Ömer Kozan

Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure

Background— Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. Methods and Results— We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74–0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52–0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro–B-type natriuretic peptide and troponin) versus enalapril. Conclusions— Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

Prevalence of the metabolic syndrome among Turkish adults.

Objective:To determine prevalence of the metabolic syndrome (MS) in a sample representing Turkish population using United States Adult Treatment Panel-3 guidelines.Design:The study included random samples from both urban and rural populations in the seven geographical regions of Turkey. The population for this analysis were 2108 men (1372 in urban and 736 in rural areas) and 2151 women (1423 in urban and 728 in rural areas) with a mean age of 40.9±14.9 years (range 20–90).Results:The prevalence of the MS diagnosed using the Adult Treatment Panel III criteria was 33.9% (1442 of 4259) and differed significantly in men (28%) and women (39.6%). The prevalence of syndrome increased with age in men, from 10.7% in subjects aged 20–29 years to 49% in those aged over 70 years. The prevalence increased with age in women, from 9.6% in subjects aged 20–29 years to 74.6% in those aged 60–69 years, and decreased to 68.6% in those over 70 years of age. The prevalence of the syndrome was similar in urban (33.8%) and rural (33.9%) population. We found 26.8, 26.4, 19.3, 10.9 and 3.6% of the population had at least 1, 2, 3, 4 or 5 components, respectively. We found 57.2, 32.3 and 10.6% of the subjects with MS had 3, 4 and 5 components, respectively.Conclusions:The prevalence of the MS in the adult Turkish population is very high, especially in women. Our findings have important implications for public health in Turkey.

Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial

Background—The angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) reduced cardiovascular morbidity and mortality compared with enalapril in patients with heart failure (HF) and reduced ejection fraction (EF) in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. We evaluated the influence of EF on clinical outcomes and on the effectiveness of sacubitril/valsartan compared with enalapril. Methods and Results—Eight thousand three hundred ninety-nine patients with New York Heart Association class II to IV HF with reduced EF [left ventricular EF (LVEF) ⩽40%] were randomized to sacubitril/valsartan 97/103 mg twice daily versus enalapril 10 mg twice daily and followed for a median of 27 months. The primary study end point was cardiovascular death or HF hospitalization. LVEF was assessed at the sites and recorded on case report forms. We related LVEF to study outcomes and assessed the effectiveness of sacubitril/valsartan across the LVEF spectrum. The mean LVEF in PARADIGM-HF, reported by sites, was 29.5 (interquartile range, 25–34). The risk of all outcomes increased with decreasing LVEF. Each 5-point reduction in LVEF was associated with a 9% increased risk of cardiovascular death or HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.05–1.13; P<0.001), a 9% increased risk for CV death (hazard ratio, 1.09; 95% confidence interval, 1.04–1.14), a 9% increased risk in HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.04–1.14) and a 7% increased risk in all-cause mortality (hazard ratio, 1.07; 95% confidence interval, 1.03–1.12) in adjusted analyses. Sacubitril/valsartan was effective across the LVEF spectrum, with no evidence of heterogeneity, when modeled either in tertiles (P interaction=0.87) or continuously (P interaction=0.95). Conclusions—In patients with HF and reduced EF enrolled in PARADIGM-HF, LVEF was a significant and independent predictor of all outcomes. Sacubitril/valsartan was effective at reducing cardiovascular death and HF hospitalization throughout the LVEF spectrum. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.Background— The angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) reduced cardiovascular morbidity and mortality compared with enalapril in patients with heart failure (HF) and reduced ejection fraction (EF) in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. We evaluated the influence of EF on clinical outcomes and on the effectiveness of sacubitril/valsartan compared with enalapril. Methods and Results— Eight thousand three hundred ninety-nine patients with New York Heart Association class II to IV HF with reduced EF [left ventricular EF (LVEF) ≤40%] were randomized to sacubitril/valsartan 97/103 mg twice daily versus enalapril 10 mg twice daily and followed for a median of 27 months. The primary study end point was cardiovascular death or HF hospitalization. LVEF was assessed at the sites and recorded on case report forms. We related LVEF to study outcomes and assessed the effectiveness of sacubitril/valsartan across the LVEF spectrum. The mean LVEF in PARADIGM-HF, reported by sites, was 29.5 (interquartile range, 25–34). The risk of all outcomes increased with decreasing LVEF. Each 5-point reduction in LVEF was associated with a 9% increased risk of cardiovascular death or HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.05–1.13; P <0.001), a 9% increased risk for CV death (hazard ratio, 1.09; 95% confidence interval, 1.04–1.14), a 9% increased risk in HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.04–1.14) and a 7% increased risk in all-cause mortality (hazard ratio, 1.07; 95% confidence interval, 1.03–1.12) in adjusted analyses. Sacubitril/valsartan was effective across the LVEF spectrum, with no evidence of heterogeneity, when modeled either in tertiles ( P interaction=0.87) or continuously ( P interaction=0.95). Conclusions— In patients with HF and reduced EF enrolled in PARADIGM-HF, LVEF was a significant and independent predictor of all outcomes. Sacubitril/valsartan was effective at reducing cardiovascular death and HF hospitalization throughout the LVEF spectrum. Clinical Trial Registration— URL: . Unique identifier: [NCT01035255][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01035255&atom=%2Fcirchf%2F9%2F3%2Fe002744.atom

