Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse outcomes in left heart disease (LHD). This study sought to characterize the pathophysiology of ...PVD across the spectrum of PH in LHD.
Patients with PH-LHD mean pulmonary artery (PA) pressure >20 mmHg and PA wedge pressure (PAWP) ≥15 mmHg and controls free of PH or LHD underwent invasive haemodynamic exercise testing with simultaneous echocardiography, expired air and blood gas analysis, and lung ultrasound in a prospective study. Patients with PH-LHD were divided into isolated post-capillary PH (IpcPH) and PVD combined post- and pre-capillary PH (CpcPH) based upon pulmonary vascular resistance (PVR <3.0 or ≥3.0 WU). As compared with controls (n = 69) and IpcPH-LHD (n = 55), participants with CpcPH-LHD (n = 40) displayed poorer left atrial function and more severe right ventricular (RV) dysfunction at rest. With exercise, patients with CpcPH-LHD displayed similar PAWP to IpcPH-LHD, but more severe RV-PA uncoupling, greater ventricular interaction, and more severe impairments in cardiac output, O2 delivery, and peak O2 consumption. Despite higher PVR, participants with CpcPH developed more severe lung congestion compared with both IpcPH-LHD and controls, which was associated lower arterial O2 tension, reduced alveolar ventilation, decreased pulmonary O2 diffusion, and greater ventilation-perfusion mismatch.
Pulmonary vascular disease in LHD is associated with a distinct pathophysiologic signature marked by greater exercise-induced lung congestion, arterial hypoxaemia, RV-PA uncoupling, ventricular interdependence, and impairment in O2 delivery, impairing aerobic capacity. Further study is required to identify novel treatments targeting the pulmonary vasculature in PH-LHD.
Abstract
Exercise intolerance is a primary manifestation in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with abnormal hemodynamics and a poor quality of ...life. Two multiparametric scoring systems have been proposed to diagnose HFpEF. This study sought to determine the performance of the H
2
FPEF and HFA-PEFF scores for predicting exercise capacity and echocardiographic findings of intracardiac pressures during exercise in subjects with dyspnea on exertion referred for bicycle stress echocardiography. In a subset, simultaneous expired gas analysis was performed to measure the peak oxygen consumption (VO
2
). Patients with HFpEF (n = 83) and controls without HF (n = 104) were enrolled. The H
2
FPEF score was obtainable for all patients while the HFA-PEFF score could not be calculated for 23 patients (feasibility 88%). Both H
2
FPEF and HFA-PEFF scores correlated with a higher E/e′ ratio (r = 0.49 and r = 0.46), lower systolic tricuspid annular velocity (r = − 0.44 and = − 0.24), and lower cardiac output (r = − 0.28 and r = − 0.24) during peak exercise. Peak VO
2
and exercise duration decreased with an increase in H
2
FPEF scores (r = − 0.40 and r = − 0.32). The H
2
FPEF score predicted a reduced aerobic capacity (AUC 0.71,
p
= 0.0005), but the HFA-PEFF score did not (
p
= 0.07). These data provide insights into the role of the H
2
FPEF and HFA-PEFF scores for predicting exercise intolerance and abnormal hemodynamics in patients presenting with exertional dyspnea.
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•The demonstration of elevated left ventricular (LV) filling pressure, in which echocardiography plays a central role, is crucial in diagnosing heart failure with preserved ejection fraction (HFpEF) ...in euvolemic patients with dyspnea.•Exercise stress echocardiography may enhance the diagnosis of HFpEF by detecting elevation in LV filling pressures that develop only during exercise.•Echocardiography also provides valuable insight into the pathophysiology and underlying phenotypes of HFpEF.•Exercise stress echocardiography may allow for a better pathophysiological characterization in HFpEF.
