Ventricular Overload Research Articles

Early Outcomes of Right Ventricular Pressure and Volume Overload in an Ovine Model

Early Outcomes of Right Ventricular Pressure and Volume Overload in an Ovine Model

Maladaptive remodeling reduces survival in patients with moderate aortic stenosis and preserved ejection fraction

Abstract Background Aortic valve stenosis (AS) is a common cause of left ventricular (LV) pressure overload and subsequent hypertrophy and diastolic dysfunction. The extent of LV hypertrophy does not necessarily correlate with the severity of valve stenosis and excessive LV remodeling can be seen in moderate AS. Therefore aortic stenosis is the disease of valve and myocardium. Left ventricular hypertrophy (LVH) with different geometric patterns is associated with adverse prognosis, The concept of staging AS disease rather than merely classifying AS based on hemodynamic severity seems more appropriate. Current guidelines do not address whether aortic valve replacement should be recommended in patients with moderate aortic valve stenosis regardless of the presence of LV dysfunction. Purpose This study aimed to investigate differences in left ventricular remodeling and its impact on survival in patients with unequivocally moderate aortic stenosis and preserved LV ejection fraction. Methods We retrospectively analyzed 182 unequivocally moderate AS patients (57% were male, age was 70±9), who underwent transthoracic echocardiography from March 2018 to November 2021. AS severity was defined by specific threshold values peak velocity 3-4 m/sec, an MPG 20-40 mmHg and an AVA 1-1.5 cm. All values were concordant and suggested moderate AS. All patients were in sinus rhythm and with LV ejection fraction >50%. We calculated the LV mass index (LVMI) and ventricular geometry was assessed with a relative wall thickness (RWT). Left ventricular hypertrophy (LVH) was defined as LV mass index >95g/m2 in women and >115g/m2 in men and was defined as concentric when associated with a RWT>0.42 and eccentric when RWT was ≤0.42. Concentric remodeling was defined as normal LVM index and increased RWT. The follow-up assessment in December 2023 ascertained vital status and data on aortic valve replacement (AVR). Results LVH was present in 91 patients (50%). Eccentric LVH was present in 49 (27%), concentric LVH in 42 (23%), and concentric remodeling in 27 (15%). During a median 41 months follow-up, 49 (27%) deaths occurred. 32 (18%) patients undervent AVR. As expected, LV hypetrophy was associated with all-cause mortality (HR 2.556; CI: 1.007-6.448; p = 0.048), and if concentric hypertrophy was present mortality was even higher (HR 3.736; CI: 1.553-8.992; p = 0.003) AVR had a non-statistically significant protective effect (HR 0.654; CI: 0.193 -2.220; p = 0.496). Conclusion Maladaptive remodeling is associated with worse outcomes in patients with moderate AS. RWT is important for identification of abnormal geometry. Further studies investigating the adequate timing of AVR in patients with moderate AS with maladaptive LV response are needed.

Left ventricular pressure-strain-volume-loop and myocardial work patterns in asymptomatic severe aortic regurgitation with early disease decompensation

