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.

Twin pregnancy with sudden heart failure and pulmonary hypertension after atrial septal defect repair: A case report

BACKGROUND Pulmonary arterial hypertension(PAH)in pregnancy is one of the major obstetric complications and is considered a contraindication to pregnancy as it is classified as a class IV risk in the revised risk classification of pregnancy by the World Health Organisation.Pregnancy,with its adaptive and expectant mechanical and hormonal changes,negatively affects the cardiopulmonary circulation in pregnant women.Do patients with repaired simple congenital heart disease(CHD)develop other pulmonary and cardiac complications during pregnancy?Can pregnant women with sudden pulmonary hypertension be treated and managed in time?In this paper,we present a case of a 39-year-old woman who underwent cesarean section at 33 wk'gestation and developed PAH secondary to repaired simple CHD.Our research began by a PubMed search for"pulmonary hypertension"and"pregnancy"and"CHD"case reports.Three cases were selected to review PAH in pregnancy after correction of CHD defects.These studies were reviewed,coupled with our own clinical experience.CASE SUMMARY Herein,a case involving a woman who underwent atrial septal defect repair at the age of 34,became pregnant five years later,and had a sudden onset of PAH and right heart failure secondary to symptoms of acute peripheral edema in the third trimester of her pregnancy.As a result,the patient underwent a cesarean section and gave birth to healthy twins.Within three days after cesarean delivery,her cardiac function deteriorated as the pulmonary artery pressure increased.Effec-tive postpartum management,including diuresis,significant oxygen uptake,vasodilators,capacity and anticoagulants management,led to improvements in cardiac function and oxygenation.The patient was discharged from hospital with a stable recovery and transferred to local hospitals for further PAH treatment.CONCLUSION This case served as a reminder to obstetricians of the importance of pregnancy after repair of CHD.It is crucial for patients with CHD to receive early correction.It suggests doctors should not ignore edema of twin pregnancy.Also,it provides a reference for the further standardization of antenatal,in-trapartum and postpartum management for patients with CHD worldwide.

Hemodynamic monitoring in heart failure and pulmonary hypertension: From analog tracings to the digital age

Hemodynamic monitoring has long formed the cornerstone of heart failure(HF) and pulmonary hypertension diagnosis and management. We review the long history of invasive hemodynamic monitors initially using pulmonary artery(PA) pressure catheters in the hospital setting, to evaluating the utility of a number of implantable devices that can allow for ambulatory determination of intracardiac pressures. Although the use of indwelling PA catheters has fallen out of favor in a number of settings, implantable devices have afforded clinicians an opportunity for objective determination of a patient's volume status and pulmonary pressures. Some devices, such as the CardioM EMS and thoracic impedance monitors present as part of implantable cardiac defibrillators, are supported by a body of evidence which show the potential to reduce HF related morbidity and have received regulatory approval, whereas other devices have failed to show benefit and, in some cases, harm. Clearly these devices can convey a considerable amount of information and clinicians should start to familiarize themselves with their use and expect further development and refinement in the future.

Treatment with neurohormonal inhibitors and prognostic outcome in pulmonary arterial hypertension with risk factors for left heart disease

BACKGROUND Despite major advances in pharmacologic treatment,patients with pulmonary arterial hypertension(PAH)still have a considerably reduced life expectancy.In this context,chronic hyperactivity of the neurohormonal axis has been shown to be detrimental in PAH,thus providing novel insights on the role of neurohormonal blockade as a potential therapeutic target.AIM To evaluate the application and prognostic effect of neurohormonal inhibitors(NEUi)in a single-center sample of patients with idiopathic PAH and risk factors for left heart disease.METHODS We analyzed data retrospectively collected from our register of right heart catheterizations performed consecutively from January 1,2005 to October 31,2018.Patients on beta-blocker,angiotensin-converting enzyme inhibitor,angiotensin receptor blocker or mineralocorticoid receptor antagonist at the time of right heart catheterization were classified as NEUi users and compared to NEUi nonrecipients.RESULTS Complete data were available for 57 PAH subjects:27 of those(47.4%)were taking at least one NEUi at the time of right heart catheterization and were compared with the remaining 36 NEUi non-recipients.NEUi users were older and had a higher cardiovascular risk profile compared to non-recipients.Additionally,NEUi non-users had a higher probability of dying during the course of follow-up than NEUi recipients(56.7%vs 25.9%,log-rank P=0.020).CONCLUSION The above data highlighted a subgroup of patients with PAH and comorbidities for left heart disease in which NEUi use has shown to be associated with improved survival.Future prospective studies are needed to identify the most appropriate therapeutic strategies in this subset population.

