SGLT2-inhibitors effects on the coronary fibrous cap thickness and MACEs in diabetic patients with inducible myocardial ischemia and multi vessels non-obstructive coronary artery stenosis

Background: Sodium-glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids' plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up. Methods: In a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis. Results: At 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p < 0.05). SGLT2-I users vs. Non-SGLT2-I users, as evaluated by OCT, evidenced the highest values of minimum FCT, and lowest values of lipid arc degree and macrophage grade (p < 0.05). At the follow-up end, SGLT2-I users vs. Non-SGLT2-I users had a lower rate of MACEs [n 12 (10.8%) vs. n 57 (22.1%); p < 0.05]. Finally, Hb1Ac values (1.930, [CI 95%: 1.149-2.176]), macrophage grade (1.188, [CI 95%: 1.073-1.315]), and SGLT2-I therapy (0.342, [CI 95%: 0.180-0.651]) were independent predictors of MACEs at 1 year of follow-up. Conclusions: SGLT2-I therapy may reduce about 65% the risk to have MACEs at 1 year of follow-up, via ameliorative effects on glucose homeostasis, and by the reduction of systemic inflammatory burden, and local effects on the atherosclerotic plaque inflammation, lipids' deposit, and FCT in Mv-NOCS patients with T2DM

Cardiac syncope recurrence in type 2 diabetes mellitus patients vs. normoglycemics patients: The CARVAS study

Study hypothesis: Cardiac autonomic dysfunction might lead to higher vaso vagal syncope (VVS) recurrence rate in type 2 diabetes mellitus (T2DM) patients vs. non diabetics patients. Background: VVS recurrence might be due to alterations of autonomic system function, as assessed by heart rate variability (HRV). To date, in this study we investigated the correlation between HRV alterations and VVS recurrence at 12 months of follow up in T2DM vs. non T2DM patients. Materials and methods: In a prospective multicenter study we studied a propensity score matching (PSM) analysis of 121 T2DM vs. 121 non T2DM patients affected by VVS. Results: T2DM vs. non T2DM patients had at baseline a higher rate of HRV dysfunction, and this was linked to higher rate of VVS recurrence at 12 months of follow up (p < 0.05). Blood pressure alterations and lower LF/HF ratio were linked to higher rate of all cause syncope recurrence, and of vasodepressor, cardio inhibitory, and mixed syncope recurrence (p < 0.05). Anti hypertensive drug therapies increased the number of vasodepressor and mixed syncope events (p < 0.05); alterations of heart rate increased syncope recurrence and mixed syncope recurrence events (p < 0.05). Finally, T2DM was linked to higher rate of VVS recurrence, and specifically of vasodepressor and mixed VVS recurrence (p < 0.05). Conclusions: T2DM patients have alterations of the autonomic nervous system, as result of cardiac autonomic neuropathy. However, T2DM diagnosis and autonomic dysfunction assessed by HRV alterations predicted VVS recurrence.Study hypothesis: Cardiac autonomic dysfunction might lead to higher vaso vagal syncope (VVS) recurrence rate in type 2 diabetes mellitus (T2DM) patients vs. non diabetics patients. Background: VVS recurrence might be due to alterations of autonomic system function, as assessed by heart rate variability (HRV). To date, in this study we investigated the correlation between HRV alterations and VVS recurrence at 12 months of follow up in T2DM vs. non T2DM patients. Materials and methods: In a prospective multicenter study we studied a propensity score matching (PSM) analysis of 121 T2DM vs. 121 non T2DM patients affected by VVS. Results: T2DM vs. non T2DM patients had at baseline a higher rate of HRV dysfunction, and this was linked to higher rate of VVS recurrence at 12 months of follow up (p < 0.05). Blood pressure alterations and lower LF/HF ratio were linked to higher rate of all cause syncope recurrence, and of vasodepressor, cardio inhibitory, and mixed syncope recurrence (p < 0.05). Anti hypertensive drug therapies increased the number of vasodepressor and mixed syncope events (p < 0.05); alterations of heart rate increased syncope recurrence and mixed syncope recurrence events (p < 0.05). Finally, T2DM was linked to higher rate of VVS recurrence, and specifically of vasodepressor and mixed VVS recurrence (p < 0.05). Conclusions: T2DM patients have alterations of the autonomic nervous system, as result of cardiac autonomic neuropathy. However, T2DM diagnosis and autonomic dysfunction assessed by HRV alterations predicted VVS recurrence

Cardiac resynchronization therapy and its effects in patients with type 2 DIAbetes mellitus OPTimized in automatic vs. echo guided approach. Data from the DIA-OPTA investigators

