Matias Trbušić

Metrics of High-Density Lipoprotein Function and Hospital Mortality in Acute Heart Failure Patients

Objective The functionality of high-density lipoprotein (HDL) is impaired in chronic ischaemic heart failure (HF). However, the relationship between HDL functionality and outcomes in acute HF (AHF) has not been studied. The present study investigates whether the metrics of HDL functionality, including HDL cholesterol efflux capacity and HDL-associated paraoxonase (PON)-1 arylesterase (AE) activity are associated with hospital mortality in AHF patients. Methods and Results The study was performed as a prospective, single-centre, observational research on 152 patients, defined and categorised according to the ESC and ACCF/AHA Guidelines for HF by time of onset, final clinical presentation and ejection fraction. The mean age of the included patients (52% female) was 75.2 years (SD 10.3) and hospital mortality was 14.5%. HDL cholesterol efflux capacity was examined by measuring the capacity of apoB depleted serum to remove tritium-labelled cholesterol from cultured macrophages. The AE activity of the HDL fraction was examined by a photometric assay. In a univariable regression analysis, low cholesterol efflux, but not AE activity, was significantly associated with hospital mortality [odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64–0.96, p = 0.019]. In multivariable analysis progressively adjusting for important clinical and laboratory parameters the association obtained for cholesterol efflux capacity and hospital mortality by univariable analysis, despite a stable OR, did not stay significant (p = 0.179). Conclusion Our results suggest that HDL cholesterol efflux capacity (but not AE activity) contributes to, but is not an independent risk factor for, hospital mortality in AHF patients. Larger studies are needed to draw firm conclusions.

Hypochloraemia as a predictor of developing hyponatraemia and poor outcome in acute heart failure patients

AIMS Heart failure (HF) is a major public health issue currently affecting more than 23 million patients worldwide. Hyponatraemia has been shown to be a predictor of poor outcome in patients with acute and chronic HF. Therefore, we aimed at finding a marker for early detection of patients at risk for developing hyponatraemia. To this end, the present study investigated the relationship between initial serum chloride and follow-up sodium levels in acute heart failure (AHF) patients. METHODS AND RESULTS The present study was performed as a prospective, single-centre, observational research with a total of 152 hospitalised AHF patients. Compared to patients with initial normochloraemia, patients with initial hypochloraemia had a statistically significantly higher incidence of hyponatraemia after a 3-month follow-up [P<0.001; odds ratio (OR)=27.08, CI: 4.3-170.7]. A similar finding was obtained upon exclusion of patients with initial hyponatraemia with Fishers test [P=0.034; odds ratio (OR)=15.5, CI:1.7-140.6]. Binary logistic regression revealed a significantly increased in-hospital mortality in the hypochloraemic/normonatriaemic (OR=4.08, CI 1.08-15.43, P=0.039), but not in the hypochloraemic/hyponatraemic, normochloraemic/hyponatraemic or normonatriaemic/normochloraemic patients. Ejection fraction (EF) at admission was significantly higher in hypochloraemic/normonatriaemic, compared to normonatriaemic/normochloraemic patients, but similar to EF in both hypochloraemic/hyponatraemic and normochloraemic/hyponatraemic patients. The N-terminal precursor Brain Natriuretic Peptide (Nt-proBNP) levels at admission were significantly lower in hypochloraemic/normonatriaemic compared to hypochloraemic/hyponatraemic and normonatriaemic/normochloraemic patients, respectively. CONCLUSION The data show that initial low serum chloride concentration is predictive of developing hyponatraemia and associated with increased in-hospital mortality in AHF patients.

Serum Concentration of HDL Particles Predicts Mortality in Acute Heart Failure Patients

Clinical studies have shown that assessing circulating concentrations of high-density lipoprotein (HDL) particles by nuclear magnetic resonance (NMR) spectroscopy is superior to HDL-cholesterol in predicting cardiovascular risk. We tested the hypothesis that circulating concentrations of HDL particles predict 3-month mortality of patients with acute heart failure (AHF). Out of 152 included patients, 52% were female, additionally the mean patient age was 75.2 ± 10.3 years, and three-month mortality was 27%. Serum lipoprotein profile at admission was determined by NMR spectroscopy. Univariate logistic regression analyses revealed a significant inverse association of total (odds ratio (OR) 0.38 per 1-SD increase, 95% confidence interval (CI) 0.23–0.60, p < 0.001) and small HDL particle concentrations (OR 0.35 per 1-SD increase, 95% CI 0.19–0.60, p < 0.001) with 3-month mortality, whereas concentrations of large HDL particles (p = 0.353) or HDL-cholesterol (p = 0.107) showed no significant association. After adjustment for age, sex, mean arterial pressure, low-density lipoprotein cholesterol, glomerular filtration rate, urea, and N-terminal pro-brain natriuretic peptide, both the total and small HDL particle concentrations remained significantly associated with 3-month mortality. Based on our results, we conclude that total and small HDL particle concentrations strongly and independently predict 3-month mortality in AHF patients.

