Misperceptions and management of LDL-cholesterol in secondary prevention of patients with familial hypercholesterolemia in cardiology practice: Real-life evidence from the EPHESUS registry.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common inherited disease, leading to premature atherosclerotic cardiovascular disease (ASCVD) due to elevated low-density lipoprotein cholesterol (LDL-C) levels. Achieving LDL-C goals is extremely important for preventing the complications of this fatal disease. We evaluated the management of FH patients with ASCVD in cardiology practice. METHODS: We analyzed patients with ASCVD from the nationwide EPHESUS registry, which was conducted in 40 cardiology outpatient clinics, and compared those with and without FH. RESULTS: Of the 1482 consecutively enrolled patients with ASCVD, 618 (41.7%) had FH, among which 455 were categorized as 'Possible FH' and 163 as 'Probable or Definite FH'. Proposed LDL-C goals were not attained in more than 90% of the patients with FH. The proportion of those on statin therapy was 77% for possible and 91% for probable or definite FH, whereas 34.2 % and 59.4% were in use of high-intensity statins, respectively. None of the patients were on PCSK-9 inhibitors, and only 2 used ezetimibe. Adverse media coverage was the most common cause of statin discontinuation (32.5% in 'possible FH' and 45.7% in 'probable/definite FH'). The negative impact of media in the decision to stop lipid lowering therapy (LLT) was increasing with education level. CONCLUSIONS: In real life most of the FH patients with ASCVD are undertreated in cardiology practice regarding statin dosing and combined LLT. Drug discontinuation rates are notably high and are mostly media-related, and side effects very rarely cause cessation of LLT. Urgent measures are needed to increase the awareness of FH among healthcare providers and patients and to develop improved treatment strategies aimed at preventing the complications of FH.

How Did the Updated 2019 European Society of Cardiology/European Atherosclerosis Society Risk Categorization for Patients with Diabetes Affect the Risk Perception and Lipid Goals? A Simulated Analysis of Real-life Data from EPHESUS Study.

BACKGROUND: The recent 2019 European Society of Cardiology/European Atherosclerosis Society practice guidelines introduced a new risk categorization for patients with diabetes. We aimed to compare the implications of the 2016 and 2019 European Society of Cardiology/European Atherosclerosis Society guidelines with regard to the lipid-lowering treatment use, low-density lipoprotein cholesterol goal attainment rates, and the estimated proportion of patients who would be at goal in an ideal setting. METHODS: Patients with diabetes were classified into 4 risk categories according to 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidemia guidelines from the database of EPHESUS (cross-sectional, observational, countrywide registry of cardiology outpatient clinics) study. The use of lipid-lowering treatment and low-density lipoprotein cholesterol goal attainment rates were then compared according to previous and new guidelines. RESULTS: This analysis included a total of 873 diabetic adults. Half of the study population (53.8%) were on lipid-lowering treatment and almost one-fifth (19.1%) were on high-intensity statins. While low-density lipoprotein cholesterol goal was achieved in 19.5% and 7.5% of patients, 87.4% and 69.6% would be on target if their lipid-lowering treatment was intensified according to 2016 and 2019 European Society of Cardiology/European Atherosclerosis Society lipid guidelines, respectively. The new target <55 mg/dL could only be achieved in 2.2% and 8.1% of very high-risk primary prevention and secondary prevention patients, respectively. CONCLUSION: The control of dyslipidemia was extremely poor among patients with diabetes. The use of lipid-lowering treatment was not at the desired level, and high-intensity lipid-lowering treatment use was even lower. Our simulation model showed that the high-dose statin plus ezetimibe therapy would improve goal attainment; however, it would not be possible to get goals with this treatment in more than one-third of the patients.

Dabigatran for stroke prevention in real life in a sample of population from Turkey: D-SPIRIT registry.

