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.

Inappropriate Use of Aspirin in Real-Life Cardiology Practice: Results from the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) Study.

BACKGROUND: Indications and appropriateness of aspirin use have not been well investigated in Turkey. AIMS: To investigate the prescription patterns and appropriateness of aspirin in a real-world clinical setting. STUDY DESIGN: Cross-sectional study. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) is a cross-sectional and multicenter study that included 5007 consecutive patients aged 18 or over who presented to 30 different cardiology outpatient clinics from 14 cities throughout Turkey. Only patients using aspirin (80-325 mg) were included. The study population was divided into 2 groups regarding the use of aspirin: primary prevention (PP) group and secondary prevention (SP) group. The indication of aspirin use was evaluated following the 2016 European Society of Cardiology (ESC) and the 2016 United States Preventative Services Task Force (USPTF) guidelines in the PP group. RESULTS: A total of 5007 patients (mean age 62.15 ± 11.05, 39% female) were enrolled. The PP group included 1132 (22.6%) patients, and the SP group included 3875 (77.4%) patients. Of the 1132 patients, inappropriate use of aspirin was determined in 100% of the patients according to the ESC guidelines, and 71% of the patients according to the USPTF guidelines. Multivariate logistic regression analysis showed age OR: 0.98 CI (0.97-0.99) P = .037, smoking OR: 0.60 CI (0.44-0.82) P = .001, heart failure OR: 2.11 CI (1.14-3.92) P = .017, hypertension OR: 0.51 CI (0.36-0.74) P < .001, diabetes mellitus OR: 0.34 CI (0.25-0.47) P < .001, oral anticoagulant use OR: 3.01 CI (1.10-8.25) P = .032, and female sex OR: 2.73 CI (1.96-3.80) P < .001 were independent predictors of inappropriate aspirin use in PP patients. CONCLUSION: Although there are considerable differences between the USPTF and the ESC guidelines with respect to recommendations for aspirin use in PP, inappropriate use of aspirin in Turkey is frequent in real-world practice for both guidelines. Besides, heart failure, oral anticoagulant use, and the female sex of the patients were independent predictors of inappropriate use of aspirin.

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.

Knowledge and attitudes towards hypertriglyceridaemia and associated residual risk amongst cardiologists in Turkey.

BACKGROUND: Hypertriglyceridemia (HTG) is an important component of residual risk. The knowledge regarding its treatment might not be at a desired level which might prevent patients from receiving the maximum benefit. We aimed to investigate the knowledge and attitudes of Turkish cardiologists who responded to a survey regarding HTG treatment. METHODS: A multiple-choice survey was conducted to analyze Turkish cardiologists' management of HTG. The questionnaire was submitted by the Turkish Society of Cardiology to all its members. RESULTS: A total of 160 cardiologists responded to the survey. The mean age was 37.5±8.5 years, and 35 (21.9%) of the participants were female. Most of the participants (88%) thought HTG was a risk factor, and 75% of them felt confident in diagnosing and treating HTG. Patient compliance (41%), polypharmacy (33%), and lack of treatment options (15%) were the most common problems obstructing treatment of HTG. A proportion of 96% of the participants knew about non-high-density lipoprotein cholesterol, which is a good surrogate marker of atherogenic dyslipidemia; however, only 39% were using it as a treatment goal. In the case of low-density lipoprotein cholesterol at goal but with HTG (residual risk), the first choice for treatment was fibrates (94%). Half of cardiologists had never used omega-3 fatty acids as a treatment option. CONCLUSIONS: Although most of the participating cardiologists felt competent treating HTG, there was a knowledge gap in the treatment of atherogenic dyslipidemia and management of residual risk. Evidence of the benefit of lowering triglycerides from cardiovascular outcome trials is eagerly awaited. There is also an unmet need of increasing patient compliance and managing polypharmacy.

Rationale, design, and methodology of the EPIC (Epidemiology of Polypharmacy and Potential Drug-Drug Interactions in Elderly Cardiac Outpatients) study.

