Left bundle branch pacing vs biventricular pacing in heart failure patients with left bundle branch block:A systematic review and meta-analysis

BACKGROUND Left bundle branch pacing(LBBP)is a novel pacing modality of cardiac resynchronization therapy(CRT)that achieves more physiologic native ventricular activation than biventricular pacing(BiVP).AIM To explore the validity of electromechanical resynchronization,clinical and echocardiographic response of LBBP-CRT.METHODS Systematic review and Meta-analysis were conducted in accordance with the standard guidelines as mentioned in detail in the methodology section.RESULTS In our analysis,the success rate of LBBP-CRT was determined to be 91.1%.LBBP CRT significantly shortened QRS duration,with significant improvement in echocardiographic parameters,including left ventricular ejection fraction,left ventricular end-diastolic diameter and left ventricular end-systolic diameter in comparison with BiVP-CRT.CONCLUSION A significant reduction in New York Heart Association class and B-type natriuretic peptide levels was also observed in the LBBP-CRT group vs BiVP-CRT group.Lastly,the LBBP-CRT cohort had a reduced pacing threshold at follow-up as compared to BiVP-CRT.

Single-Nucleus RNA Sequencing Reveals Cardiac Macrophage Landscape in Hypoplastic Left Heart Syndrome

Background:Hypoplastic left heart syndrome(HLHS)is one of the most challenging congenital heart diseases in clinical treatment.In cardiac tissues,resident macrophages fulfill critical functions in maintaining a stable cardiac state and have strong regenerative capacity and organ specificity.However,the molecular mechanisms of macro-phages in HLHS remained unclear.Methods:Single-nucleus RNA sequencing(snRNA-seq)data of HLHS and healthy control(donors)samples obtained from the Gene Expression Omnibus(GEO)database were normalized and clustered using the Seurat package.The“FindMarkers”function was used to screen differentially expressed genes(DEGs)between the HLHS and donor groups and to analyze the functional enrichment of the set of genes of interest.Finally,cell-cell communication,pseudotime,and single-cell regulatory network inference and cluster-ing(SCENIC)analyses were used to study the mechanisms of macrophages in HLHS.Results:Based on the snRNA-seq data of HLHS and donors,we identified a total of 9 cell clusters,among which the proportion of macrophages was significantly less in the HLHS group than in the control group.Subdivision of macrophage subpopulations(Macrophages 1,2,and 3)showed that Macrophages 1 was mainly involved in nervous system development,angiogenesis,and apoptotic processes.In addition,analysis of communication between Macro-phages 1 and cardiomyocytes revealed that ligand-acceptor pairs such as GAS6/AXL,IL6,IGF1,THY1,and L1CAM were present only in the donor group.Finally,pesudotime and SCENIC analyses demonstrated that FOXO3 and ELF2 played a critical role for Macrophages 1 to maintain cardiac function in patients with HLHS.Conclusion:Our study improved the current understanding of the molecular mechanisms of macrophage devel-opment in HLHS,showing that manipulating the regulatory role of macrophages in the heart can be a novel treat-ment for HLHS.

Chemical Preconditioning by 3-nitropropionic Acid Reduces Ischemia-reperfusion Injury in Rat Heart

Summary： This study was designed to investigate the cardioprotective effects of preconditioning with 3-nitropropionic acid, an inhibitor of mitochondrial succinate dehydrogenase. 16 isolated rat hearts were randomly divided into two groups, a treatment group and a control group. The rats of the treatment group were treated intraperitoneally with 3-nitropropionic ac;.d （3-NPA, 4 mg/kg） and the rats of the control group were treated with saline. 24 h after the treatment, the isolated hearts were mounted on a Langendorff apparatus. After 30 min, the hearts were subjected to 30min ischemia and 60-min reperfusion. The HR, LVDP and ±dp/dtmax were measured at preischemia and 30 min, 60 min after the reperfusion. Coronary effluent was collected 15 min after the reperfusion for the determination of CK and LDH. At the end of the 60-min reperfusion the heart was removed for the determination of myocardial SOD and MDA. Our results showed that in the 3-NPA group LVDP and ±dp/dt recovered significantly better, myocardial MDA, CK and LDH were significantly lower and the myocardial SOD was significantly higher than in the control group. It is concluded that chemical preconditioning by 3-nitropropionate has cardioprotective effects against ischemia-reperfusion injury.

