Obesity Paradox in the Intrahospital and Follow-Up Phases of the Acute Coronary Syndrome: A Meta-Analysis and Systematic Review.

BACKGROUND: Obesity is an important risk factor for the development of dyslipidemia, diabetes mellitus, hypertension, coronary artery disease, ventricular dysfunction, congestive heart failure (HF), stroke, and cardiac arrhythmias. OBJECTIVES: This meta-analysis brings comprehensive evaluation about still controversial association between the body mass index (BMI) and the outcomes of acute coronary syndrome. METHOD: PubMed/ScienceDirect databases were systematically searched for studies with baseline parameters, primary (HF, cardiogenic shock, cardiac arrest, reinfarction, stroke, death, total in-hospital complications) and secondary outcomes (reinfarction, stroke, death, total major adverse cardiovascular events [MACE]) in relation to BMI strictly classified into four groups (underweight [<18.5 kg/m2], normal weight [18.5-24.9 kg/m2], overweight [25.0-29.9 kg/m2], and obese [≥30.0 kg/m2], grouped into mildly obese [30.0-34.9 kg/m2] and severely obese [≥35.0 kg/m2]). RESULTS: We included 24 studies, with 585,919 participants (55.5% males), aged 66.8 years. Underweight was negatively associated with hypertension, hyperlipidemia and diabetes, and positively with primary outcomes {HF (odds ratio [OR] = 1.37, confidence interval [CI] [1.15-1.63]), cardiogenic shock (OR = 1.43, CI [1.04-1.98]), stroke (OR = 1.21, CI [1.05-1.40]), overall death (OR = 1.64, CI [1.20-2.26]), total in-hospital complications (OR = 1.39, CI [1.24-1.56])} and secondary outcomes during 34-month follow-up {cardiovascular/overall death (OR = 3.78, CI [1.69-8.49]/OR = 2.82, CI [2.29-3.49]), respectively, total MACE (OR = 2.77, CI [2.30-3.34])} (for all p < 0.05). Obesity had positive association with hypertension, hyperlipidemia, diabetes and smoking, and negative with primary outcomes {reinfarction (OR = 0.83, CI [0.76-0.91]), stroke (OR = 0.67, CI [0.54-0.85]), overall death (OR = 0.55, CI [0.49-0.63]), total in-hospital complications (OR = 0.81, CI [0.70-0.93])} and secondary outcomes {cardiovascular/overall death (OR = 0.77, CI [0.66-0.88]/OR = 0.62, CI [0.53-0.72]), respectively, total MACE (OR = 0.63, CI [0.60-0.77])} (for all p < 0.05). This negative association with several primary outcomes (cardiogenic shock, overall death, total in-hospital complications) and secondary outcomes (cardiovascular/overall death, total MACE) was more pronounced in mild obesity (p < 0.05). These results give an "obesity paradox" with a bimodal pattern (slightly U-shaped). CONCLUSIONS: Obesity is positively associated with traditional cardiovascular risk factors and negatively with primary and secondary outcomes, which confirms the persistence of overall "obesity paradox."

Haemoglobin A1c-based screening for prediabetes and diabetes mellitus: a multi-center study in Croatian adult population.

INTRODUCTION: Based on the hypothesis that there is a substantial rate of adults with prediabetes and undiagnosed diabetes mellitus (DM), our aim was to perform haemoglobin A1c (HbA1c)-based screening in a cohort of Croatian adults and estimate the prevalence of prediabetes and undiagnosed DM according to American Diabetes Association criteria. MATERIALS AND METHODS: This multi-center, cross-sectional study performed in six Croatian hospitals included 5527 patients aged 40 to 70 years admitted to the Emergency Department or undergoing a primary care check-up. Haemoglobin A1c was measured from leftover whole blood samples using the enzymatic method on either Alinity c or Architect c-series analyser (Abbott Laboratories, Chicago, USA). Haemoglobin A1c between 39-47 mmol/mol was classified as prediabetes, while ≥ 48 mmol/mol as undiagnosed DM. RESULTS: After exclusion of 435 patients with known DM, the final cohort included 5092 patients (median age 57; 56% males). A total of 882 (17.3%) patients had HbA1c values between 39 and 47 mmol/mol. There were 214 (4.2%) patients with HbA1c ≥ 48 mmol/mol. Prediabetes prevalence ranged from 14.2% to 20.5%, while undiagnosed DM from 3.3% to 7.3%, with statistically significant differences among settings (P < 0.001). Age-stratified analysis showed that prediabetes and undiagnosed DM prevalence increase with age (P < 0.001), being 25.4% and 5.8%, respectively, in patients aged 60 to 70 years. CONCLUSION: Underlying impairment of glucose metabolism was identified in about one in five adults, with significant number of patients with already overt DM. These results should serve as a starting point for further steps directed towards promotion of preventive measures for DM in Croatia.

Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer.

Trastuzumab has improved the prognosis of HER2 positive breast cancer, but cardiotoxicity remains a concern. We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case-control study included 1056 patients with early-stage HER2 positive breast cancer that received adjuvant trastuzumab. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) > 15% in patients without previous cardiomyopathy, or > 10% in patients with baseline LVEF of < 50%. Patient characteristics and cardiac parameters were compared in 78 (7.38%) cases and 99 randomly assigned controls, and the polymorphism was genotyped using real-time polymerase chain reaction. Cardiotoxicity was independently associated with advanced age (P = 0.024), lower body mass index (P = 0.023), left breast involvement (P = 0.001), N3 status (P = 0.004), diabetes (P = 0.016), and a family history of coronary artery disease (P = 0.019). Genotype distribution was as follows: A/A (Ile/Ile) was found in 111 (62.7%) patients, A/G (Ile/Val) in 60 (33.9%) patients, and G/G (Val/Val) in 6 (3.4%) patients. The genotype was not associated with cardiotoxicity or the severity of heart failure, reversibility, and recovery time. We found no association between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity; therefore, we do not recommend routine cardiotoxicity-risk stratification using this polymorphism.

The epidemiological and clinical features of odontogenic infective endocarditis.

Antibiotic prophylaxis (AP) of infective endocarditis (IE) in dental practice is a controversial topic. We evaluated the characteristics of the odontogenic IE and assessed the practice and sources of information pertaining to the topic utilized by the Croatian dentists. We conducted a retrospective review of consecutive medical charts of adult patients with IE, admitted to the University Hospital for Infectious Diseases in Zagreb, Croatia, between January 2007 and December 2017. In addition, a cross-sectional, self-reporting questionnaire survey was conducted with participation of 348 Croatian dentists. Of the 811 admissions for suspected IE (40.3% of all Croatian and 92.1% of all Zagreb hospitals), 386 patients were confirmed as definite IE: 68 with odontogenic IE and 318 with IE of other origin. Their first hospital admissions were analyzed. Definite odontogenic IE was defined as a positive echocardiographic result in conjunction with two separate positive blood cultures showing exclusive oral cavity pathogen or Streptococcus viridans associated with current or recent (< 1 month) dental, periodontal, or oral cavity infection. The annual number of new odontogenic IE patients appeared constant over time. In 91.2% of the cases, odontogenic IE was not preceded by a dental procedure; poor oral health was found in 51.5% of patients, and 47.1% had no cardiac condition that increases the IE risk. In-hospital mortality was 5.1% with conservative treatment and 4.5% with cardiac surgery and was much lower for odontogenic IE than in non-odontogenic IE (14.6% and 34.4%, respectively). An increasing number of admissions for non-odontogenic IE were observed in parallel with an increasing number of staphylococcal IE. Surveyed dentists (500 invited, 69.6% responded) were aware of the AP recommendations, but were largely reluctant to treat patients at risk. In people with poor oral health, AP should be considered regardless of cardiac risk factors. Improvement of oral health should be the cornerstone of odontogenic IE prevention.

Clinical Management of High and Very High Risk Patients with Hyperlipidaemia in Central and Eastern Europe: An Observational Study.

INTRODUCTION: A retrospective/prospective observational study was conducted to explore the current management of hyperlipidaemia in high-risk (HR) and very high risk (VHR) patients in central/eastern Europe and Israel. METHODS: The study enrolled adult patients who were receiving lipid-lowering therapy and attending a specialist (cardiologist/diabetologist/lipidologist) or internist for a routine visit at 57 sites (including academic/specialist/internal medicine centres) across Bulgaria, Croatia, Czech Republic, Israel, Poland, Romania and Slovakia. Data were collected from medical records, for the 12 months before enrolment, with/without ≤ 6 months' additional prospective follow-up. RESULTS: A total of 1244 patients, mean (SD) age 63.3 (11.3) years were included (307 with familial hypercholesterolaemia (FH), 943 secondary prevention patients). Almost all patients (98.1%) were receiving statins (76.7% monotherapy/21.4% combined therapy), with 53.1% receiving high-intensity statin therapy: 127 patients (10.2%) had adverse events attributed to statin intolerance. Mean (SD) low density lipoprotein cholesterol (LDL-C) levels were 3.3 (1.7) mmol/L at the first, and 2.7 (1.3) mmol/L at the last, visit of the retrospective phase of observation, with little change during the prospective phase. Less than one-quarter (23.8%; 95% CI 17.29-31.45%) of HR patients and less than half (42.0%; 39.05-44.98%) of VHR patients achieved their risk-based LDL-C targets of < 2.5 and < 1.8 mmol/L, respectively. Less than 15% of FH patients reached these targets (10.9% (5.6-18.7%) of HR and 12.1% (8.0-17.4%) of VHR patients). The revised 2016 ESC/EAS target for HR patients (2.6 mmol/L) was met by 28.5% (21.44-36.38%) of HR patients overall. Almost one-half of patients (42.1%) experienced one or more cardiovascular events during observation. CONCLUSION: Our findings confirm that, despite widespread statin use, a substantial proportion of patients treated for hyperlipidaemia in central/eastern Europe and Israel, particularly those with FH, do not reach recommended LDL-C targets, thus remaining at risk of cardiovascular events. FUNDING: Amgen (Europe) GmbH.

