Echocardiographic validation of pulmonary hypertension due to heart failure with reduced ejection fraction in mice.
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ABSTRACT:
SUBMITTER: Dayeh NR
PROVIDER: S-EPMC5778040 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
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Echocardiographic validation of pulmonary hypertension due to heart failure with reduced ejection fraction in mice.
Dayeh Nour R NR Tardif Jean-Claude JC Shi Yanfen Y Tanguay Mégane M Ledoux Jonathan J Dupuis Jocelyn J
Scientific reports 20180122 1
Pulmonary hypertension (PH) associated with left heart diseases is the most prevalent cause of PH. The scarcity of studies exploring the pathophysiology and therapies of group II PH resides in the lack of validated small animal models with non-invasive determination of the presence and severity of PH. Heart failure (HF) was induced in mice by coronary artery ligation. Mice developed PH as evidenced by an elevated right ventricular (RV) systolic pressure and RV hypertrophy. Detailed non-invasive ...[more]
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Project description:AimsFailure of right ventricular (RV) function worsens outcome in pulmonary hypertension (PH). The adaptation of RV contractility to afterload, the RV-pulmonary artery (PA) coupling, is defined by the ratio of RV end-systolic to PA elastances (Ees/Ea). Using pressure-volume loop (PV-L) technique we aimed to identify an Ees/Ea cut-off predictive for overall survival and to assess hemodynamic and morphologic conditions for adapted RV function in secondary PH due to heart failure with reduced ejection fraction (HFREF).Methods and resultsThis post hoc analysis is based on 112 patients of the prospective Magdeburger Resynchronization Responder Trial. All patients underwent right and left heart echocardiography and a baseline PV-L and RV catheter measurement. A subgroup of patients (n = 50) without a pre-implanted cardiac device underwent magnetic resonance imaging at baseline. The analysis revealed that 0.68 is an optimal Ees/Ea cut-off (area under the curve: 0.697, P < 0.001) predictive for overall survival (median follow up = 4.7 years, Ees/Ea ≥ 0.68 vs. <0.68, log-rank 8.9, P = 0.003). In patients with PH (n = 76, 68%) multivariate Cox regression demonstrated the independent prognostic value of RV-Ees/Ea in PH patients (hazard ratio 0.2, P < 0.038). Patients without PH (n = 36, 32%) and those with PH but RV-Ees/Ea ≥ 0.68 showed comparable RV-Ees/Ea ratios (0.88 vs. 0.9, P = 0.39), RV size/function, and survival. In contrast, secondary PH with RV-PA coupling ratio Ees/Ea < 0.68 corresponded extremely close to cut-off values that define RV dilatation/remodelling (RV end-diastolic volume >160 mL, RV-mass/volume-ratio ≤0.37 g/mL) and dysfunction (right ventricular ejection fraction <38%, tricuspid annular plane systolic excursion <16 mm, fractional area change <42%, and stroke-volume/end-systolic volume ratio <0.59) and is associated with a dramatically increased short and medium-term all-cause mortality. Independent predictors of prognostically unfavourable RV-PA coupling (Ees/Ea < 0.68) in secondary PH were a pre-existent dilated RV [end-diastolic volume >171 mL, odds ratio (OR) 0.96, P = 0.021], high pulsatile load (PA compliance <2.3 mL/mmHg, OR 8.6, P = 0.003), and advanced systolic left heart failure (left ventricular ejection fraction <30%, OR 1.23, P = 0.028).ConclusionsThe RV-PA coupling ratio Ees/Ea predicts overall survival in PH due to HFREF and is mainly affected by pulsatile load, RV remodelling, and left ventricular dysfunction. Prognostically favourable coupling (RV-Ees/Ea ≥ 0.68) in PH was associated with preserved RV size/function and mid-term survival, comparable with HFREF without PH.