Gradual Clamping Reduced Ischemia-Reperfusion Injury in an Isolated Rat Heart Model

Objectives: We hypothesized that the organisms and their organs or tissues could adapt themselves to the gradual changes of environment for surviving or reducing damage. This study explored whether gradual clamping (GC) could reduce myocardial ischemia-reperfusion (IR) injury in rat heart. Methods: Twelve rats were randomized to IR group and GC group, then the hearts were isolated and perfused with Langendorff apparatus. Before cardioplegia, the perfusion was stopped abruptly in IR group while slowly with 5-minute in GC group. The hearts were subjected to 30-minute ischemia and 60-minute reperfusion. The left ventricular develop pressure (LVDP) and systolic pressure (LVSP), the maximal rate of the increase and decrease of left ventricular pressure (+dp/dtmax, ﹣dp/dtmax) were measured by polygraph system at different time points. The recovery of the variables was expressed as the ratio of these values at individual time point after reperfusion to the baseline respectively. Results: The recovery of LVDP after reperfusion was better than that in IR group (P = 0.034). No significant difference in the recovery of LVSP, +dp/dtmax and ﹣dp/dtmax between groups was observed. Conclusions: Gradual clamping could improve the recovery of LVDP after IR, suggesting that gradual clamping could reduce myocardial IR injury.

The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury

A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion （I/R） injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin （mTOR） inhibitors, adenosine monophosphate-activated protein kinase （AMPK） modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.

Real-time Three-dimensional Echocardiographic Assessment of Left Ventricular Remodeling Index in Patients with Hypertensive Heart Disease and Coronary Artery Disease

Left ventricular remodeling index （LVRI） was assessed in patients with hypertensive heart disease （HHD） and coronary artery disease （CAD） by real-time three-dimensional echocardiography （RT3DE）. RT3DE data of 18 patients with HHD, 20 patients with CAD and 22 normal controis （NC） were acquired. Left ventricular end-diastolic volume （EDV） and left ventricular end-diastolic epicardial volume （EDVepi） were detected by RT3DE and two-dimensional echocardiography Simpson biplane method （2DE）. LVRI （left ventricular mass/EDV） was calculated and compared. The results showed that LVRI measurements detected by RT3DE and 2DE showed significant differences inter-groups （P〈0.01）. There was no significant difference in NC group （P〉0.05）, but significant difference in HHD and CAD intra-group （P〈0.05）. There was good positive correlations between LVRI detected by RT3DE and 2DE in NC and HHD groups （t=0.69, P〈0.01; r=0.68, P〈0.01）, but no significant correlation in CAD group （r=0.30, P〉0.05）. It was concluded that LVRI derived from RT3DE as a new index for evaluating left ventricular remodeling can provide more superiority to LVRI derived from 2DE.

Diagnosis and treatment of heart failure with preserved left ventricular ejection fraction

Nearly six million people in United States have heart failure.Fifty percent of these people have normal left ventricular(LV)systolic heart function but abnormal diastolic function due to increased LV myocardial stiffness.Most commonly,these patients are elderly women with hypertension,ischemic heart disease,atrial fibrillation,obesity,diabetes mellitus,renal disease,or obstructive lung disease.The annual mortality rate of these patients is 8%-12%per year.The diagnosis is based on the history,physical examination,laboratory data,echocardiography,and,when necessary,by cardiac catheterization.Patients with obesity,hypertension,atrial fibrillation,and volume overload require weight reduction,an exercise program,aggressive control of blood pressure and heart rate,and diuretics.Miniature devices inserted into patients for pulmonary artery pressure monitoring provide early warning of increased pulmonary pressure and congestion.If significant coronary heart disease is present,coronary revascularization should be considered.