Abstract Background Severe aortic regurgitation (AR) is associated with left ventricular (LV) pressure and volume overload, leading to irreversible myocardial damage often before the onset of guidelines triggers for aortic valve surgery. Therefore, the development of sensitive imaging markers to detect the early impact of pressure-volume overload imposed by AR on LV geometry and function is needed. Aim To describe patterns of LV pressure-strain-volume loops, their components and myocardial work in asymptomatic patients with significant AR and preserved LV ejection fraction with early disease progression. Methods This multicenter study consisted of 95 consecutive patients (84.1% male, 45±14 years) with asymptomatic significant AR, in sinus rhythm, and preserved LV ejection fraction (EF) >50%, who did not have any indication for aortic valve surgery as per current guidelines. Comprehensive echocardiography was analyzed by an experienced operator blinded to clinical outcome. Pressure-strain-volume loops (PSVL), their components, and myocardial work were analyzed using customized software. Results During a median follow-up of 1375 [interquartile range 1041-1783] days, a total of 34 (36%) patients developed the class I indication for aortic valve surgery, i.e. either symptoms or LV dysfunction (AVsurg group). At baseline, LVEF (64±5% vs. 64±7%;p=0.748), global longitudinal strain (-17.6 ± -2.4% vs. -18.5 ± -2.4%; p=0.112), global myocardial work index (1963±429 vs.1900±340 mmHg%; p=0.429) or global constructive work (2371±495 vs. 2287±368 mmHg%; p=0.390) did not differ significantly between groups. In contrast, global wasted work was significantly higher (149[90-204] vs.106[80-152] mmHg%; p=0.031) in the Avsurg group compared to the patients without progression for AV surgery indication (CON group). Moreover, the AVsurg group showed a larger PSVL area than the CON group probability due to the larger strain-volume (234 [129-380] vs.155 [88-216] %mL; p=0.021) and pressure-volume (12504 [9318- 15073] vs. 10192 [8004-11918] mmHg.mL; p=0.002) component, while the pressure-strain loop was similar between groups (Figure 1). Conclusions Non-invasive pressure-strain-volume loop reflects early changes in LV geometry and function due to chronic pressure-volume overload in significant AR. Patients with early disease decompensation show larger PSVL than stable individuals. The clinical utility of this index needs to be investigated in future studies. Figure 1

Usefulness of echocardiographic parameters of myocardial work in the evaluation of left ventricular function in patients with severe aortic valve stenosis undergoing transcatheter aortic valve impla

Abstract Background Myocardial work (MW) is a new echocardiographic parameter used in the assessment of cardiac energy expenditure. Purpose The aim of the current study was to evaluate changes in left ventricular MW parameters in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). Methods One hundred and thirty five consecutive patients who underwent TAVI at one center were evaluated before and after procedure by transthoracic echocardiography (TTE) with the assessment of MW indices: global constructive work (GCW), global wasted work (GWW), global work index (GWI) and global work efficiency (GWE). Results The comparison of MW parameters before and on average after 5.9 days after TAVI showed a significant increase in GCW: 1314,48± 487,53 vs 1438,22 ± 468,86 (p<0,001), GWW: 238,82 ± 160,67 vs 258,84 ± 145,09 (p= 0,045) and GWI: 966,45 ± 456,06 vs 1045,16 ± 428,68 and no significant change in GWE: 81,55 ± 10,46 vs 82,47 ± 7,75 (p=0,401). The increase in GCW and GWI parameters after TAVI strongly correlated with left ventricular ejection fraction (LVEF) and pressure aortic gradient (PGA) before the procedure. A significant increase in GWE was observed in patients with LVEF <30% (p=0,043). Conclusions Echocardiographic assessment of myocardial work parameters is a valuable method of documenting hemodynamic changes in patients with severe aortic stenosis before and after TAVI. Long-term left ventricular overload in patients with aortic stenosis results in a global decrease of myocardial work parameters, therefore, rapid decompression increases the effective work of the heart.

Usefulness of Echocardiographic Parameters of Myocardial Work in Patients with Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

