Project description:AimsThe prognostic significance of left ventricular (LV) diastolic dysfunction (LVDD) severity in patients with dilated cardiomyopathy (DCM) remains uncertain. This study aimed to evaluate the association of LVDD severity and elevated left atrial pressure (eLAP) with patient outcomes in stable, non-acutely decompensated patients with DCM.MethodsThis single-centre, retrospective, observational study involved 740 DCM patients (either inpatients or outpatients) managed at our tertiary cardiac centre between 2010 and 2021. Due to incomplete data, 96 patients were excluded. LVDD and eLAP were assessed using echocardiography according to the 2016 guidelines of the European Association of Cardiovascular Imaging (EACVI). The primary outcomes were all-cause mortality and heart failure (HF)-related mortality.ResultsThe final cohort comprised of 644 DCM patients [mean age: 52 ± 12 years, LV ejection fraction (LVEF): 26 ± 10%]. Over a median follow-up period of 41 (18.5-66.7) months, 105 (16.3%) patients died: 8 (5.3%) patients in the normal left atrial pressure (nLAP) group and 97 (19.6%) patients in the eLAP group. eLAP was identified as an independent prognostic factor for both all-cause mortality [hazard ratio (HR) 2.0; 95% confidence interval (CI) 1.1-3.7; P = 0.01] and HF-related mortality (HR 2.5; 95% CI 1.01-6.5; P = 0.04), even after adjusting for LVEF and atrial fibrillation (AF) presence. Additionally, HF-related mortality rates were significantly higher in patients with moderate to severe LVDD compared with those with mild LVDD [5 (3.3%) vs. 67 (13.6%), P < 0.05].ConclusionsThis study's findings highlight the importance of assessing the severity of LVDD in patients with DCM, which provides incremental prognostic information over LVEF.
Project description:Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are yet unknown. Research is hampered by the lack of a good RVF model. Our aim was to study the pathophysiology of RVF in a rat model of chronic pressure load. Wistar rats (n=19) were subjected to pulmonary artery banding (PAB, 1.1mm) or sham surgery (CON). All PAB rats developed RVF (reduced cardiac output, RV stroke volume, TAPSE, increased end diastolic pressure, all p<0.05 vs. CON) but clinical symptoms of RVF (inactivity, ruffled fur, dyspnea, ascites) necessitating termination ensued in a subset (5/12) of rats (RVF+) after a period of 52±5 days. Rats with RVF+ had significantly worse RV function and pericardial effusion and liver congestion compared to RVF rats without symptoms (all p<0.05), despite similar pressure load (p=NS RVF vs. RVF+). Chronic pulmonary artery banding invariably leads to RV failure in rats, and a subset transitions to advanced clinical RVF. RVF is characterized by enhanced contractility, progressive diastolic dysfunction and derangement of energy metabolism, thus improving diastolic function and targeting RV metabolism may be the keys to treating RVF. Total RNA optainded ( Heart) of 7 Controls ,5 RVF+ and 4 RVF samples where used for this array study
Project description:Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are yet unknown. Research is hampered by the lack of a good RVF model. Our aim was to study the pathophysiology of RVF in a rat model of chronic pressure load. Wistar rats (n=19) were subjected to pulmonary artery banding (PAB, 1.1mm) or sham surgery (CON). All PAB rats developed RVF (reduced cardiac output, RV stroke volume, TAPSE, increased end diastolic pressure, all p<0.05 vs. CON) but clinical symptoms of RVF (inactivity, ruffled fur, dyspnea, ascites) necessitating termination ensued in a subset (5/12) of rats (RVF+) after a period of 52±5 days. Rats with RVF+ had significantly worse RV function and pericardial effusion and liver congestion compared to RVF rats without symptoms (all p<0.05), despite similar pressure load (p=NS RVF vs. RVF+). Chronic pulmonary artery banding invariably leads to RV failure in rats, and a subset transitions to advanced clinical RVF. RVF is characterized by enhanced contractility, progressive diastolic dysfunction and derangement of energy metabolism, thus improving diastolic function and targeting RV metabolism may be the keys to treating RVF.
