Left ventricular diastolic function in relation to the urinary proteome: A proof-of-concept study in a general population

Background

In previous studies, we identified two urinary proteomic classifiers, termed HF1 and HF2, which discriminated subclinical diastolic left ventricular (LV) dysfunction from normal. HF1 and HF2 combine information from 85 and 671 urinary peptides, mainly up- or down-regulated collagen fragments. We sought to validate these classifiers in a population study.

Methods

In 745 people randomly recruited from a Flemish population (49.8 years; 51.3% women), we measured early and late diastolic peak velocities of mitral inflow (E and A) and mitral annular velocities (e' and a') by conventional and tissue Doppler echocardiography, and the urinary proteome by capillary electrophoresis coupled with mass spectrometry.

Results

In the analyses adjusted for sex, age, body mass index, blood pressure, heart rate, LV mass index and intake of medications, we expressed effect sizes per 1-SD increment in the classifiers. HF1 was associated with 0.204 cm/s lower e' peak velocity (95% confidence interval, 0.057–0.351; p = 0.007) and 0.145 higher E/e' ratio (0.023–0.268; p = 0.020), while HF2 was associated with a 0.174 higher E/e' ratio (0.046–0.302; p = 0.008). According to published definitions, 67 (9.0%) participants had impaired LV relaxation and 96 (12.9%) had elevated LV filling pressure. The odds of impaired relaxation associated with HF1 was 1.38 (1.01–1.88; p = 0.043) and that of increased LV filling pressure associated with HF2 was 1.38 (1.00–1.90; p = 0.052).

Conclusions

In a general population, the urinary proteome correlated with diastolic LV dysfunction, proving its utility for early diagnosis of this condition.     

Sinoatrial node electrical activity modulates pulmonary vein arrhythmogenesis

Background

Sinoatrial node (SAN) dysfunction increases the occurrences of atrial fibrillation (AF). The pulmonary veins (PVs) play a critical role in the pathophysiology of AF. The purpose of this study was to evaluate whether SAN electrical activity can modulate PV arrhythmogenesis.

Methods

Conventional microelectrodes and multi-electrode array system were used to simultaneously record the electrical activity and conduction properties of rabbit SAN and PV tissue preparations with and without SAN–PV interruptions before and after perfusion with Anemonia sulcata toxin (ATX)-II (100 nM) or isoproterenol (1 μM).

Results

ATX-II significantly increased PV beating rates, which overdrove SAN electrical activity with the occurrences of PV burst firings in 5 (56%) of 9 tissue preparations, and induced SAN–PV conduction block in 6 (67%) of 9 preparations. After SAN–PV disconnection, ATX-II induced burst firing and early afterdepolarizations in 8 (89%) of 9 PVs. Moreover, the multi-electrode array found that ATX-II reversed the electrical conduction between the SAN and PV with an increase in electrical activity from 1.8 ± 0.6 to 2.9 ± 0.6 Hz (P < 0.05) in SAN–PV preparations (n = 7). In contrast, isoproterenol did not reverse electrical conduction between the SAN and PV with an increase in electrical activity from 1.8 ± 0.2 to 3.0 ± 0.3 Hz (P < 0.005) in SAN–PV preparations (n = 7).

Conclusions

SAN electrical activity modulates PV arrhythmogenesis. SAN–PV conduction blocks can increase PV arrhythmogenesis.     

N-acylhydrazone derivative ameliorates monocrotaline-induced pulmonary hypertension through the modulation of adenosine AA2R activity

Background

Pulmonary arterial hypertension (PAH) is a disease that results in right ventricular (RV) dysfunction. While pulmonary vascular disease is the primary pathological focus, RV hypertrophy and RV dysfunction are the major determinants of prognosis in PAH. The aim of this study was to investigate the effects of (E)-N′-(3,4-dimethoxybenzylidene)-4-methoxybenzohydrazide (LASSBio-1386), an N-acylhydrazone derivative, on the lung vasculature and RV dysfunction induced by experimental PAH.

Methods

Male Wistar rats were injected with a single dose (60 mg/kg, i.p.) of monocrotaline (MCT) and given LASSBio-1386 (50 mg/kg, p.o.) or vehicle for 14 days. The hemodynamic, exercise capacity (EC), endothelial nitric oxide synthase (eNOS), adenosine A_2A receptor (A_2AR), sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a), phospholamban (PLB) expression, Ca^2 +-ATPase activity and vascular activity of LASSBio-1386 were evaluated.