Background: Myocardial work (MW) is a new echocardiographic parameter used in the assessment of cardiac energy expenditure. The aim of the current study was to evaluate changes in left ventricular MW parameters in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). Methods: One hundred and thirty five consecutive patients who underwent TAVI at one center were evaluated before and after the procedure using transthoracic echocardiography (TTE) to assess the following MW indices: global constructive work (GCW), global wasted work (GWW), global work index (GWI) and global work efficiency (GWE). Results: The comparison of MW parameters before and an average of 5.9 days after TAVI showed an increase in GCW, GWW and GWI, and no significant change in GWE. A detailed analysis showed an increase in GCW and GWI only in patients with the worst initial global longitudinal strain (GLS) > -8.0%: 845.2 vs. 852.2; p < 0.001 and 469.7 vs. 499.0 mmHg%; p < 0.001, respectively, whereas in the group of patients with GLS < -16.0%, a reduction in these indices was observed: 2135.8 vs. 2043.0; p < 0.001 and 1732.4 vs. 1633.1 mmHg%; p < 0.001. The significant increase in GWE was observed in patients with left ventricular ejection fraction (LVEF) < 30%: 77.7 vs. 72.0; p = 0.043 and GLS > -8.0%: 74.4 vs. 71.0 mmHg%; p < 0.001. The increase in GCW and GWI parameters after TAVI was strongly correlated with LVEF and pressure aortic gradient (PGA) before the procedure. Conclusions: Echocardiographic assessment of myocardial work parameters is a valuable method of documenting hemodynamic changes in patients with severe aortic stenosis before and after TAVI. Long-term left ventricular overload in patients with aortic stenosis results in a global reduction of myocardial work parameters; therefore, in patients with the lowest LVEF and GLS, the increased GCW, GWI and GWE reflect energy reserves enabling a rapid increase in the effective work of the heart.

Extracellular Matrix Instability and Chronic Inflammation Underlie Maladaptive Right Ventricular Pressure Overload Remodeling and Failure in Male Mice.

Right ventricular dysfunction (RVD) portends increased death risk for heart failure (HF) and pulmonary arterial hypertension (PAH) patients, regardless of left ventricular function or disease etiology. In both, RVD arises from chronic RV pressure overload and represents advanced cardiopulmonary disease. RV remodeling responses and survival rates of patients, however, differ by sex. Men develop more severe RVD and die at younger ages than do women. Mechanistic details of this sexual dimorphism in RV pressure overload remodeling are incompletely understood. We sought to elucidate the cardiac histologic and molecular pathophysiology underlying the sex-specific RV remodeling phenotypes, maladaptive (decompensated RVD with RV failure) versus adaptive (compensated RVD). We subjected male (M-) and female (F-) adult mice to moderate pulmonary artery banding (PAB) for 9wks. Mice underwent serial echocardiography, cardiac MRI, RV pressure-volume loop recordings, histologic and molecular analyses. M-PAB developed severe RVD with RV failure (RVF), increased RV collagen deposition and degradation, extracellular matrix (ECM) instability, and recruitment and activation of macrophages. Despite equal severity and chronicity of RV pressure overload, F-PAB had more stable ECM, lacked chronic inflammation, and developed mild RVD without RVF. ECM destabilization and chronic activation of recruited macrophages are associated with maladaptive RV remodeling and RVF in M-PAB. These two RV remodeling phenotypes suggest that adverse ECM remodeling and chronic inflammation are also sex-dependent, thereby contributing to the sexual dimorphism of RV pressure overload remodeling. Further mechanistic studies are needed to assess their pathogenic roles and potential as targets for RVD therapy and RVF prevention.

Eccentric hypertrophy impairs outcome after TAVR.

Aortic stenosis (AS) induces cardiac remodeling upon chronic left ventricular (LV) pressure overload. Here, we analyzed the clinical outcome of patients undergoing transcatheter aortic valve replacement (TAVR) for symptomatic AS with regard to varying LV hypertrophy patterns. Moreover, we investigated the genetic influence on development of different hypertrophy patterns, measured by polygenic risk scores (PRS). 1703 patients with severe AS undergoing TAVR were categorized according to LV mass index and relative wall thickness in four subgroups: normal geometry (NG, n = 57), concentric remodeling (CR; n = 388), concentric hypertrophy (CH; n = 993) and eccentric hypertrophy (EH; n = 265). Data was analyzed retrospectively with regard to clinical outcome. In a substudy, 520 patients affected by CH (n = 237), EH (n = 139) or CR (n = 164) were analyzed using two PRS that have been previously associated with hypertrophic and dilated cardiomyopathy. 1year after TAVR, for EH, in contrast to the remaining groups (NG, CR, CH), a significant difference in all-cause mortality was observable (mortality 17.4% EH, 14.0% NG, 12.4% CR, 14.0% CH, p = 0.001). This difference was observed up to 4years (mortality 41.9% EH, 26.9% CH, 28.1% CR, 26.4% NG, p = 0.001). Of note, higher percentiles in a PRS for hypertrophic cardiomyopathy were associated with a reduced likelihood of EH in patients with AS (p = 0.046). The EH group had a statistically significant poorer 1-year and 5-year outcomes than the other groups. PRS might help predict myocardial reactions in patients with aortic stenosis in future.

