PrevAleNce and Associated factors of inappropriaTe dosing of direct Oral anticoaguLants In pAtients with Atrial Fibrillation: the ANATOLIA-AF Study.

PURPOSE: Inappropriate dosing of direct oral anticoagulants is associated with an increased risk of stroke, systemic embolism, major bleeding, cardiovascular hospitalization, and death in patients with atrial fibrillation. The main goal of the study was to determine the prevalence and associated factors of inappropriate dosing of direct oral anticoagulants in real-life settings. METHODS: This study was a multicenter, cross-sectional, observational study that included 2004 patients with atrial fibrillation. The study population was recruited from 41 cardiology outpatient clinics between January and May 2021. The main criteria for inappropriate direct oral anticoagulant dosing were defined according to the recommendations of the European Heart Rhythm Association. RESULTS: The median age of the study population was 72 years and 58% were women. Nine-hundred and eighty-seven patients were prescribed rivaroxaban, 658 apixaban, 239 edoxaban, and 120 dabigatran. A total of 498 patients (24.9%) did not receive the appropriate dose of direct oral anticoagulants. In a logistic regression model, advanced age, presence of chronic kidney disease and permanent atrial fibrillation, prescription of reduced doses of direct oral anticoagulants or edoxaban treatment, concomitant use of amiodarone treatment, and non-use of statin treatment were significantly associated with potentially inappropriate dosing of direct oral anticoagulants. CONCLUSION: The study demonstrated that the prevalence of inappropriate direct oral anticoagulant dosing according to the European Heart Rhythm Association recommendations was 24.9% in patients with atrial fibrillation. Several demographic and clinical factors were associated with the inappropriate prescription of direct oral anticoagulants.

Gender-related clinical and management differences in patients with chronic heart failure with reduced ejection fraction.

AIM: Gender-related differences have been described in the clinical characteristics and management of patients with chronic heart failure with reduced ejection fraction (HFrEF). However, published data are conflictive in this regard. METHODS: We investigated differences in clinical and management variables between male and female patients from the ATA study, a prospective, multicentre, observational study that included 1462 outpatients with chronic HFrEF between January and June 2019. RESULTS: Study population was predominantly male (70.1%). In comparison to men, women with chronic HFrEF were older (66 ± 11 years vs 69 ± 12 years, P < .001), suffered more hospitalisations and presented more frequently with NYHA class III or IV symptoms. Ischaemic heart disease was more frequent in men, whereas anaemia, thyroid disease and depression were more frequent in women. No difference was seen between genders in the use rate of renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, or ivabradine, or in the proportion of patients achieving target doses of these drugs. Regarding device therapies, men were more often treated with an implantable cardioverter-defibrillator (ICD) and women received more cardiac resynchronisation therapy. CONCLUSION: In summary, although management seemed to be equivalent between genders, women tended to present with more symptoms, require hospitalisation more frequently and have different comorbidities than men. These results highlight the importance of gender-related differences in HFrEF and call for further research to clarify the causes of these disparities. Gender-specific recommendations should be included in future guidelines in HFrEF.

Body mass index is a predictor of presence of fragmented QRS complexes on electrocardiography independent of underlying cardiovascular status.

BACKGROUND: Fragmented QRS (fQRS) as a sign of myocardial fibrosis indicates adverse outcomes in various cardiovascular diseases. However, there are no clear data regarding relationship between obesity and fQRS. We aimed to investigate whether high body mass index (BMI) predicts fQRS on electrocardiography (ECG) independent of underlying cardiovascular status. METHODS: A total of 1530 patients were included into the study. Patients were divided into three groups according to BMI (normal, overweight and obese). Groups were compared regarding frequency of fQRS on ECG and we investigated the correlation between BMI and fQRS. RESULTS: Among study population, 841 patients had normal BMI, 402 patients were overweight, and 287 patients were obese. Obese patients had significantly higher frequency of fQRS on ECG compared to non-obese patients (p < 0,001). Furthermore, multivariate logistic regression analysis revealed that BMI is an independent predictor of presence of fQRS on ECG (OR:1,220, 95% CI: 1,177-1,266, p < 0.0001). CONCLUSION: BMI predicts fQRS independent of underlying cardiovascular status. Similar to cardiovascular diseases, BMI should be taken into consideration when using fQRS as a prognostic marker.

