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Studies on the history of sexual violence against women are well known (Kalra & Bhugra 2013; O'Toole et al., 2007; Terry & Hoare 2007), but not a lot of attention has been paid to the history of women who were treated in psychiatric hospitals for the consequences of sexual trauma. Most experts considered the history of sexual abuse of women from the perspective of victims who had not been institutionalized within health care institutions. However there have been few scientific publications that have dealt with the history of female psychiatric patients (Seferovic 2019; Tasca et al. 2012). In order to expand the existing knowledge of this subcategory of the female population and thereby create history teaching material elaborating the causes and consequences of sexual violence they experienced, it is important to encourage archival research into their psychiatric medical records. The goal of introducing this sensitive and controversial topic into history teaching is to make secondary school students aware of the cultural conditioning of sexual violence against women throughout history, and to sensitize them to the consequences of these traumatic experiences for their psychosocial functioning. This article describes the research Jelena Seferovic has done examining the medical records of female patients who were treated at the Royal Institute for the Mentally Ill, the first psychiatric hospital in Croatia during the late nineteenth and early twentieth centuries.

Background: To analyze the characteristics and prognosis of a contemporary cohort of patients with myocardial infarction with non-obstructed coronaries (MINOCA) were referred for cardiac magnetic resonance (CMR) imaging, focusing on late gadolinium enhancement (LGE) patterns. Methods: We retrospectively examined and prospectively followed up with 135 patients (49 ± 21 years old, 48% female) undergoing CMR imaging due to a MINOCA diagnosis from 2014 to 2016. We grouped and analyzed the sample according to ischemic (focal or transmural) and non-ischemic LGE patterns. The primary outcome was cardiac-related death; the secondary outcome was a composite of cardiac-related rehospitalizations, the new occurrence of acute myocardial infarction (AMI), heart failure (HF), or arrhythmias. Results: CMR exams were performed after a median of 28 days from the acute event. One-third of the ischemic MINOCA were first managed as myocarditis, while CMR helped to adopt a different therapy regimen in 22% of patients (30/135). After a median follow-up of 2.3 years, more cardiac-related deaths occurred in the ischemic than non-ischemic group (2 vs. 1, p = 0.36), but it was not statistically significant. The ischemic group also experienced more cardiac-related-rehospitalizations (42%, p < 0.001). In a multivariable Cox regression model, dyslipidemia, reduced left ventricular ejection fraction, ST-elevation at the hospitalization, and the LGE transmural pattern were the independent predictors of cardiac-related rehospitalizations. Conclusions: In a contemporary cohort of MINOCA patients who underwent CMR, ischemic and non-ischemic patterns had distinct features and outcomes. Among the MINOCA patients, CMR can identify patients at higher risk who require more aggressive therapeutic approached and strict follow-up. [ABSTRACT FROM AUTHOR]