Homeostatic Role of Decorin in Right Ventricular Pressure Overload and Pulmonary Hypertension Induced Remodeling

Homeostatic Role of Decorin in Right Ventricular Pressure Overload and Pulmonary Hypertension Induced Remodeling

Left atrial decompression during veno-arterial extracorporeal membrane oxygenation using a single multi-stage drainage cannula with a transseptal approach: Clinical significance and medical management of LAVA ECMO

Extracorporeal Membrane Oxygenation (ECMO) is a life-support treatment used in critically ill patients that temporarily acts as the heart and lungs. It is used in numerous clinical scenarios where the patient’s heart and/or lungs are too sick to work on their own. With ECMO, a patient’s blood is removed from the body and pumped through an artificial lung, where oxygen is added and carbon dioxide is removed. There are two types of ECMO support: VV ECMO and VA ECMO. VV ECMO is used when a patient’s lungs need additional support, and VA ECMO is used when a patient’s heart and lungs need additional support. Although ECMO therapy can be life-saving, it is a supportive therapy, not a disease-modifying treatment. There are numerous techniques and strategies used to implement ECMO, all in which come with their own risks, complications, and possible emergencies. Cannulation strategy is determined by a multitude of factors, such as materials available, patient presentation, concurrent venous/arterial access, specific patient anatomy, clinical diagnosis, provider training, etc. One major complication specific to VA ECMO is left ventricular overload, which can create a lethal cascade of issues for a patient receiving this mode of support. This manuscript will discuss the products and materials needed, cannulation techniques, configurations, and clinical significance of left atrial veno-arterial extracorporeal membrane oxygenation (LAVA ECMO). We will focus on clinical scenarios that allow for LAVA ECMO and unique considerations for this complex cannulation strategy. Additionally, we will address the use of LAVA ECMO in patients where traditional left atrial venting and decompression techniques are contraindicated. Finally, current data pertaining to patient outcomes related to the use of LAVA ECMO will be discussed in length, giving a synopsis of the benefits of using a single multi-stage drainage cannula with a transseptal approach for left atrial decompression in VA ECMO

Right ventricular volume overload reboots cardiomyocyte proliferation via immune responses

BackgroundRight ventricular volume overload (RVVO) is one of the most important hemodynamic characteristics in children with congenital heart disease (CHD) and heart failure, and cardiomyocyte (CM) proliferation is one of the most vital factors for improving cardiac performance. However, whether and how RVVO reboots CM proliferation remains elusive.Methods and resultsWe first created a neonatal RVVO mouse model via abdominal aorta and inferior vena cava-fistula microsurgery at postnatal day 7 (P7), the edge of CM proliferation window. We subsequently performed bulk RNA-seq, single cell RNA-seq/flow cytometry, and immunofluorescence staining on the right ventricles (RV) of RVVO mice at P14/P21, defined as prepubertal stage, revealing that RVVO temporarily reboots prepubertal CM proliferation via immune responses.ConclusionsIn considering the importance of RVVO and CM proliferation, this study may bring an opportunity to create a novel paradigm to treat pediatric CHDs or heart failure.Graphical

Corrected partial anomalous pulmonary vein connection associated with lung resection: a case report