The Definition of Sarcomeric and Non-Sarcomeric Gene Mutations in Hypertrophic Cardiomyopathy Patients: A Multicenter Diagnostic Study Across Türkiye.

BACKGROUND: Hypertrophic cardiomyopathy is a common genetic heart disease and up to 40%-60% of patients have mutations in cardiac sarcomere protein genes. This genetic diagnosis study aimed to detect pathogenic or likely pathogenic sarcomeric and non-sarcomeric gene mutations and to confirm a final molecular diagnosis in patients diagnosed with hypertrophic cardiomyopathy. METHODS: A total of 392 patients with hypertrophic cardiomyopathy were included in this nationwide multicenter study conducted at 23 centers across Türkiye. All samples were analyzed with a 17-gene hypertrophic cardiomyopathy panel using next-generation sequencing technology. The gene panel includes ACTC1, DES, FLNC, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, PTPN11, TNNC1, TNNI3, TNNT2, TPM1, and TTR genes. RESULTS: The next-generation sequencing panel identified positive genetic variants (variants of unknown significance, likely pathogenic or pathogenic) in 12 genes for 121 of 392 samples, including sarcomeric gene mutations in 30.4% (119/392) of samples tested, galactosidase alpha variants in 0.5% (2/392) of samples and TTR variant in 0.025% (1/392). The likely pathogenic or pathogenic variants identified in 69 (57.0%) of 121 positive samples yielded a confirmed molecular diagnosis. The diagnostic yield was 17.1% (15.8% for hypertrophic cardiomyopathy variants) for hypertrophic cardiomyopathy and hypertrophic cardiomyopathy phenocopies and 0.5% for Fabry disease. CONCLUSIONS: Our study showed that the distribution of genetic mutations, the prevalence of Fabry disease, and TTR amyloidosis in the Turkish population diagnosed with hypertrophic cardiomyopathy were similar to the other populations, but the percentage of sarcomeric gene mutations was slightly lower.

Real-World Evaluation of Anticoagulant Treatment Patterns in Patients with Atrial Fibrillation: Data from Multicenter ROTA Study.

OBJECTIVE: Oral anticoagulant therapy is the cornerstone of atrial fibrillation management to prevent stroke and systemic embolism. However, there is limited real-world information regarding stroke and systemic embolism prevention strategies in patients with atrial fibrillation. The aim of the ROTA study is to obtain the real-world data of anticoagulant treatment patterns in patients with atrial fibrillation. METHODS: The ROTA study is a prospective, multicenter, and observational study that included 2597 patients with atrial fibrillation. The study population was recruited from 41 cardiology outpatient clinics between January 2021 and May 2021. RESULTS: The median age of the study population was 72 years (range: 22-98 years) and 57.4% were female. The median CHA2DS2-VASc and HAS-BLED scores were 4 (range: 0-9) and 1 (range: 0-6), respectively. Vitamin K antagonists and direct oral anticoagulants were used in 15.9% and 79.4% of patients, respectively. The mean time in therapeutic range was 52.9% for patients receiving vitamin K antagonists, and 76% of those patients had an inadequate time in therapeutic range with <70%. The most common prescribed direct oral anticoagulants were rivaroxaban (38.1%), apixaban (25.5%), and edoxaban (11.2%). The rate of overuse of vitamin K antagonists and direct oral anticoagulants was high (76.1%) in patients with low stroke risk, and more than one-fourth of patients on direct oral anticoagulant therapy were receiving a reduced dose of direct oral anticoagulants. Among patients who were on direct oral anticoagulant treatment, patients with apixaban treatment were older, had higher CHA2DS2-VASc and HAS-BLED scores, and had lower creatinine clearance than the patients receiving other direct oral anticoagulants. CONCLUSIONS: The ROTA study provides important real-world information about anticoagulant treatment patterns in patients with atrial fibrillation.time in therapeutic range with <70%.

