Evaluation of demographic and clinical characteristics of female patients presenting with MINOCA and differences between male patients: A subgroup analysis of MINOCA-TR registry.

OBJECTIVE: Although the prevalence and rate of myocardial infarction with non-obstructive coronary arteries (MINOCA) are higher in women than in men in previous cohorts, potential demographic and clinical differences between women who are diagnosed with MINOCA versus myocardial infarction with obstructive coronary arteries (MIOCA) have not been studied till date. In this study, we aimed to document these characteristics and to compare them between female patients with MINOCA and MIOCA. METHODS: The study was a subgroup analysis of the MINOCA-TR study. The study was a multi-center, observational cohort study that was conducted in Turkey between March 2018 and October 2018. In this study, 477 (29.3%) female patients who had been diagnosed with acute myocardial infarction were evaluated. RESULTS: Of these women, 49 (10.3%) were diagnosed with MINOCA (mean age 58.9±12.9 years) and 428 (89.7%) had a final diagnosis of MIOCA (mean age 67.4±11.8 years). The prevalence of hypertension, hyperlipidemia, and diabetes mellitus was significantly lower in the MINOCA group than in the MIOCA group. In addition, the MINOCA group had higher rates of recent flu history and non-ST elevation myocardial infarction (NSTEMI) presentation than the MIOCA group. There were significant clinical differences in patients with MINOCA in terms of sex. The female patients were older, had higher systolic blood pressures, and lower hemoglobin levels than male patients. CONCLUSION: The study revealed that the prevalence of traditional coronary artery disease risk factors was lower in female patients with MINOCA than in those who had final diagnosis of MIOCA.

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.

Current clinician perspective on non-vitamin K antagonist oral anticoagulant use in challenging clinical cases.

OBJECTIVE: The evolution of non-vitamin K antagonist anticoagulants (NOACs) has changed the horizon of stroke prevention in atrial fibrillation (SPAF). All 4 NOACs have been tested against dose-adjusted warfarin in well-designed, pivotal, phase III, randomized, controlled trials (RCTs) and were approved by regulatory authorities for an SPAF indication. However, as traditional RCTs, these trials have important weaknesses, largely related to their complex structure and patient participation, which was limited by strict inclusion and extensive exclusion criteria. In the real world, however, clinicians are often faced with complex, multimorbid patients who are underrepresented in these RCTs. This article is based on a meeting report authored by 12 scientists studying atrial fibrillation (AF) in diverse ways who discussed the management of challenging AF cases that are underrepresented in pivotal NOAC trials. METHODS: An advisory board panel was convened to confer on management strategies for challenging AF cases. The article is derived from a summary of case presentations and the collaborative discussions at the meeting. CONCLUSION: This expert consensus of cardiologists aimed to define management strategies for challenging cases with patients who underrepresented in pivotal trials using case examples from their routine practice. Although strong evidence is lacking, exploratory subgroup analysis of phase III pivotal trials partially informs the management of these patients. Clinical trials with higher external validity are needed to clarify areas of uncertainty. The lack of clear evidence about complex AF cases has pushed clinicians to manage patients based on clinical experience, including rare situations of off-label prescriptions.

Prevalence and clinical profile of patients with myocardial infarction with non-obstructive coronary arteries in Turkey (MINOCA-TR): A national multi-center, observational study.

OBJECTIVE: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is a relatively new term that is characterized by clinical evidence of MI with normal or near-normal coronary arteries on coronary angiography (QCA). To date, there have been no population-based studies on the prevalence of MINOCA in Turkey. The aim of this nationwide study was to document the prevalence and demographics of MINOCA in a Turkish population. METHODS: MINOCA-TR is national, multi-center, prospective, all-comer study that was conducted in 32 hospitals. All consecutive patients who were ≥18 years old, diagnosed with MI according to the Third Universal Definition of Myocardial Infarction, and had undergone QCA were included in the study. Patients with stable coronary artery disease, unstable angina pectoris, a history of revascularization, and type 4/5 MI were excluded. RESULTS: A total of 1793 patients who were diagnosed with MI and had undergone QCA were screened between March 2018 and October 2018, of whom 1626 (mean age: 61.5±12.5 years, 70.7% male) were enrolled from 32 centers. The prevalence of MINOCA was 6.7% (n=109) in the overall study population. Compared with non-MINOCA patients, those with MINOCA were younger, had a higher prevalence of the female gender, and had a history of flu. The percentages of current smokers, ST-segment elevated myocardial infarction patients, and those with a history of hypertension, diabetes mellitus, and hyperlipidemia were significantly lower in MINOCA patients (p<0.05, for all). Also, the median left ventricular ejection fraction as seen on echocardiography and the ratio of Killip Class I status at presentation was significantly higher in MINOCA patients than in non-MINOCA patients (p<0.001). Patients with MINOCA received a preload dose of P2Y12 antagonist before QCA less often than non-MINOCA patients (p<0.001). CONCLUSION: The prevalence of MINOCA in Turkey is 6.7% in patients who were admitted with MI. Also, as compared to non-MINOCA patients, the MINOCA patients were exposed to fewer traditional risk factors of coronary artery disease.