IntroductionPartial anomalous pulmonary venous connection (PAPVC) is a potential cause of right-sided heart failure. Notably, a risk of sudden circulatory failure exists during lung surgery. Only a few reports of PAPVC complicated by lung cancer requiring lobectomy exist. Here, we report a case of left lower lung lobectomy complicated by an anomalous connection of the left upper pulmonary vein requiring revascularization.Case presentationA 66-year-old man was found with an abnormal mass shadow in the left lower lung field on chest radiography. Bronchoscopy revealed lung adenocarcinoma. Preoperative contrast-enhanced computed tomography showed that the left upper pulmonary vein did not perfuse the left atrium but was connected to the left brachiocephalic vein. Preoperative transthoracic echocardiography revealed right atrial and ventricular enlargement. The clinical diagnosis was stage IB (T2aN0M0). We decided to perform a left lower lobectomy and correct the PAPVC to maintain oxygenation after the lobectomy. The PAPVC was ligated, and the stump of the left upper pulmonary vein was anastomosed to the left atrial appendage without cardiopulmonary bypass. Postoperative contrast-enhanced computed tomography revealed intact reconstructed vessels. Postoperative transthoracic echocardiography showed no right ventricular overload. The patient’s postoperative clinical course following the surgical procedure was uneventful. Furthermore, the patient was followed up without any complications.ConclusionsThis rare case of successful surgical correction can inform clinicians of similar cases.

Cardiovascular magnetic resonance imaging in mitral valve disease.

This paper describes the role of cardiovascular magnetic resonance (CMR) imaging in assessing patients with mitral valve disease. Mitral regurgitation (MR) is one of the most prevalent valvular heart diseases. It often progresses without significant symptoms, leading to left ventricular overload, dysfunction, frequent decompensated heart failure episodes, and excess mortality. Cardiovascular magnetic resonance assessment is recommended for MR when routine ultrasound imaging information is insufficient or discordant. A well-planned CMR can provide an in-depth assessment of the mitral valve apparatus, leaflet morphology, and papillary muscles. In addition, it can precisely inform the impact of MR on left atrial and ventricular remodelling. The review aims to highlight established and emerging techniques for morphological assessment, flow assessment (including regurgitation and stenosis), myocardial assessment, and haemodynamic assessment of mitral valve disease by CMR. It also proposes a simplified clinical flow chart for CMR assessment of the mitral valve.

Left ventricle unloading during veno-arterial extracorporeal membrane oxygenation: review with updated evidence.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used to treat medically refractory cardiogenic shock and cardiac arrest, and its usage has increased exponentially over time. Although VA-ECMO has many advantages over other mechanical circulatory supports, it has the unavoidable disadvantage of increasing retrograde arterial flow in the afterload, which causes left ventricular (LV) overload and can lead to undesirable consequences during VA-ECMO treatment. Weak or no antegrade flow without sufficient opening of the aortic valve increases the LV end-diastolic pressure, and that can cause refractory pulmonary edema, blood stagnation, thrombosis, and refractory ventricular arrhythmia. This hemodynamic change is also related to an increase in myocardial energy consumption and poor recovery, making LV unloading an essential management issue during VA-ECMO treatment. The principal factors in effective LV unloading are its timing, indications, and modalities. In this article, we review why LV unloading is required, when it is indicated, and how it can be achieved.

Abstract 4135289: Renal Blood Perfusion is Closely Related to Right Ventricular Volume Overload in Congestive Heart Failure