Importance: Heart failure with preserved ejection fraction (HFpEF) is often characterized by nitric oxide deficiency.Objective: To evaluate the efficacy and adverse effects of praliciguat, an oral soluble guanylate cyclase stimulator, in patients with HFpEF.Design, Setting, and Participants: CAPACITY HFpEF was a randomized, double-blind, placebo-controlled, phase 2 trial. Fifty-nine sites enrolled 196 patients with heart failure and an ejection fraction of at least 40%, impaired peak rate of oxygen consumption (peak V̇o2), and at least 2 conditions associated with nitric oxide deficiency (diabetes, hypertension, obesity, or advanced age). The trial randomized patients to 1 of 3 praliciguat dose groups or a placebo group, but was refocused early to a comparison of the 40-mg praliciguat dose vs placebo. Participants were enrolled from November 15, 2017, to April 30, 2019, with final follow-up on August 19, 2019.Interventions: Patients were randomized to receive 12 weeks of treatment with 40 mg of praliciguat daily (n = 91) or placebo (n = 90).Main Outcomes and Measures: The primary efficacy end point was the change from baseline in peak V̇o2 in patients who completed at least 8 weeks of assigned dosing. Secondary end points included the change from baseline in 6-minute walk test distance and in ventilatory efficiency (ventilation/carbon dioxide production slope). The primary adverse event end point was the incidence of treatment-emergent adverse events (TEAEs).Results: Among 181 patients (mean [SD] age, 70 [9] years; 75 [41%] women), 155 (86%) completed the trial. In the placebo (n = 78) and praliciguat (n = 65) groups, changes in peak V̇o2 were 0.04 mL/kg/min (95% CI, -0.49 to 0.56) and -0.26 mL/kg/min (95% CI, -0.83 to 0.31), respectively; the placebo-adjusted least-squares between-group difference in mean change from baseline was -0.30 mL/kg/min ([95% CI, -0.95 to 0.35]; P = .37). None of the 3 prespecified secondary end points were statistically significant. In the placebo and praliciguat groups, changes in 6-minute walk test distance were 58.1 m (95% CI, 26.1-90.1) and 41.4 m (95% CI, 8.2-74.5), respectively; the placebo-adjusted least-squares between-group difference in mean change from baseline was -16.7 m (95% CI, -47.4 to 13.9). In the placebo and praliciguat groups, the placebo-adjusted least-squares between-group difference in mean change in ventilation/carbon dioxide production slope was -0.3 (95% CI, -1.6 to 1.0). There were more dizziness (9.9% vs 1.1%), hypotension (8.8% vs 0%), and headache (11% vs 6.7%) TEAEs with praliciguat compared with placebo. The frequency of serious TEAEs was similar between the groups (10% in the praliciguat group and 11% in the placebo group).Conclusions and Relevance: Among patients with HFpEF, the soluble guanylate cyclase stimulator praliciguat, compared with placebo, did not significantly improve peak V̇o2 from baseline to week 12. These findings do not support the use of praliciguat in patients with HFpEF.Trial Registration: ClinicalTrials.gov Identifier: NCT03254485. [ABSTRACT FROM AUTHOR]

In the review, Santos-Ferreira et al. [[1]] discuss different aspects of the association between two frequent comorbidities, type 2 diabetes (T2D) and heart failure (HF). The first trial of patients with prevalent HF found that the risk of worsening HF or death from CV causes was lower in those who received dapagliflozin compared to placebo, regardless of the presence of T2D. [Extracted from the article]