Rationale and design of the Myocardial Infarction with Non-obstructive Coronary Arteries in Turkish Population (MINOCA-TR) study.

OBJECTIVE: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is a new term to define the syndrome of clinical evidence of MI occurring in the absence obstructive coronary artery disease. Given that there is believed to be a large number of MINOCA cases, effective diagnostic and therapeutic strategies are needed. Documentation of the demographic parameters and diagnostic methods used in existing cases is a first step. The purpose of this study is documentation of the prevalence, demographic details, and possible etiological causes, as well as inpatient and 1-year prognosis data of MINOCA patients in the Turkish population. METHODS: The MINOCA-TR Study is a national, multi-center, prospective, observational study. A sample of 1028 conse-cutive MI patients who undergo diagnostic angiography will be enrolled. This is a cohort study that will include patients from 32 different centers. After an initial screening/enrollment visit, follow-up will be performed at the time of hospital discharge for the overall MI study population. Patients diagnosed as MINOCA will be followed up with 3 prospective office or telephone visits as part of the Prospective MINOCA Registry. CONCLUSION: Demographic information, clinical characteristics, management strategies, and inpatient prognostic indicators will be documented in the cross-sectional portion of the registry. Additional diagnostic data, therapeutic strategies, and prognostic relevance will be recorded in the 12 months of the prospective research. The results are expected to inform future diagnostic and therapeutic strategies and enhance understanding of the condition by highlighting the national burden of the disease from a medical and a public health perspective, as well as stimulate future research focusing on the MINOCA population.

Remote monitoring with cardiac implantable electronic device to follow up pharmacodynamic effects of sacubitril/ valsartan treatment: A case report.

Cardiac implantable electronic devices include remote monitoring tools intended to guide heart failure management. These tools allow for observation of some physiological functions, such as intrathoracic impedance (ITI), patient activity (PA), and heart rate variability (HRV). Sacubitril/valsartan is recommended in the current guidelines as foundational therapy for patients with heart failure and reduced ejection fraction. However, the effects of sacubitril/valsartan treatment on these physiological parameters remain unclear. To the best of our knowledge, this is the first case objectively documenting improvements in ITI, PA, and HRV values with sacubitril/valsartan treatment.

Enhancing Solubility and Bioavailability of Rosuvastatin into Self Nanoemulsifying Drug Delivery System.

OBJECTIVE: The aim of this study was to develop new Rosuvastatin calcium (RCa) self nanoemulsifying drug delivery system (SNEDDS) and to evaluate the bioavailability and pharmacodynamic effect of RCa-SNEDDS in Yorkshire pigs. METHODS: Firstly, SNEDDS was developed and prepared then RCa was incorporated into SNEDDS which was evaluated regarding their characterization, stability properties, drug release profiles, permeation and cytotoxicity studies. Finally, in vivo performance of RCa-SNEDDS (F1-RCa-SNEDDS) was examined by pharmacokinetic and pharmacodynamics studies. The average droplet size of RCa- SNEDDS ranged between 200 and 250 nm. RCa-SNEDDS that contained 12.8% Oleic acid, 11 % Labrafil M, 3.3 % Labrasol and 4.4 % Transcutol HP were found to be stable and exhibited approximately 4-fold higher permeation than commercial tablet (Crestor® 20 mg tablet). RESULTS: In pharmacokinetic studies, when F1-RCa-SNEDDS and commercial tablet were administered orally, F1-RCa-SNEDDS showed higher bioavailability of RCa than commercial tablet. Respectively, in pharmacodynamic studies, triglyceride and total cholesterol levels were significantly reduced with F1- RCa-SNEDDS formulation by 37% and 19% when compared to baseline values. CONCLUSION: However, these decreases with commercial formulation were only 6% and 2% respectively. According to these findings, development formulation could be potentially used to enhance the oral absorption of RCa.

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.

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.

Inadvertent implantation of pacemaker lead in the left ventricle: kill two birds with one stone.

We report an asymptomatic patient in whom the intravenous pacemaker (PM) lead was inadvertently implanted in LV through the perforated interventricular septum. He had no embolic events during the last 9 years after the implantation. Possible explanation of the uncomplicated follow-up period is that the patient had been taking warfarin because of mechanical mitral valve prosthesis.

