventricular mechanics using exercise echocardiography in asymptomatic patients with severe mitral stenosis.

We aimed to evaluate the effect of exercise echocardiography (EE) on Right ventricular (RV) deformation parameters in asymptomatic patients with severe rheumatic mitral stenosis (MS) (mitral valve area ≤ 1.5 cm2, stage C) and to determine the relation between symptoms and severity of MS. 38 rheumatic MS patients in stage C underwent EE. 20 Patients were defined; as an exercise intolerance group who couldn't reach a maximum heart rate according to their age during exercise due to developing dyspnea The remaining 18 patients who reached a maximum heart rate without dyspnea were defined; as an exercise tolerance group. RV echocardiographic parameters at baseline and peak exercise were compared between the groups. While RV global strain (RV GLS) (21.02 ± 3.33 vs. 21.92 ± 3.03) and RV free wall longitudinal strain (RV FWLS) (23.41 ± 5.66 vs. 25.08 ± 5.00) at baseline were similar in both groups (P = 0.390 P = 0.343), RV GLS (23.38 ± 4.30 vs. 26.05 ± 3.24) and RV FWLS (24.24 ± 5.78 vs. 28.05 ± 4.62) at peak exercise were reduced in exercise intolerance group (P = 0.040 P = 0.033). The best correlations were found between exercise capacity and RV FWLS at baseline and peak exercise in all MS patients (respectively; r = 0.627 P < 0.001; r = 0.697 P < 0.001). RV mechanics has approved the reliability of EE in patients with asymptomatic patients with severe MS. During exercise RV contractile reserve could diminish in MS patients with stage C who develop dyspnea. Moreover, since our study has a close relationship between exercise capacity and RV mechanics, using RV mechanics during exercise echocardiography may be useful for risk stratification in MS patients with severe MS.

Unusual presentation of right ventricular branch occlusion during percutaneous coronary intervention

Right ventricular (RV) infarction usually occurs in the setting of inferior wall myocardial infarction due to proximal right coronary artery (RCA) occlusion. A rarer cause of RV infarction involves an isolated RV branch occlusion during a percutaneous coronary intervention (PCI) to revascularize the RCA. In this case, the isolated RV branch occlusion resulted in transient unexpected ST-segment elevations in the anterior precordial leads. The patient developed transient chest pain peri-procedurally and repeat angiography showed widely patent stents but complete occlusion of the isolated RV branch. This case highlights a rare and unusual presentation of RV branch occlusion with anterior ST-segment elevations. Keywords: coronary artery disease, percutaneous coronary intervention, right ventricular infarction

Right ventricular-pulmonary artery coupling for prognostication in acute pulmonary embolism.

Acute pulmonary embolism (PE) increases pulmonary pressure and impair right ventricular (RV) function. Echocardiographic investigation can quantify this mismatch as the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) ratio. The aim of the study was to investigate the prognostic capabilities of TAPSE/PASP ratio in patients with acute PE. We utilized the RIETE registry to analyze consecutive hemodynamically stable PE patients. We used multivariable logistic regression analyses to assess the association between the TAPSE/PASP ratio and 30-day all-cause mortality across the strata of European Society of Cardiology (ESC) risk categories. We included 4,478 patients, of whom 1,326 (30%) had low-risk, 2,425 (54%) intermediate-low risk, and 727 (16%) intermediate-high risk PE. Thirty-day mortality rates were 0.7%, 2.3% and 3.4%, respectively. Mean TAPSE/PASP ratio was 0.65±0.29 in low-risk patients, 0.46±0.30 in intermediate-low risk, and 0.33±0.19 in intermediate-high risk patients. In multivariable analyses, there was an inverse association between TAPSE/PASP ratio and 30-day mortality (adjusted OR 1.32 [95%CI 1.14-1.52] per 0.1 decrease in TAPSE/PASP). TAPSE/PASP ratio below optimal cut-points was associated with increased mortality in low- (<0.40, aOR: 5.88; 95%CI:1.63-21.2), intermediate-low (<0.43, aOR: 2.96; 95%CI:1.54-5.71) and intermediate-high risk patients (<0.34, aOR: 4.37; 95%CI:1.27-15.0). TAPSE/PASP <0.44 showed net reclassification improvement of 18.2% (95%CI:0.61-35.8) vs. RV/LV ratio >1, and 27.7% (95%CI:10.2-45.1) vs. ESC risk strata. Decreased TAPSE/PASP ratio was associated with increased mortality. The ratio may aid in clinical decision-making, particularly for intermediate-risk patients for whom the discriminatory capability of the current risk stratification tools is limited.