Cardiac evaluation of renal transplant candidates with heart failure

Patients with advanced kidney disease are at elevated risk of developing heart failure and appropriate risk stratification is important to permit them to receive kidney transplantation.The American Heart Association and American College of Cardiology joint statement provides guidance on risk stratification for the major cause of heart failure for these patients in its recommendations for coronary heart disease.Herein we provide an overview of the available literature on risk strati-fication for nonischemic heart failure and functional heart disease states such as pulmonary hypertension.Many of these options for optimizing these patients be-fore transplant include optimizing their volume status,often with more agg-ressive ultrafiltration.Kidney transplantation remains the treatment of choice for patients with advanced kidney disease and cardiac disease,the correction of the azotemic substances with kidney transplantation has been associated with imp-roved survival than remaining on dialysis long-term.The findings in the studies reviewed here are expected to help clinicians refine current strategies for evalua-ting potential kidney transplant recipients.

Ambulatory pulmonary artery pressure monitoring in advanced heart failure patients

Heart failure (HF) is an emerging epidemic associate with significant morbidity, mortality, and health care expenditure. Although there were major advances in pharmacologic and device based therapies for the management of HF, mortality of this condition remains high. Accurate monitoring of HF patients for exacerbations is very important to reduce recurrent hospitalizations and its associated complications. With the failure of clinical signs, tele-monitoring, and laboratory bio-markers to function as early markers of HF exacerbations, more sophisticated techniques were sought to accurately predict the circulatory status in HF patients in order to execute timely pharmacological intervention to reduce frequent hospitalizations. CardioMEMSTM (St. Jude Medical, Inc., Saint Paul, Minnesota) is an implantable, wireless pulmonary arterial pressure (PAP) monitoring system which transmits the patient’s continuous PAPs to the treating health care provider in the ambulatory setting. PAP-guided medical therapy modification has been shown to significantly reduce HF-related hospitalization and overall mortality. In advanced stages of HF, wireless access to hemodynamic information correlated with earlier left ventricular assist device implantation and shorter time to heart transplantation.

A Case of Pediatric Heart Failure Caused by Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery: Case Report and Literature Review

A female patient aged 3 months and 10 days was admitted to the cardiology department because of symptoms of heart failure.According to the echocardiography results,the patient received a diagnosis of primary endocardial fi broelastosis and was treated withγ-globulin,prednisone,digoxin,and diuretics.Coronary computed tomographic angiography and coronary angiography were performed as there was no improvement after 2 months of treatment.Finally,the patient received a diagnosis of anomalous origin of the left coronary artery from the pulmonary artery(ALCAPA).ALCAPA is a rare congenital heart defect that can cause severe heart failure during infancy,and is easily misdiagnosed clinically.In this report,we show the process of misdiagnosis of the case and consult the relevant literature,hoping to improve the understanding and early diagnosis of ALCAPA.

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.