Urginea Maritima (Squill) Toxicity

A 55 year-old female ingested two bulbs of Urginea maritime (squill) plant as a folk remedy for her arthritic pains. Her past history was significant for Hashimoto thyroiditis and she was hypothyroid upon presentation. Subsequent effects resembling those seen with cardiac glycoside intoxication included nausea, vomiting, seizures, hyperkalemia, atrioventricular block and ventricular arrhythmias resembling digitalis toxicity. A serum digoxin level by an enzyme immunoassay method was 1.59 ng/mL. Despite supportive treatment and pacing, the patient expired from ventricular arrhythmias 30 h after ingestion. Squill has been recognized since antiquity for the clinical toxicity of its cardiac glycosides, but this appears to be the first report of a fatality since 1966.

Influences of Acute and Chronic Aerobic Exercise on the Plasma Homocysteine Level

Background and Aims: Elevated plasma homocysteine (PH) levels have been identified as a risk factor for cardiovascular diseases. The aims of this study were to investigate the influences of submaximal acute aerobic exercise and aerobic training on PH levels and lipid profiles. Methods: 69 volunteersubjects (21.12 ± 2.08 years) were randomized to three groups as acute, training and control groups. Examination and blood samples were collected before and immediately after exercise in the acute group and before and 6 weeks later in the training and control groups. Results: A significant increase in PH concentration was recorded immediately after aerobic exercise, compared with baseline values (p = 0.001). Although, in the training group, total cholesterol (p = 0.00) and LDL cholesterol (p = 0.001) decreased significantly after training, no significant changes in PH concentration, HDL cholesterol (p = 0.087) and triglyceride (p = 194) levels were found. Conclusions: It can be said that the PH level increases following submaximal acute aerobic exercise, but does not alter after submaximal aerobic training due to training duration or intensity. Therefore, submaximal aerobic training decreases lipid profiles independent of the PH level.

Contribution of mitral valve reserve capacity to sustained symptomatic improvement after balloon valvutomy in mitral stenosis: Implications for restenosis for restenosis