Results and conclusions

The RV systolic pressure was elevated in the PAH model and reduced from 49.6 ± 5.0 mm Hg (MCT group) to 27.2 ± 2.1 mm Hg (MCT + LASSBio-1386 group; P < 0.05). MCT administration also impaired the EC, increased the RV and pulmonary arteriole size, and promoted endothelial dysfunction of the pulmonary artery rings. In the PAH group, the eNOS, A_2AR, SERCA2a, and PLB levels were changed compared with the control; in addition, the Ca^2 +-ATPase activity was reduced. These alterations were related with MCT-injected rats, and LASSBio-1386 had favorable effects that prevented the development of PAH. LASSBio-1386 is effective at preventing endothelial and RV dysfunction in PAH, a finding that may have important implications for ongoing clinical evaluation of A_2AR agonists for the treatment of PAH.     

Blood biomarkers and their potential role in pulmonary arterial hypertension associated with congenital heart disease. A systematic review

Background

The development of pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) is multifactorial with a number of biomarkers serving as mediators of neurohormonal activation [B-type natriuretic peptide (BNP) and its N-terminal-pro-fragment (NT-proBNP)], endothelial dysfunction [asymmetric dimethylarginine (ADMA)] and cellular proliferation [vascular endothelial growth factor (VEGF)].

Methods

We systematically reviewed the literature for trials studying the role of these biomarkers in the clinical evaluation, prognosis and management of patients with PAH related to CHD (CHD–PAH).

Results

Twenty-six studies were included in the systematic review, involving a total of 1113 patients with CHD–PAH. These patients had higher BNP, NT-proBNP and ADMA levels and higher VEGF expression when compared with healthy controls. Baseline and serial values of plasma levels of natriuretic peptides were shown to be significant predictors of survival. ADMA concentration was elevated in patients with CHD–PAH when compared with patients with simple CHD without PAH, whereas VEGF expression was particularly high in patients with CHD and persistent PAH after corrective surgery of the underlying heart disease.

Conclusion

Right heart dysfunction, endothelial inflammation and proliferation are mirrored by plasma levels of the corresponding biomarkers among patients with CHD–PAH. There is early evidence to suggest that natriuretic peptides, in particular, may be a simple and effective tool for determining prognosis and timing for therapeutic interventions in patients with CHD–PAH.     

奥氮平联合奥拉西坦治疗老年精神分裂患者认知功能障碍的对照研究

目的 探讨奥氮平联用奥拉西坦对老年精神分裂症患者认知功能障碍的改善作用。方法 随机选取2017年8月-2018年3月新乡医学院第二附属医院收治的老年精神分裂症伴认知功能障碍的患者60例进行前瞻性研究,随机分为单用奥氮平治疗组（单用组）,奥氮平联合奥拉西坦治疗组（联用组）,每组30例。分别于实验前,治疗后4,8周对2组患者采用阳性和阴性症状量表（positive and negative syndrome scale,PANSS）进行病情严重程度评价,采用韦斯数字广度测验（digital span test,DS）、威斯康星卡片分类测试（Wisconsin card sorting tes,WCST）进行认知功能评价;并于4周末上午空腹抽血,监测肝功和血脂变化。同时招募30名60~75岁健康受试者为正常组,进行上述评价。结果 单用组和联用组PANSS各项评分,治疗4周较治疗前降低（P<0.05）、治疗8周较治疗4周降低（P<0.05）。单用组和联用组的DS和WCST各项评分治疗4周较治疗前均有明显改善（P<0.05）,且联用组DS的正背项和总分、WCST的正确应答数明显高于单用组（P<0.05）;2组的DS各项评分治疗8周较治疗4周均有明显改善（P<0.05）,且联用组较单用组改善明显（P<0.05）,WCST中正确应答数、错误应答数和完成分类数有明显改善（P<0.05）,且联用组较单用组改善明显（P<0.05）。4周末2组ALT、AST、TC和TG均较治疗前升高（P<0.05）,但2组间无显著差异（P>0.05）。结论 奥氮平联合奥拉西坦可有效改善老年精神分裂症患者的认知功能障碍,且疗效优于单用奥氮平。     

Prolonged impact of home versus clinic-based management of chronic heart failure: Extended follow-up of a pragmatic,multicentre randomized trial cohort

Objectives

We compared the longer-term impact of the two most commonly applied forms of post-discharge management designed to minimize recurrent hospitalization and prolong survival in typically older patients with chronic heart failure (CHF).