Background: Cardiorenal syndrome (CRS) involves a bidirectional relationship where dysfunction in one organ exacerbates the other. A key factor in this interaction is the impact of right ventricular (RV) volume overload on renal blood flow, which is vital for the progression and management of heart failure (HF). Objective: This study aims to explore and quantify the relationship between right ventricular volume overload, i.e, echocardiographic assessments of right ventricular diameter (RVD), and the time-to-peak (TTP) of renal blood flow in patients with HF measured by 99mTc-DTPA renal scintigraphy. Methods: This single-center study included 304 stable, ambulatory HF patients admitted between October 2017 and August 2022. HF was diagnosed based on the 2016 ESC guidelines. Echocardiographic parameters, including RVD, and TTP of renal blood flow measured by 99mTc-DTPA renal scintigraphy, were collected. Statistical analysis was conducted using SPSS and R software, with Spearman correlation analysis used to assess the relationship between echocardiographic parameters and TTP. Results: The study showed there was a significant correlation between RVD and TTP (rs=0.535, P &lt;0.001), indicating that RV volume overload is closely related to impaired renal perfusion. The median TTP among the study population was 27.25 seconds (IQR: 21-39 seconds). Corrected for body surface area (BSA), RVD was found to be significantly higher in patients with heart failure with reduced ejection fraction (HFrEF) compared to heart failure with preserved ejection fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF) (HFrEF: 20.62 mm/m 2 , HFmrEF: 18.72 mm/m 2 , HFpEF: 18.09 mm/m 2 ; p &lt; 0.001). Furthermore, right atrial diameter (RAD) corrected for BSA (RAD/BSA) demonstrated the strongest correlation with TTP in the HFrEF subgroup (rs=0.602, p&lt;0.001). Conclusions: Our findings highlight the significant impact of right ventricular volume overload on renal perfusion, providing valuable insights into the pathophysiology of CRS. These results suggest that therapeutic strategies aimed at reducing RV overload could enhance renal perfusion and improve overall outcomes in HF patients.

Features of acute coronary syndrome after a COVID-19 in the aspect of pulmonary hypertension

BACKGROUND: After recovery from COVID-19 patients may develop new risk factors that lead to changes in cardiopulmonary interactions, i.e. an increase in the afterload on the right ventricle due to increased pressure in the pulmonary artery and change in pulmonary vascular resistance. It can be assumed that the presence of such a spectrum of problems can influence the severity of dyspnea and the development of pathogenetic events (pulmonary hypertension, right ventricular failure, subendocardial ischemia), which in turn can determine the outcome. AIM: To identify the characteristics of acute coronary syndrome after a COVID-19, taking into account angiographic data on coronary artery lesions and hemodynamic manifestations. MATERIALS AND METHODS: A comparative analysis of the clinical and hemodynamic consequences of the COVID-19 and the development of acute coronary syndrome in 157 patients was carried out. The group 1 included 69 patients who had had COVID-19 (vaccinated — 24.6%) during the 6 months preceding acute coronary syndrome; group 2 — 88 patients without a history of COVID-19 (vaccinated — 42%). The 12-lead electrocardiogram has been used in the diagnosis of subendocardial ischemia in acute coronary syndrome. The ST segment displacement in lead aVR was analyzed. RESULTS: After COVID-19, dispnoe occurred in 52% of the patients and in 14.8% without previous infection. Echocardiographic signs of right ventricular overload were present in 42% of the patients in group 1 and 10.2% in group 2. The mean pressure in the pulmonary artery was increased after COVID-19 in 58% of the patients in group 1 and in 10.2% of group 2 in the range from 20 to 24 mm Hg and in the range from 25 to 36 mm Hg in 29% of the patients in group 1 and 2.3% of the patients in group 2. The average value of left ventricular ejection fraction in the patients who had had COVID-19 was 55.9 ± 14%, which was less than in the patients in the control group (63.2 ± 5.5%; p 0.001). ST segment elevation in lead aVr indicated high incidence of subendocardial ischemia. 40.6% in group 1, and 11.4% in group 2 (χ2 = 17.9; p 0.001); in group 1 vaccinated — 17.6%, and not vaccinated — 48.1% (χ2 = 4.9; p = 0.027), in group 2 vaccinated — 8.1%, and not vaccinated — 13.7% (χ2 = 0.7; p = 0.41). All the patients had drug-eluting stents implanted in the infarct-related artery. After stenting, no recurrence of pain or further increase in chest pain was observed. CONCLUSIONS: After coronavirus infection COVID-19, 58% of patients have increased mean pressure in the pulmonary artery in the range from 20 to 24 mm Hg and in the range from 25 to 36 mm Hg in 29%. Atherothrombosis is the main mechanism of acute coronary syndrome after COVID-19 coronavirus infection. The main feature of acute coronary syndrome after a coronavirus infection COVID-19 is increased pressure in the pulmonary artery after a lung injury, which must be taken into account when planning surgical treatment tactics and management tactics in the postoperative period.