OBJECTIVE: The aim of this study is to assess the prevalence of polypharmacy, inappropriate drug use, and drug-drug interactions (DDIs) in elderly patients presenting at outpatient cardiology clinics in Turkey. METHODS: The EPIC (Epidemiology of Polypharmacy and Potential Drug-Drug Interactions in Elderly Cardiac Outpatients) study will be an observational, real-world, multicenter study conducted to evaluate DDIs and polypharmacy in elderly cardiac outpatients. All consecutive patients (aged ≥65 years) admitted to outpatient cardiology clinics between July 30, 2018 and July 30, 2019 who provide written, informed consent will be enrolled. A total of approximately 5000 patients are to be enrolled in this non-interventional study. All of the data will be collected at one point in time and current clinical practice will be evaluated (ClinicalTrials.gov NCT03370523). RESULTS: Patient demographics, comorbid disease characteristics, laboratory test results, and details of medication use will be collected using self-reports and medical records. The severity of comorbid disease will be recorded and scored according to Charlson Comorbidity Index (CCI) and patients will be divided into 3 groups: mild, those with a CCI score of 1-2; moderate, those with a CCI score of 3-4; and severe, those with a CCI score of ≥5. Polypharmacy will be defined as the use of 5 or more medications at one time. DDIs will be determined using the Lexicomp Online drug interaction screening tool and potentially inappropriate medications will be defined based on the 2015 update of the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Severe drug interactions will be defined as those in category D or X. CONCLUSION: EPIC will be the first large-scale study in Turkey to evaluate polypharmacy, potentially inappropriate medications, and DDIs in elderly cardiac outpatients in a real-world clinical setting.

Geographical Variations in Patients with Heart Failure and Preserved Ejection Fraction: A Sub-Group Analysis of the APOLLON Registry

Background: Clinical characteristics of patients with heart failure may vary geographically. However, limited data are available regarding the geographical differences of patients with heart failure and preserved ejection fraction. Aims: The present subgroup analysis aims to investigate the geographical differences in clinical characteristics, management, and primary etiology of patients with heart failure and preserved ejection fraction in Turkey. Study Design: A cross-sectional study. Methods: A comPrehensive, ObservationaL registry of heart faiLure with mid-range and preserved ejection fractiON (APOLLON) is a multicenter and observational study conducted in seven regions of Turkey (NCT03026114). The present study is a post-hoc analysis of the APOLLON registry. In this substudy, we compared the clinical characteristics of 819 consecutive patients with heart failure and preserved ejection fraction (mean age, 67 years; 57.8% women) admitted to cardiology outpatient units in different geographical regions. Results: Based on the geographical distribution of the entire Turkish population, the highest number of patients enrolled were from Marmara (271 patients, 33.1%). All demographical characteristics, clinical and laboratory findings, comorbidities, primary etiology, and medications prescribed were significantly different between the regions. Furthermore, inter-regional gender differences were identified. Comparatively, the Aegean and Mediterranean regions had older patients with heart failure and preserved ejection fraction (p<0.001), and the Black Sea, Southeast, and East Anatolia regions had predominantly male patients (51.2, 54.5, and 56.9%, respectively; p=0.002). Notably, the Mediterranean and Southeast Anatolia had more symptomatic patients, and history of hospitalization for heart failure was more prevalent in Southeast Anatolia (33.3%, p<0.001). Prevalence of atrial fibrillation was higher in the Mediterranean and Southeast Anatolia regions (51 and 48.5%, p<0.001), and patients with heart failure and preserved ejection fraction had a higher prevalence of hypertension in the Mediterranean, Southeast Anatolia, and Black Sea regions (p=0.002). Angiotensin-converting enzyme inhibitors were more frequently prescribed in East Anatolia (52.3%, p=0.001), and the prevalence of patients with heart failure and preserved ejection fraction using loop diuretics (48.8%, p=0.003) was higher in the Black Sea region. Conclusion: This study was the first to show geographical differences in clinical characteristics of patients with heart failure and preserved ejection fraction in Turkey. Determination of the clinical characteristics of the heart failure and preserved ejection fraction population based on the geographical region may enables physicians to adopt a region-specific clinical approach toward heart failure and preserved ejection fraction.

Design and rationale for the ASSOS study: Appropriateness of aspirin use in medical outpatients a multicenter and observational study.

OBJECTIVE: The aim of this study was to describe the current status of aspirin use and the demographic characteristics of patients on aspirin for primary and secondary prevention of cardiovascular diseases. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) trial was a multicenter, cross-sectional, and observational study conducted in Turkey. The study was planned to include 5000 patients from 14 cities in Turkey. The data were collected at one visit, and the current clinical practice regarding aspirin use was evaluated (ClinicalTrials.gov number NCT03387384). RESULTS: The study enrolled all consecutive patients who were admitted to the outpatient cardiology clinics from March 2018 until June 2018. Patients should be at least 18 years old, have signed written informed consent, and on aspirin (80-325 mg) therapy within the last 30 days. Cardiologists from the hospital participates in the study. Patients were divided into 2 categories according to presence or absence of atherosclerotic cardiovascular disease, namely secondary prevention group and primary prevention group, respectively. The appropriate use of aspirin in the primary and secondary prevention groups was assessed according to the European Society of Cardiology guidelines and US Preventive Services Task Force. The patients' gastrointestinal bleeding risk factors and colorectal cancer risk were evaluated. CONCLUSION: The ASSOS registry will be the most comprehensive and largest study in Turkey evaluating the appropriateness of aspirin use. The results of this study help understand the potential misuse of aspirin in a real-world setting.