Left atrial diameter and atrial fibrillation,but not elevated NT-proBNP,predict the development of pulmonary hypertension in patients with HFpEF

Background The determinants of pulmonary hypertension(PH)due to heart failure with preserved ejection fraction(HFpEF)have been poorly investigated in patients with cardiovascular diseases(CVD).Methods From July 12017 to March 312019,a total of 149 consecutive HFp EF patients hospitalized with CVD were enrolled in this prospective cross-sectional study.A systolic pulmonary artery pressure(PASP)>35 mm Hg estimated by echocardiography was defined as PH-HFp EF.Logistic regression was performed to establish predictors of PH in HFpEF patients.Results Overall,the mean age of participants was 72±11 years,and 74(49.7%)patients were females.A total of 59(39.6%)patients were diagnosed with PH-HFpEF by echocardiography.The left atrial diameter(LAD)was related to the ratio of the transmitral flow velocities/mitral annulus tissue velocities in early diastole(E/E’)and the left ventricular diameter in systole(LVDs).N-Terminal pro B-type natriuretic peptide(NT-proBNP)was not found to be associated with LAD and impaired diastolic or systolic function of the left ventricle.Multivariable logistic regression showed that atrial fibrillation(AF)increased the risk of PH-HFpEF incidence 3.46-fold with a 95%confidence interval(CI)of 1.44–8.32,P=0.005.Meanwhile,LAD≥45 mm resulted in a 3.43-fold increased risk,95%CI:1.51–7.75,P=0.003.However,the significance levels of NT-proBNP,age and LVEF were underpowered in the regression model.Two variables,AF and LAD≥45 mm,predicted the PH-HFpEF incidence(C-statistic=0.773,95%CI:0.695–0.852,P<0.001).Conclusions Two parameters associated with electrical and anatomical remodelling of the left atrium were related to the incidence of PH in HFpEF patients with CVD.

Why there is a need to discuss pulmonary hypertension other than pulmonary arterial hypertension?

Pulmonary hypertension(PH) is a condition characterized by the elevation of the mean pulmonary artery pressure above 25 mm Hg and the pulmonary vascular resistance above 3 wood units. Pulmonary arterial hypertension(PAH) is an uncommon conditionwith severe morbidity and mortality, needing early recognition and appropriate and specific treatment. PH is frequently associated with hypoxemia, mainly chronic obstructive pulmonary disease and DPLD and/or left heart diseases(LHD), mainly heart failure with reduced or preserved ejection fraction. Although in the majority of patients with PH the cause is not PAH, a significant number of published studies are still in regard to group Ⅰ PH, leading to a logical assumption that PH due to other causes is not such an important issue. So, is there a reason to discuss PH other than PAH? Chronic lung diseases, mainly chronic obstructive lung disease and DPLD, are associated with a high incidence of PH which is linked to exercise limitations and a worse prognosis. Although pathophysiological studies suggest that specific PAH therapy may benefit such patients, the results presented from small studies in regard to the safety and effectiveness of the specific PAH therapy are discouraging. PH is a common complication of left heart disease and is related to disease severity, especially in patients with reduced ejection fraction. There are two types of PH related to LHD based on diastolic pressure difference(DPD, defined as diastolic pulmonary artery pressure- mean PAWP): Isolated post-capillary PH, defined as PAWP > 15 mm Hg and DPD < 7 mm Hg, and combined post-capillary PH and pre-capillary PH, defined as PAWP > 15 mm Hg and DPD ≥ 7 mm Hg. The potential use of PAH therapies in patients with PH related to left heart disease is based on a logical pathobiological rationale. In patients with heart failure, endothelial dysfunction has been proposed as a cause of PH and hence as a target for treatment, supported by the presence of increased endothelin-1 activity and impaired nitric oxide-dependent vasodilation. Unfortunately, so far, there is no evidence supporting the use of specific PAH therapies in patients with PH related to left heart disease. In conclusion, the presence of PH in patients with conditions other than PAH contributes to the severity of the disease, affecting the outcome and quality of life. The disappointing results regarding the effectiveness of specific PAH therapies in patients withchronic lung diseases and LHD underline the need for seeking new underlying mechanisms and thus novel therapies targeting PH due to left heart disease and/or lung diseases.