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.

Clinical characteristics and in-hospital outcomes of acute decompensated heart failure patients with and without atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. The impact of AF on in-hospital outcomes in acute decompensated heart failure (ADHF) is controversial. The aim of this study is to determine the prevalence of AF among hospitalized patients with ADHF and describe the clinical characteristics and in-hospital outcomes of these patients with and without AF. METHODS: We examined the multicenter, observational data from the real-life data of hospitalized patients with HF: Journey HF-TR study in Turkey that studied the clinical characteristics and in-hospital outcomes of hospitalized patients with ADHF between September 2015 and September 2016. RESULTS: Of the 1,606 patients hospitalized with ADHF, 626 (39%) had a history of AF or developed new-onset AF during hospitalization. The patients with AF were older (71±12 vs. 65±13 years; p<0.001) and more likely to have a history of hypertension, valvular heart disease, and stroke. The AF patients were less likely to have coronary artery disease and diabetes. In-hospital adverse event rates and length of in-hospital stay were similar in ADHF patients, both with and without AF. In-hospital all-cause mortality rate was higher in patients with AF than in patients without AF, although the difference was not statistically significant (8.9% vs. 6.8%; p=0.121). CONCLUSION: AF has been found in more than one-third of the patients hospitalized with ADHF, and it has varied clinical features and comorbidities. The presence of AF is not associated with increased adverse events or all-cause mortality during the hospitalization time.

Adherence to guideline-directed medical and device Therapy in outpAtients with heart failure with reduced ejection fraction: The ATA study.

OBJECTIVE: Despite recommendations from heart failure guidelines on the use of pharmacologic and device therapy in patients with heart failure with reduced ejection fraction (HFrEF), important inconsistencies in guideline adherence persist in practice. The aim of this study was to assess adherence to guideline-directed medical and device therapy for the treatment of patients with chronic HFrEF (left ventricular ejection fraction ≤40%). METHODS: The Adherence to guideline-directed medical and device Therapy in outpAtients with HFrEF (ATA) study is a prospective, multicenter, observational study conducted in 24 centers from January 2019 to June 2019. RESULTS: The study included 1462 outpatients (male: 70.1%, mean age: 67±11 years, mean LVEF: 30%±6%) with chronic HFrEF. Renin-angiotensin system (RAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and ivabradin were used in 78.2%, 90.2%, 55.4%, and 12.1% of patients, respectively. The proportion of patients receiving target doses of medical treatments was 24.6% for RAS inhibitors, 9.9% for beta-blockers, and 10.5% for MRAs. Among patients who met the criteria for implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT), only 16.9% of patients received an ICD (167 of 983) and 34% (95 of 279) of patients underwent CRT (95 of 279). CONCLUSION: The ATA study shows that most HFrEF outpatients receive RAS inhibitors and beta-blockers but not MRAs or ivabradin when the medical reasons for nonuse, such as drug intolerance or contraindications, are taken into account. In addition, most eligible patients with HFrEF do not receive target doses of pharmacological treatments or guideline-recommended device therapy.

Drug Adherence in Patients With Nonvalvular Atrial Fibrillation Taking Non-Vitamin K Antagonist Oral Anticoagulants in Turkey: NOAC-TR.