The relationship between adiponectin, NT-pro-BNP and left ventricular ejection fraction in non-cachectic patients with systolic heart failure: an observational study.

OBJECTIVE: NT-pro-brain natriuretic peptide (NT-proBNP) has been shown to be an accurate diagnostic marker in patients with heart failure (HF). Adiponectin (Adp) levels are increased in HF but its diagnostic value is still uncertain in these patients. The study was designed to investigate the possible association of these markers in non-cachectic patients with newly diagnosed systolic heart failure. METHODS: Fifty-seven systolic HF patients and 20 matched controls were enrolled in an observational cross-sectional study. Physical and echocardiographic examinations were performed and serum Adp, NT-proBNP, tumor necrosis factor-alpha (TNF-α) levels were measured. Study variables were compared between the groups. Correlation analyses were done and the diagnostic validity of the markers was compared with ROC analysis. RESULTS: Adp and NT-proBNP levels were significantly higher in HF group (20.19±12.9 vs. 7.65±4.6 µg/mL; p<0.001 and 1051.74±606.2 vs. 222.53±65.6 pg/mL; p=0.002; respectively). TNF-α levels were similar between the groups (2.83±1.8 vs. 2.08±1.2 pg/mL; p=0.582). Correlation analysis showed significant association among Adp and NT-proBNP levels, (r=0.448; p<0.001), and left ventricular ejection fraction (LVEF) values (r=-0.466; p<0.001). The Adp and NT-proBNP showed comparable diagnostic performances with mean [95% confidence interval] areas under the curves of 0.857 (0.771-0.944) and 0.888 (0.815-0.960), respectively. CONCLUSION: There were significant correlation between Adp levels with NT-proBNP levels and LVEF values but no any association between Adp levels with body mass index values and TNF-α levels in patients with newly diagnosed systolic heart failure. The result may arouse suspicion about the hypothesis, which proposes that Adp levels simply reflects disease severity or cardiac cachexia in patients with HF.

Long pentraxin-3 measured at late phase associated with GRACE risk scores in patients with non-ST elevation acute coronary syndrome and coronary stenting.

OBJECTIVES: We analyzed pentraxin 3 (PTX3) levels and the relation of PTX3 levels with GRACE risk scores in 39 patients with non-ST elevation acute coronary syndrome (ACS) and stabile angina after stenting. STUDY DESIGN: Seventeen patients with ACS and 22 patients with stabile angina who underwent coronary stenting were included in the study. PTX3 levels were measured serially at admission, at the 8th hour and at the 24th hour after stenting. RESULTS: While diabetes and hypertension were more frequent in the stabile angina group, leukocyte counts were significantly higher in the ACS group. PTX3 levels measured at the 8th hour were significantly higher in the ACS group compared to the stabile angina group (p=0.003). Strong correlations were observed between 24th hour PTX3 levels and GRACE scores calculated for risk of death and death/MI at admission (in-hospital/to 6 months), and for risk of death/MI at discharge to 6 months (R=0.571, p=0.01, R=0.564, p=0.01; R=0.558, p=0.02, R=0.512, p=0.03; R=0.653, p=0.004, respectively). CONCLUSION: The serum PTX3 levels may provide important information for the early risk stratification of patients with ACS who underwent coronary stenting.

[The evaluation of hypertensive patients who are supposedly under control according to office blood pressure measurements with ambulatuar blood pressure monitoring: an observational prospective study in three big cities (AKB3IL study)]. / Ofis ölçümleri ile kan basincinin kontrol altinda oldugu düsünülen hipertansiyonlu hastalarin ambulatuvar kan basinci monitörizasyonu ile degerlendirilmesi: Üç büyük ilde ileriye dönük gözlem çalismasi (AKB3IL çalismasi).

OBJECTIVES: The aim of the study is to evaluate hypertensive patients who are supposedly under control according to office blood pressure measurements with 24 hour ambulatuar blood pressure monitoring for determining their actual controlled hypertension rate. In addition, we investigate the adherence ratio of blood pressure measurements to current guidelines. STUDY DESIGN: Nine hundred-forty hypertensive patients supposedly under control according to office blood pressure measurements were enrolled in the study. Twenty-four hour ambulatuar blood pressure monitoring was performed on all of them. RESULTS: Actual controlled hypertension was determined in 617 (65.6%) patients whereas 323 (34.4%) patients had uncontrolled hypertension. The blood pressure measurements that were over threshold values were seen mostly at night and in the early morning during ambulatuar blood pressure monitoring. Nocturnal and early morning hypertension was determined in most of the patients who were supposedly under control according to office blood pressure measurements. This was especially true in patients with high cardiovascular risk such as diabetes mellitus, chronic kidney failure, and metabolic syndrome. CONCLUSION: Efficacy of antihypertensive therapy during 24 hour and the early morning period is essential for optimal risk modification.