Heart failure and left ventricular dysfunction in older patients with chronic kidney disease: the China Hypertension Survey (2012‒2015)

Background Heart failure(HF)is a leading cause of hospitalization and mortality for older chronic kidney disease(CKD)patients.However,the epidemiological data is scarce.We aimed to determine the prevalence of left ventricular(LV)dysfunction and HF,and to explore the risk factors for HF among those patients.Methods This is a cross-sectional analysis of the China Hypertension Survey conducted between October 2012 and December 2015.A total of 5,808 participants aged≥65 years were included in the analysis.Self-reported history of HF and any other cardiovascular diseases was acquired.2-D and Doppler echocardiography were used to assess LV dysfunction.CKD was defined as either estimated glomerular filtration rate(eGFR)<60 mL/min per 1.73 m2 or urinary albumin to creatinine ratio(ACR)≥30 mg/g.Results Among CKD patients aged≥65 years,the weighted prevalence of HF,heart failure with preserved ejection fraction(HFpEF),heart failure with mid-range ejection fraction(HFmrEF),and heart failure with reduced ejection fraction(HFrEF)was 4.8%,2.5%,0.8%,and 1.7%,respectively.The weighted prevalence of HF was 5.0%in patients with eGFR<60 mL/min per 1.73 m2,and was 5.9%in patients with ACR≥30 mg/g.The prevalence of LV systolic dysfunction was 3.1%,and while it was 8.9%for moderate/severe diastolic dysfunction.Multivariate analysis showed that smoking was significantly associated with the risk of HF.Furthermore,age,smoking,and residents in rural areas were significantly associated with a risk of LV diastolic dysfunction.Conclusions The prevalence of HF and LV dysfunction was high in older patients with CKD,suggesting that particular strategies will be required.

Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure

Objective: To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.Methods: Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet,pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency.Results: Compared with the control group, 4 phase automatic depolarization velocity,spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly(P < 0.01) and action potential amplitude reduced(P < 0.01) in model group. Moreover, repolarization 50% and 90% increased(P < 0.01).Conclusions: There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure.

Post-myocardial infarction giant left ventricular pseudoaneurysm presenting with severe heart failure

Left ventricle(LV) pseudoaneurysm is a late mechanical complication of myocardial infarction.A giant LV pseudoaneurysm is a rare presentation.We report a case of giant LV pseudoaneurysm in a post-MI patient who presented with gross congestive heart failure.The patient had a successful surgical repair of the aneurysm and had a favorable 3-mo outcome.The imaging modality and surgical treatment of the pseudoaneurysm are discussed.

Shortness of breath in clinical practice: A case for left atrial function and exercise stress testing for a comprehensive diastolic heart failure workup

The symptom cluster of shortness of breath(SOB) contributes significantly to the outpatient workload of cardiology services. The workup of these patients includes blood chemistry and biomarkers, imaging and functional testing of the heart and lungs. A diagnosis of diastolic heart failure is inferred through the exclusion of systolic abnormalities, a normal pulmonary function test and normal hemoglobin, coupled with diastolic abnormalities on echocardiography. Differentiating confounders such as obesity or deconditioning in a patient with diastolic abnormalities is difficult. While the most recent guidelines provide more avenues for diagnosis, such as incorporating the left atrial size, little emphasis is given to understanding left atrial function, which contributes to at least 25% of diastolic left ventricular filling; additionally, exercise stress testing to elicit symptoms and test the dynamics of diastolic parameters, especially when access to the "gold standard" invasive tests is lacking, presents clinical translational gaps. It is thus important in diastolic heart failure work up to understand left atrial mechanics and the role of exercise testing to build a comprehensive argument for the diagnosis of diastolic heart failure in a patient presenting with SOB.