| S-EPMC8318446 | biostudies-literature
Project description:BackgroundWe hypothesized that pulmonary venous hypertension in heart failure (HF) leads to predominate remodeling of pulmonary veins and that the severity of venous remodeling is associated with the severity of pulmonary hypertension (PH) in HF.MethodsPatients with HF (n=108; 53 preserved and 55 reduced ejection fraction) with PH (HF-PH; pulmonary artery systolic pressure [PASP] ≥40 mm Hg) were compared to normal controls (n=12) and patients with primary pulmonary veno-occlusive disease (PVOD; n=17). In lung specimens from autopsy (control, HF-PH, and 7 PVOD) or surgery (10 PVOD), quantitative histomorphometry was performed in all analyzable arteries (n=4949), veins (n=7630), and small indeterminate vessels (IV; n=2168) to define percent medial thickness (arteries) and percent intimal thickness (%IT) (arteries, veins, and IV) relative to external diameter.ResultsThe average arterial percent medial thickness (control, 6.9; HF-PH, 11.0; PVOD, 15.0), arterial %IT (control, 4.9; HF-PH, 14.9; PVOD, 31.1), venous %IT (control, 14.0; HF-PH, 24.9; PVOD, 43.9), and IV %IT (control, 10.6; HF-PH, 25.8; PVOD, 50.0) in HF-PH were higher than controls (P<0.0001 for all) but lower than PVOD (P≤0.005 for all). PASP (mm Hg) was lower in HF-PH (median, 59 [interquartile range, 50-70]) than in PVOD (median, 91 [interquartile range, 82-103]). PASP correlated with arterial percent medial thickness (r=0.41) and arterial %IT (r=0.35) but more strongly with venous %IT (r=0.49) and IV %IT (r=0.55) (P<0.0001 for all). Associations between PASP and venous or IV %IT remained significant after adjusting for arterial percent medial thickness and %IT and did not vary by HF type. In patients with right heart catheterization (30 HF-PH, 14 PVOD), similar associations between the transpulmonary gradient and pulmonary vascular remodeling existed, with numerically stronger associations for venous and IV %IT. Although the PASP was slightly higher in patients with HF-PH with right ventricular dysfunction, pulmonary vascular remodeling was not more severe. Pulmonary vascular remodeling severity was associated with reductions in the diffusing capacity of the lungs.ConclusionsIn HF, PH is associated with global pulmonary vascular remodeling, but the severity of PH correlates most strongly with venous and small IV intimal thickening, similar to the pattern observed in PVOD. These findings expand our understanding of the pathobiology of PH in HF.
| S-EPMC5915920 | biostudies-literature
Project description:AimsPulmonary hypertension (PH) represents an important phenotype among the broader spectrum of patients with heart failure with preserved ejection fraction (HFpEF), but its mechanistic basis remains unclear. We hypothesized that activation of endothelin and adrenomedullin, two counterregulatory pathways important in the pathophysiology of PH, would be greater in HFpEF patients with worsening PH, and would correlate with the severity of haemodynamic derangements and limitations in aerobic capacity and cardiopulmonary reserve.Methods and resultsPlasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM), central haemodynamics, echocardiography, and oxygen consumption (VO2) were measured at rest and during exercise in subjects with invasively-verified HFpEF (n = 38) and controls free of HF (n = 20) as part of a prospective study. Plasma levels of CT-proET-1 and MR-proADM were highly correlated with one another (r = 0.89, P < 0.0001), and compared to controls, subjects with HFpEF displayed higher levels of each neurohormone at rest and during exercise. C-terminal pro-endothelin-1 and MR-proADM levels were strongly correlated with mean pulmonary artery (PA) pressure (r = 0.73 and 0.65, both P < 0.0001) and pulmonary capillary wedge pressure (r = 0.67 and r = 0.62, both P < 0.0001) and inversely correlated with PA compliance (r = -0.52 and -0.43, both P < 0.001). As compared to controls, subjects with HFpEF displayed right ventricular (RV) reserve limitation, evidenced by less increases in RV s' and e' tissue velocities, during exercise. Baseline CT-proET-1 and MR-proADM levels were correlated with worse RV diastolic reserve (ΔRV e', r = -0.59 and -0.67, both P < 0.001), reduced cardiac output responses to exercise (r = -0.59 and -0.61, both P < 0.0001), and more severely impaired peak VO2 (r = -0.60 and -0.67, both P < 0.0001).ConclusionSubjects with HFpEF display activation of the endothelin and adrenomedullin neurohormonal pathways, the magnitude of which is associated with pulmonary haemodynamic derangements, limitations in RV functional reserve, reduced cardiac output, and more profoundly impaired exercise capacity in HFpEF. Further study is required to evaluate for causal relationships and determine if therapies targeting these counterregulatory pathways can improve outcomes in patients with the HFpEF-PH phenotype.Clinical trial registrationNCT01418248; https://clinicaltrials.gov/ct2/results? term=NCT01418248&Search=Search.