Methods

We followed a multi-center randomized controlled trial cohort of Australian patients hospitalized with CHF and initially allocated to home-based or specialized CHF clinic-based intervention for 1368 ± 216 days. Blinded endpoints included event-free survival from all-cause emergency hospitalization or death, all-cause mortality and rate of all-cause hospitalization and stay.

Results

280 patients (73% male, aged 71 ± 14 years and 73% left ventricular systolic dysfunction) were initially randomized to home-based (n = 143) or clinic-based (n = 137) intervention. During extended follow-up (complete for 274 patients), 1139 all-cause hospitalizations (7477 days of hospital stay) and 121 (43.2%) deaths occurred. There was no difference in the primary endpoint; 20 (14.0%) home-based versus 13 (7.4%) clinic-based patients remained event-free (adjusted HR 0.89, 95% CI 0.70 to 1.15; p = 0.378). Significantly fewer home-based (51/143, 35.7%) than clinic-based intervention (71/137, 51.8%) patients died (adjusted HR 0.62, 95% CI 0.42 to 0.90: p = 0.012). Home-based versus clinic-based intervention patients accumulated 592 and 547 all-cause hospitalizations (p = 0.087) associated with 3067 (median 4.0, IQR 2.0 to 6.8) versus 4410 (6.0, IQR 3.0 to 12.0) days of hospital stay (p < 0.01 for rate and duration of hospital stay).

Conclusions

Relative to clinic-based intervention, home-based intervention was not associated with prolonged event-free survival. Home-based intervention was, however, associated with significantly fewer all-cause deaths and significantly fewer days of hospital stay in the longer-term.

Trial registration

Australian New Zealand Clinical Trials Registry number 12607000069459 (http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81803)     

Heart Failure in Remission for More than 13 Years after Removal of a Left Ventricular Assist Device

Mechanical cardiac unloading with use of a left ventricular assist device (LVAD) is associated with substantial improvements in left ventricular function and enables subsequent LVAD explantation in some patients. We describe the case of a 35-year-old man with dilated nonischemic cardiomyopathy who was supported with an LVAD for 9 months. After the device was removed, he led a normal life for 13 years and 4 months. However, at 49 years of age, he presented with new signs and symptoms of heart failure, necessitating implantation of a 2nd LVAD. Afterwards, he has remained asymptomatic. This case is unique in that the patient lived a normal life for longer than a decade before renewed left ventricular decompensation necessitated repeat LVAD therapy. Histologic examination revealed few changes between the first device''s removal in 1999 and the 2nd device''s implantation in 2012.     

Emergent Surgical Pulmonary Embolectomy in a Pregnant Woman: Case Report and Literature Review

Acute pulmonary embolism is a leading cause of death during pregnancy and delivery in the United States. We describe the case of a 25-year-old woman who presented in car-diogenic shock in week 38 of her first pregnancy. After the emergent cesarean delivery of a healthy male neonate, the mother underwent immediate surgical pulmonary embolec-tomy. We confirmed the diagnosis of pulmonary embolism intraoperatively by means of transesophageal echocardiography and removed large clots from the patient''s pulmonary arteries. Mother and child were doing well, 27 months later. In addition to presenting our patient''s case, we discuss the other relevant reports and the options for treating massive pulmonary embolism during pregnancy.     

Coronary Artery Manifestations of Fibromuscular Dysplasia

Fibromuscular dysplasia (FMD) involving the coronary arteries is an uncommon but important condition that can present as acute coronary syndrome, left ventricular dysfunction, or potentially sudden cardiac death. Although the classic angiographic “string of beads” that may be observed in renal artery FMD does not occur in coronary arteries, potential manifestations include spontaneous coronary artery dissection, distal tapering or long, smooth narrowing that may represent dissection, intramural hematoma, spasm, or tortuosity. Importantly, FMD must be identified in at least one other noncoronary arterial territory to attribute any coronary findings to FMD. Although there is limited evidence to guide treatment, many lesions heal spontaneously; thus, a conservative approach is generally preferred. The etiology is poorly understood, but there are ongoing efforts to better characterize FMD and define its genetic and molecular basis. This report reviews the clinical course of FMD involving the coronary arteries and provides guidance for diagnosis and treatment strategies.