OBJECTIVE: The D-SPIRIT registry is designed to investigate the safety and effectiveness of dabigatran etexilate in patients with atrial fibrillation in routine clinical practice. METHODS: D-SPIRIT is the first national, multicenter, prospective, observational, postmarketing registry that investigates the usage of dabigatran in real life. A total of 326 noveloral anticoagulant-eligible patients with atrial fibrillation who have been taking dabigatran etexilate therapy for stroke prevention at least 6 months from 9 different centers were enrolled into the registry. Patients were followed up for 2 years to evaluate the effectiveness and safety of the treatment. All adverse clinical events including bleeding, thromboembolic events, stroke, systemic embolism, transient ischemic attack, myocardial infarction, and all-cause death were recorded. RESULTS: The mean age was 71.1±9.6 years, and 57.4% of the study participants were female. The mean CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack [TIA], vascular disease, age 65-74 years, sex category) score was 3.4±1.6. The cumulative adverse clinical events rate was 6.30% per year. The rate for embolic events including TIA, ischemic stroke, and peripheral embolism was 1.26% per year. The rate for major bleeding was 2.20% per year, and the mortality rate was 0.94% per year. CONCLUSION: This registry obtained an important overview of the current safety and effectiveness of the dabigatran etexilate in Turkey. Our results indicate similar rates of thromboembolic and bleeding events with pivotal phase 3 trial and other real-life registries. However, rate of undertreatment usage of dabigatran etexilate in real life was found to be considerable.

Management of LDL-cholesterol levels in patients with Diabetes Mellitus in Cardiology Practice: Real-life evidence of Under-treatment from the EPHESUS registry.

BACKGROUND AND AIMS: Effective treatment of high low-density lipoprotein cholesterol (LDL-C) levels has been shown to improve cardiovascular outcomes of patients with diabetes mellitus (DM). Herein, we aimed to provide insight to the real-life management of patients with DM in terms of LDL-C goal attainment and adherence to lipid management recommendations. Our objective was also to reveal the reasons of poor LDL-C goal attainment by assessing the perceptions of both physicians and patients. METHODS: We compared the diabetic and non-diabetic patients from the database of a nationwide registry conducted in cardiology outpatient clinics with regard to the demographic characteristics, educational status, comorbidities, medications, laboratory parameters and LDL-C goal attainment. Also, both the patients and attending physicians were surveyed to analyse perceptions and awareness of hypercholesterolemia. RESULTS: Of the 1868 consecutively enrolled patients, 873 (47%) had DM. Proportion of patients on statins was significantly lower in patients with DM (67.8% vs 55.3%; P < .001). The proportion of patients who attained LDL-C targets were lower among the diabetic patients (17.8% vs 15%; P = .06). The most common causes of the discontinuation of statin therapy were negative media coverage about statins (32.1%), and recommendations of physicians to stop the lipid lowering therapy (29.6%). Analysis of the physician survey revealed that the physicians could determine the off-target patients accurately (negative predictive value 98.4%) while the positive predictive value (48.8%) was low. The reasons for not attaining the LDL-C goals in diabetic patients were not prescription of statins (38%) and inadequate (eg low-dose, non-adherent) statin (28.3%) dosages. CONCLUSIONS: In real-life clinical cardiology practice, diabetic patients are far below the recommended LDL-C treatment goals. High-intensity statin treatment in diabetic population is still avoided because of the concerns about polypharmacy and drug interactions. Also, the inertia of physicians and even cardiologists is probably a major cause of refraining of prescription of optimal statin dosages.

The reasons of poor lipid target attainment for secondary prevention in real life practice: Results from EPHESUS.