Left ventricular assist devices as destination therapy in stage D heart failure

1 Introduction? Mechanical circulatory support (MCS) has increasingly become an important management opportunity for patients with stage D heart failure (HF) with remarkable impact on patient survival and quality of life. Early clinical trials have demonstrated improved outcomes of durable left ventricular assist device (LVAD) support compared with optimal medical management.[1] As technology advanced, continuous flow LVADs outperformed pulsatile flow devices in clinical trials and the field migrated to HeartMate (Abbott Laboratories, Abbott Park, IL) and HeartWare (Medtronic, Minneapolis, MN) devices due to their clinical superiority. Among the continuous flow devices.

Cardiac resynchronization therapy for heart failure induced by left bundle branch block after transcatheter closure of ventricular septal defect

A 54-year-old female patient with congenital heart disease had a persistent complete left bundle branch block three months after closure by an Amplatzer ventricular septal defect occluder. Nine months later, the patient suffered from chest distress, palpitation, and sweating at daily activities, and her 6-min walk distance decreased significantly （155 m）. Her echocardiography showed increased left ventricular end-diastolic diameter with left ventricular ejection fraction of 37%. Her symptoms reduced significantly one week after received cardiac resynchronization therapy. She had no symptoms at daily activities, and her echo showed left ventricular ejection fraction of 46%and 53%. Moreover, left ventricular end-diastolic diameter decreased 6 and 10 months after cardiac resynchronization therapy, and 6-min walk dis-tance remarkably increased. This case demonstrated that persistent complete left bundle branch block for nine months after transcatheter closure with ventricular septal defect Amplatzer occluder could lead to left ventricular enlargement and a significant decrease in left ventricular systolic function. Cardiac resynchronization therapy decreased left ventricular end-diastolic diameter and increased left ventricular ejection fraction, thereby improving the patient’s heart functions.

Arterial hypertension and electrocardiographic diagnosis of left ventricular hypertension in the group of geriatric patients with coronary heart disease living in the far north

As a result of research, high prevalence of arterial hypertension has been identified in the group of patients with coronary heart disease aged 60 and older. Most often, occurring form of arterial hypertension among geriatric patients is isolated systolic arterial hypertension (ISAH). The comparison of two ethnic groups of the population has showed higher levels of systolic and diastolic blood pressure (SBP and DBP) in the group of patients of non-indigenous nationality, rather than Yakut patients. Correlation was recorded in the group of non-indigenous patients as they age. Significant increase in the level of SBP was identified in the group of senile and long-livers than in the elderly. Detection of ECG signs of LVH showed the lowest specificity of Cornell voltage criterion comparing to Sokolow-Lyon criterion with its more often occurrence. ECG-signs of left ventricle hypertrophy are significantly more often established by Sokolow-Lyon criterion for men, Cornell voltage—for women. Correlation has been found between the presence of LVH and combination of Cornell voltage criterion with both Gubner-Ungerleider and Sokolow-Lyon criteria.

Left Ventricle Geometry Remolding after Heart Transplantation:A Two-dimensional Ultrasound Study