Background: This is the first randomised controlled trial to assess the impact of unsupervised high-intensity interval training on cardiovascular autonomic function in adults with type 2 diabetes. Methods: A total of 22 individuals with type 2 diabetes (age 60 ± 2 years, 17 males) lay in a supine position for 20 min for evaluation of cardiovascular autonomic function, which included (1) time domain measures of heart rate variability, (2) frequency domain measures of heart rate variability and blood pressure variability and (3) baroreflex receptor sensitivity. Participants were randomised into 12 weeks of high-intensity interval training (3 sessions/week) or standard care control group. Results: After 12 weeks, the between-group change in HbA1c (%) was significant (high-intensity interval training: 7.13 ± 0.31 to 6.87 ± 0.29 vs Control: 7.18 ± 0.17 to 7.36 ± 0.21, p = 0.03). There were no significant changes in measures of heart rate variability; R-R interval (ms) (high-intensity interval training: 954 ± 49 to 973 ± 53 vs Control: 920 ± 6 to 930 ± 32, p = 0.672), low frequency/high frequency (high-intensity interval training: 0.90 ± 0.21 to 0.73 ± 0.07 vs Control: 1.20 ± 0.29 to 1.00 ± 0.17, p = 0.203), or blood pressure variability; systolic blood pressure low frequency/high frequency (high-intensity interval training: 0.86 ± 0.21 to 0.73 ± 0.10 vs Control: 1.06 ± 0.26 to 0.91 ± 0.14, p = 0.169). At baseline, HbA1c was negatively correlated with baroreflex receptor sensitivity (r = –0.592, p < 0.01). Conclusion: High-intensity interval training improves glycaemic control but has limited effect on cardiovascular autonomic regulation in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction. We investigated the association of diabetic retinopathy and neuropathy with increased risk of recurrent cardiovascular (CV) events in 6068 patients with type 2 diabetes mellitus (T2DM) and recent acute coronary syndrome (ACS) enrolled in the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA). Methods. History of retinopathy and neuropathy as well as duration of T2DM were self-reported at screening. Proportional hazards regression models were used to assess relationships between retinopathy, neuropathy, and recurrent CV events. Results. At screening, retinopathy and neuropathy were reported in 10.7% and 17.5% of patients, respectively, while 5.7% reported both. When adjusted for randomized treatment only, both retinopathy and neuropathy were associated with a primary composite outcome (CV death, nonfatal MI, stroke, or hospitalization for unstable angina) (retinopathy: HR 1.44, 95% CI 1.19–1.75; neuropathy: HR 1.33, 95% CI 1.12–1.57), CV composite (CV death, nonfatal MI, stroke, hospitalization for heart failure (HF)) (retinopathy: HR 1.57, 95% CI 1.31–1.88; neuropathy: HR 1.38, 95% CI 1.19–1.62), myocardial infarction (retinopathy: HR 1.38, 95% CI 1.08–1.76; neuropathy: HR 1.26, 95% CI 1.02–1.54), HF hospitalization (retinopathy: HR 2.03, 95% CI 1.48–2.78; neuropathy: HR 1.71, 95% CI 1.30–2.27), and all-cause mortality (retinopathy: HR 1.65, 95% CI 1.28–2.12; neuropathy: HR 1.43, 95% CI 1.14–1.78). When included in the same model, and adjusted for T2DM duration, there were no independent associations of either with CV outcomes, while T2DM duration remained strongly associated with all outcomes. Addition of demographic characteristics and CV risk factors did not further alter these relationships. Conclusions. In patients with T2DM and recent ACS, a history of retinopathy and/or neuropathy and longer T2DM duration could be considered clinical markers for high risk of recurrent CV events. This trial is registered with the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome), ClinicalTrials.gov registration number NCT01147250. [ABSTRACT FROM AUTHOR]

Background: The risk stratification of patients with diabetes mellitus (DM) is a major objective for the clinicians, and it can be achieved by coronary flow velocity reserve (CFVR) or with coronary artery calcium score (CS). CS evaluates underlying coronary atherosclerotic plaque burden and CFVR estimates both presence of coronary artery stenosis and microvascular function. Consequently, CFVR may provide unique risk information beyond the extent of coronary atherosclerosis. Aim: Our aim is to assess joint prognostic value of CFVR and CS in asymptomatic DM patients. Materials and methods: We prospectively included 200 asymptomatic patients (45,5 % male, mean age 57,35 ± 11,25), out of which, there were 101 asymptomatic patients with DM and 99 asymptomatic patients without DM, but with one or more conventionally risk factors for coronary artery disease. We analyzed clinical, biochemical, metabolic, inflammatory parameters, CS by Agatston method, transthoracic Doppler echocardiography CFVR of left anterior descending artery and echocardiographic parameters. Results: Total CS and CS LAD were significantly higher, while mean CFVR was lower in diabetics compared to the nondiabetics. During 1 year follow-up, 24 patients experienced cardio-vascular events (one cardiovascular death, two strokes, three myocardial infarctions, nine new onsets of unstable angina and nine myocardial revascularizations): 19 patients with DM and five non DM patients, (p = 0,003). Overall event free survival was significantly higher in non DM group, compared to the DM group (94,9 % vs. 81,2 %, p = 0,002 respectively), while the patients with CS ≥200 and CFVR <2 had the worst outcome during 1 year follow up in the whole study population as well as in the DM group. At multivariable analysis CFVR on LAD (HR 12.918, 95 % CI 3.865-43.177, p < 0.001) and total CS (HR 13.393, 95 % CI 1.675-107.119, p = 0.014) were independent prognostic predictors of adverse events in DM group of patients. Conclusion: Both CS and CFVR provide independent and complementary prognostic information in asymptomatic DM patients. When two parameters are analyzed together, the risk stratification ability improves, even when DM patients are analyzed together with non DM patients. As a result, DM patients with CS ≥200 and CFVR <2 had the worst outcome. Consequently, the use of two tests identified subset of patients who can derive the most benefit from the intensive prevention measures. [ABSTRACT FROM AUTHOR]