Abstract Objectives . To explain the discrepancy between the symptomatic status of patients and the hemodynamically calculated mitral valve area during long-term follow-up after mitral balloon valvulotomy, mitral valve orifice variability alter dobutamine infusion was investigated in two groups of patients. Background . A significant increase in aortic valve area with increased aortic transvalvular flow has been reported in patients with calcific aortic stenosis after aortic balloon valvulotemy. A similar phenomenon with regard to the mitral valve has not been studied in detail. Methods . Group 1 comprised 10 patients (mean age 33 ± 9 years) with untreated mitral stenosis. Group 2 comprised 29 consecutive patients (mean age 32 ± 7 years) who underwent successful percutaneous mitral balloon valvulotomy 13 ± 2 months before the study. Results . After dobutamine infusion, heart rate and cardiac index increased significantly in both groups. The mean pulmonary artery pressure, mitral valve gradient and pulmonary capillary pressure remained unchanged in Group 2 but increased significantly in Group 1. The mean mitral valve area was significantly larger in Group 2 after dobutamine infusion that at baseline (1.9 ± 0.5 vs. 2.4 ± 0.6 cm 2 , p 2 , p = NS). The mean mitral valve area in seven patients in Group 2 (24%) was ≤1.5 cm 2 before dobutamine infusion (1.3 ± 0.4 cm 2 ), which was defined as restenosis. In five of these seven patients who had minimal or no symptoms, the mitral valve area increased significantly after dobutamine infusion (1.3 ± 0.1 vs. 1.9 ± 0.1 cm 2 ). in the other two patients who were symptomatic, the mitral valve area did not change after dobutamine infusion. These two patients were iden- tified as having “tree” restenosis, and reduction of the mitral valve was performed in both. Conclusions . In patients who underwent mitral balloon valvulotomy, increased mitral valve reserve capacity contributed to symptomatic improvement on long-term follow-up. Dobutamine infusion may be helpful in detecting clinically significant restenosis.

Treatment and control of hypertension in Turkish population: a survey on high blood pressure in primary care (the TURKSAHA study)

Although the management and the control rates of hypertension are generally low throughout the world, there are substantial differences between the countries. The aim of this study was to determine the control rate of blood pressure and the characteristics of the patients who have been admitted to primary care units in Turkey. Our study included 16 270 patients aged above 18 years who were diagnosed as hypertensive in representative nationwide sample of 1000 primary care units in Turkey. The mean age of the patients was 60±11 years (60.1% women). Of 16 270 patients, 15 187 (93.3%) were on an antihypertensive treatment, whereas 1083 (6.7%) were receiving no treatment. The patients who were women, diabetic, smoker, obese, and those who had a concomitant cardiovascular disease (CVD) had a higher rate of antihypertensive treatment. Of 15 187 treated patients, 4912 (30.2%) had a controlled systolic blood pressure, 7063 (43.4%) a controlled diastolic blood pressure, and in 3931 (24.2%), both were under control. A logistic regression analysis demonstrated that age (OR 1.33), diabetes (OR 4.96), body mass index (OR 1.41) and the presence of a CVD (OR 1.19) were predictors for blood pressure being under control. The blood pressure control rates ranged between 16.6 and 30.5% among seven geographical regions. In the primary care units in Turkey, the blood pressure control rate is consistently low in treated hypertensive patients. In addition, there are differences between the geographical regions in both the proportion of those receiving medications and the blood pressure control rates.

Heart fAilure Prevalence and Predictors in TurkeY (HAPPY) Çalışması

OBJECTIVES The aim of this study was to determine the prevalence of heart failure (HF) in adult residents of Turkey based on echocardiography and N-terminal B type natriuretic factor. STUDY DESIGN 4650 randomly selected residents aged ≥ 35 years were enrolled. Height, weight, waist and hip circumference, and blood pressure measurements were taken, and a 12-lead ECG was performed. Advanced age, hypertension (HT), diabetes mellitus (DM), obesity, and chronic renal failure (CRF) were assessed. History of any heart disease, any abnormal ECG, or an NT-proBNP ≥ 120 pg/mL was accepted as echocardiography indication. Patients with systolic and/or diastolic dysfunction, or NT-proBNP ≥ 2000 pg/mL were classified as having HF if their functional capacity was NYHA ≥ Class II, and were classified as having asymptomatic left ventricular dysfunction (ASVD) if their functional capacity was NYHA <Class I. RESULTS The absolute and estimated prevalences were 2.9% and 6.9% for HF, and 4.8% and 7.9% for ASVD, respectively. Advanced age, male gender, history of heart disease, HT and CRF were independent predictors of HF. In patients with ejection fraction (EF) <50%, HF prevalence was higher in men, while HF prevalences were higher in women when EF ≥ 50%. In global sum, HF and ALVD prevalence were similar in male and females. CONCLUSION The prevalences of HF and ASVD are higher in Turkey when compared with western countries, despite a younger Turkish population. The established predictors of HF are valid for Turkey as well. There is a significant ASVD population in Turkey with similar characteristics and risk factors to HF. Focusing on the early detection and treatment of ASVD may prevent the progression to HF, and therefore would decrease the prevalence of HF in Turkey.