Objectives: To evaluate the effects of cardiac resynchronization therapy (CRTd) in patients with type 2 diabetes mellitus (T2DM) optimized via automatic vs. echocardiography-guided approach. Background: The suboptimal atrio-ventricular (AV) and inter-ventricular (VV) delays optimization reduces CRTd response. Therefore, we hypothesized that automatic CRTd optimization might improve clinical outcomes in T2DM patients. Methods: We designed a prospective, multicenter study to recruit, from October 2016 to June 2019, 191 consecutive failing heart patients with T2DM, and candidate to receive a CRTd. Study outcomes were CRTd responders rate, hospitalizations for heart failure (HF) worsening, cardiac deaths and all cause of deaths in T2DM patients treated with CRTd and randomly optimized via automatic (n 93) vs. echocardiography-guided (n 98) approach at 12 months of follow-up. Results: We had a significant difference in the rate of CRTd responders (68 (73.1%) vs. 58 (59.2%), p 0.038), and hospitalizations for HF worsening (12 (16.1%) vs. 22 (22.4%), p 0.030) in automatic vs. echocardiography-guided group of patients. At multivariate Cox regression analysis, the automatic guided approach (3.636 [1.271\u201310.399], CI 95%, p 0.016) and baseline highest values of atrium pressure (automatic SonR values, 2.863 [1.537\u20136.231], CI 95%, p 0.006) predicted rate of CRTd responders. In automatic group, we had significant difference in SonR values comparing the rate of CRTd responders vs. non responders (1.24 \ub1 0.72 g vs. 0.58 \ub1 0.46 g (follow-up), p 0.001), the rate of hospitalizations for HF worsening events (0.48 \ub1 0.29 g vs. 1.18 \ub1 0.43 g, p 0.001), and the rate of cardiac deaths (1.13 \ub1 0.72 g vs. 0.65 \ub1 0.69 g, p 0.047). Conclusions: Automatic optimization increased CRTd responders rate, and reduced hospitalizations for HF worsening. Intriguingly, automatic CRTd and highest baseline values of SonR could be predictive of CRTd responders. Notably, there was a significant difference in SonR values for CRTd responders vs. non responders, and about hospitalizations for HF worsening and cardiac deaths. Clinical trial ClinicalTrials.gov Identifier NCT04547244

Care of Ebola Survivors and Factors Associated With Clinical Sequelae—Monrovia, Liberia

BackgroundThe Eternal Love Winning Africa (ELWA) Clinic was the first clinic to provide free, comprehensive care to Ebola virus disease (EVD) survivors in Liberia. The objectives of this analysis were to describe the demographics and symptoms of EVD survivors at ELWA from January 2015 through March 2017 and to identify risk factors for development of sequelae.MethodsPatients' demographic and clinical information was collected by chart review in June 2016 and March 2017. Associations with clinical sequelae were analyzed using the chi-square test, t test, and multivariate logistic regression.ResultsFrom January 2015 to March 2017, 329 EVD survivors were evaluated at ELWA. Most survivors experienced myalgia/arthralgia (73%; n = 239) and headache (53%; n = 173). The length of time from Ebola Treatment Unit (ETU) discharge to first clinic visit ranged from 0 to 30 months. Many visits (30%) occurred 24 or more months after ETU discharge. The proportion of visits for headache, weight loss, joint pain, visual problems, insomnia, fatigue, memory loss, decreased libido, depression, and uveitis decreased over time. More men than women had visits for depression; however, these differences were not significant. Symptom prevalence differed in adults and children; significantly more adults experienced myalgia/arthralgia (77% vs 44%), visual problems (41% vs 12%), post-EVD-related musculoskeletal pain (42% vs 15%), and insomnia (17% vs 2%).ConclusionsEVD survivors frequented ELWA for EVD-related symptoms many months after ETU discharge, indicating a long-term need for care. Reported symptoms changed over time, which may reflect eventual resolution of some sequelae

The secret life of the mitral valve

In secondary mitral regurgitation, the concept that the mitral valve (MV) is an innocent bystander, has been challenged by many studies in the last decades. The MV is a living structure with intrinsic plasticity that reacts to changes in stretch or in mechanical stress activating biohumoral mechanisms that have, as purpose, the adaptation of the valve to the new environment. If the adaptation is balanced, the leaflets increase both surface and length and the chordae tendineae lengthen: the result is a valve with different characteristics, but able to avoid or to limit the regurgitation. However, if the adaptation is unbalanced, the leaflets and the chords do not change their size, but become stiffer and rigid, with moderate or severe regurgitation. These changes are mediated mainly by a cytokine, the transforming growth factor-β (TGF-β), which is able to promote the changes that the MV needs to adapt to a new hemodynamic environment. In general, mild TGF-β activation facilitates leaflet growth, excessive TGF-β activation, as after myocardial infarction, results in profibrotic changes in the leaflets, with increased thickness and stiffness. The MV is then a plastic organism, that reacts to the external stimuli, trying to maintain its physiologic integrity. This review has the goal to unveil the secret life of the MV, to understand which stimuli can trigger its plasticity, and to explain why the equation “large heart = moderate/severe mitral regurgitation” and “small heart = no/mild mitral regurgitation” does not work into the clinical practice

Uveitis and Systemic Inflammatory Markers in Convalescent Phase of Ebola Virus Disease

We report a case of probable Zaire Ebola virus–related ophthalmologic complications in a physician from the United States who contracted Ebola virus disease in Liberia. Uveitis, immune activation, and nonspecific increase in antibody titers developed during convalescence. This case highlights immune phenomena that could complicate management of Ebola virus disease–related uveitis during convalescence

Monastic governance: forgotten prospects for public institutions

To overcome agency problems, public sector reforms started to introduce businesslike incentive structures to motivate public officials. By neglecting internal behavioral incentives, however, these reforms often do not reach their stated goals. Our research analyzes the governance structure of Benedictine monasteries in order to gain new insights into solving agency problems in public institutions. A comparison is useful because members of both organizational forms, public organizations and monasteries, see themselves as responsible participants in their community and claim to serve the public good. We study monastic governance from an economic perspective. Benedictine monasteries in Baden-Württemberg, Bavaria, and German-speaking Switzerland have an average lifetime of almost 500 years, and only a quarter of them broke up because of agency problems. We argue that they were able to survive for centuries due to an appropriate governance structure, relying strongly on the intrinsic motivation of the members and internal control mechanisms. This governance approach differs in several aspects from current public sector reforms. JEL Classification: D73, G3, Z12, H83 Keywords: Public Governance, New Public Management, Public Sector Reform, Psychological Economics, Agency Problems, Monasteries, Benedictine Orde