Correlation analysis between lung ultrasound scores and pulmonary arterial systolic pressure in patients with acute heart failure admitted to the emergency intensive care unit

Background:No convenient,inexpensive,and non-invasive screening tools exist to identify pulmonary hypertension(PH)-left heart disease(LHD)patients during the early stages of the disease course.This study investigated whether different methods of lung ultrasound(LUS)could be used for the initial investigation of PH-LHD.Methods:This was a single-center prospective observational study which was performed in the Zigong Fourth People’s Hospital.We consecutively enrolled patients with heart failure(HF)admitted to the emergency intensive care unit from January 2018 to May 2020.Transthoracic echocardiography and LUS were performed within 24 h before discharge.We used the Spearman coefficient for correlation analysis between ultrasound scores and pulmonary arterial systolic pressure(PASP).Bland-Altman plots were generated to inspect possible bias,and receiver operating characteristic(ROC)curves were calculated to assess the relationship between ultrasound scores and an intermediate and high echocardiographic probability of PH-LHD.Results:Seventy-one patients were enrolled in this study,with an overall median age of 79(interquartile range:71.5–84.0)years.Among the 71 patients,36(50.7%)cases were male,and 26(36.6%)had an intermediate and high echocardiographic probability of PH.All four LUS scores in patients with an intermediate and high probability of PH were significantly higher than in patients with a low probability of PH(P<0.05).The correlation coefficient(r)between different LUS scoring methods and PASP was moderate for the 6-zone(r=0.455,P<0.001),8-zone(r=0.385,P=0.001),12-zone(r=0.587,P<0.001),and 28-zone(r=0.535,P<0.001)methods.In Bland-Altman plots,each of the four LUS scoring methods had a good agreement with PASP(P<0.001).The 8-zone and 12-zone methods showed moderately accurate discriminative values in differentiating patients with an intermediate and high echocardiographic probability of PH(P<0.05).

Long-term Efficacy of Pulmonary Artery Desnervation Treatment in Heart Failure With Preserved Ejection Fraction:A Subgroup Analysis of 3-year Results From the PADN-5 Study

Objective:The Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure(PADN-5)study proved that pulmonary artery denervation(PADN)is associated with significant improvements in hemodynamic and clinical outcomes in patients with combined pre-and post-capillary pulmonary hypertension(CpcPH).This study aimed to assess the 3-year clinical results of PADN in patients who had heart failure with preserved ejection fraction(HFpEF)developing into CpcPH(HFpEF-CpcPH).Methods:In this post hoc analysis of the PADN-5 trial,38 patients with HFpEF were included in screening out of 98 patients with CpcPH who were randomly assigned to treatment with sildenafil and sham PADN(sham PADN(plus sildenafil)group,abbreviated as sham group)or PADN(PADN group).HFpEF in the PADN-5 trial was defined as a left ventricular ejection fraction≥50%,and CpcPH was defined as a mean pulmonary arterial pressure≥25 mmHg,a pulmonary arterial wedge pressure>15 mmHg,and a pulmonary vascular resistance>3.0 WU.The changes in the 6-minute walk distance(6-MWD)and the plasma concentration of N-terminal pro-brain natriuretic peptide(NT-proBNP)at 6-month and 3-year follow-up,as well as the clinical endpoint of the occurrence of clinical worsening,defined as cardiopulmonary-related death,rehospitalization,or heart or lung transplantation at 3-year follow-up were examined.Results:Thirty-eight patients with HFpEF-CpcPH were assigned to the PADN group(n=19)or the sham group(n=19).At the 6-month follow-up,6-MWD(433(275,580)m vs.342(161,552)m),and reductions in NT-proBNP(−47%(−99%,331%)vs.−12%(−82%,54%))were significantly improved in the PADN group(all P<0.05).Over the 3-year follow-up period,PADN treatment resulted in marked increases in 6-MWD(450(186,510)m vs.348(135,435)m)and reductions in NT-proBNP(−55%(−99%,38%)vs.−10%(−80%,95%))(all P<0.05).Clinical worsening was experienced by 12 patients(63%)in the sham group,but by only 5 patients(26%)in the PADN group(hazard ratio=0.149,95%confidence interval:0.038–0.584,P=0.006).The 6-MWD and PADN treatments were independent predictors of clinical deterioration in patients with HFpEF-CpcPH.Conclusions:PADN therapy is associated with improvements in exercise capacity and clinical outcomes.PADN therapy may have a potential role in patients with HFpEF-CpcPH for whom current treatment options are limited.