Impact of preoperative cardiology consultation prior to intermediate-risk surgical procedures.

BACKGROUND: Patients undergoing noncardiac, nonvascular surgery (NCNVS) are at risk of perioperative cardiovascular events. However, benefits of cardiology consultation (CC) in patients with known or suspected cardiac disease undergoing intermediate-risk NCNVS is unknown. METHODS: The study group included 700 consecutive patients referred for CC before intermediate-risk NCNVS in a tertiary-care teaching hospital. The control group included 1200 age-matched and sex-matched consecutive patients proceeded to the intermediate-risk surgery without preoperative CC during the same period. Patients older than 18 years who underwent an elective, NCNVS were enrolled. Requests for consultation were made either by surgeon or an attending anaesthesiologist. All patients underwent a complete preoperative clinical evaluation. RESULTS: Of the 700 patients who were referred for CC in the study group, 530 patients (75.7%) had no additional recommendations, and 170 patients (24.3%) underwent additional preoperative tests or had a change in preoperative therapy. Only 20 (2.8%) patients' NCNVS were delayed based on the cardiologists' recommendation and 680 patients eventually had their surgeries. Major cardiovascular and noncardiovascular complication rates were similar in the study and in the control groups (12.9% vs 13.6%, P = 0.273 and 25.2% vs 26%, P = 0.432 respectively). CONCLUSIONS: Preoperative CC in patients who underwent intermediate-risk NCNVS does not affect either perioperative management or outcome of surgery.

Predictive role of left atrial and ventricular mechanical function in postoperative atrial fibrillation: a two-dimensional speckle-tracking echocardiography study.

OBJECTIVE: The aim of this study was to determine the role of left-sided mechanical parameters in postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass grafting (CABG). METHODS: Ninety patients with coronary artery disease and normal left ventricular (LV) function in sinus rhythm were enrolled in the study. Preoperative LV and left atrial (LA) mechanics were evaluated by two-dimensional (2D) speckle-tracking echocardiography (STE), including strain and rotation parameters, and volume indices. Patients were monitored in order to detect POAF during the postoperative period. RESULTS: Twenty-three of 90 patients (25.6%) developed POAF. Age (p<0.001) and preoperative beta blocker usage (p=0.001) were the clinical parameters associated with POAF. Left atrial maximum volume index (LAV[max]i) increased, and peak left atrial longitudinal strain (PALS) was impaired in POAF patients (p=0.001, p<0.001, respectively). Left ventricular twist (LVtw) and left ventricular peak untwisting velocity (UntwV) were augmented in POAF patients (p=0.013, p=0.009, respectively). Receiver operating characteristic analysis showed N-terminal pro-brain natriuretic peptide (NT-proBNP) levels above 70 pg/ml and predicted POAF with a sensitivity of 74% and specificity of 78% (area under curve: 0.758, 95% confidence interval [CI] 0.631-0.894, p<0.001). Logistic regression analysis demonstrated that age (odds ratio [OR] 1.1, CI 1.01-1.20, p=0.034), preoperative beta blocker usage (OR 8.84, CI 1.36-57.28, p=0.022), NT-proBNP (values >70 pg/ml, OR 22.377, CI 3.286-152.381, p<0.001), PALS (OR 0.86, CI 0.75-0.98, p=0.023), and UntwV (OR 1.02, CI 1.00-1.04, p=0.029) were the independent predictors of POAF. CONCLUSION: The combination of 2D STE, clinical, and biochemical parameters may help predict POAF.

Treatment of Prosthetic Valve Thrombosis: Current Evidence and Future Directions.

Prosthetic heart valve thrombosis (PVT) is a rare but serious complication with high morbidity and mortality. The optimal treatment of the PVT is controversial and depends on thrombus location and size, the patient's functional class, the risk of surgery or thrombolysis, and the clinician's experience. Although surgical therapy has been the traditional therapeutic approach, studies with low-dose and slow-infusion rates of thrombolytic agents have revealed excellent results. This article reviews the various treatment options in patient with PVT.