| S-EPMC7963136 | biostudies-literature
Project description:BackgroundAlthough pulmonary congestion can be quantified in heart failure (HF) by means of lung ultrasonography (LUS), little is known about LUS findings (B-lines) in different HF phenotypes. This prospective cohort study investigated the prevalence and clinical and echocardiographic correlates of B-lines in ambulatory HF patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction compared with hypertensive patients. We related LUS findings to 12-month HF hospitalizations and all-cause mortality.Methods and resultsWe used LUS to examine hypertensive (n = 111), HFpEF (n = 46), and HFrEF (n = 73) patients (median age 66 y, 56% male, 79% white, and median EF 55%) undergoing clinically indicated outpatient echocardiography. B-line number was quantified offline, across 8 chest zones, blinded to clinical and echocardiographic characteristics. The proportion of patients with ≥3 B-lines was lower in hypertensive patients (13.5%) compared with both HFrEF (45.2%, P < .001) and HFpEF (34.8%; P = .05). HF patients with ≥3 B-lines had a higher risk of the composite outcome (age- and sex-adjusted hazard ratio 2.62, 95% confidence interval 1.15-5.96; P = .022).ConclusionsWhen performed at the time of outpatient echocardiography, LUS findings of pulmonary congestion differ between patients with known HF and those with hypertension, and may be associated with adverse outcomes.
| S-EPMC5895087 | biostudies-literature
Project description:AimsThis study aimed to investigate the prognostic value of dynamic changes in left ventricular ejection fraction (EF) for cardiovascular (CV) outcomes in an all-comer heart failure (HF) population with reduced EF (HFrEF, EF < 40%). We sought to identify independent factors related to improvement in EF and to identify risk factors for increased risk of CV events in the subgroups of improved EF (iEF) and non-improved EF (niEF), respecively.Methods and resultsThis is a retrospective sub-analysis from the REDEAL HF trial, which included consecutive patients with chronic HF who were hospitalized from July 2009 to December 2017. Baseline and follow-up echocardiography data (interval ≥12 months) of 573 consecutive patients with HFrEF were analysed. iEF was defined as absolute improvement in EF ≥ 10% and follow-up EF over 40%. The primary endpoint was defined as a composite endpoint of cardiovascular (CV) death, CV hospitalization, or appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular arrhythmia. EF improved in 37.2% of patients with HFrEF during follow-up (median period of 17 months). iEF was independently associated with shorter HF duration (>4 vs. ≤4 years, odd ratio [OR] = 0.477, 95% CI 0.305-0.745), no coronary artery disease (CAD vs. no CAD, OR = 0.583, 95% CI 0.396-0.858), and no ICD implantation (ICD vs. no ICD, OR = 0.341, 95% CI 0.228-0.511). Compared with niEF, iEF was significantly and independently associated with lower all-cause mortality (22.1% vs. 31.1%, P = 0.019; hazard ratio [HR] = 0.674, 95% CI 0.469-0.968), lower CV mortality (8.9% vs. 16.1%, P = 0.015; HR = 0.539, 95% CI 0.317-0.916), and lower CV events risk (27.2% vs. 49.2%, P < 0.001; HR 0.519, 95% CI 0.381-0.708), after adjustment for age, sex, duration of HF, and other clinical risk factors. Hypertension (HR = 2.452, P = 0.032) and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP >1153 pg/mL, HR = 4.372, P < 0.001) were identified as independent risk factors for CV events in the iEF subgroup. ICD implantation (HR = 1.533, P = 0.011), elevated NT-proBNP (HR = 1.626, P = 0.018), increased left atrial volume index (HR = 1.461, P = 0.021), reduced lateral mitral annular plane systolic excursion (HR = 1.478, P = 0.025), and reduced tricuspid plane systolic excursion (HR = 1.491, P = 0.039) were identified as risk factors for CV events in the niEF subgroup.ConclusionsImprovement in EF is independently related to the longer survival and lower CV related mortality and hospitalization rate of HFrEF. Elevated baseline NT-proBNP is identified as the strongest prognostic factor associated with increased CV events risk in HFrEF patients both with and without improved EF, regardless of age, sex, duration of HF, and other clinical risk factors.