Establishment of adult right ventricle failure in ovine using a graded, animal-specific pulmonary artery constriction model

Background: Right ventricle failure(RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients. Currently, the mechanisms of RVF are not fully understood and it is partly due to the lack of large animal models in adult RVF. In this study, we aim to establish a model of RVF in adult ovine and examine the structure and function relations in the RV.Methods: RV pressure overload was induced in adult male sheep by revised pulmonary artery constriction(PAC). Briefly, an adjustable hydraulic occluder was placed around the main pulmonary artery trunk. Then, repeated saline injection was performed at weeks 0, 1, and 4, where the amount of saline was determined in an animal-specific manner. Healthy, age-matched male sheep were used as additional controls. Echocardiography was performed bi-weekly and on week 11 post-PAC, hemodynamic and biological measurements were obtained.Results: This PAC methodology resulted in a marked increase in RV systolic pressure and decreases in stroke volume and tricuspid annular plane systolic excursion, indicating signs of RVF. Significant increases in RV chamber size, wall thickness, and Fulton's index were observed. Cardiomyocyte hypertrophy and collagen accumulation(particularly type III collagen) were evident, and these structural changes were correlated with RV dysfunction.Conclusion: In summary, the animal-specific, repeated PAC provided a robust approach to induce adult RVF, and this ovine model will offer a useful tool to study the progression and treatment of adult RVF that is translatable to human diseases.

基于中和医派以丹参注射液治疗肺动脉高压所致右心衰竭临床观察

目的 研究中和派思想指导下,以丹参注射液治疗肺动脉高压所致右心衰竭的临床效果。方法 收集2021年1月—2022年2月九江市第一人民医院收治的肺动脉高压伴右心衰竭患者111例,按随机数字表法分为3组,分别为对照组、西药组和联合组,每组37例;对照组采用临床常规治疗方案,西药组在对照组的基础上加用托伐普坦,联合组在西药组基础上加用丹参注射液,3组均治疗28 d,观察临床疗效及血清N末端B型利钠肽原(NT-proBNP)、β2微球蛋白(β2-MG)水平。结果联合组总有效率为94.59%(35/37)、西药组总有效率为89.19%(33/37),均显著高于对照组的78.38%(29/37)(P<0.05)。与治疗前比较,3组中医临床症状体征积分均明显降低,且治疗后联合组中医临床症状体征积分低于西药组及对照组(P<0.05)。与治疗前比较,3组患者NT-proBNP、β2-MG水平均明显降低(P<0.05),且联合组NT-proBNP、β2-MG水平明显低于西药组及对照组(P<0.05)。结论 丹参注射液联合托伐普坦治疗肺动脉高压伴右心衰竭,能够显著提高临床效果、改善临床症状、降低患者血清NT-proBNP、β2-MG水平,值得临床应用。

Prevalence, risk factors, and survival associated with pulmonary hypertension and heart failure among patients with underlying coronary artery disease: a national prospective, multicenter registry study in China

Background: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH.Methods: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded.Results: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF];left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF];LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH.Conclusions: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients.Trial Registration: ClinicalTrials.gov, NCT02164526.