Heart failure with preserved ejection fraction in pigs causes shifts in posttranscriptional checkpoints.

Left ventricular pressure overload (LVPO) can lead to heart failure with a preserved ejection fraction (HFpEF) and LV chamber stiffness (LV Kc) is a hallmark. This project tested the hypothesis that the development of HFpEF due to an LVPO stimulus will alter posttranscriptional regulation, specifically microRNAs (miRs). LVPO was induced in pigs (n = 9) by sequential ascending aortic cuff and age- and weight-matched pigs (n = 6) served as controls. LV function was measured by echocardiography and LV Kc by speckle tracking. LV myocardial miRs were quantified using an 84-miR array. Treadmill testing and natriuretic peptide-A (NPPA) mRNA levels in controls and LVPO were performed (n = 10, n = 9, respectively). LV samples from LVPO and controls (n = 6, respectively) were subjected to RNA sequencing. LV mass and Kc increased by over 40% with LVPO (P < 0.05). A total of 30 miRs shifted with LVPO of which 11 miRs correlated to LV Kc (P < 0.05) that mapped to functional domains relevant to Kc such as fibrosis and calcium handling. LVPO resulted in reduced exercise tolerance (oxygen saturation, respiratory effort) and NPPA mRNA levels increased by fourfold (P < 0.05). RNA analysis identified several genes that mapped to specific miRs that were altered with LVPO. In conclusion, a specific set of miRs are changed in a large animal model consistent with the HFpEF phenotype, were related to LV stiffness properties, and several miRs mapped to molecular pathways that may hold relevance in terms of prognosis and therapeutic targets.NEW & NOTEWORTHY Heart failure with preserved ejection fraction (HFpEF) is an ever-growing cause for the HF burden. HFpEF is particularly difficult to treat as the mechanisms responsible for this specific form of HF are poorly understood. Using a relevant large animal model, this study uncovered a unique molecular signature with the development of HFpEF that regulates specific biological pathways relevant to the progression of this ever-growing cause of HF.

CILP1 and NTproBNP in pulmonary hypertension and right ventricular pressure overload: a translational experimental study

Abstract Introduction Cartilage intermediate layer protein 1 (CILP1) has emerged as a novel marker of right ventricular (RV) dysfunction in pulmonary hypertension (PH), although there is still little evidence on its role in different scenarios of RV pressure overload. The aim of our study was to analyze CILP1 as a biomarker of RV remodeling and PH severity, and compare it with N-terminal pro-brain natriuretic peptide (NTproBNP), in different experimental models of RV pressure overload. Methods Three different experimental models of RV pressure overload compared to a sham procedure were evaluated in 24 Yucatan pigs: chronic postcapillary PH by pulmonary vein banding (M1, n=6); chronic PH by aorto-pulmonary shunting (M2, n=6); RV pressure overload by PA banding (thus without PH) (M3, n=6); and sham procedure (M0, n=6). Animals were evaluated at 8 months after surgery by right heart catheterization, cardiac magnetic resonance (CMR), and blood/histological sampling. Levels of CILP1 and NTproBNP at the RV myocardium and blood were determined with dedicated ELISA and compared among groups by Wilcoxon test with Bonferroni correction. Associations between biomarkers and RV performance indices and pulmonary arterial pressure (PAP) were assessed with Spearman correlation test. Results M1 animals developed chronic postcapillary PH with normal left ventricular (LV) performance and RV maladaptive hypertrophy (RV fibrosis and systolic dysfunction). M2 animals developed chronic precapillary PH associated with LV dilatation and RV maladaptive hypertrophy. On contrast, M3-animals developed severe RV pressure overload (without PH) and hypertrophy but maintained normal RV systolic function. CILP1 and NTproBNP levels were moderately correlated (R=0.56, p=0.002). CILP1 levels in RV myocardium and plasma were significantly higher in M1, whereas NTproBNP plasma levels were significantly higher in M2 (Figure 1). CILP1 in plasma and RV myocardium significantly correlated with PAP, while myocardial CILP1 levels also correlated with RV extracellular volume (RV-ECV) by CMR (Figure 2). NTproBNP myocardial levels correlated with RV ejection fraction and RV-ECV and plasmatic levels correlated with PAP (Figure 2). Conclusions CILP1 levels were increased in the presence of PH and isolated RV dysfunction, whereas NTproBNP levels were increased in the model of PH, RV dysfunction and LV remodeling. Myocardial levels of both peptides correlated with diffuse fibrosis, estimated by CMR, whereas plasmatic levels of both biomarkers correlated with PAP. This suggests that CILP1 may be a more specific marker of RV dysfunction in PH, being less dependent of LV parameters.CILP1 and NTproBNP levels among modelsCorrelation with PAP &amp; RV remodeling