Acute Heart Failure developed as worsening of Chronic Heart Failure is associated with increased mortality compared to de novo cases

Acute heart failure (AHF) emerges either de novo or from worsening of chronic heart failure (CHF). The aim of the present study was to evaluate the association between worsening of CHF and mortality in AHF patients. Out of 152 included AHF patients, 47 (30.9%) were de novo AHF patients and 105 (69%) were AHF patients with worsening of CHF. The proportion dying in hospital (19.0% vs. 4.3%, p = 0.023) and within 3 months after hospitalization (36.6% vs. 6.7%, p < 0.001) was significantly higher in AHF patients with worsening of CHF. Logistic regression analyses also showed a significant positive association of AHF emerging as worsening of CHF with hospital mortality [odds ratio (OR) and 95% confidence interval (CI): 5.29 (1.46–34.10), p = 0.029] and 3-month mortality [8.09 (2.70–35.03), p = 0.001]. While the association with hospital mortality was no longer significant after adjusting for comorbidities and clinical as well as laboratory parameters known to be associated with mortality in heart failure patients, the association with 3-month mortality remained significant. We conclude that compared to de novo AHF, AHF evolved from worsening of CHF is a more severe condition and is associated with increased mortality.

Metabolic Syndrome Modulates Association between Endothelial Lipase and Lipid/Lipoprotein Plasma Levels in Acute Heart Failure Patients

We hypothesised that the established association of endothelial lipase (EL) plasma levels with atherogenic lipid profile is altered in acute heart failure (AHF) and additionally affected by overlapping metabolic syndrome (MetS). We examined the association of EL plasma levels and lipid/lipoprotein plasma levels in AHF patients without and with overlapping MetS. The study was performed as a single-centre, observational study on 152 AHF patients, out of which 85 had overlapping MetS. In the no-MetS group, EL plasma levels were significantly positively correlated with plasma levels of atherogenic lipids/lipoproteins, including total cholesterol, low-density lipoprotein (LDL)-cholesterol, total LDL particles and triglycerides, but also with plasma levels of antiatherogenic high-density lipoprotein (HDL)-cholesterol, total HDL particles and small HDL particles. In the MetS group, EL plasma levels were positively correlated with triglyceride and small LDL-particle levels, and significantly negatively correlated with plasma levels of large HDL particles as well as with LDL- and HDL-particle size, respectively. EL- and lipid/lipoprotein- plasma levels were different in the no-MetS patients, compared to MetS patients. The association of EL with atherogenic lipid profile is altered in AHF and additionally modified by MetS, which strongly modulates EL- and lipid/lipoprotein-plasma levels in AHF.

Serum concentrations of asymmetric and symmetric dimethylarginine are associated with mortality in acute heart failure patients

Background Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine are established predictors of total and cardiovascular mortality. However, the predictive capacity of ADMA and SDMA for hospital and 3-months mortality of patients with acute heart failure (AHF) is unknown. Methods & results Out of 152 included AHF patients, 79 (52%) were female, and the mean patient age was 75.2 ± 10.3 years. Hospital and three-month mortality rates were 14.5% and 27.4%, respectively. Serum ADMA and SDMA levels at admission, determined by reversed phase high performance liquid chromatography, were higher in patients having at least one of the three signs implying venous volume overload (enlarged liver, ascites, peripheral edema), a consequence of right-sided heart failure, compared to patients without those signs. Univariable logistic regression analyses revealed a significant positive association of ADMA and SDMA concentrations with hospital mortality [odds ratio (OR) and 95% confidence interval (CI) per standard deviation (SD) increase: 2.22 (1.37–3.79), p = 0.002, and 2.04 (1.34–3.18), p = 0.001, respectively], and 3-months mortality [2.06 (1.36–3.26), p = 0.001, and 2.52 (1.67–4.04), p < 0.001, respectively]. These associations remained significant after adjusting for age, sex, mean arterial pressure, low-density lipoprotein cholesterol, glomerular filtration rate, and N-terminal pro-brain natriuretic peptide. Conclusions We conclude that ADMA and SDMA concentrations are associated with hospital and 3-month mortality and are increased by venous volume overload in AHF patients.