Treatment of mild-to-moderate hypertension with calcium channel blockers: a multicentre comparison of once-daily nifedipine GITS with once-daily amlodipine

SUMMARY Background: Hypertension is one of the most important causes of cardiovascular disease, and treatment of hypertension leads to a significant reduction in cardiovascular mortality and morbidity. Although calcium channel blockers are regarded as an important part of the therapeutic armamentarium against cardiovascular diseases, and are among the most frequently prescribed antihypertensive medications, concern has been aroused about these drugs, particularly the short-acting dihydropyridine derivatives. However, the value of nifedipine GITS (Adalat-Crono*), the long-acting dihydropyridine, is in need of being re-established. * Adalat-Crono is a registered tradename of Bayer AG, Leverkusen, Germany Objective:To compare the effectiveness, safety and tolerability of once-daily nifedipine and amlodipine treatment in patients with mild-to-moderate essential hypertension. Design: Randomised multicentre trial with an open comparison of treatments for 12 weeks, with a preceding placebo run-in period of 2 weeks (patients on beta-blockers at the time of enrolment entered a mandatory 2-week wash-out period before being allowed in the placebo run-in period; this wash-out period was one week for patients using any antihypertensive medication other than beta-blockers). Setting: Nine centres (all university hospitals) in Turkey. Patients: 155 patients with essential hypertension (diastolicblood pressure 95-109 mmHg). Interventions: Initial treatment (step 1) consisted of 30mg nifedipine GITS (n = 76; (Adalat-Crono tablets), or 5mg amlodipine (n = 79; Norvasc* 5-mg tablets), either administered once daily, as a morning dose, or if the blood pressure was not below 140/90 mmHg, or the reduction in diastolic blood pressure was lower than 10 mmHg after a treatment period of 6 weeks, the dose was increased (Step 2) to 60 mg once daily in the nifedipine group, or 10 mg once daily in the amlodipine group. Main efficacy parameter: Diastolic blood pressure at trough after 12 weeks of active compound therapy adjusted to baseline. Results: After 12 weeks of treatment, the mean diastolic blood pressure was 83.1 and 81.9 mmHg, in the nifedipine and amlodipine groups, respectively (p = 0.436). The mean decrease in systolic blood pressure (28.5 ± 11.9 and 28.2 ± 11.2 mmHg in the nifedipine and amlodipine groups, respectively) and the mean decrease in diastolic blood pressure (16.4 ± 7.0 and 17.5 ± 6.9 mmHg in the nifedipine and amlodipine groups, respectively), as well as the responder rates (88.1% and 92.1%, in the nifedipine and amlodipine groups, respectively) were comparable at the end of the study. No significant differences between groups were detected in the efficacy parameters assessed in this study. Both drugs were well tolerated. The overall incidence of adverse events was 7.9% in the nifedipine group and 10.1% in the amlodipine group. However, more patients discontinued treatment prematurely in the amlodipine group (13 patients; 19.7%), than in the nifedipine group (four patients; 5.6%). Conclusions: The results of this study demonstrated that once-daily nifedipine in GITS formulation and amlodipine are comparably safe and effective treatment options in patients with mild-to-moderate essential hypertensi on.

Catheter-induced vasospasm in the right external iliac and femoral arteries during a cardiac diagnostic procedure.

Catheter-induced vasospasm of small caliber arteries, such as the coronary arteries, is frequently observed during cardiac catheterization, but obstruction of the large caliber arteries has not previously been reported. Here we present two cases in which femoral and external iliac arteries were totally obstructed due to spasm during diagnostic coronary angiography.