Renin blockade: a double-edged sword?

Aliskiren, a direct renin inhibitor, blocks the first step of the renin–angiotensin–aldosterone system (RAAS), thereby reducing plasma renin activity and the circulating levels of angiotensin I, angiotensin II, and aldosterone. Extensive RAAS blockade can be achieved through the administration of aliskiren; however, renin blockade is a double-edged sword because the renin/prorenin receptor-associated pathway is also reportedly modulated by direct renin inhibitor. This research highlight discusses the findings of a recent clinical study of aliskiren and explores the complex interactions of key molecules in the RAAS pathway in response to aliskiren administration

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Renin blockade: a double-edged sword?

Aliskiren, a direct renin inhibitor, blocks the first step of the renin–angiotensin–aldosterone system (RAAS), thereby reducing plasma renin activity and the circulating levels of angiotensin I, angiotensin II, and aldosterone. Extensive RAAS blockade can be achieved through the administration of aliskiren; however, renin blockade is a double-edged sword because the renin/prorenin receptor-associated pathway is also reportedly modulated by direct renin inhibitor. This research highlight discusses the findings of a recent clinical study of aliskiren and explores the complex interactions of key molecules in the RAAS pathway in response to aliskiren administration

Is Exercise Training Appropriate for Patients With Advanced Heart Failure Receiving Continuous Inotropic Infusion? A Review

Exercise-based rehabilitation programs have been reported to have beneficial effects for patients with heart failure. However, there is little evidence about whether this is the case in patients with more severe heart failure. In particular, there is a question in the clinical setting whether patients with advanced heart failure and continuous inotropic infusion should be prescribed exercise training. In contrast, many studies conclude that prolonged immobility associated with heart failure profoundly impairs physical function and promotes muscle wasting that could further hasten the course of heart failure. By contrast, exercise training has various effects not only in improving exercise capacity but also on vascular function, skeletal muscle, and autonomic balance. In this review, we summarize the effectiveness and discuss methods of exercise training in patients with advanced heart failure receiving continuous inotropic agents such as dobutamine

Surgical Interventions for Late Aortic Valve Regurgitation Associated with Continuous Flow-Left Ventricular Assist Device Therapy: Experience Gained and Lessons Learned

This study aimed to investigate the outcomes of surgical interventions for symptomatic moderate-to-severe aortic regurgitation (AR), including aortic valve replacement (AVR) and repair (AVP), in 184 patients who underwent continuous flow-left ventricular assist device (Cf-LVAD) implantation as a bridge-to-transplant (BTT) between November 2007 and April 2020. Ten patients (median age, 34 (25–41) years; 60% men) underwent surgical interventions (AVR, n = 6; AVP, n = 4) late after cf-LVAD implantation. The median duration after the device implantation was 34 (24–44) months. Three patients required additional tricuspid valve repair. Aortic valve suturing resulted in severe recurrent AR 6 months postoperatively, due to leaflet cutting in one patient. Seven patients with AVR survived without regurgitation during the study period, except for one non-survivor complicated by liver failure due to postoperative right heart failure. Therefore, six patients after AVP (n = 4) and AVR (n = 2) underwent successful heart transplantation 7 (4–13) months after aortic intervention. Kaplan–Meier analysis showed no significant difference in overall survival through 5 years after cf-LVAD implantation, regardless of the surgical AV intervention chosen (log-rank test, p = 0.86). In conclusion, surgical interventions (AVR or AVP) for patients with an ongoing cf-LVAD are safe, effective, and viable options

The Efficacy of Lactulose for the Treatment of Hyperammonemic Encephalopathy Due to Severe Heart Failure

Hyperammonemic encephalopathy secondary to heart failure is rare and there had been little reports about effective treatment. Organ hypoperfusion or congestion by heart failure may lead to various organ dysfunctions, and liver and intestinal circulatory impairment might cause ammonia metabolic failure. Here, we report on the case of a patient with hyperammonemic encephalopathy that was secondary to heart failure, which was effectively treated by lactulose

Myocardial recovery evaluation from ventricular assist device in patients with dilated cardiomyopathy

Abstract Aims The removal of left ventricular assist device (LVAD) after myocardial recovery can provide survival benefits with freedom from LVAD‐associated complications. However, in the absence of standardization, the weaning evaluation and surgical strategy differ widely among centres. Therefore, we analysed the experiences of LVAD explantation with our protocol in dilated cardiomyopathy (DCM) patients and investigated the validity of our weaning evaluation and surgical strategy from the perspective of optimal long‐term survival. Methods and results All LVAD explantation patients in our institution between May 2012 and May 2020 were enrolled. All patients were evaluated by our three‐phase weaning assessment: (i) clinical stability with improved cardiac function under LVAD support; (ii) haemodynamic stability shown by ramp‐loading and saline‐loading test; (iii) intraoperative pump‐off test. Explant surgery involved removal of the whole system including driveline, pump, sewing ring and outflow‐graft, and closure of an apical hole. Intra‐operative, peri‐operative, and post‐operative outcomes, including all‐cause mortality and LVAD associated major complications, were retrospectively analysed. A total of 12 DCM patients (DuraHeart, n = 2; EVAHEART, n = 2; HeartMate II, n = 6; HeartMate 3, n = 2) had myocardial recovery after a median 10 months [interquartile range (IQR); 6.3–15 months] support and qualified for our LVAD explantation study protocol [median age: 37 y, IQR; 34–41 years; 83% men]. The median left ventricular ejection fraction was 20% (IQR; 12–23%) at LVAD‐implantation and 54% (IQR: 45–55%) before LVAD explantation (P < 0.001). There were no perioperative complications and median ICU stay was 4 days (IQR; 2–4 days). All patients were discharged after a median of 24 days (IQR: 17–28 days) postoperatively. No patient suffered from any cardiac event (heart failure hospitalization, re‐implantation of LVAD, or heart transplantation) at a median of 40 months (IQR: 17–58 months) follow up. All patients are alive with NYHA functional class 1 with preserved left ventricular function. Conclusions The evaluation of LVAD explant candidates by our weaning protocol was safe and effective. In the patients completing our protocol successfully, LVAD explantation is feasible and an excellent long‐term cardiac event free‐survival seems to be achieved

Influence of atrial fibrillation on oxygen uptake and exercise tolerance in cardiovascular patients; close association with heart rate response

To investigate the effect of atrial fibrillation (AF) on the oxygen uptake and exercise tolerance, we evaluated cardiopulmonary exercise test (CPET) data in AF patients and heart rate-matched controls with sinus rhythm (cSR) who received ambulatory cardiac rehabilitation. We compared CPET data between AF (N = 27) and cSR patients (N = 106) who had similar HRs at rest and the peak points. Oxygen uptake (VO2)/kg and relative O2 pulse (ml/bpm/kg) at rest and the anaerobic threshold (AT) level was not different between AF and cSR patients, but these parameters above the AT level were significantly lower in AF than in cSR patients. Concisely the parallel increase of relative O2 pulse during exercise was blunted above the respiratory compensation level (Rc) in the AF group. In addition, the HR change during exercise was inversely correlated with the increase of the O2 pulse above the AT level and this inverse correlation was more prominent in AF patients than in cSR patients. In conclusion, the value of VO2 was significantly lower above the AT level in AF patients. The trend of O2 pulse above the AT level was strongly associated with the detrimental response of HR increase and the response was markedly exaggerated in the AF patients. Keywords: Atrial fibrillation, Oxygen uptake, O2 pulse, Heart rate response, Hemodynamic tren