Adherence to non-vitamin K antagonist oral anticoagulants (NOACs) is an important factor for ensuring efficacy and safety in nonvalvular atrial fibrillation (NVAF). There are controversial results regarding NOAC adherence in real-world data and there are no data about NOAC adherence in Turkish population. This study investigated the NOAC adherence based on self-report, factors affecting nonadherence, and the relation of the adherence level with efficacy and safety outcomes. This multicenter cross-sectional study included 2738 patients (59% female) using NOAC (dabigatran, apixaban, and rivaroxaban) due to NVAF for more than 3 months with >30 days of supply between September 1, 2015, and February 28, 2016. To measure the adherence level, an 8-item Morisky Medication Adherence Scale was used. The mean age of the patients was 70 ± 10 years. Of the 2738 patients, 44% were receiving dabigatran, 38% rivaroxaban, and 18% apixaban. A total of 630 (23%) patients had high medication adherence, 712 (26%) moderate adherence, and 1396 (51%) low adherence. Nonadherence had related to stroke (5.6% vs 2.5%, P < .001) and minor (21.2% vs 11.1%, P < .001) and major (6.1% vs 3.7%, P = .004) bleeding rates. The adherence to NOAC was found to be quite low in Turkey. Nonadherence is associated with bleeding and thromboembolic cardiovascular events. Age, taking NOAC twice a day, and the additional noncardiac diseases, depression, and dementia were the independent factors affecting poor medication adherence.

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.

The effect of long-term continuous positive airway pressure treatment on systolic and diastolic function in patients with obstructive sleep apnoea syndrome: a five year observational study.

OBJECTIVE: Evaluation of the long-term effects of continuous positive airway presure (CPAP) on mean heart rate and left ventricular systolic and diastolic parameters in obstructive sleep apnea syndrome (OSAS) using conventional and tissue Doppler techniques. METHODS: This prospective cohort study is designed to evaluate the long-term effects of CPAP treatments in normotensive OSAS patients. Initially 40 patients aged from eighteen to fifty five with documented OSAS syndrome were evaluated within one month of CPAP treatment. All had high self-reported compliance with treatment. From the latter, 21 patients with uninterrupted CPAP therapy (for at least 5 years, 5 hours per day) were included in the study and further evaluated with treatment. The left ventricular systolic function was assessed on apical four- chamber view using modified Simpson method and diastolic function was evaluated with classic transmitral pulsed and tissue Doppler techniques. Paired t test and Wilcoxon signed rank test had been used to compare the clinical and echocardiography data before and after treatment period. RESULTS: A comparison of values assessed after one month and after 5 years of CPAP therapy, revealed a significant increase in the acceleration time(AT) Em/Am ratio and ejection time (ET) (AT: p=0.04; Em/Am ratio p=0.03 ET: p=0.04) while a significant decrease was observed on deceleration time (DT), isovolumetric relaxation time (IRT), myocardial performance index (MPI), mitral regurgitation (MR) and 24 hour mean heart rate (HR) in all subjects (DT: p=0.02; IVRT: p=0,04; MPI: p=0,01; MR: p≤0.001; HR: p=0.004). CONCLUSION: We observed a significant improvement in the left ventricular systolic and diastolic function and a significant decrease of 24-hour heart rate and mitral regurgitation with unchanged ejection fraction of the left ventricle with long-term CPAP treatment similar to short-term treatment studies. The long-term maintenance of the beneficial effect of CPAP throughout the 5 year long-term treatment can be one of the pathophysiologic mechanisms that may explain the decrease of cardiovascular mortality observed with long-term CPAP therapy in OSAS patients.

Strenuous exercise induced syncope due to coronary artery anomaly.

Coronary artery anomalies are among the neglected topics in cardiology. Anomalous origin of the left main coronary artery from the right sinus of valsalva is a rare coronary anomaly observed in 0.15% of patients. During exercise, the distended aorta and pulmonary artery with increased blood flow may squeeze the Left Main Coronary Artery (LMCA) between them. Even though arrhythmias are common causes of syncope, one should also think about aberrant coronary artery in the patients with syncope of unexplained origin. Patients experiencing exercise induced syncope accompanied by symptoms of coronary ischemia (typically: chest pain, ischemic findings on ECG, and raised cardiac markers) should be referred to diagnostic coronary angiography.