We analyzed (a) insulin sensitivity (IS), (b) plasma insulin (PI), and (c) plasminogen activator inhibitor-1 (PAI-1) in type 2 diabetes (T2D) patients with (group A) and without (group B) atherothrombotic ischemic stroke (ATIS), nondiabetics with ATIS (group C), and healthy controls (group D). IS was determined by minimal model (Si). Si was lower in A versus B (1.18±0.67 versus 2.82±0.61 min−1/mU/L × 104; P<0.001) and in C versus D (3.18±0.93 versus 6.13±1.69 min−1/mU/L × 104; P<0.001). PI and PAI-1 were higher in A versus B (PI: 19.61±4.08 versus 14.91±1.66 mU/L; P<0.001, PAI-1: 7.75±1.04 versus 4.57±0.72 mU/L; P<0.001) and in C versus D (PI: 15.14±2.20 versus 7.58±2.05 mU/L; P<0.001, PAI-1: 4.78±0.98 versus 3.49±1.04 mU/L; P<0.001). Si correlated with PAI-1 in T2D patients and nondiabetics, albeit stronger in T2D. Binary logistic regression identified insulin, PAI-1, and Si as independent predictors for ATIS in T2D patients and nondiabetics. The results imply that insulin resistance and fasting hyperinsulinemia might exert their atherogenic impact through the impaired fibrinolysis. [ABSTRACT FROM AUTHOR]

We analyzed the level of (a) CXCR3+ (Th1) and CCR4+ (Th2) T memory cells (b) interferon-γ inducible chemokine (IP-10)(Th1) and thymus and activation-regulated chemokine (TARC)(Th2), in 51 first degree relatives (FDRs) of type 1 diabetics (T1D) (17 high risk FDRs (GADA+, IA-2+) and 34 low risk FDRs (GADA-, IA-2-)), 24 recent-onset T1D (R-T1D), and 18 healthy subjects. T memory subsets were analyzed by using four-color immunofluorescence staining and flowcytometry. IP-10 and TARC were determined by ELISA. High risk FDRs showed higher levels of CXCR3+ and lower level of CCR4+ T memory cells compared to low risk FDRs (64.98 ± 5.19 versus 42.13 ± 11.11; 29.46 ± 2.83 versus 41.90 ± 8.58%, resp., P < 0.001). Simultaneously, both IP-10 and TARC levels were increased in high risk versus low risk FDRs (160.12 ± 73.40 versus 105.39 ± 71.30; 438.83 ± 120.62 versus 312.04 ± 151.14 pg/mL, P < 0.05). Binary logistic regression analysis identified the level of CXCR3+ T memory cells as predictors for high risk FDRs, together with high levels of IP-10. The results imply that, in FDRs, the risk for T1D might be strongly influenced by enhanced activity of Th1 and diminished activity of Th2 autoimmune response. [ABSTRACT FROM AUTHOR]