OBJECTIVE: There are lack of studies considering the suboptimal management of dyslipidemia especially in cardiology outpatient clinics. This study was conducted to assess the patient adherence to cholesterol treatment recommendations and attainment of low-density-lipoprotein cholesterol (LDL-C) goals. METHODS: EPHESUS (NCT02608645) is a national, observational and multicenter registry which has been designed as a cross-sectional study to allow inclusion of all consecutive patients with hypercholesterolemia in cardiology outpatient clinics. The present subgroup analyses of the EPHESUS trial included patients with known peripheral artery disease or atherosclerotic cerebrovascular disease, and coronary heart disease namely secondary prevention. RESULTS: The present analysis of the EPHESUS study included 1482 patients (62.79 ± 10.4 years, 38.2% female) with secondary prevention from 40 sites in Turkey. Regarding recommended lipid targets for LDL-C, only 267 patients (18%) were below the target of 70 mg/dL. Females were significantly more off-target when compared with male patients (396, 85.5% vs 67, 14.5%; P = 0.017). Moreover, the achievement of LDL-C goal was significantly decreased with illiteracy (233, 19.2% vs 35, 13.1%; P = 0.02). Patients who think that the cholesterol treatment should be terminated when the cholesterol level of a patient has normalised were higher in the off-target group (34.0% vs 24.7%, P < 0.001). Besides, physician perceptions about LDL-C goal for secondary prevention were significantly related with LDL-C target attainment. CONCLUSIONS: EPHESUS is an important study with large population in terms of representing real-life practice of the adherence to dyslipidemia guidelines in secondary prevention patients in Turkey. Perceptions, knowledge, and compliance with the guidelines for secondary prevention have increased, but it is far below from the desired levels even in cardiology outpatient clinics. There is a need for patients' and physicians' education regarding the treatment of hyperlipidemia.

Directly ventricular septal defect closure without using arteriovenous wire loop: Our adult case series using transarterial retrograde approach.

OBJECTIVE: The standard transcatheter ventricular septal defects (VSD) closure procedure is established with arteriovenous (AV) loop and is called as antegrade approach. The directly retrograde transarterial VSD closure without using AV loop might be better option as shortens the procedure time and decreases radiation exposure. METHODS: Our series consist of twelve sequential adult cases with congenital VSDs (seven with perimembranous, four with muscular, one with postoperative residuel VSD). The mean age was 26.9 (Range 18-58), the mean height was 168.75 cm (Range 155-185cm), and the mean body mass index was 23.4 (Range 17.3-28.4). Maximum and minimum defect sizes were 10 and 5 mm and the mean defect size was 6.24 mm. The procedure was performed with left heart catheterization and advancing the delivery sheath over the stiff exchange wire then VSD occlusion from left side. RESULTS: The defects were successfully closed with this technique in eleven patients. In sixth patient, the defect could not be cannulated by the delivery sheath, as the tip of the sheath did not reach the defect and VSD was closed with same sheath by standard transvenous approach using AV loop. We didn't encounter any complication releated to semilunar or atrioventricular valves. Atrioventricular conduction system was not affected by the procedure in any patients. The median procedure and fluoroscopy times were 66 and 16.5 minutes respectively. CONCLUSION: Transarterial retrograde VSD closure without using AV loop simplifies the procedure, decreases the radiation exposure, and shortens the procedure time. The only limitation in adult patients is delivery sheath length.

OPERATOR DEPENDENCY OF THE RADIATION EXPOSURE IN CARDIAC INTERVENTIONS: FEASIBILITY OF ULTRA LOW DOSE LEVELS.

INTRODUCTION: Mean radiation exposure in invasive cardiology varies greatly between different centres and interventionists. The International Commission on Radiological Protection and the EURATOM Council stipulate that, despite reference values, 'All medical exposure for radiodiagnostic purposes shall be kept as low as reasonably achievable' (ALARA). The purpose of this study is to establish the effects of the routine application of ALARA principles and to determine operator and procedure impact on radiation exposure in interventional cardiology. MATERIALS AND METHODS: A total of 240 consecutive cardiac interventional procedures were analysed. Five operators performed the procedures, two of whom were working in accordance with ALARA principles (Group 1 operators) with the remaining three working in a standard manner (Group 2 operators). Radiation exposure levels of these two groups were compared. RESULTS: Total fluoroscopy time and the number of radiographic runs were similar between groups. However, dose area product and cumulative dose were significantly lower in Group 1 when compared with Group 2. Radiation levels of Group 1 were far below even the reference levels in the literature, thus representing an ultra-low-dose radiation exposure in interventional cardiology. CONCLUSION: By use of simple radiation reducing techniques, ultra-low-dose radiation exposure is feasible in interventional cardiology. Achievability of such levels depends greatly on operator awareness, desire, knowledge and experience of radiation protection.