Drospirenone-containing oral contraceptives and risk of adverse outcomes after myocardial infarction.

BACKGROUND: The association between oral contraceptives (OC) and myocardial infarction remains controversial. The new generation contraceptive Yasmin (30 µg ethinyl estradiol and 3 mg drospirenone) has a lower estrogen and newer progestin component. To date, there are no data available for the myocardial infarction risk and outcome for drospirenone. We aimed to investigate the effect of Yasmin use on cardiovascular outcomes in patients with acute ST segment elevation myocardial infarction (STEMI) undergoing primary angioplasty. METHODS: We retrospectively evaluated 1851 patients who underwent primary angioplasty for acute STEMI. Of them, 440 female patients (23.8%) composed the study population and 12 female (2.7%) were taking the oral contraceptive-Yasmin at the time of infarction. Patients were divided into two groups based on their age (≥50 (n = 339) and <50 years old). Patients under 50 years-old (n = 101) were separated into two groups according to use of OC therapy (OC (+) group n = 12; OC (-) group n = 89). RESULTS: Patients who were older than 50-year-old were more likely to have comorbid conditions like diabetes mellitus and hypertension than other groups. Current smoking status was significantly higher in OC (+) group than OC (-) group (P = 0.007). There was a significant difference in favour of OC (+) group when compared with OC (-) group for the increased angiographic thrombus burden according to both TIMI and Yip classification (P = 0.045 and P = 0.029, respectively). The incidence of final TIMI 3 flow and post-procedural complete ST resolution were significantly lower in OC (+) group (P = 0.019, P = 0.002, respectively). In multivariate logistic regression analysis, use of OC was found to be an independent predictor of high grade thrombus burden (OR 5.13, 95% CI 1.07-24.60, P = 0.04). CONCLUSION: This is the first study to evaluate the myocardial infarction risk and its subsequent clinical sequelae in women having a STEMI while taking the OC-Yasmin. Women on the oral contraception Yasmin, who underwent coronary revascularization had a lower post-procedural complete ST resolution and worse left ventricular function. Furthermore, OC use with Yasmin is an independent predictor of a high-grade thrombus burden.

The importance of papillary muscle dyssynchrony in predicting the severity of functional mitral regurgitation in patients with non-ischaemic dilated cardiomyopathy: a two-dimensional speckle-tracking echocardiography study.

AIMS: In our study, we investigated the impact of papillary muscle systolic dyssynchrony (DYS-PAP) and the configuration of mitral leaflets in the prediction of significant functional mitral regurgitation (MR) with two-dimensional (2D) speckle-tracking strain analysis in non-ischaemic dilated cardiomyopathy (DCM) patients with sinus rhythm. METHODS: Thirty-six non-ischaemic DCM patients (left ventricular ejection fraction <40%) with sinus rhythm were recruited. The quantification of functional MR was performed using the proximal isovelocity surface area method. The configuration of mitral leaflets [mitral annulus, coaptation height (CH), and tethering distances for papillary muscles] was evaluated in the parasternal long-axis and apical four-chamber views. The assessment of DYS-PAP was performed by applying 2D speckle-tracking imaging to the apical four-chamber view for anterolateral papillary muscle and to the apical long-axis view for posteromedial papillary muscle. RESULTS: Fifteen (41.6%) patients had mild MR and 21 (58.3%) patients had moderate or moderate-to-severe MR. Patients with higher levels of MR had larger mitral annulus size (P = 0.02), tethering-AL (P = 0.04), higher MR volume (P < 0.0001), effective regurgitant orifice area (P < 0.0001), and DYS-PAP (P < 0.0001) values, but lower CH (P = 0.001), global longitudinal (P = 0.005), radial (P = 0.03), and circumferential strain (P = 0.01) than those with mild MR. Receiver operating characteristic analysis was performed to assess the utility of DYS-PAP to predict moderate or moderate-to-severe functional MR. A DYS-PAP value >30 ms predicted moderate-to-severe MR with 85% sensitivity and 87% specificity [area under the curve: 0.897, 95% confidence interval (CI): 0.781-0.999, P < 0.0001]. Logistic regression analysis revealed that DYS-PAP (odds ratio: 3.2, 95% CI: 1.22-47.7, P = 0.037) was the only independent predictor of moderate or moderate-to-severe functional MR. CONCLUSION: DYS-PAP is correlated with functional MR in non-ischaemic DCM patients with sinus rhythm. A DYS-PAP cut-off value of 30 ms is a useful tool to identify patients with moderate-to-severe functional MR.