Artificial intelligence-enabled reconstruction of the right ventricular pressure curve using the peak pressure value: a proof-of-concept study

Abstract Aims Conventional echocardiographic parameters of right ventricular (RV) function are afterload-dependent. Therefore, incorporating RV pressures may enable the formulation of new parameters that reflect intrinsic RV function accurately. Accordingly, we sought to develop an artificial intelligence–based method to reconstruct the RV pressure curve based on the peak RV pressure. Methods and Results We invasively acquired RV pressure in 29 heart failure patients before and after implanting a left ventricular (LV) assist device. Using these tracings, we trained various machine learning models to reconstruct the RV pressure curve of the entire cardiac cycle based on the peak value of the curve. The best-performing model was compared with two other methods that estimated RV pressures based on a reference LV and RV pressure curve, respectively. Seventeen consecutive patients from another centre who underwent right heart catheterization and simultaneous echocardiography served as an external validation cohort. Among the evaluated algorithms, multilayer perceptron (MLP) achieved the best performance with an R2 of 0.887 (0.834–0.941). The RV and LV reference curve–based methods achieved R2 values of 0.879 (0.815–0.943) and 0.636 (0.500–0.771), respectively. During external validation, MLP exhibited similarly good performance [R2 0.911 (0.873–0.948)], which decreased only modestly if the echocardiography-derived peak RV pressure was used instead of the invasively measured peak RV pressure [R2 0.802 (0.694–0.909)]. Conclusions The proposed method enables the reconstruction of the RV pressure curve using only the peak value as input. Thus, it may serve as a fundamental component for developing new echocardiographic tools targeting the afterload-adjusted assessment of RV function.

Impact of diabetes mellitus on right ventricular dysfunction and ventricular interdependence in hypertensive patients with heart failure with reduced ejection fraction assessed via 3.0 T cardiac MRI

BackgroundHypertension (HTN) and diabetes mellitus (DM) are two common comorbidities of heart failure with reduced ejection fraction (HFrEF), each of which can cause right ventricular (RV) dysfunction. The aim of this study was to investigate the impact of DM on RV dysfunction and ventricular interdependence in hypertensive HFrEF patients via cardiac magnetic resonance imaging (MRI) feature tracking.MethodsThis study included 249 patients with HFrEF: 77 HFrEF controls, 97 with hypertensive HFrEF (HTN-HFrEF [DM-]) and 75 with hypertensive HFrEF and comorbid DM (HTN-HFrEF [DM+]). The cardiac MRI-derived biventricular global radial (GRS), circumferential (GCS) and longitudinal (GLS) peak strains were obtained and compared among the groups. Multivariable linear regression and mediation analyses were used to evaluate the effects of DM and left ventricular (LV) strain on RV strain.ResultsThe biventricular GLS and GLS of segments 8, 9 and 14 of the interventricular septum (IVS) decreased gradually from the HFrEF control group to the HTN-HFrEF (DM−) group to the HTN-HFrEF (DM+) group (all P < 0.05). Patients with DM had even lower biventricular GCS and IVS strains in all directions in specific segments than did those without DM and the HFrEF controls (all P < 0.05). DM was independently associated with impaired RVGLS and RVGCS (both P < 0.05) in hypertensive HFrEF patients. The difference in RVGLS between the hypertensive HFrEF subgroups was partly mediated by LVGLS [β = 0.80, 95% CI (0.39–1.31)], and that of RVGCS was partly mediated by LVGCS [β = 0.28, 95% CI (0.01–0.62)].ConclusionsIn hypertensive HFrEF patients, comorbid DM may have aggravated RV dysfunction and was an independent determinant of impaired RV strain. RV dysfunction might be directly affected by DM and partially mediated by LV strain through unfavorable ventricular independence.

Proteomic Signatures of Right Ventricular Outcomes in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a disease of progressive right ventricular (RV) failure with high morbidity and mortality. Our goal is to investigate proteomic features and pathways associated with RV-focused outcomes including mortality, RV dilation, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in PAH. Participants in a single-institution cohort with 3 years of follow-up underwent proteomic profiling of their plasma using 7288 aptamers (targeting 6467 unique human proteins). Partial least squares discriminant analysis was performed to assess global protein variation associated with mortality, RV dilation, and NT-proBNP levels. Differentially abundant proteins and enriched pathways associated with outcomes were identified following baseline adjustments. RV vulnerability models estimated associations for individuals with similar afterload following adjustment for pulmonary vascular resistance. A total of 117 participants with PAH were included. Partial least squares discriminant analysis of the proteome showed clear separation between survivors and nonsurvivors, participants with dilated versus nondilated RVs, and across NT-proBNP levels. Proteins and pathways involving the ECM (extracellular matrix) were upregulated in participants who died during follow-up, those with severe RV dilation, and those with higher levels of NT-proBNP. Pulmonary vascular resistance adjustment reinforced the importance of ECM proteins in the association with RV vulnerability, independent of afterload. These findings were confirmed in independent PAH cohorts with available plasma proteomics and RV tissue gene and protein expression. Distinct plasma proteomic profiles are associated with mortality, RV dilation, and NT-proBNP in PAH. Proteins and pathways governing tissue remodeling are strongly associated with poor outcomes, may mediate RV vulnerability to right heart failure, and represent promising candidates as biomarkers and potential therapeutic targets.

