Beta-Blockers and Hypertension: Some Questions and Answers.

INTRODUCTION: International guidelines have removed b-blockers from first-line treatment of hypertension, limiting their use to patients with compelling indications. The position of guidelines stems from the results of studies performed with the 1st and 2nd generation of b-blockers, which concluded that these drugs have lower cardiovascular protection, compared with other antihypertensive agents. AIM: The aim of our mini review is to answer to some questions about the effect of b-blockers on hypertension and cardiovascular protection and if these effects are different from those of other antihypertensive drugs, particularly in young and elderly patients. METHODS: We evaluated the relevant systematic reviews and meta-analyses, which reported the effectiveness of b-blockers on blood pressure and cardiovascular outcomes, compared with placebo/no treatment and with other antihypertensive agents. RESULTS: Beta-blockers, decreased high blood pressure with no significant difference from other common antihypertensive agents. Moreover b-blockers, compared with placebo, lowered the risk of major cardiovascular outcomes, while, compared with other drug classes, the reported results are very heterogeneous. Therefore it is difficult, globally, to find a difference between b-blockers and other drug classes. CONCLUSIONS: Rather than looking for differences in the cardiovascular protective effect between b-blockers and other antihypertensive agents, we have to consider the different pathophysiology of hypertension in young [sympathetic hyperactivity] and elderly patients [arterial stiffness, high aortic systolic pressure]. Considering these aspects, non-vasodilating b-blockers are preferred, as first-line, in young/middle aged hypertensive subjects, while vasodilating b-blockers, are most appropriate, in elderly patients, for the favourable hemodynamic profile.

Do Statins Counteract the Effect of Antidiabetic Drugs? Results of the SCEAD Study.

PURPOSE: Diabetes and dyslipidemia are leading causes of mortality and morbidity. According to international guidelines, statins are the cornerstone of treatment in patients with diabetes and/or dyslipidemia. However, statins and antidiabetic agents have opposite pharmacological effects, because statins, particularly atorvastatin and rosuvastatin, impair glucose homeostasis, increasing the risk of new-onset diabetes, whereas antidiabetic drugs improve glycemic homeostasis. The aim of this study was to investigate the effect of atorvastatin, rosuvastatin, and pitavastatin on glucose homeostasis in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia during stable treatment with hypoglycemic drugs. MATERIALS AND METHODS: The study was conducted as a pilot, prospective, randomized, open label, parallel group with blinded-endpoints (PROBE) study. Of 180 recruited patients with T2DM and dyslipidemia, 131 were randomized to atorvastatin (n=44), rosuvastatin (n=45), and pitavastatin (n=42) and treated for 6 months. RESULTS: Fasting plasma glucose (FPG) marginally decreased in patients assigned to atorvastatin (-3.5 mg/dL, p=0.42) and rosuvastatin (-6.5 mg/dL, p=0.17), while it decreased much more in patients treated with pitavastatin (-19.0 mg/dL, p<0.001). Mean glycated hemoglobin A1c (HbA1c ) values remained unchanged during treatment with atorvastatin (-0.10%, p=0.53) and rosuvastatin (0.20%, p=0.40), but were significantly reduced with pitavastatin (-0.75%, p=0.01). Atorvastatin, rosuvastatin, and pitavastatin significantly lowered (p<0.001) plasma levels of total cholesterol, low-density lipoprotein-cholesterol, and triglycerides, while high-density lipoprotein-cholesterol (HDL-C) levels increased significantly (p=0.04) only in the pitavastatin group. CONCLUSION: The results of the present study suggest that pitavastatin affects FPG and HbA1c less than atorvastatin and rosuvastatin in patients with T2DM and concomitant dyslipidemia. Lipid-lowering efficacies were not significantly different among the three statins, with the exception of HDL-C, which increased significantly with pitavastatin. Although the pharmacological mechanism of pitavastatin on glucose homeostasis in patients with T2DM during stable antidiabetic therapy is not known, it can be assumed that pitavastatin has less drug interaction with hypoglycemic agents or that it increases plasma levels of adiponectin.

Angiotensin receptor neprilysin inhibitor for patients with heart failure and reduced ejection fraction: Real-world experience from Turkey (ARNi-TR).