Heart failure with preserved ejection fraction (HFpEF) represents one of the greatest unmet needs in modern cardiology given its diagnostic difficulty and limited therapeutic options. Echocardiography provides valuable information on cardiac structure, function, and hemodynamics and plays a central role in the evaluation of HFpEF. Echocardiography is crucial in identifying HFpEF among patients with dyspnea, especially when overt congestion is absent. The combination of echocardiographic indices of diastolic function, clinical characteristics, and natriuretic peptide tests has been proposed in the diagnostic evaluation of patients with suspected HFpEF. Echocardiography also provides valuable insight into the pathophysiology and underlying phenotypes of HFpEF. Exercise stress echocardiography can also detect abnormalities that develop only during exercise. This may enhance the diagnosis of HFpEF by demonstrating elevation in the left ventricular filling pressure and may have potential for better pathophysiological characterization. This review focuses on the role of echocardiography in the diagnostic evaluation and phenotyping of HFpEF. We also discuss the potential role of exercise stress echocardiography for the diagnosis and disease phenotyping of HFpEF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Studies with short-term follow-up have demonstrated favorable effects of weight loss (WL) on the heart, but little information is available regarding long-term effects or effects of visceral fat ...reduction.
The purpose of this study was to evaluate the effects of long-term WL following bariatric surgery on cardiac structure, function, ventricular interaction, and body composition, including epicardial adipose thickness and abdominal visceral adipose tissue (VAT).
A total of 213 obese patients underwent echocardiography before and >180 days following bariatric surgery. Abdominal VAT area was measured by computed tomography in 52 of these patients.
After 5.3 years (IQR: 2.9-7.9 years), body mass index (BMI) decreased by 22%, with favorable reductions in blood pressure, fasting glucose, and left ventricular (LV) remodeling in the full sample. In the subgroup of patients with abdominal computed tomography, VAT area decreased by 30%. In all subjects, epicardial adipose thickness was reduced by 14% (both P < 0.0001) in tandem with reductions in ventricular interdependence. LV and right ventricular longitudinal strain improved following WL, but left atrial (LA) strain deteriorated, while LA volume and estimated LA pressures increased. In subgroup analysis, LV wall thickness and strain correlated more strongly with VAT than BMI at baseline, and reductions in LV mass following surgery were correlated with decreases in VAT, but not BMI.
In this observational study, weight loss following bariatric surgery was associated with epicardial fat reduction, reduced ventricular interaction, LV reverse remodeling, and improved longitudinal biventricular mechanics, but LA myopathy and hemodynamic congestion still progressed. Reduction in visceral fat was associated with favorable cardiac effects, suggesting this might be a key target of WL interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ketone body β-hydroxybutyrate (βOHB) and fibroblast growth factor-21 (FGF21) have been proposed to mediate systemic metabolic response to fasting. However, it remains elusive about the signaling ...elicited by ketone and FGF21 in the heart. Stimulation of neonatal rat cardiomyocytes with βOHB and FGF21 induced peroxisome proliferator-activated receptor α (PPARα) and PGC1α expression along with the phosphorylation of LKB1 and AMPK. βOHB and FGF21 induced transcription of peroxisome proliferator-activated receptor response element (PPRE)-containing genes through an activation of PPARα. Additionally, βOHB and FGF21 induced the expression of Nrf2, a master regulator for oxidative stress response, and catalase and Ucp2 genes. We evaluated the oxidative stress response gene expression after 24 h fast in global Fgf21-null (Fgf21
) mice, cardiomyocyte-specific FGF21-null (cmFgf21
) mice, wild-type (WT), and Fgf21
littermates. Fgf21
mice but not cmFgf21
mice had unexpectedly higher serum βOHB levels, and higher expression levels of PPARα and oxidative stress response genes than WT mice or Fgf21
littermates. Notably, expression levels of oxidative stress response genes were significantly correlated with serum βOHB and PGC1α levels in both WT and Fgf21
mice. These findings suggest that fasting-induced βOHB and circulating FGF21 coordinately regulate oxidative stress response gene expression in the heart.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used incretin-based therapy for the treatment of type 2 diabetes. We investigated the cardioprotective effect of a DPP-4 inhibitor, vildagliptin (
...vilda
), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated with either vehicle or
vilda
, followed by transverse aortic constriction (TAC). After 3 weeks of TAC, cardiac hypertrophy and impairment of systolic function were attenuated in
vilda
-treated mice. Pressure–volume analysis showed that
vilda
treatment significantly improved left-ventricular contractile efficiency in TAC heart. Myocardial energy substrate analysis showed that
vilda
treatment significantly increased glucose uptake as well as fatty acid uptake. Fibroblast growth factor 21 (FGF21), a peptide involved in the regulation of energy metabolism, increased in TAC heart and was further increased by
vilda
treatment. FGF21 was strongly expressed in cardiac fibroblasts than in cardiomyocytes in mouse heart after TAC with
vilda
treatment.