| S-EPMC10053299 | biostudies-literature
Project description:AimsWhile right ventricular (RV) dysfunction is associated with worse prognosis in co-morbid pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF), the mechanisms driving RV dysfunction are unclear. We evaluated the extent and clinical correlates of diffuse RV myocardial fibrosis in PH-HFpEF, as measured by cardiovascular magnetic resonance-derived extracellular volume (ECV).Methods and resultsWe prospectively enrolled participants with PH-HFpEF (n = 14), pulmonary arterial hypertension (PAH; n = 13), and controls (n = 8). All participants underwent high-resolution cardiovascular magnetic resonance, and case subjects (PH-HFpEF and PAH) additionally underwent right heart catheterization. T1 mapping was performed using high-resolution modified look-locker inversion recovery with a 1 × 1 mm2 in-plane resolution. RV free wall T1 values were quantified, and ECV was calculated. Participants with PH-HFpEF were older and carried higher rates of hypertension and obstructive sleep apnoea than those with PAH. While RV ECV was similar between PH-HFpEF and PAH (33.1 ± 8.0 vs. 34.0 ± 4.5%; P = 0.57), total pulmonary resistance was lower in PH-HFpEF compared with PAH [PH-HFpEF: 5.68 WU (4.70, 7.66 WU) vs. PAH: 8.59 WU (8.14, 12.57 WU); P = 0.01]. RV ECV in PH-HFpEF was associated with worse indices of RV structure (RV end-diastolic volume: r = 0.67, P = 0.01) and RV function (RV free wall strain: r = 0.59, P = 0.03) but was not associated with RV afterload (total pulmonary resistance: r = 0.08, P = 0.79). Conversely, there was a strong correlation between RV ECV and RV afterload in PAH (r = 0.57, P = 0.04).ConclusionsDiffuse RV fibrosis, as measured by ECV, is present in PH-HFpEF and is associated with adverse RV structural and functional remodelling but not degree of pulmonary vasculopathy. In PH-HFpEF, diffuse RV fibrosis may occur out of proportion to the degree of RV afterload.
| S-EPMC7083501 | biostudies-literature
Project description:AimsThe presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFpEF). To date, neither established heart failure therapies nor pulmonary vasodilators proved beneficial. This study investigated the efficacy of chronic treatment with the oral soluble guanylate cyclase stimulator riociguat in patients with PH-HFpEF.Methods and resultsThe phase IIb, randomized, double-blind, placebo-controlled, parallel-group, multicentre DYNAMIC trial assessed riociguat in PH-HFpEF. Patients were recruited at five hospitals across Austria and Germany. Key eligibility criteria were mean pulmonary artery pressure ≥25 mmHg, pulmonary arterial wedge pressure >15 mmHg, and left ventricular ejection fraction ≥50%. Patients were randomized to oral treatment with riociguat or placebo (1:1). Patients started at 0.5 mg three times daily (TID) and were up-titrated to 1.5 mg TID. The primary efficacy endpoint was change from baseline to week 26 in cardiac output (CO) at rest, measured by right heart catheterization. Primary efficacy analyses were performed on the full analysis set. Fifty-eight patients received riociguat and 56 patients placebo. After 26 weeks, CO increased by 0.37 ± 1.263 L/min in the riociguat group and decreased by -0.11 ± 0.921 L/min in the placebo group (least-squares mean difference: 0.54 L/min, 95% confidence interval 0.112, 0.971; P = 0.0142). Five patients dropped out due to riociguat-related adverse events but no riociguat-related serious adverse event or death occurred.ConclusionThe vasodilator riociguat improved haemodynamics in PH-HFpEF. Riociguat was safe in most patients but led to more dropouts as compared to placebo and did not change clinical symptoms within the study period.
| S-EPMC9492239 | biostudies-literature
Project description:Background Both ventilatory abnormalities and pulmonary hypertension (PH) are frequently observed in patients with heart failure with reduced ejection fraction. We aim to investigate the association between ventilatory abnormalities and PH in heart failure with reduced ejection fraction, as well as their prognostic impacts. Methods and Results A total of 440 ambulatory patients (age, 66.2±15.8 years; 77% men) with left ventricular ejection fraction ≤40% who underwent comprehensive echocardiography and spirometry were enrolled. Total lung capacity, forced vital capacity, and forced expiratory volume in the first second were obtained. Pulmonary arterial systolic pressure was estimated. PH was defined as a pulmonary arterial systolic pressure of >50 mm Hg. The primary end point was all-cause mortality at 5 years. Patients with PH had significantly reduced total lung capacity, forced vital capacity, and forced expiratory volume in the first second. During a median follow-up of 25.9 months, there were 111 deaths. After accounting for age, sex, body mass index, renal function, smoking, left ventricular ejection fraction, and functional capacity, total lung capacity (hazard ratio [HR] per 1 SD, 0.66; 95% CI per 1 SD, 0.46-0.96), forced vital capacity (HR per 1 SD, 0.64; 95% CI per 1 SD, 0.48-0.84), and forced expiratory volume in the first second (HR per 1 SD, 0.72; 95% CI per 1 SD, 0.53-0.98) were all significantly correlated with mortality in patients without PH. Kaplan-Meier curve demonstrated impaired pulmonary function, defined as forced expiratory volume in the first second ≤58% of predicted or forced vital capacity ≤65% of predicted, was associated with higher mortality in patients without PH (HR, 2.85; 95% CI, 1.66-4.89), but not in patients with PH (HR, 1.05; 95% CI, 0.61-1.82). Conclusions Ventilatory abnormality was more prevalent in patients with heart failure with reduced ejection fraction with PH than those without. However, such ventilatory defects were related to long-term survival only in patients without PH, regardless of their functional status.