新型无植入心房分流导管单中心安全性及有效性研究

目的初步评估基于射频切割的新型无植入心房分流导管用于治疗慢性心力衰竭(心衰)的安全性和有效性。方法本研究为前瞻性单组研究。2023年1—12月于首都医科大学附属北京安贞医院连续入选5例符合标准的心衰患者,采用深圳佰特威心房分流导管行心房分流术。术前及术后即刻行右心导管测量肺毛细血管楔压(PCWP)、右心房压(RAP)、肺动脉压(PAP)、全肺阻力(TPR)、肺血管阻力(PVR)及肺/体循环血流量比(Qp/Qs);术后对患者进行90 d随访,完善超声心动图、右心导管检查及心脏功能学评价指标。研究主要终点为手术成功;次要终点包括术后90 d临床成功、超声心动图变化、6 min步行距离(6MWD)变化、纽约心脏病协会(NYHA)心功能分级变化、堪萨斯城心肌病问卷调查(KCCQ)评分变化及N末端B型脑钠肽前体(NT-proBNP)水平变化。安全性终点为术后90 d主要不良心脑血管事件及器械相关不良事件。结果5例患者均成功实现左心房向右心房分流。与术前相比,5例患者术后即刻PCWP均明显下降,手术成功率100%,术前和术后即刻RAP、PAP、TPR和PVR无明显变化。随访90 d后,4例患者存在持续的左心房向右心房分流,且PCWP较基线明显减低,临床成功率80%。与术前相比,5例患者术后90 d左心室射血分数均有所升高,左心室舒张末期容积均有所降低,三尖瓣瓣环收缩期位移、右心室面积变化分数无明显受损;KCCQ评分、6MWD均有所提高,NT-proBNP水平均有所下降,NYHA心功能分级无明显变化。随访期内无死亡,无心衰再住院,无脑卒中相关不良事件,无器械相关不良事件。结论新型无植入心房分流导管可安全有效地改善心衰患者血流动力学、超声心动图及心脏功能学评价指标,未来仍需更大规模的临床研究验证其临床长期有效性。

心房分流术研究进展及启示

虽然心力衰竭(心衰)的药物和器械治疗均取得了较大进步,但心衰患者整体仍预后较差。心衰的血流动力学异常表现为左心房压升高和肺淤血,既往研究表明降低左心房压可改善心衰患者的症状和预后,因此左心系统超负荷可能是心衰治疗的一个潜在靶点。心房分流术旨在制造一定程度稳定可控的左向右心内分流,将心衰患者失代偿的左心容量和压力负荷恢复至代偿状态,从而改善心衰症状及预后,目前全球范围内仍处于临床研究阶段,已有数据表明心房分流术可降低心衰患者静息或运动时左心房压,改善肺淤血,提高患者活动耐量和临床心功能,但尚无研究证实其可以改善心衰再入院和死亡等临床终点事件。未来的研究重点在于筛选能从心房分流术中获益的心衰患者,明确心衰病因、右心功能和肺血管阻力可逆性的评估以及依据射血分数的心衰分型可能是筛选患者的关键因素。

心房分流术应用于射血分数降低的心力衰竭患者的探索性研究

目的:探索心房分流术对射血分数降低的心力衰竭(HFrEF)患者心功能和临床预后的影响。方法:本研究为前瞻性单组研究,连续入选2021年12月至2022年12月在首都医科大学附属北京安贞医院采用D-Shant心房分流器行心房分流术的15例HFrEF患者。术前及术后即刻行右心导管测量肺毛细血管楔压(PCWP)、右心房平均压(RAP)、跨房间隔梯度压差、肺动脉平均压、全肺阻力(TPR)、肺血管阻力(PVR)、心脏指数(CI)及肺循环血流量/体循环血流量(Qp/Qs);术后对患者进行12个月随访,采用超声心动图评估患者心脏结构和功能变化,采用NYHA心功能分级、6分钟步行距离(6MWD)、堪萨斯城心肌病问卷(KCCQ)评分评估患者心功能,收集患者全因死亡、心力衰竭再住院以及器械相关不良事件等信息。结果:所有患者均成功接受心房分流术。与术前相比,术后即刻患者的PCWP、跨房间隔梯度压差、TPR均显著下降,Qp/Qs显著升高(P均<0.01),肺动脉平均压、RAP、PVR和CI的差异均无统计学意义(P均>005)。术后即刻与术后12个月的心房分流器分流孔径、分流速度及分流压差差异均无统计学意义(P均>0.05)。与术前相比,术后12个月患者的左心室射血分数显著升高,NYHA心功能分级改善,KCCQ评分增高,6MWD>450 m的患者例数增加,N末端B型利钠肽原水平显著下降(P均<0.05),右心房内径、右心室面积变化率的差异均无统计学意义(P均>005)。12个月随访期内无患者死亡,无器械相关不良事件,2例患者因心力衰竭再住院。结论:小样本探索性研究表明心房分流术可有效改善HFrEF患者的血液动力学指标,随访12个月时患者心功能明显改善。