Design and rationale of dabigatran's stroke prevention in real life in Turkey (D-SPIRIT).

OBJECTIVE: The D-SPIRIT registry is designed to investigate the safety and efficacy of dabigatran etexilate in patients with nonvalvular atrial fibrillation (NVAF) and to collect data on outcomes in clinical practice. METHODS: The D-SPIRIT is a national, prospective, observational, post-marketing registry involving patients with NVAF who have been taking dabigatran etexilate therapy for stroke prevention for a minimum of 6 months prior to enrollment. The registry will collect and analyze data from routine care, enrolling up to 600 patients in 9 centers. Patients will be followed up for 2 years to evaluate effectiveness and safety. A sample size of 600 subjects is proposed based on the following assumptions; Two-sided significance level of 0.05 (1-sided significance level of 0.025), ischemic stroke incidence rate of 0.768%-1.111%, hemorrhagic stroke incidence rate of 0.109%-0.130%, transient ischemic attack incidence rate of 0.722%-0.623%, therapy discontinuation incidence rate of 40% at day 730, and duration of enrollment period of 12 months with non-uniformed enrollment rate. Ethics approval was given by Dokuz Eylül University Ethics Committee of Clinical Research (2014/54) and approved by the Turkish Ministry of Health. CONCLUSION: Potential results of D-SPIRIT registry will add data from clinical practice to those from the RE-LY trial to expand knowledge of dabigatran etexilate treatment in patients with NVAF.

Spontaneous spinal epidural hematoma developing after percutaneous coronary intervention: early diagnosis, early intervention, and good outcome.

A 56-year-old female patient hospitalized with diagnosis of acute coronary syndrome underwent early coronary intervention. Anticoagulant and antithrombotic treatment was administered, including acetylsalicylic acid, clopidogrel, and heparin in periprocedural period. Severe back pain and rapidly progressing paraplegia developed in early period of follow-up. The patient underwent surgery immediately after diagnosis of spontaneous spinal epidural hematoma (SSEH) causing pressure, and decompression was performed. The patient rapidly improved without recurrence through early diagnosis and early surgical intervention. A common problem encountered by interventional cardiologists is back pain in patients who have undergone interventions in the femoral region and have lain in the same position for an extended period. Clinical onset of SSEH includes similar complaints, a fact of which cardiologists should be aware. Early diagnosis and early intervention may provide a good outcome, as is reported in the present case.

Association of overhydration and cardiac dysfunction in patients have chronic kidney disease but not yet dialysis.

BACKGROUND/AIM: Fluid overload and cardiac dysfunction is well established in hemodialysis patients. But in predialysis chronic kidney disease, the association of fluid overload and cardiac dysfunction is relatively unknown. In this study, we aimed to investigate the relationship between fluid overload and cardiac dysfunction in predialysis chronic kidney disease patients. METHOD: We enrolled 107 consecutive patients in our study. Fluid overload was assessed via body composition monitor. Patients were dichotomized according to the fluid overload status. The patients with FO < 1.1L were determined as normovolemic and those with FO ≥ 1.1L as hypervolemic according to the previously reported physiologic model. Left atrial volume index (LAVI), left ventricular end-diastolic-end-systolic index (LVEDVI, LVESVI), E/e', LVMI and global longitudinal left ventricular left ventricular strain (GLS-%) were evaluated in each patient as markers of cardiac dysfunction. Arterial stiffness was also assessed by Mobil-O-Graph(®) 24h pulse wave analysis monitor and pWV values were recorded. RESULTS: Fifty-five patients were normovolemic and 52 patients were hypervolemic. LAVI, LVMI, LDEDVI, LVEDSVI, E/e' were increased in hypervolemic patients. Also in hypervolemic patients pulse wave velocity was increased and GLS was decreased. Multivariate analysis showed that FO was independently associated with GLS which is the most specific echo-parameter for left ventricular dysfunction. CONCLUSION: FO was independently associated with cardiac dysfunction in patients with chronic kidney disease not ongoing dialysis. Effective treatment of hypervolemia may be important in these patients to avoid further cardiac damage.