We analyzed (a) insulin sensitivity (IS) and (b) glutathione peroxidase (GSH-Px), glutathione reductase (GR), and superoxide dismutase (SOD) antioxidant enzyme activity in type 2 diabetic (T2D) patients with atherothrombotic infarction (ATI) (group A), lacunar infarction (LI) (B), or without stroke (C) and in nondiabetics with ATI (D), LI (E), or without stroke (F). ATI and LI were confirmed by brain imaging IS levels were determined by minimal model (Si index), and the enzyme activity by spectrophotometry. In T2D patients, Si was lower in A and B versus C (1.14 ± 0.58, 1.00 ± 0.26 versus 3.14 ± 0.62 min-1/mU/lx104, P < 0.001) and in nondiabetics in D and E versus F (3.38 ± 0.77, 3.03 ± 0.72 versus 6.03 ± 1.69 min-1/mU/lx104, P < 0.001). Also, GSH-Px and GR activities were lower in A and B versus C (GSH-Px: 21.96 ± 3.56, 22.51 ± 1.23 versus 25.12 ± 1.67; GR: 44.37 ± 3.58, 43.50 ± 2.39 versus 48.58 ± 3.67 U/gHb; P < 0.001) and in D and E versus F (GSH-Px: 24.75 ± 3.02, 25.57 ± 1.92 versus 28.56 ± 3.91; GR: 48.27 ± 6.81, 49.17 ± 6.24 versus 53.67 ± 3.96 U/gHb; P < 0.001). Decreases in Si and GR were significantly related to both ATI and LI in T2D. Our results showed that decreased IS and impaired antioxidant enzymes activity influence ischemic stroke subtypes in T2D. The influence of insulin resistance might be exerted on the level of glutathione-dependent antioxidant enzymes. [ABSTRACT FROM AUTHOR]

Background: Impaired nitric oxide (NO) signaling has been implicated in the progression of diabetic kidney disease (DKD). Praliciguat (PRL) is a soluble guanylate cyclase stimulator that augments NO signaling in vitro and reduces proteinuria and fasting plasma glucose in the ZSF1 rat model of DKD. Methods: We evaluated the safety and efficacy of PRL in adults (25-75 y) with type 2 diabetes, eGFR 30-75 mL/min/1.73 m2, urine albumin creatinine ratio (UACR) 200-5000 mg/g, hemoglobin A1c (HbA1c) <12%, systolic blood pressure (BP) 110-160 mmHg, on stable glucose-lowering and renin angiotensin system-inhibition therapy. Participants were randomized 1:1:1 to placebo (PBO), PRL 20 mg, or PRL 40 mg daily for 12 weeks. Two first morning void specimens for UACR were collected at baseline and weeks 1, 4, 8, 12. Adverse events, 24 h BP and serum chemistry were also assessed. The primary efficacy endpoint was change from baseline (CFB) in UACR to weeks 8 and 12 analyzed by mixed-effect repeated measures model to compare pooled PRL vs. PBO. Results: A total of 156 participants enrolled and 140 completed treatment. Model estimates of mean UACR CFB [90% CI] [intent-to-treat (ITT)] were -28% [-36, -18] for pooled PRL and -15% [-27, 0] for PBO; PBO-adjusted UACR CFB was -15% [-31, 4] (p=0.17). Quality checks identified a site with data inconsistent with that from the overall study population. In a post-hoc sensitivity analysis excluding this site, PBO-adjusted UACR CFB for PRL was -20% [-33, 5], nominal p=0.03. PBO-adjusted CFB for other variables at week 12 (ITT) were 24 h systolic BP -4.2 mmHg [-7.5, -0.8], 24 h heart rate 3.4 bpm [1.6, 5.2], HbA1c -0.27% [-0.50, 0.03], and cholesterol 10.1 mg/dL [-19.2, -1.0]. Both praliciguat doses were well tolerated. Conclusion: PRL did not significantly reduce UACR in the primary ITT analysis, but positive trends in UACR, BP, and metabolic variables warrant further clinical study of PRL in DKD. Disclosure: J.P. Hanrahan: Employee; Self; Cyclerion Therapeutics. I. de Boer: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Consultant; Self; George Clinical, Goldfinch Bio, Ironwood Pharmaceuticals. G. Bakris: Consultant; Self; Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship; Self; Bayer AG, Novo Nordisk Inc., Vascular Dynamics. P. Wilson: Employee; Self; Cyclerion Therapeutics. J.D. Wakefield: Stock/Shareholder; Self; Cyclerion Therapeutics. J.P. Seferovic: Employee; Self; Cyclerion Therapeutics. J. Chickering: None. M. Cressman: Employee; Self; Covance, LabCorp. M. Currie: Employee; Self; Cyclerion Therapeutics. Stock/Shareholder; Self; Cyclerion Therapeutics. G.T. Milne: None. A.T. Profy: Employee; Self; Cyclerion Therapeutics, Ironwood Pharmaceuticals. Employee; Spouse/Partner; UpToDate. Stock/Shareholder; Self; Cyclerion Therapeutics, Ironwood Pharmaceuticals. Funding: Cyclerion Therapeutics [ABSTRACT FROM AUTHOR]