| S-EPMC9075473 | biostudies-literature
Project description:AimsHeart failure with mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared with heart failure (HF) with reduced ejection fraction (EF). We assessed whether left ventricular ejection fraction (LVEF) trajectory can be used to identify groups of patients with HFmrEF who have different clinical outcomes in a large retrospective study of patients with serial imaging.Methods and resultsPatients with HF and ≥2 echocardiograms performed ≥6 months apart were included if the LVEF measured 40-49% on the second study. Patients were classified as HFmrEF-Increasing if LVEF had increased ≥10% (n = 450), HFmrEF-Decreasing if LVEF had decreased ≥10% (n = 512), or HFmrEF-Stable if they did not meet other criteria (n = 389). The primary outcome was all-cause mortality or cardiovascular hospitalization after the second echocardiogram. Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, co-morbidities, and medications. In total, 1351 patients with HFmrEF (median age 74, 64.2% male) were included with 28.8% exhibiting stable LVEF. During median follow-up of 15.3 months, the composite outcome occurred in 811 patients. During follow-up, patients with HFmrEF-Increasing were less likely to experience the primary outcome [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.60-0.88, P < 0.001] compared with HFmrEF-Stable. Patients with HFmrEF-Decreasing were more likely to experience the composite outcome in unadjusted analyses (unadjusted HR 1.19, 95% CI 1.01-1.40, P = 0.040) but not adjusted analyses (adjusted HR 1.16, 95% CI 0.98-1.37, P = 0.092). Associations with death or HF hospitalizations were similar (HFmrEF-Increasing: adjusted HR 0.72, 95% CI 0.59-0.88, P = 0.005; HFmrEF-Decreasing: adjusted HR 1.20, 95% CI 1.01-1.44, P = 0.044). Patients with HFmrEF-Decreasing had a similar risk of the composite outcome as patients with HF with reduced EF (adjusted HR 1.03, 95% CI 0.89-1.20, P = 0.670). Patients with HFmrEF-Increasing were less likely to experience the composite outcome compared with patients with HF with preserved EF (adjusted HR 0.73, 95% CI 0.62-0.87, P < 0.001).ConclusionsAmongst patients with HFmrEF, those exhibiting positive LVEF trajectory were less likely to experience adverse outcomes after correcting for important confounders including medical therapy. Categorizing HFmrEF patients based on LVEF trajectory provides meaningful clinical information and may assist clinicians with management decisions.
| S-EPMC9065872 | biostudies-literature
Project description:BackgroundChronic congestive heart failure is a common condition that, if untreated, markedly impairs the quality of life and is associated with a high risk of recurrent hospitalization and death.MethodsThis review is based on articles retrieved by a selective search in PubMed, as well as on relevant guidelines.ResultsEvidence-based treatment options are available only for congestive heart failure with a low ejection fraction. Pharma - cotherapy is based on neurohumoral inhibition of the renin-angiotensin-aldosterone system and the adrenergic system. The prognosis of patients with this condition has been further improved recently through the introduction of combined angiotensin receptor antagonists and neprilysin inhibitors. Modern implantable devices are a further component of treatment. Implantable defibrillators and special pacemakers for cardiac resynchronization are well established; the utility of alternative devices (baroreflex modulation or cardiac contractility modulation) needs to be investigated in further studies. It was recently shown that the catheter-based treatment of secondary mitral regurgitation with a MitraClip improves the outcome of selected patients.ConclusionThe treatment of chronic systolic heart failure as recommended in the relevant guidelines, with drugs and implanted devices if indicated, can significantly improve the clinical outcome.
| S-EPMC7643567 | biostudies-literature