Project description:Aim The severity of cardiac impairment in acute heart failure (AHF) predicts outcome, but challenges remain to identify prognostically important non-invasive parameters of cardiac function. Left ventricular ejection fraction (LVEF) is relevant, but only in those with reduced LV systolic function. We aimed to assess the standard and advanced parameters of left and right ventricular (RV) function from echocardiography in predicting long-term outcomes in AHF. Methods A total of 418 consecutive AHF patients presenting over 12 months were prospectively recruited and underwent bedside echocardiography within 24 h of recruitment. We retrospectively assessed 8 RV and 5 LV echo parameters of the cardiac systolic function to predict 2-year mortality, using both guideline-directed and study-specific cutoffs, based on the maximum Youden indices via ROC analysis. For the RV, these were the tricuspid annular plane systolic excursion, RV fractional area change, tissue Doppler imaging (TDI) peak tricuspid annular systolic wave velocity, both peak- and end-systolic RV free wall global longitudinal strain (RV GLS) and strain rate (mean RV GLSR), RV ejection fraction (RVEF) derived from a 2D ellipsoid model and the ratio of the TAPSE to systolic pulmonary artery pressure (SPAP). For the LV, these were the LVEF, mitral regurgitant ΔP/Δt (MR dP/dt), the lateral mitral annular TDI peak systolic wave velocity, LV GLS, and the LV GLSR. Results A total of 7/8 parameters of RV systolic function were predictive of 2-year outcome, with study cutoffs like international guidelines. A cutoff of < −1.8 s–1 mean RV GLSR was associated with worse outcome compared to > −1.8 s–1 [HR 2.13 95% CI 1.33–3.40 (p = 0.002)]. TAPSE:SPAP of > 0.027 cm/mmHg (vs. < 0.027 cm/mmHg) predicted worse outcome [HR 2.12 95% CI 1.53–2.92 (p < 0.001)]. A 3-way comparison of 2-year mortality by LVEF from the European Society of Cardiology (ESC) guideline criteria of LVEF > 50, 41–49, and < 40% was not prognostic [38.6% vs. 30.9 vs. 43.9% (p = 0.10)]. Of the 5 parameters of LV systolic function, only an MR dP/dt cutoff of < 570 mmHg was predictive of adverse outcome [HR 1.63 95% CI 1.01–2.62 (p = 0.047)]. Conclusion With cutoffs broadly like the ESC guidelines, we identified RV dysfunction to be associated with adverse prognosis, whereas LVEF could not identify patients at risk.
Project description:Aldosterone infusion results in left ventricular hypertrophy (LVH) and hypertension and may involve profibrotic and proinflammatory mechanisms. In turn, hypertension is the major cause of diastolic heart failure (HF). Adiponectin, an adipose-derived plasma protein, exerts antiinflammatory and anti-hypertrophic effects and is implicated in the development of hypertension and systolic HF. We thus tested the hypothesis that hypoadiponectinemia in aldosterone-induced hypertension exacerbated cardiac remodeling and diastolic HF. Wild-type (WT) or adiponectin-deficient (APNKO) mice underwent saline or aldosterone infusion and uninephrectomy and were fed 1% salt water for 4 wk. Blood pressure was increased in aldosterone-infused WT (132 +/- 2 vs. 109 +/- 3 mm Hg; P < 0.01) and further augmented in APNKO mice (140 +/- 3 mm Hg; P < 0.05 vs. aldosterone-infused WT). LVH was increased in aldosterone-infused WT vs. WT mice (LV/body weight ratio, 4.8 +/- 0.2 vs. 4.1 +/- 0.2 mg/g) and further increased in aldosterone-infused APNKO mice (LV/body weight ratio, 6.0 +/- 0.4 mg/g). Left ventricular ejection fraction was not decreased in either aldosterone-infused WT or APNKO hearts. Pulmonary congestion however was worse in APNKO mice (P < 0.01). The ratio of early ventricular filling over late ventricular filling (E/A) and the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e'), measures of diastolic function, were increased in aldosterone-infused WT hearts and further increased in APNKO hearts (P < 0.05 for both). Renal function and cardiac fibrosis were no different between both aldosterone-infused groups. Aldosterone increased matrix metalloproteinase-2 expression in WT hearts (P < 0.05 vs. WT and P < 0.01 vs. APNKO). Myocardial atrial natriuretic peptide, interferon-gamma, and TNF-alpha expression were increased in aldosterone-infused WT hearts. Expression of these proteins was further increased in aldosterone-infused APNKO hearts. Therefore, hypoadiponectinemia in hypertension-induced diastolic HF exacerbates LVH, diastolic dysfunction, and diastolic HF. Whether or not adiponectin replacement prevents the progression to diastolic HF will warrant further study.