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&amp;lt;0.001 and 0.777 (95% CI: 0.675-0.878), p&amp;lt;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 &amp;gt;44mmHg and RV/LV&amp;gt;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.

Renal Semaphorin 3C mediates cardiac adaptive response

Abstract Cardiorenal syndrome, characterized by reciprocal heart-kidney interactions that progressively promote dysfunction in both organs, is associated with a high mortality rate. However, the mechanisms linking the two organs are insufficiently understood. Here we report that semaphorin 3C (SEMA3C) is a novel cardioprotective mediator secreted from the kidney. SEMA3C was highly expressed in the renal proximal tubules in mice. Renal Sema3c expression and circulating SEM3C were reduced by the left ventricular pressure overload that induced renal remodeling. Proximal tubule-specific secretory Sema3c deletion exacerbated cardiac hypertrophy, fibrosis and dysfunction after the pressure overload, suggesting renal SEMA3C is important for the proper cardiac adaptive response. Mechanistically, SEMA3C inhibits pathological cardiac remodeling at least partly by inhibiting Akt, ERK and Wnt/β-catenin signaling in cardiomyocytes. In heart failure patients, the plasma SEMA3C level was decreased and the low plasma SEMA3C was associated with poor cardiac outcomes. Collectively, our results show that SEMA3C produced by the kidney pivotally contributes to the cardiac stress response and its reduction contributes to the progression of heart failure. SEMA3C signaling appears to be an attractive therapeutic and diagnostic target for cardiorenal syndrome.

Development of predictive models for differential diagnosis of hypertrophic cardiomyopathy

Aim. To develop predictive models for differential diagnostics of hypertrophic phenotype in patients with concomitant diseases, as well as to validate through independent assessment.Material and methods. The study included an analysis of 1169 medical records from the medical information system of patients with severe myocardial hypertrophy and a preliminary diagnosis of hypertrophic cardiomyopathy (HCM) (I42.1, I42.2). The patients were divided into 3 following groups: patients with a probable HCM, patients with moderate myocardial hypertrophy (&gt;15 mm) due to a known disease, and patients with severe myocardial hypertrophy that cannot be explained by left ventricular pressure overload ("gray zone"). The original dataset contains 74 parameters. Machine learning models of the following classes were created and optimized: logistic regression, support vector machine, decision tree, and gradient boosting decision trees.Results. All models have sufficient accuracy in detecting HCM, but the accuracy of ruling out the diagnosis is quite low. The use of a machine learning model using logistic regression reduced the HCM misdiagnosis risk in the group of questionable diagnosis to 31%.Conclusion. Four predictive models for differential diagnosis of severe left ventricular myocardial hypertrophy were developed to improve the HCM diagnosis. Blinding validation showed that logistic regression is the most optimal model for clinical practice.