Safety and outcomes with use of FlowTriever for mechanical thrombectomy i n acute pulmonary embolism

Objectives: Mortality in the pulmonary embolism (PE) risk categories has historically been reported between 30% and 40% in high-risk and &lt;15% in intermediate-risk group. In those who survive, there is a high rate of morbidity with dyspnea and exercise intolerance. Advanced therapies with a favorable safety profile have the potential to improve outcomes. We present the largest single-center data set studied to-date for safety, mortality, and outcomes post-mechanical thrombectomy including functional assessment 3 months post-discharge. Material and Methods: We analyzed retrospective database of patients with PE undergoing catheter directed mechanical thrombectomy (CDMT). We report clinical characteristics and outcomes stratified by PE risk categories. Comparison in the groups has been made using analysis of variance method. Results: A total of 365 patients were evaluated in the CDMT group. Among these 81 (22%) presented with high-risk and 261 (71%) with intermediate-risk PE. The average age at diagnosis was 61 ± 17 years with male-to-female distribution ratio of 1.2. Most common risk factors being reduced mobility (18%), malignancy (15%), recent surgery (13%), and hormonal therapy (12%). Mortality within 30 days of PE diagnosis was 8.6% (7/81) in high-risk, 1.7% (4/230) in intermediate-high-risk groups. There were no deaths in intermediate-low and low-risk group post-CDMT. Before thrombectomy, 349 (95%) patients had right heart strain, 307 (84%) had elevated troponin, and 197 (54%) had elevated B-type natriuretic peptide. Post-procedure echocardiogram at 3 month revealed improvement in the right ventricular (RV) fractional area change (27.53 ± 10.38% to 39.73 ± 8.3%, P &lt; 0.01), tricuspid annular plane systolic excursion (10.9 ± 8.3 mm to 21.81 ± 4.75 mm), and RV systolic pressure (43.96 ± 14.48 mmHg to 28.47 ± 7.88 mmHg, P &lt; 0.01). At 3 months post-thrombectomy, the majority (74%) of the patients fell into non-to-negligible functional limitation. Conclusion: We present a descriptive analysis of outcomes including improved mortality, and functional assessment of patients undergoing CDMT.

Serial and regional assessment of the right ventricular molecular and functional response to pressure-loading.

Right ventricular(RV) function determines outcomes in RV pressure-loading. A better understanding of the time-course and regional distribution of RV remodeling may help optimize targets and timing for therapeutic intervention. We sought to characterize RV remodeling between zero and 6-weeks after initiation of RV pressure-loading. Thirty-six rats were randomized to either sham surgery or to pulmonary artery banding(PAB). After echocardiography and conductance catheter studies, groups of rats were euthanized at 1-week, 3-weeks and 6-weeks after sham surgery, or induction of RV pressure-loading, for RV histological, RNA and molecular analysis. A vigorous inflammatory response characterized by increased RV inflammatory cytokines, chemokines and macrophage markers was observed at 1-week following PAB. Metabolic changes, TGF-β1 canonical signaling, collagenous fibrosis deposition and apoptosis were already significantly increased by 1-week after PAB. Genes marking fibroblast activation were upregulated at 1-week but not 6-week post-PAB surgery. Mitochondrial dysfunction as evidenced by increased PDK activity and decreased PDH phosphorylation significantly at 6-week post PAB. These processes preceded the development of overt myocardial hypertrophy and impaired echo parameters of systolic and diastolic function which occurred significantly from 3-weeks after PAB. RV myocardial inflammation, metabolic shift, metabolic gene transcription and pro-fibrotic signaling occur early after initiation of pressure-loading when RV pressures are only moderately elevated, before the development of overt myocardial hypertrophy and dysfunction, suggesting that adaptive hypertrophy and maladaptive remodeling occur simultaneously. These results suggest that therapeutic intervention to reduce adverse RV remodeling may be needed earlier and at lower thresholds than currently employed.