A rare case of Corynebacterium Spp. native mitral valve endocarditis – case report and review of literature

ORCID: Krešimir Kordić, https://orcid.org/0000-0002-9707-6946 • Nikola Kos, https://orcid.org/0000-0001-8829-2543 Nikola Bulj, https://orcid.org/0000-0002-7859-3374 • Matias Trbušić, https://orcid.org/0000-0001-9428-454X Ivo Darko Gabrić, https://orcid.org/0000-0003-4719-4634 • Ozren Vinter, https://orcid.org/0000-0002-4236-7594 Igor Rudež, https://orcid.org/0000-0002-7735-6721 • Diana Delić-Brkljačić, https://orcid.org/0000-0002-7116-2360

Metabolic acidosis: expected and fatal adverse effects of metformin and empagliflozin: a case series and literature review

Metformin, a well-known first-line diabetes therapy, and the recently developed sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin are widely used oral antihyperglycemic drugs in the long-term treatment of type 2 diabetes mellitus (T2DM). Metabolic acidosis is a potentially fatal adverse effect (AE) of these drugs with a high mortality rate. However, the reported incidence of metabolic acidosis in clinical practice has been proven to be very low. Nevertheless, it should be considered that the event rates are based on confounded data and spontaneous case reports. Metformin increases plasma lactate levels by inhibiting mitochondrial respiration, which, accompanied by elevated plasma metformin concentrations (in renal impairment) and a secondary event that further disrupts lactate production (e.g., hypoperfusion, sepsis), typically leads to metformin-associated lactic acidosis (MALA). At the same time, SGLT2 inhibitors are thought to promote ketogenesis and precipitate ketoacidosis by their extra-pancreatic glucuretic mode of action. The present article describes 3 patients suffering from severe metabolic acidosis caused by metformin or empagliflozin, presents similar cases reported in the literature, and assesses the possible etiopathogenesis of the metabolic derangement. Diabetic patients should be educated about the importance of regular fluid and food intake as well as regular blood and urine glucose and ketone self-checkups, whereas physicians should be more aware that the key to an effective use of all glucose-lowering medication is appropriate patient selection, counseling, and follow-up. It is a good clinical sense which will ensure that physicians are able to translate pharmaceutical advances into clinical benefits for patients with T2DM. 1 Department of Medicine, Psychiatric Hospital dr Ivan Barbot, Popovača 2 Department of Medicine, Sisters of Charity University Hospital Centre, Zagreb 3 University of Zagreb School of Medicine, Zagreb, Croatia Miriam Čupić1, Jelena Dumančić1, Ines Potočnjak2, Iva Klobučar2, Matias Trbušić3,2, Vesna Degoricija3,2 Corresponding author: Vesna Degoricija, MD, PhD; Department of Medicine, Sisters of Charity University Hospital Centre, Vinogradska cesta 29, 10 000 Zagreb, Croatia; Telephone number: +385915033747; Fax number: +38513769067; E-mail: vesna.degoricija@gmail.com. DOI: 10.21040/eom/2016.2.3.6 Received: August 21st 2016 Accepted: September 10th 2016 Published: September 15th 2016 Copyright:

Spontaneous pneuomopericardium: an unusual complication of abdominal carcinoma.

2016;11(3-4):140. VII. nacionalni sastanak o kardiovaskularnim intervencijama s međunarodnim sudjelovanjem VI. sastanak intervencijskih kardioloskih medicinskih sestara i tehnicara Pneumopericardium is a rare condition defined as a collection of air in the pericardial cavity. It is usually caused by blunt or penetrating chest injuries, iatrogenic causes (bone marrow puncture, thoracic surgery, pericardiocentesis, endoscopic procedures), and infectious pericarditis with gas-producing organisms.1,2

Left radial approach in patients with ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

2. Trbusic M, Gabric ID, Planinc D, Krcmar T, Pintaric H. What happens when transradialists use transbrachial approach. J Invasive Cardiol. 2013;25 (Suppl E):30E. UvOD: Od 2011. primarni postav naseg laboratorija za invazivnu kardiologiju promijenjen je s femoralnog u lijevi radijalni i danas se oko 95% svih postupaka ucini lijevim ili desnim „nefemoralnim“ pristupom. Primarna perkutana koronarna intervencija (PCI) u bolesnika s infarktom miokarda s elevacijom ST-segmenta (STEMI) je najzahtjevniji oblik koronarne intervencije i stoga operateri moraju biti dobro obuceni u radijalnom pristupu. Cilj istraživanja bio je utvrditi je li u bolesnika sa STEMI, kojima je primarna PCI ucinjena lijevim radijalnim pristupom, iskustvo operatera, kao i doba dana kada je intervencija ucinjena, utjecalo na uspjeh postupka, bolesnikovu i operaterevu sigurnost.