Impact of anxiety level on circadian rhythm of blood pressure in hypertensive patients.

INTRODUCTION: Considering the high prevalence rates and growing incidences of hypertension (HT) and anxiety disorders in the modern world, a full understanding of anxiety's relationship to HT is crucial. In this study we aimed to investigate the effects of anxiety level on circadian rhythm of blood pressure (BP) in hypertensive patients. MATERIAL AND METHOD: This cross-sectional study included 160 previously diagnosed essential hypertensive patients (80 female, 80 male, mean age: 55.3±15.1 years). All participants underwent 24 h ambulatory blood pressure monitoring (ABPM) and filled State-Trait Anxiety Inventory (STAI) (trait) Questionnaire. The study population was divided into 2 groups according to their STAI scores; an anxiety group (n=97; STAI ≥45) and a control group (n=63; STAI<44). Clinical characteristics, laboratory findings and ABPM measurements were compared between the groups. RESULTS: There was no significant difference between the groups for ABPM parameters except morning blood pressure surge (MBPS). Anxiety group had a significantly higher MBPS compared to control group (14.4±17.0 vs 9.1±11.9 mmHg, P:0.03). Multivariate analysis showed that duration of HT and STAI score were the only independent predictors of MBPS. CONCLUSION: Patients' anxiety level is associated with MBPS which is an independent risk factor for cardiovascular complications. Assessment and control of anxiety seems to be worthy in effective treatment of hypertension.

Optimal treatment of unligated side branch of internal mammary artery: Coil, amplatzer vascular plug or graft stent? A case report and literature review.

Coronary artery steal syndromes may occur following coronary artery bypass grafting as a result of the presence of large side-branches arising from the internal mammary artery (IMA). Coil embolization, Amplatzer Vascular Plug and graft stents are all used for the treatment of such syndromes. The literature contains limited data on the long-term success of these treatment methods. There is no large series regarding occluded IMA side branches causing coronary steal phenomena, and data on long-term follow-up of this treatment method is also very limited. This report presented two cases and their treatment, and reviewed the advantages and disadvantages of treatment methods and the factors that affect successful treatment.

Evaluation of the impact of warfarin time in therapeutic range on outcomes of patients with atrial fibrillation in Turkey: perspectives from the observational, prospective WATER Registry.

BACKGROUND: Warfarin is highly efficacious in reducing stroke risk in patients with atrial fibrillation (AF). However, its safety and efficacy in stroke prevention is markedly influenced by its time in therapeutic range (TTR). The quality of anticoagulant therapy varies considerably among countries. Representative data concerning the quality of anticoagulant therapy and its effects on clinical outcomes in Turkey are lacking. METHODS: Warfarin in Therapeutic Range (WATER) registry is a prospective, observational study which followed 572 AF patients (mean age 67.3 ± 12 years; females 60%; 71% non-valvular AF) treated with warfarin. RESULTS: At a median of 22-month follow-up, the mean TTR value was 42.3 ± 18% (median: 40%) for the whole population and lower in non-valvular AF su group than valvular AF subgroup (40.3 ± 18 vs. 46.9 ± 19, respectively, p < 0.001). Death, cardiac hospital-ization and minor bleeding rates were higher in the group with TTR value < 40% than the group with > 40% (3.4% vs. 5.9%; 28.6% vs. 35.4%; 36.5% vs. 41.7%, respectively, all of them p < 0.001). A correlation analysis showed a negative correlation between age and TTR value (r = -0.178, p < 0.001). Mean CHA2DS2VASc score was 3.63 ± 1.5 and mean HASBLED score was 2.38 ± 1.01 in the non-valvular AF group. A negative correlation was observed between TTR levels and CHA2DS2VASc score. CONCLUSIONS: WATER provides insight into the anticoagulation control status of AF patients in Turkey. The quality of anticoagulation was poor. Strategies should be undertaken by clinicians and patients to improve TTR. New oral anticoagulant agents may be perfect alternatives for non-valvular AF patients.