Background and Objectives: Impaired nitric oxide signaling through soluble guanylate cyclase has been implicated in the pathophysiology of diabetic kidney disease. Praliciguat, a soluble guanylate cyclase stimulator that amplifies nitric oxide signaling, inhibited kidney inflammation and fibrosis in animal models., Design, Setting, Participants, & Measurements: In a phase 2 trial, 156 adults with type 2 diabetes, eGFR 30-75 ml/min per 1.73 m 2 , and urine albumin-creatinine ratio 200-5000 mg/g treated with renin-angiotensin system inhibitors were randomly allocated 1:1:1 to placebo, 20 mg praliciguat, or 40 mg praliciguat daily for 12 weeks. The primary efficacy and safety outcomes were change from baseline to weeks 8 and 12 in urine albumin-creatinine ratio and treatment-emergent adverse events, respectively. Other outcomes assessed were 24-hour ambulatory BP and metabolic parameters., Results: Of 156 participants randomized, 140 (90%) completed the study. The primary efficacy analysis demonstrated a mean change from baseline in urine albumin-creatinine ratio of -28% (90% confidence interval, -36 to -18) in the pooled praliciguat group and -15% (-28 to 0.4) in the placebo group (difference -15%; -31 to 4; P =0.17). Between-group decreases from baseline to week 12 for praliciguat versus placebo were seen in mean 24-hour systolic BP (-4 mm Hg; -8 to -1), hemoglobin A1c (-0.3%; -0.5 to -0.03), and serum cholesterol (-10 mg/dl; -19 to -1). The incidence of treatment-emergent adverse events was similar in the pooled praliciguat and placebo groups (42% and 44%, respectively). Serious adverse events, events leading to study drug discontinuation, and events potentially related to BP lowering were reported at higher frequency in the 40-mg group but were similar in 20-mg and placebo groups., Conclusions: Praliciguat treatment for 12 weeks did not significantly reduce albuminuria compared with placebo in the primary efficacy analysis. Nonetheless, the observed changes in urine albumin-creatinine ratio, BP, and metabolic variables may support further investigation of praliciguat in diabetic kidney disease., Clinical Trial Registry Name and Registration Number: A Study to Evaluate the Soluble Guanylate Cyclase (sGC) Stimulator IW-1973 in Diabetic Nephropathy/Diabetic Kidney Disease as Measured by Albuminuria, NCT03217591., (Copyright © 2021 by the American Society of Nephrology.)