Sexual Activity in Patients with Cardiac Diseases.

In this article, we outline the latest guidelines published by the American Heart Association on sexual activity in patients with coronary artery disease, heart failure, structural heart diseases, arrhythmias, implanted pacemakers or cardioverter defibrillators, as well as on treatment options of sexual dysfunction. Sexual activities are similar to mild/moderate physical activity during a short period. Most patients are recommended to involve in sexual activity after prior comprehensive evaluation of physical condition. Those with stable cardiac symptoms and good functional capacity are at a low risk of adverse cardiovascular events, and others require treatment or stabilization before involving in sexual activity. Stress testing is useful in evaluating safety of sexual activity in patients with questionable or undetermined risk. Treatment of sexual dysfunction includes counseling of patients and their sexual partners, and drug treatment with phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) which have been demonstrated to be safe and effective, in men, and with serotonin reuptake inhibitors (flibanserin) and local vaginal estrogen administration in women. In conclusion, in routine clinical practice, patients should be approached individually and multidisciplinarily in order to detect and eliminate the factors that interfere with normal sexual activities and disturb the quality of life.

THE ROLE OF TILT-TABLE TEST IN DIFFERENTIAL DIAGNOSIS OF UNEXPLAINED SYNCOPE.

The aim of this retrospective study (February 2012-September 2014) was to assess the role of head-up tilt-table test in patients with unexplained syncope. It was performed on 235 patients at Clinical Department of Cardiology, Sestre milosrdnice University Hospital Center. Patients were classified according to test indications: group A (convulsive syncope, n = 30), group B (suspected vasovagal syncope, n = 180), and group C (paroxysmal vertigo, n = 25). The groups were analyzed and compared according to demographic data (age and gender), referral specialist (cardiologist, neurologist, and others), and test results (positive/negative) with specific response (cardioinhibitory, vasodepressor, or mixed). Groups A and B were referred most frequently by neurologists and cardiologists (p < 0.05). The test was positive in 34 (14.5%) of all evaluated patients (5 in group A and 29 in group B), of which 13 (38.2%) had cardioinhibitory, 11 (32.4%) mixed and 10 (29.4%) vasodepressor response. In the cardioinhibitory subgroup, three patients (23.1%, 2 males/1 female, mean age 28.5 years) with normal electroencephalography were on antiepileptics. During head-up tilt-table testing, they had bradycardia (heart rate 30.0 ± 5.0 beats/min) and prolonged asystole (13.7 ± 11.0 seconds) with development of typical convulsions. These three subjects got a permanent pacemaker (atrial/ventricular stimulation, heart rate control) and anticonvulsive therapy was slowly withdrawn with no syncope recurrence during 24-month follow up. In conclusion, head-up tilt-table test has an important role in the evaluation of patients with unexplained syncope and in differential diagnosis of vasovagal syncope. The indication for pacemaker implantation, strictly following the European Society of Cardiology guidelines, proved to be effective in preventing syncope relapses in patients with cardioinhibitory convulsive syncope.

The association of ventricular tachycardia and endothelial dysfunction in the setting of acute myocardial infarction with ST elevation.

BACKGROUND: Ventricular tachycardia (VT) is frequently seen in ischemic settings like acute myocardial infarction with ST segment elevation (STEMI). Endothelial dysfunction (ED) represents inflammation and the loss of all protective features of the endothelium. We aimed to examine the association between VT and ED in patients with STEMI. MATERIAL/METHODS: The study included 90 subjects (30 with VT and acute STEMI, 30 with STEMI without VT, and 30 controls). Sera of all subjects were tested on ED markers by enzyme immunoassay: sICAM-1 (intracellular adhesive molecule-1), sVCAM-1 (vascular adhesive molecule-1), P- and E-selectins, and VEGF (vascular endothelial growth factor). In addition, CRP (C-reactive protein) was detected. RESULTS: Significantly increased values of low-density lipoprotein, triglycerides, leukocytes, creatinine, and the number of cigarettes smoked were observed among patients with VT+STEMI in comparison to controls. The levels of E-selectin were significantly lower in the VT+STEMI group than in the other groups, while the levels of VCAM-1 were significantly higher in the groups with STEMI and VT+STEMI compared to the controls. Lower levels of VEGF were recorded in STEMI and VT+STEMI groups compared to the control group. A significant correlation between CRP and VCAM-1 in patients with VT +STEMI was demonstrated. CONCLUSIONS: We showed that ED may have a role in the immunopathogenesis of VT in patients with STEMI. The role of sE- selectin and correlation of sVCAM-1 with CRP as possible ED predictive markers in patients with VT+STEMI should be further investigated in a large cohort of patients.