Left atrial appendage function in mitral stenosis: is it determined by cardiac rhythm?

BACKGROUND AND AIM OF THE STUDY: The left atrial appendage (LAA) is a common source of cardiac thrombus formation associated with systemic embolism in patients with mitral stenosis (MS). Low flow velocities in the LAA are important factors in the development of thrombosis. Whilst oral anticoagulant therapy is used routinely in MS with atrial fibrillation (AF), the characteristics of LAA contractile functions and the protective role of oral anticoagulant treatment in patients with MS in sinus rhythm (SR) are unclear. The study aim was to compare LAA contractile functions in patients with MS who were either in SR or had AF. METHODS: The study population comprised 51 patients with MS, who had undergone both standard transthoracic and transesophageal echocardiography. The patients were allocated to two groups, according to the presence of AF or SR. Ten healthy, gender-matched subjects were included in the study as a control group. RESULTS: Except for age, the characteristics of the groups were similar. In patients with SR and AF, the LAA contractile functions were significantly lower than in controls. While the LAA contractile functions of the SR group were significantly lower than the AF group (LAA emptying/filling velocity: 26 +/- 7/24 +/- 8 versus 19 +/- 5/17 +/- 5 cm/s; p = 0.002 and p = 0.001, respectively, LAA maximum/minimum area: 5.4 +/- 1.2/3.2 +/- 0.9 versus 6.2 +/- 1.1/3.7 +/- 0.8 cm2, p = 0.02 and p =0.02, respectively), no statistically significant differences were observed between patients in SR with mitral valve area (MVA) <1.5 cm2 and patients in AF. Four SR patients (13%) and six AF patients (27%) had LAA thrombus. A strong correlation was observed between the MVA and LAA peak emptying/filling velocity in patients with MS in SR (r = 0.739, p = 0.0001 and r = 0.728, p = 0.0001, respectively). CONCLUSION: The study results showed that LAA contractile function is diminished in patients with moderate-severe MS in SR, and to a similar degree as patients in AF. It was concluded that patients with moderate-severe MS in SR have a higher risk for thromboembolic events than MS patients in AF.

A floating thrombus in sinus of valsalva complicated with cardiogenic shock in a patient with plasminogen activator inhibitor 1 4G/5G polymorphism.

Thrombus in sinus of Valsalva is unusual reason for acute myocardial infarction. We demonstrated a case with floating thrombus in sinus of Valsalva obstructing the right coronary ostium intermittently, and causing cardiogenic shock. The patient was diagnosed with multiplane transesophageal echocardiography and treated successfully with surgical removal of mass. A homozygote polymorphism of plasminogen activator inhibitor (PAI) 1 4G/5G was found. This is the first report demonstrating a patient with PAI 1 polymorphism and thrombus of Valsalva complicated with cardiogenic shock.

The influence of α-adducin gene polymorphism on response of blood pressure to exercise in patients with hypertension.

OBJECTIVE: Clinical studies have indicated that an excessive response of blood pressure (BP) to exercise predicts risk of cardiovascular mortality. Although the mechanism responsible for the excessive BP response to exercise has not been revealed, there are some plausible mechanisms linking with underlying structural abnormalities in the cardiovascular system. Carriers of the Trp460 allele of the α-adducin Gly460Trp polymorphism have an increased risk of hypertension. The aim of the present study was to examine the influence of α-adducin gene polymorphism on response of BP to exercise in patients with hypertension. METHODS: The cross-sectional observational study consisted of 49 hypertensive patients (29 women and 20 men; mean age, 53.1±8.8 years). All participants underwent a multistage exercise treadmill test according to the Bruce protocol. Arterial BPs were compared at rest, peak exercise and end of the recovery phase. Patients were classified according to their α-adducin gene polymorphisms; Gly460Gly homozygotes - Group 1 (n=28) and Trp460Trp homozygotes and Gly460Trp heterozygotes - Group 2 (n=21). Statistical analysis was performed using Chi-square, unpaired t, Mann-Whitney U and ANCOVA tests. RESULTS: Mean exercise duration and mean exercise capacity in metabolic equivalents were not different between Group 1 and 2. The major finding of the study was that systolic BP responses at peak exercise and recovery period (3. min) were significantly higher (p=0.036) in hypertensive patients carrying at least one Trp460 allele of the α-adducin gene. CONCLUSION: Our results suggest that genetic variants that alter renal function and/or vasoreactivity are logical candidates to explain some of the individual variability in the BP response to exercise.