Heart failure (HF) and diabetes mellitus (DM) frequently coexist, with a prevalence of DM of 35-40% in patients with HF, independent of the level of impairment of the ejection fraction (EF). Furthermore, DM is considered a strong independent risk factor for the progression of HF with either preserved or reduced EF and is associated with poor prognosis. The ability of neprilysin inhibitors to elevate levels of biologically active natriuretic peptides has made them a potential therapeutic approach in HF. In the Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, a dual-acting angiotensin-receptor-neprilysin inhibitor, sacubitril/valsartan was superior to enalapril in reducing the risks of death and HF hospitalization in patients with HF with reduced EF. In addition, in a post-hoc analysis of this trial, among patients with DM, treatment with sacubitril/valsartan resulted in improved glycemic control compared with enalapril. Also, there are additional studies suggesting beneficial metabolic effects of this class of drugs. In this review we discuss potential mechanisms of sacubitril/valsartan effect on glycemic control. Sacubitril/valsartan concomitantly blocks the renin-angiotensin system and inhibits neprilysin, a ubiquitous enzyme responsible for the breakdown of more than 50 vasoactive peptides, including the biologically active natriuretic peptides, bradykinin, angiotensin I and II, endothelin 1, glucagon, glucagon-like peptide-1, insulin-B chain, and others. There are a number of potential mechanisms by which inhibition of neprilysin may lead to improvement in glycemic control, with most evidence suggesting modulation of neprilysin circulating substrates. Although there is some evidence suggesting the improvement of glucose metabolism by renin-angiotensin system inhibition, this effect is most likely modest. As these mechanisms are not fully understood, detailed mechanistic studies, as well as large randomized clinical trials in patients with DM, are needed to further clarify beneficial metabolic properties of sacubitril/valsartan., Competing Interests: Conflict of interest statement: Dr. Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and has consulted for Abbott, Action Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GSK, Ironwood, Lilly, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent. Dr. Seferovic is a full time employee of Cyclerion Therapeutics. Dr. Seely reports no conflicts of interest., (© The Author(s), 2020.)

Left ventricular mass index (LVMI) increase has been described in hypertension (HTN), but less is known about its association with type 2 diabetes (T2DM). As these conditions frequently co-exist, we investigated the association of T2DM, HTN and both with echocardiographic parameters, and hypothesized that patients with both had highest LVMI, followed by patients with only T2DM or HTN. Study population included 101 T2DM patients, 62 patients with HTN and no T2DM, and 76 patients with T2DM and HTN, excluded for ischemic heart disease. Demographic and clinical data, biochemical measurements, stress echocardiography, transthoracic 2D Doppler and tissue Doppler echocardiography were performed. Multivariable logistic regression was used to determine the independent association with T2DM. Linear regression models and Pearson's correlation were used to assess the correlations between LVMI and other parameters. Patients with only T2DM had significantly greater LVMI (84.9 ± 20.3 g/m 2 ) compared to patients with T2DM and HTN (77.9 ± 16 g/m 2 ) and only HTN (69.8 ± 12.4 g/m 2 ). In multivariate logistic regression analysis, T2DM was associated with LVMI (OR 1.033, 95%CI 1.003-1.065, p = 0.029). A positive correlation of LVMI was found with fasting glucose (p < 0.001) and HbA1c (p = 0.0003). Increased LVMI could be a potential, pre-symptomatic marker of myocardial structural change in T2DM.

Introduction: The aim of this study was to evaluate oxidative stress markers (OSM) and catecholamine levels in patients with dilated cardiomyopathy (DCM) before and after cardiopulmonary exercise testing, and to investigate the association between changes in these markers and the New York Heart Association classification (NYHA) and left ventricular ejection fraction (LVEF) in these patients., Methods: We evaluated 74 patients with DCM and 80 control subjects without DCM. Patients were grouped according to NYHA stages I/II or III/IV. Eligible participants were considered to be those with LVEF values <45%. The OSM analysed included superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPX). The catecholamines analysed included adrenaline, noradrenaline, and dopamine. Vitamin C was also evaluated. All values were obtained before and after cardiopulmonary exercise testing., Results: There was a significant increase in GR, adrenaline, and noradrenaline after testing in the DCM patients. A significant difference between controls and patients in CAT and evaluated catecholamines was observed after testing. A significant increase in GR, GPX, adrenaline, and noradrenaline for patients in NYHA I/ II, and in CAT, GR, adrenaline, noradrenaline, and dopamine for patients in NYHA III/IV, was found between the different times of observation. LVEF before testing showed a significant positive correlation with GPX, and a negative correlation with noradrenaline and adrenaline. After testing a significant negative correlation was found with SOD and GR., Conclusions: The results of our study demonstrate the complexity of the neurohumoral mechanisms and physiological alterations in the failing heart in DCM patients. Further studies are needed, including other biomarkers and larger samples of patients, in order to improve our understanding of the aetiopathogenesis of DCM development and progression.