Orthostatic intolerance: postural orthostatic tachycardia syndrome with overlapping vasovagal syncope.

A 28-year-old female with a history of situational syncope and a new-onset right sided hemiparesis is described. Tilt-up table test revealed the postural orthostatic tachycardia syndrome followed by vasovagal syncope. Neurological and internal medicine tests showed no particular disorders. The patient underwent autonomic physical training and the tilt-up test performed three months later showed improvement of the autonomic system in terms of lower heart beat rate of the postural orthostatic tachycardia syndrome and longer duration of the test. This case report describes longstanding idiopathic dysautonomia that can be improved by nonpharmacological treatment, while reminding that this medical condition may also be the cause of syncope.

Successful primary percutaneous coronary intervention in the first trimester of pregnancy.

A 28-year-old patient, medical nurse, in 10th week of her second pregnancy suffered ventricular fibrillation just after entering the waiting room of the emergency department. After she was successfully defibrillated, electrocardiography revealed a large acute anteroseptolateral ST elevation myocardial infarction. Urgent coronarography was done (premedication with 300 mg of aspirin and 600 mg of clopidogrel) with 90 min door-to-balloon time. Proximal left anterior descending occlusion was found, primary percutaneous coronary intervention was done using Amazonia CroCo 3.0/12 bare-metal stent, and Thrombolysis in Myocardial Infarction III flow was achieved. During the procedure, the patient was wrapped in lead apron. Because of postresuscitational agitation, procedure was done in intravenous anesthesia. The revealed risk factors were smoking and hypercholesterolemia. PAI-1 gene 4G/4G genotype and Apo E gene E2/E4 genotype were also found. Estimated X-ray dosage that fetus received during the procedure was 0.45 mSv, which is less than the upper safe limit in pregnancy. All drugs given to our patient (clopidogrel, aspirin, ivabradine, bisoprolol, anesthetics, low-molecular-weight heparin, and unfractionated heparin) have B or C Food and Drug Administration Pregnancy Category. Fetal ultrasonography showed normal fetal growth, and, after consultation with our team, the patient decided to maintain the pregnancy. Before discharge echocardiography showed left ventricle of normal size with anteroseptolateral hypokinesia, small apical aneurysm, left ventricular ejection fraction of 40-45%, and diastolic dysfunction grade II, without pulmonary hypertension. At the 36th week of pregnancy, the patient was hospitalized and closely monitored; clopidogrel and aspirin were discontinued, and low-molecular-weight heparin was administered. She gave birth to a normal boy by vaginal delivery with epidural anesthesia and without any complication.

Electrophysiological effects, efficacy and safety of intravenous propafenone in termination of atrioventricular nodal reentrant tachycardia and atrioventricular reentrant tachycardia: a prospective non-randomized interventional study.

The aim of this prospective, non-randomized interventional study was to assess electrophysiological effects, efficacy and safety of intravenous propafenone in termination of atrioventricular nodal reentrant tachycardia (AVNRT) and orthodromic atrioventricular reentrant tachycardia (AVRT). This single-center study was carried out at Department of Cardiology, Sestre milosrdnice University Hospital in Zagreb, Croatia, between January 1, 2005 and December 31, 2006. Eligibility requirements were fulfilled by a total of 70 patients with AVNRT (n=37) and AVRT (n=33). The intervention consisted of the electrophysiological study aimed at inducing tachycardia, followed by intravenous administration of 2 mg/kg propafenone in both groups. The main outcome measures were safety and efficacy of 2 mg/kg intravenous propafenone in tachycardia termination and re-induction. Out of 37 patients with AVNRT, propafenone managed to terminate it in 28 (75.7%) patients, while tachycardia was not inducible in 25 (67.56%) patients. Out of 33 patients with AVRT, propafenone managed to terminate AVRT in 29 (87.9%) patients, while tachycardia was not inducible in 22 (66.66%) patients. The overall propafenone efficacy in tachycardia termination was 81.42%. No propafenone-related adverse effects were recorded during the study period. Propafenone was found to be a safe and effective anti-arrhythmic drug and can be justifiably administered for AVNRT and AVRT termination. It could be considered as an alternative to adenosine and verapamil.