The relationship between platelet indices and clinical features of coronary artery disease.

BACKGROUND: Platelets play a key role in the development and progression of cardiovascular disease. The degree of platelet activation may be assessed by platelet indices such as platelet count, mean platelet volume (MPV) and platelet distribution width (PDW). AIM: To evaluate the relationship between platelet indices and clinical features of coronary artery disease (CAD). METHODS: Our population is represented by a total of 441 consecutive patients undergoing coronary angiography. Patients were divided into three groups according to their clinical presentation: Patients with stable angina (Group I), with acute coronary syndrome (Group II), and with a normal coronary angiogram (Group III). All demographic and clinical features were collected retrospectively. Platelet indices were measured in all patients. RESULTS: There was no statistical difference for platelet count, MPV and PDW values among the groups. Correlation analysis showed a positive association between platelet count and Gensini scoring (Kendall's tau b, r = 0.312, p = 0.037, two-tailed)and also age (Kendall's tau b, r = 0.518, p = 0.001, two-tailed) in patients with CAD. However, there was no significant correlation between Gensini scoring and MPV or PDW values in these patients. CONCLUSIONS: PDW and MPV may not be related to the clinical features or presentation and extent of CAD. Our study findings add to the conflicting results of previous studies in this area. Prospective trials with longer follow-up periods and larger samples are warranted to conclusively define the role of platelet indices in CAD.

Anomalous origin of the right vertebral artery from the ascending aorta in the presence of an aberrant right subclavian artery.

We present a case of a 63-year-old man who was admitted to the hospital due to an acute coronary syndrome. Angiographic and magnetic resonance angiography examination showed an abnormal right vertebral artery originating from the ascending aorta, just above the left coronary sinus Valsalva in addition to aberrant retro-esophageal right subclavian artery. The variations and the incidence of various abnormal origins of the right vertebral artery are also reviewed.

The relationship between angiotensin converting enzyme gene polymorphism, coronary artery disease, and stent restenosis: the role of angiotensin converting enzyme inhibitors in stent restenosis in patients with diabetes mellitus.

Patients with diabetes mellitus (DM) have advanced atherosclerosis compared with nondiabetics. Restenosis after intracoronary stent implantation occurs frequently in diabetic patients. Angiotensin II is an important growth factor for the development of neointimal hyperplasia after vascular injury. The aim of our study was to evaluate the relationships between angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and coronary artery disease (CAD) and stent restonosis in diabetic patients. One hundred and thirty consecutive patients with CAD and 47 consecutive patients (14 males, mean age, 58.0 +/- 10.0) without CAD were enrolled in the study. All patients had type 2 (noninsulin dependent) DM. The patients with CAD underwent percutaneous transluminal coronary angioplasty (PTCA) and stenting. Ninety-four (59 males, mean age, 60.3 +/- 9.8) underwent control coronary angiography at the end of the follow-up period (mean duration, 9.1 +/- 2.9 months). ACE gene I/D genotyping was identified in all patients. No significant difference was found among patients with and without CAD with respect to ACE gene I/D polymorphism (P = 0.460). In the control coronary angiography, stent restenosis and new lesion development were comparable in each genotyping subgroup. However, a significant relationship was observed between restenosis and the use of ACE inhibitors (ACEI) in patients with D allele (ACEI ratio, 43.5% in the restenosis group and 56.5% in non-restenotic group, P < 0.05). We did not find any relationship between ACE gene I/D polymorphism and CAD and stent restenosis and new lesion development in diabetic patients. On the other hand, ACEI treatment may reduce stent restenosis in type 2 diabetic patients with D allele (DD or ID).