The function of the transplanted heart will be affected by acute allograft rejection, chronic rejection, high blood pressure and so on, which may induce the reconstruction of the left ventricle and the increase of left ventricular mass （LVM）, and eventually lead to left ventricular hypertrophy that will significantly affect the prognosis of heart transplantation （HT）. The purpose of this study was to dy- namically monitor the changes of left ventricular geometric patterns after HT using two-dimensional echocardiography and to understand the remodeling process and its possible influencing factors. The left ventricular internal diameter, interventricular septal wall thickness, posterior wall thickness at end dias- tole were measured and the relative wall thickness （RWT）, left ventricular mass, left ventricular mass index were calculated respectively in 34 HT patients and 34 healthy volunteers by two-dimensional echocardiography. The type of left ventricular geometry was identified based on the echocardiographic determination of LVM index （LVMI） and RWT. The HT patients were divided into three groups ac- cording to the time length after surgery： A （3 months postoperatively）, B （6 months postoperatively） and C （12 months postoperatively）. We compared the parameters of left ventricle between HT group and normal control group, and explored the risk factors causing the increase of LVM. The results showed that 4 patients （16%） in group A had concentric remodeling. Nine patients （34.62%） in group B had re- construction, including 5 cases of concentric remodeling, 2 cases of concentric hypertrophy and 2 cases of eccentric hypertrophy. The hypertrophy incidence rate was 15.4% in group B. 15 patients （62.5%） had reconstruction in group C, including 9 cases of concentric remodeling, 5 cases of concentric hyper- trophy, and 1 case of eccentric hypertrophy. The prevalence of hypertrophy was 25%. Multivariate analysis showed that hypertension and acute rejection history were the risk factors that resulted in left ventricular hypertrophy. It is concluded that the left ventricular remodeling occurs following cardiac transplantation at an early stage and the incidence of left ventricular hypertrophy increases with survival time. In this study, the one-year prevalence of left ventricular hypertrophy was 25% after surgery. Hy- pertension and acute rejection history are risk factors that can predict the left ventricular hypertrophy.

IN PATIENTS WITH HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY AND CORONARY HEART DISEASE,CORONARY FLOW RESERVE IS SIMILARLY IMPAIRED

Coronary blood flow reserve (CFR) was assessed by transesophageal Doppler echocardiography in normal subjects (group A. n=20),hypertensive non-left ventricular hypertrophy (non-LVH)Patients (group B,n=22). hypertensive patients with LVH(group C.n=32)and coronary heart disease patients (group D. n=33) with the volume sample placed at the bifurcation of the left main and left main and left descending coronary artery. Coronary blood flow velocity (CBFV)was evaluated at rest.2 minutes after dipyridamole (0. 56mg/kg. i. v.) . and 2 minutes after aminophylline i.v. The ratio of dipyridamole to rest maximal diastolic velocity (D/R PDV) was considered the index of coronary blood flow reserve.It was found that D/R PDV was significantly less in groups C and D compared with that in groups A and B (D PDC,1.84±0. 57. 1. 57±0. 41 versus 2.59±0.70 and 2.22+0.58,respectively),with no difference in D/R PDV between groups C and D.Twenty-four out of 32 patients in group C with D/R PDV were less than 2.0 compared to 29 out of 33 patients in group D (P>0.05).Significant negative correlation was found between D/R PDV. D/R PSV and interseptal thickness. left ventricular mass index in hypertensive patients.These data show that impaired CFR in hypertensive patients with LVH is comparable to that in patients with coronary heart disease.

Evolvement of left ventricular assist device： the implications on heart failure management

Heart failure （HF） is a potentially fatal disease that affects increasing number of people worldwide. Although heart transplant is the ＂gold standard＂ therapy for HF, due to the limited availability of organs, many patients died when waiting for the transplant. Left ventricular assist device （LVAD）, as a mechanical circulatory support, has become a new light for patients with HF. With the technical advancements, LVADs work not only as a bridge to transplant, but also assist heart recovery and even as a destination therapy in long-term treatment. This observation paper reviewed the development of LVAD and its clinical roles. The challenges and possible solutions in nursing care for pa- tients with LVAD at different stage of implantation were discussed. The healthcare professionals could obtain a better understanding about the LVAD treatment for HF patients.