心脏磁共振组织特征追踪技术评估左心衰合并肺高压的临床价值

目的基于心脏磁共振特征追踪(cardiac magnetic resonance feature tracking,CMR-FT)技术定量分析左心衰合并肺高压(pulmonary hypertension due to left heart failure,PH-LHF)患者的心肌应变参数并探讨心脏磁共振(cardiac magnetic resonance,CMR)在评估PH-LHF患者中的应用价值。材料与方法回顾性分析2018年9月至2020年9月期间215例确诊为左心衰(left heart failure,LHF)患者的临床和CMR参数,根据心脏超声测量的收缩期肺动脉压将患者分为两组,即LHF组(n=129)和PH-LHF组(n=86)。比较两组的基线资料和CMR参数包括心血管形态参数、心室容积功能参数以及心室心房应变参数。通过单因素及多因素logistic回归分析CMR参数中PH-LHF的独立预测因子,并绘制受试者工作特征(receiver operating characteristics,ROC)曲线评估CMR参数的诊断价值。结果PH-LHF患者组左右心室舒张末期容积指数、收缩末期容积指数、右心室心肌质量指数、室间隔角、左心房最大直径及面积、初始T1值均高于LHF组,而左右心室射血分数、右心室每搏输出量指数、右心室心脏指数低于LHF组。PH-LHF组左心室整体纵向应变、整体周向应变以及应变率、右心室整体周向应变、左心房主动应变、被动应变、总应变均不同程度下降。多因素logistic回归分析显示CMR参数中右心室射血分数,左心室整体周向应变,左心房主动应变和左心房最大直径是PH-LHF的独立预测因子。ROC曲线分析结果显示临床模型、CMR模型、联合模型诊断PH-LHF的AUC值分别为0.773、0.777、0.828,并且DeLong检验显示当加入CMR参数后,临床模型诊断效能提升(0.773 vs.0.828,P<0.05)。结论基于CMR-FT技术的心肌应变参数可以定量评估心室心房应变,反映PH-LHF患者的心肌功能以及运动情况,多参数CMR在诊断评估LHF是否合并PH中具有较好的临床增益价值。

右心室功能不全患者β-羟丁酸代谢特征及与临床指标的相关性分析

目的 探讨右心室功能不全(RVD)患者β-羟丁酸(β-OHB)代谢特征及与临床指标的相关性。方法 选择2021年10月至2023年10月在该院心血管内科治疗的38例RVD患者纳入病例组。对照组按照年龄、性别、心血管危险因素等进行匹配,最终纳入47例研究对象。根据RVD患者疾病类型将其分为致心律失常性右室心肌病(ARVC)组和肺动脉高压(PAH)组2个亚组。检测并对比所有研究对象的血浆N末端-B型脑钠肽前体(NT-proBNP)及β-OHB水平。采用Pearson相关分析RVD患者β-OHB水平与其他指标的相关性。结果 病例组、对照组在年龄、性别、体质量指数、吸烟,以及合并高血压、高脂血症、糖尿病患者比例等方面比较,差异均无统计学意义(P>0.05);与对照组比较,病例组血浆NT-proBNP和β-OHB水平明显升高(P<0.05)。ARVC组患者的血浆NT-proBNP[(2 126.1±708.9)pg/mL]和β-OHB[(142.4±55.9)μmol/L]水平高于PAH组患者[(688.4±317.7)pg/mL、(30.6±13.8)μmol/L],差异均有统计学意义(P<0.05)。Pearson相关分析显示,血浆β-OHB水平与NT-proBNP(r=0.734,P<0.001)和右心室舒张末期直径(r=0.445,P=0.005)呈正相关,与肺动脉压呈负相关(r=-0.423,P=0.008)。结论 RVD患者血浆β-OHB水平明显升高,尤其是ARVC患者高于单纯PAH患者,提示病理性的右室心肌病患者发生了显著的β-OHB水平改变。