OBJECTIVE: Heart failure (HF) is a growing public health problem with high morbidity and mortality. Recently, angiotensin receptor neprilysin inhibitor (ARNi) has emerged as a promising treatment for HF with reduced ejection fraction (HFrEF). Here, we shared our experience with the use of ARNi in HFrEF from multiple centers in Turkey. METHODS: The ARNi-TR is a multicenter, noninterventional, retrospective, observational study. Overall, 779 patients with HF from 22 centers in Turkey who were prescribed sacubitril/valsartan were examined. Initial clinical status, biochemical and echocardiographic parameters, and New York Heart Association functional class (NYHA-FC) values were compared with follow-up values after 1 year of ARNi use. In addition, the effect of ARNi on number of annual hospitalizations was investigated, and the patients were divided into 2 groups, depending on whether ARNi was initiated at hospitalization or under outpatient clinic control. RESULTS: N-terminal pro-brain natriuretic peptide (NT-proBNP), left-ventricle ejection fraction (LV-EF), and NYHA-FC values improved significantly in both groups (all parameters, p<0.001) within 1-year follow-up. In both groups, a decrease in hemoglobin A1c (HbA1c) values was observed in ARNi use (p<0.001), and a decrease in daily diuretic doses and hospitalizations owing to HF were observed after ARNi use (all comparisons, p<0.001). Hypotension (16.9%) was the most common side effect in patients using ARN. CONCLUSION: The ARNi-TR study offers comprehensive real-life data for patients using ARNi in Turkey. The use of ARNi has shown significant improvements in FC, NT-proBNP, HbA1c levels, and LV-EF. Likewise, reductions in the number of annual hospitalizations and daily furosemide doses for HF were seen in this study.

A Rare Access Site Complication after Transcatheter Aortic Valve Implantation.

In the majority of patients undergoing transcatheter aortic valve implantation, the transfemoral access is the suggested approach due to its less invasive nature and feasibility in patients with suitable vascular anatomy. The complications of the transfemoral access site are generally vascular; however, we herein present a rare case of colon perforation following the transfemoral procedure owing to prior abdominal surgery. A transfemoral aortic valve was inserted on account of severe aortic stenosis and a high probability of surgical mortality. The patient developed acute abdomen following the procedure. Hemicolectomy was performed because of colonic perforation caused by femoral catheterization. The patient was well at 3 months' follow-up.

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

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

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

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

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

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

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

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

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.

A new device for paravalvular leak closure.

Percutaneous closure of a prosthetic paravalvular leak (PVL) is a challenging procedure. Operators must use devices constructed for other applications. We present the use of a device which is specifically designed for PVL closure. To the best of our knowledge, there is no publication in MEDLINE reporting the use of the device.

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 platelet indices and clinical features of coronary artery disease.

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

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.

N-acetylcysteine in preventing contrast-induced nephropathy assessed by cystatin C.

AIMS: Prophylactic oral N-acetylcysteine (NAC) has been widely used for prevention of contrast-induced nephropathy (CIN). However, clinical studies have not been demonstrating this effect consistently because of evidence that NAC can alter serum creatinine levels without affecting glomerular filtration rate (GFR). We investigated NAC for the prevention of CIN by monitoring creatinine and cystatin C. METHODS: We enrolled 113 patients (49 patients in NAC group and 64 patients in control group) with normal to subnormal GFR who were scheduled for cardiovascular procedures. Patients in NAC group receive acetylcysteine 600 mg twice a day, on the day before and on the day of cardiovascular procedure. All patients received a periprocedural intravenous infusion ("volume expansion") of 1 ml/kg/h with 0.45% saline for 24 h (12 h before and 12 h after exposure to contrast medium). Serum cystatin C and creatinine levels were measured before and at 12, 24, and 48 h after procedure. RESULTS: The incidence of cystatin C-based CIN was 28.5% (n = 14) in NAC and 23.4% (n = 15) in control group (p = 0.663) and serum creatinine-based CIN was 12.2% (n = 6) in NAC and 17.2% (n = 11) in control group (P= 0.468). In this study, oral NAC had no effect on the prevention of CIN in patients undergoing cardiovascular procedures. CONCLUSION: In this study, oral NAC administration does not reduce neither the incidence of cystatin C-based CIN nor serum creatinine-based CIN in patients undergoing cardiovascular procedures.

Digoxin intoxication: An old enemy in modern era.

OBJECTIVES: Although development of new treatment modalities limited digoxin usage, digoxin intoxication is still an important issue which could be easily overlooked. In this report, we analyzed a case series definitively diagnosed as digoxin intoxication in the modern era. METHODS: We analyzed 71 patients hospitalized with digoxin intoxication confirmed by history, complaints, clinical and electrocardiograph (ECG) findings, and serum digoxin levels > 2.0 ng/mL, during a five year period. The demographic and clinical data, indications for digoxin use, digoxin dosage, concurrent medications, laboratory data, hospital monitoring, and ECG findings were obtained from all patients. RESULTS: Thirty-eight of 71 patients (53.5%) had symptoms of heart failure during admission or later. Sixty-four percent of patients were older than 75 years. The percentage of females was 67%. Atrial fibrillation, hypertension and gastrointestinal complaints were more frequent in the females (64% in females, 30% in males, P = 0.007; 81% in female, 52% in males, P = 0.01; 50% in female, 17.3% in males, P = 0.008, respectively). The mortality rate during the hospital course was 7%. CONCLUSIONS: This report demonstrated the reduced mortality rates in patients with digoxin intoxication over the study period. Gastrointestinal complaints are the most common symptoms in this population.