EFFECTIVE INVERSION OF LEFT HEART REMODELING BY PHENYLALANINE IN ESSENTIAL HYPERTENSION

Objective The aim is to ascertain whether phenylalanine (Phe) can inverse the left heart"remodeling" in patients with essential hypertension. Methods The changes of echocardiographic variables werecompared aler 3,6 and 9 months of observation between the Phe intervention group (Phe 1g/d+amiloride complex1 tablet/d, 20 cases) and control group (placebo 1g/d+amiloride complex 1 tablet/d, 20 cases) with eitherinterventricular septum and (or) post- wall thickness≥12mm, and were carried on further to compare incross- over trial. Results (1) Phe improved elfectively the left heart and systolic dyslunction; while theimprovement, also shown in control group due to the concurrent use of diuretic antihypertensive drug-amiloridecomplex, was much less evident than that in Phe group. (2) The disturbed left heart structure and systolic functionwere improved prominently while placebo was crossed over to Phe, and the improvement decreased afer Phe wascrrossed over to placebo. (3) The changes almost attained to its peak level after 6 months and not improved furtherat 9 months. (4) The differences seen between above 2 groops could not be eoplained by their diverse drops of bloodpressure. Conclusion Phe does exert an indopendent inverse effect on cardiac "remodeling", which mightimplicate an important clinical oplication upon the prevention and control of essential hypertension and itscomplications.

Optimal timing of same-admission orthotopic heart transplantation after left ventricular assist device implantation

AIM To investigate the impact of timing of same-admission orthotopic heart transplant(OHT) after left ventricular assist device(LVAD) implantation on in-hospital mortality and post-transplant length of stay.METHODS Using data from the Nationwide Inpatient Sample from 1998 to 2011, we identified patients 18 years of age or older who underwent implantation of a LVAD and for whom the procedure date was available. We calculated in-hospital mortality for those patients who underwent OHT during the same admission as a function of time from LVAD to OHT, adjusting for age, sex, race, household income, and number of comorbid diagnoses. Finally, we analyzed the effect of time to OHT after LVAD implantation on the length of hospital stay post-transplant.RESULTS Two thousand and two hundred patients underwent implantation of a LVAD in this cohort. One hundred and sixty-four(7.5%) patients also underwent OHT duringthe same admission, which occurred on average 32 d(IQR 7.75-66 d) after LVAD implantation. Of patients who underwent OHT, patients who underwent transplantation within 7 d of LVAD implantation("early") experienced increased in-hospital mortality(26.8% vs 12.2%, P = 0.0483) compared to patients who underwent transplant after 8 d("late"). There was no statistically significant difference in age, sex, race, household income, or number of comorbid diagnoses between the early and late groups. Post-transplant length of stay after LVAD implantation was also not significantly different between patients who underwent early vs late OHT. CONCLUSION In this cohort of patients who received LVADs, the rate of in-hospital mortality after OHT was lower for patients who underwent late OHT(at least 8 d after LVAD implantation) compared to patients who underwent early OHT. Delayed timing of OHT after LVAD implantation did not correlate with longer hospital stays post-transplant.

Animal models of pulmonary hypertension due to left heart disease

Pulmonary hypertension due to left heart disease(PH-LHD) is regarded as the most prevalent form of pulmonary hypertension(PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with left heart disease(LHD). Clinically, there are no drugs or treatments that directly address PH-LHD, and treatment of LHD alone will not also ameliorate PH. To target the underlying physiopathological alterations of PH-LHD and to develop novel therapeutic approaches for this population, animal models that simulate the pathophysiology of PH-LHD are required. There are several available models for PH-LHD that have been successfully employed in rodents or large animals by artificially provoking an elevated pressure load on the left heart, which by transduction elicits an escalated pressure in pulmonary artery. In addition, metabolic derangement combined with aortic banding or vascular endothelial growth factor receptor antagonist is also currently applied to reproduce the phenotype of PH-LHD. As of today, none of the animal models exactly recapitulates the condition of patients with PH-LHD. Nevertheless, the selection of an appropriate animal model is essential in basic and translational studies of PH-LHD. Therefore, this review will summarize the characteristics of each PH-LHD animal model and discuss the advantages and limitations of the different models.