Vilda
treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism and exert
vilda
-mediated beneficial effects in stressed heart.
Vilda
induced a metabolic regulator, FGF21 expression in cardiac fibroblasts via Sirt1, and increased contractile efficiency in murine pressure-overloaded heart.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Myocardial deformation imaging is now readily available during routine echocardiography and plays an important role in the advanced care of cardiovascular diseases. Its clinical value in detecting ...subtle myocardial dysfunction, by helping diagnose disease and allowing prediction of disease progression and earlier pharmacological intervention, has been demonstrated. Strain imaging has been the most studied and clinically used technique in the field of cardio-oncology. A relative percent reduction in left ventricular (LV) global longitudinal strain > 15% from baseline is considered a marker of early subclinical LV dysfunction and may have the potential to guide early initiation of cardioprotective therapy. The role of strain imaging is expanding to other fields, such as cardiac amyloidosis, other cardiomyopathies, valvular heart diseases, pulmonary hypertension, and heart failure with preserved ejection fraction. It is also used for the evaluation of the right ventricle and atria. This review aims to provide a current understanding of the roles of strain imaging in the evaluation and management of patients with cardiovascular diseases in clinical practice.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Fibroblast growth factor 21 (FGF21) is a metabolic hormone having anti-oxidative and anti-hypertrophic effects. However, the regulation of FGF21 expression during acute myocardial infarction (AMI) ...remains unclear. We tested blood samples from 50 patients with AMI and 43 patients with stable angina pectoris (sAP) for FGF21, fatty acid binding protein 4 (FABP4), a protein secreted from adipocytes in response to adrenergic lipolytic signal, and total and individual fatty acids. Compared with sAP patients, AMI patients had higher serum FGF21 levels on admission, which were significantly correlated with peak FABP4 and saturated fatty acids (SFAs) but not with peak levels of cardiac troponin T. In mice, myocardial ischemia rapidly induced FGF21 production by the heart, which accompanied activation of AMP-activated protein kinase (AMPK)-dependent pathway. Like AICAR, an activator of AMPK, catecholamines (norepinephrine and isoproterenol) and SFAs (palmitate and stearate) significantly increased FGF21 production and release by cardiac myocytes via AMPK activation. Recombinant FGF21 induced its own expression as well as members of down-stream targets of AMPK involved in metabolic homeostasis and mitochondrial biogenesis in cardiac myocytes. These findings suggest that adrenergic overdrive and resultant adipose tissue lipolysis induce cardiac AMPK-FGF21 feed-forward loop that potentially provides cardioprotection against ischemic damage.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Elevated intracardiac pressure at rest and/or exercise is a fundamental abnormality in heart failure with preserved ejection fraction (HFpEF). Fatty acid-binding protein 1 (FABP1) is proposed to be a ...sensitive biomarker for liver injury. We sought to determine whether FABP1 at rest would be elevated in HFpEF and would correlate with echocardiographic markers of intracardiac pressures at rest and during exercise. In this prospective study, subjects with HFpEF (n = 22) and control subjects without HF (n = 23) underwent resting FABP1 measurements and supine bicycle exercise echocardiography. Although levels of conventional hepatic enzymes were similar between groups, FABP1 levels were elevated in HFpEF compared to controls (45 25-68 vs. 18 14-24 ng/mL, p = 0.0008). FABP1 levels were correlated with radiographic and blood-based markers of congestion, hemodynamic derangements during peak exercise (E/e', r = 0.50; right atrial pressure, r = 0.35; pulmonary artery systolic pressure, r = 0.46), reduced exercise cardiac output (r = - 0.49), and poor exercise workload achieved (r = - 0.40, all p < 0.05). FABP1 distinguished HFpEF from controls with an area under the curve of 0.79 (p = 0.003) and had an incremental diagnostic value over the H
FPEF score (p = 0.007). In conclusion, FABP1 could be a novel hepatic biomarker that associates with hemodynamic derangements, reduced cardiac output, and poor exercise capacity in HFpEF.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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