Anemia and Iron Deficiency Predict All-Cause Mortality in Patients with Heart Failure and Preserved Ejection Fraction: 6-Year Follow-Up Study.

AIMS: The aim of this study was to assess the prevalence of anemia and iron deficiency in patients with heart failure with preserved ejection fraction (HFpEF) and its impact on clinical outcomes. METHODS: We retrospectively analyzed 212 patients with HFpEF and identified anemia as a serum hemoglobin level of less than 13 g/dL in men and less than 12 g/dL in women. Additionally, ID was defined as a serum ferritin concentration < 100 ng/mL or 100-299 ng/mL with transferrin saturation < 20%. Patients were followed up for an average of 66.2 ± 12.1 months, with the endpoint being all-cause mortality among patients with HFpEF, both with and without anemia and iron deficiency. Furthermore, we explored other predictors of all-cause mortality. RESULTS: The average age of the entire group was 70.6 ± 10.5 years, with females comprising 55% of the patients. Anemia was present in 81 (38.2%) patients, while 108 (50.9%) had iron deficiency. At the end of the follow-up period, 60 (28.3%) of the patients had passed away. Patients with anemia displayed more heart failure (HF) symptoms, diastolic dysfunction, higher NT-pro-BNP levels, and worse baseline functional capacity than those without. Similarly, patients with iron deficiency showed more pronounced HF symptoms and worse functional capacity than those without. The results from the multivariable analyses revealed that anemia (hazard ratio [HR]: 5.401, 95% confidence interval [CI]: 4.303-6.209, log-rank p = 0.001), advanced age, iron deficiency (HR: 3.502, 95% CI: 2.204-6.701, log-rank p = 0.015), decreased left ventricular ejection fraction, chronic kidney disease, and paroxysmal nocturnal dyspnea were all independently associated with all-cause mortality. CONCLUSIONS: It is essential to consider anemia and iron deficiency as common comorbidities in managing and prognosis HFpEF, as they significantly increase mortality risk.

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.

Hydroxychloroquine/azithromycin treatment, QT interval and ventricular arrhythmias in hospitalised patients with COVID-19.

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZM) are widely used in off-label treatment of novel coronavirus disease (COVID-19). However, cardiac safety of these drugs is still controversial in COVID-19. Therefore, we aimed to evaluate association of HCQ or HCQ + AZM treatment regimens, corrected QT (QTc) interval and malignant ventricular arrhythmias in hospitalized patients. METHODS: This is a single-center, retrospective and observational study. All data were extracted from the electronic medical records. The initial and post-treatment mean QTc intervals were calculated and compared in patients with HCQ alone or HCQ + AZM therapy. Associated factors with QTc prolongation, the incidence of ventricular arrhythmia during treatment and in-hospital mortality because of ventricular arrhythmias were evaluated. RESULTS: Our cohort comprised 101 hospitalized COVID-19 patients (mean age of 49.60 ± 18 years, 54.4% men). HCQ + AZM combination therapy group (n = 56) was more likely to have comorbidities. After 5-days treatment, 19 (18.8%) patients had QTc prolongation, and significant increase in the QTc interval was observed in both two groups (P < .001). However, HCQ + AZM combination group had significantly higher ΔQTc compared to HCQ group (22.5 ± 18.4 vs 7.5 ± 15.3 ms, P < .001). All of 101 patients completed the 5-days treatment without interruption. Also, no malignant ventricular arrhythmia or death secondary to ventricular arrhythmia occurred during the treatment in both groups. CONCLUSIONS: The present study revealed that although HCQ + AZM treatment was independently associated with QTc prolongation, none of patients experienced malignant ventricular arrhythmia or death during treatment. Further prospective studies are needed to determine the exact implications of these drugs on arrhythmias in patients with COVID-19.

Perioperative outcomes following a hip fracture surgery in elderly patients with heart failure with preserved ejection fraction and heart failure with a mid-range ejection fraction.

BACKGROUND: To examine the influence of heart failure (HF) with preserved ejection fraction (HFPEF) and HF with mid-range ejection fraction (HFmrEF) on perioperative cardiac and noncardiac outcomes following hip fracture surgery. METHODS: Data of elderly patients (≥ 65 years) who underwent hip fracture surgery were retrospectively analyzed in this study. Patients with a left ventricular ejection fraction (LVEF) <40% were not included in this study. The definition of preoperative HFPEF (LVEF ≥50%) and HFmrEF (LVEF 40%-49%) was based on clinical documentation of HF in patients' medical records before surgery. The primary outcomes of this study were perioperative adverse events and mortality. The secondary outcome of interest was the length of stay in the hospital. RESULTS: A total of 328 patients (mean age 79.2±8.7 years, and 57.3% female) were enrolled. Of the study population, 250 (76.2%) patients had no HF, 50 (15.2%) patients had HFPEF, and 28 (8.6%) patients had HFmrEF before surgery. The frequency of perioperative cardiovascular and non-cardiovascular complications was similar to a rate of 7.0%. The mean length of hospital stay was 8.1±5.8 days, and the in-hospital mortality rate was 4.6%. Patients with HFPEF and HFmrEF had a longer length of stay and were more likely to experience perioperative complications and death than the patients without HF. Multivariate analyses showed that the presence of HFPEF and HFmrEF were both associated with increased rates of perioperative complications and mortality. CONCLUSION: Our findings suggest that the presence of HFPEF and HFmrEF may predict perioperative adverse events and mortality in elderly patients undergoing hip fracture surgery.

Preoperative Mild Pericardial Effusion Is Associated With Perioperative Complications In Elderly Patients Following Hip Fracture Surgery.

Background: The prevalence and prognostic value of mild pericardial effusion (MPE) has not been examined in patients undergoing non-cardiac surgery. Our study aimed to assess the frequency and prognostic value of MPE in elderly patients undergoing surgery for hip fracture. Methods: This is a single center, and retrospective study including elderly patients who underwent hip fracture surgery. The medical records of all patients, aged ≥65 years with femoral neck, intertrochanteric or subtrochanteric hip fracture undergoing surgery (intramedullary hip screw, sliding compression hip screw, hemiarthroplasty, or total hip arthroplasty) from June 2014 to June 2019 were analyzed. Patients with of multiple trauma and accidents were excluded. The MPE was defined as the presence of <10 mm pericardial effusion. The primary outcomes of the study were perioperative adverse medical events and length of stay in hospital. Results: A total of 462 patients (mean age 75.2 ± 11.7 years, and 53.5% female) were enrolled. MPE was detected in 72 patients (15.6%), and 62 patients (13.4%) experienced perioperative adverse medical events. Patients with MPE were older, had higher prevalence of diabetes, coronary artery disease, and heart failure, and had longer length of stay compared to patients without MPE. Univariate analysis showed a significant association between age, diabetes, coronary artery disease, American Society of Anesthesiologists status, MPE, and perioperative adverse events. After adjustment for age, demographics, and medical history, the presence of MPE remained as significant variable associated with perioperative complications (OR: 2.543, 95% CI: 1.173-3.469, p = 0.003). Conclusion: Our study is the first to demonstrate that the presence of MPE is associated with perioperative adverse events in elderly patients undergoing hip fracture surgery.

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.