Project description:BackgroundRight ventricular (RV) dysfunction is associated with increased mortality across a spectrum of cardiovascular diseases. The role of obesity in RV dysfunction and adverse outcomes is unclear.MethodsWe examined patients undergoing right heart catheterization between 2005 and 2016 in a hospital-based cohort. Linear regression was used to examine the association of obesity with hemodynamic indices of RV dysfunction (pulmonary artery pulsatility index, right atrial pressure:pulmonary capillary wedge pressure ratio, RV stroke work index). Cox models were used to examine the association of RV function measures with clinical outcomes.ResultsAmong 8285 patients (mean age, 63 years; 40% women), higher body mass index was associated with worse indices of RV dysfunction, including lower pulmonary artery pulsatility index (β, -0.23; SE, 0.01; P<0.001), higher right atrium:pulmonary capillary wedge pressure ratio (β, 0.25; SE, 0.01; P<0.001), and lower RV stroke work index (β, -0.05; SE, 0.01; P<0.001). Over median of 7.3 years of follow-up, we observed 3006 mortality and 2004 heart failure hospitalization events. RV dysfunction was associated with a greater risk of mortality (eg, pulmonary artery pulsatility index:hazard ratio, 1.11 per 1-SD increase [95% CI, 1.04-1.18]), with similar associations with risk of heart failure hospitalization. Body mass index modified the effect of RV dysfunction on all-cause mortality (Pinteraction≤0.005 for PAPi and RA:PCWP ratio), such that the effect of RV dysfunction was more pronounced at higher body mass index.ConclusionsPatients with obesity had worse hemodynamic measured indices of RV function across a broad hospital-based sample. While RV dysfunction was associated with worse clinical outcomes including mortality and heart failure hospitalization, this association was especially pronounced among individuals with higher body mass index.
Project description:This research aimed to identify protein biomarkers of right ventricular dysfunction in patients with advanced heart failure with reduced ejection fraction (HFrEF). Samples of myocardium from both, right and left ventricles (RV, LV) were obtained from 10 HFrEF patients with right ventricular dysfunction (RVD), 10 HFrEF patients without RVD (noRVD) undergoing heart transplantation, and 10 non-failing unused donor hearts (Control). Tissue samples were homogenized and extracted using mild Triton X-100 detergent and processed by SP3 extraction to remove the detergent prior the analysis, (LFQ) proteomic analysis identified a total of 4 032 proteins in the left ventricle and 3 788 proteins in the right ventricle.
Project description:Background: The aim of this study was to assess the effect of right ventricular diastolic dysfunction on the results of 5-year follow-up of patients after coronary artery bypass grafting (CABG). Methods: Patients were enrolled in this prospective observational study examined before planned CABG from 2017 to 2018. In addition to the baseline preoperative indicators and perioperative data, the initial parameters of the left and right ventricle (RV) systolic and diastolic function were assessed. The long-term results after CABG were assessed after 5 years. The following endpoints were recorded in the remote period: coronary and non-coronary death, non-fatal myocardial infarction (MI), repeat myocardial revascularization. Results: The results of long-term follow-up were assessed in 148 patients, during which time MACE was registered in 43 patients (29.1%). In the group with MACE before CABG, a history of myocardial infarction (p = 0.008), functional class 3 NYHA of chronic heart failure (CHF) (p = 0.013), an increase in the left ventricle size, a decrease in the e'/a' ratio (p = 0.041), and the presence of the right ventricle diastolic dysfunction (p = 0.037) were more often detected. Kaplan-Meier analysis revealed a better long-term prognosis (MACE-free survival) in the group without RVDD compared to the group with RVDD (p = 0.026). Conclusions: In patients after coronary artery bypass grafting, the development of adverse events was associated with both clinical factors and the presence of right ventricular diastolic dysfunction. Survival analysis revealed a worse prognosis in patients with preoperative RVDD compared with patients without RVDD.
Project description:BackgroundPrevious studies have described echocardiographic indices of right ventricular (RV) diastolic function in patients with tetralogy of Fallot (TOF) but these indices have not been validated against invasive hemodynamic data. The purpose of this study was to determine echocardiographic predictors of severe RV diastolic dysfunction, and the impact of severe RV diastolic dysfunction on transplant-free survival.MethodsCohort study of TOF patients that underwent non-simultaneous cardiac catheterization and echocardiogram at Mayo Clinic. Based on prior studies we selected these indices for assessment: tricuspid E/A, E/e', deceleration time, pulmonary artery forward flow, dilated inferior vena cava (IVC), and hepatic vein diastolic flow reversal (HVDFR). RV diastolic function classes (normal, mild/moderate and severe dysfunction) were created using arbitrary cut-off points of the median values of right ventricular end-diastolic pressure (RVEDP) and right atrial pressure (RAP) for the cohort.ResultsAmong 173 patients (age 40 ± 13 years), 68 patients were classified as normal (RVEDP≤14 and RAP≤10), 37 as mild/moderate dysfunction (either RVEDP>14 or RAP>10), and 69 as severe dysfunction (RVEDP>14 and RAP>10). Of the indices assessed, dilated IVC had the best sensitivity of 95% (area under the curve [AUC] 0.689) while HVDFR had the best specificity of 69% (AUC 0.648) for detecting severe RV diastolic dysfunction. Severe RV diastolic dysfunction was an independent risk factor for death/transplant (hazard ratio 2.83, p = 0.009).ConclusionSevere RV diastolic dysfunction, as defined by invasive hemodynamic indices, was associated with poor prognosis. Echocardiographic indices can identify these high risk patients, and hence improve risk stratification in clinical practice.