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Öğe Baseline Characteristics of Patients With Heart Failure and Preserved Ejection Fraction in the PARAGON-HF Trial(LIPPINCOTT WILLIAMS & WILKINS, 2018) Solomon, Scott D.; Rizkala, Adel R.; Lefkowitz, Martin P.; Shi, Victor C.; Gong, JianJian; Anavekar, Nagesh; Anker, Stefan D.; Arango, Juan L.; Arenas, Jose L.; Atar, Dan; Ben-Gal, Turia; Boytsov, Sergey A.; Chen, Chen-Huan; Chopra, Vijay K.; Cleland, John; Comin-Colet, Josep; Duengen, Hans-Dirk; Echeverria Correa, Luis E.; Filippatos, Gerasimos; Flammer, Andreas J.; Galinier, Michel; Godoy, Armando; Goncalvesova, Eva; Janssens, Stefan; Katova, Tzvetana; Kober, Lars; Lelonek, Malgorzata; Linssen, Gerard; Lund, Lars H.; O'Meara, Eileen; Merkely, Bela; Milicic, Davor; Oh, Byung-Hee; Perrone, Sergio V.; Ranjith, Naresh; Saito, Yoshihiko; Saraiva, Jose F.; Shah, Sanjiv; Seferovic, Petar M.; Senni, Michele; Sibulo, Antonio S., Jr.; Sim, David; Sweitzer, Nancy K.; Taurio, Jyrki; Vinereanu, Dragos; Vrtovec, Bojan; Widimsky, Jiri; Yilmaz, Mehmet B.; Zhou, Jingmin; Zweiker, Robert; Anand, Inder S.; Ge, Junbo; Lam, Carolyn S. P.; Maggioni, Aldo P.; Martinez, Felipe; Packer, Milton; Pfeffer, Marc A.; Pieske, Burkert; Redfield, Margaret M.; Rouleau, Jean L.; Van Veldhuisen, Dirk J.; Zannad, Faiez; Zile, Michael R.; McMurray, John J. V.BACKGROUND: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. METHODS AND RESULTS: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7 +/- 8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had >= 1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), beta-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. CONCLUSIONS: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics.Öğe Coronary collateral circulation: Any effect on P-wave dispersion?(SAGE PUBLICATIONS INC, 2008) Aslan, Halil; Turgut, Okan; Yalta, Kenan; Yilmaz, Mehmet B.; Ozdemir, Ramazan; Ermis, Necip; Sezgin, Alpay T.; Yetkin, Ertan; Tandogan, Izzet; Yilmaz, AhmetCoronary collateral circulation determines the severity of ischemic myocardial damage. Increased P-wave dispersion is an independent predictor for atrial fibrillation. Consistent evidence is little about the relation between coronary collateral circulation and arrhythmia risk. In this article, the effect of coronary collateral circulation on P-wave dispersion was evaluated. Collateral grade and p-wave dispersion were ascertained in 100 patients with >= 85% diameter stenoses in left anterior descending or right coronary arteries. Left ventricular function score was also determined in all patients. Coronary collateral circulation was absent in 32 patients, whereas 68 patients had coronary collateral circulation. Patients with collateral grade A had greater left ventricular function score than did patients with collateral grade 0 (P = .048). However, there was no significant difference between P-wave dispersion of patients with and without coronary collateral circulation (P = .45). The presence of coronary collateral circulation failed to exert a beneficial decreasing effect on P-wave dispersion.Öğe Fate of Internal Mammary Artery Grafted to Left Anterior Descending Artery Is Influenced by Native Vessel Stenosis and Viable Myocardium(SAGE PUBLICATIONS INC, 2009) Yilmaz, Mehmet B.; Guray, Yesim; Altay, Hakan; Demirkan, Burcu; Caldir, Vedat; Guray, Umit; Biyikoglu, Senay F.; Sasmaz, Hatice; Kisacik, Halil L.; Korkmaz, SuleIn this study, factors leading to the failure of internal mammary artery grafting was investigated among patients with coronary bypass. In all, 1323 patients were evaluated. It was found that lower grade diameter stenosis in the native vessel during postoperative angiogram and wall motion score index independently affected the fate of internal mammary artery as a graft. Grafting with internal mammary artery to native vessels with lower grade stenosis and to myocardium with poor wall score might not be a rational approach.Öğe Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens(WILEY, 2016) Senni, Michele; McMurray, John J. V.; Wachter, Rolf; McIntyre, Hugh F.; Reyes, Antonio; Majercak, Ivan; Andreka, Peter; Shehova-Yankova, Nina; Anand, Inder; Yilmaz, Mehmet B.; Gogia, Harinder; Martinez-Selles, Manuel; Fischer, Steffen; Zilahi, Zsolt; Cosmi, Franco; Gelev, Valeri; Galve, Enrique; Gomez-Doblas, Juanjo J.; Nociar, Jan; Radomska, Maria; Sokolova, Beata; Volterrani, Maurizio; Sarkar, Arnab; Reimund, Bernard; Chen, Fabian; Charney, AlanAimsTo assess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction 35%). Methods and resultsA 5-day open-label run-in (sacubitril/valsartan 50 mg twice daily) preceded an 11-week, double-blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily (condensed' regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily (conservative' regimen)]. Patients were stratified by pre-study dose of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEI/ARB; low-dose stratum included ACEI/ARB-naive patients). Of 540 patients entering run-in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre-defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in (condensed' vs. conservative') 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre-defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down-titration over 12 weeks (77.8% vs. 84.3% for condensed' vs. conservative'; P = 0.078). Rates by ACEI/ARB pre-study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high-dose/condensed' vs. high-dose/conservative' and 84.9% vs. 73.6% (P = 0.030) for low-dose/conservative' vs. low-dose/condensed'. ConclusionsInitiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low-dose ACEI/ARB group.Öğe Renal Effects of Levosimendan: A Consensus Report(SPRINGER, 2013) Yilmaz, Mehmet B.; Grossini, Elena; Silva Cardoso, Jose C.; Edes, Istvan; Fedele, Francesco; Pollesello, Piero; Kivikko, Matti; Harjola, Veli-Pekka; Hasslacher, Julia; Mebazaa, Alexandre; Morelli, Andrea; le Noble, Jos; Oldner, Anders; Oulego Erroz, Ignacio; Parissis, John T.; Parkhomenko, Alexander; Poelzl, Gerhard; Rehberg, Sebastian; Ricksten, Sven-Erik; Rodriguez Fernandez, Luis M.; Salmenpera, Markku; Singer, Mervyn; Treskatsch, Sascha; Vrtovec, Bojan; Wikstrom, GerhardRenal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial K-ATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).Öğe Statin pretreatment and risk of in-hospital atrial fibrillation among patients undergoing cardiac surgery: a collaborative meta-analysis of 11 randomized controlled trials(OXFORD UNIV PRESS, 2015) Patti, Giuseppe; Bennett, Rachel; Seshasai, Sreenivasa Rao Kondapally; Cannon, Christopher P.; Cavallari, Ilaria; Chello, Massimo; Nusca, Annunziata; Mega, Simona; Caorsi, Carlos; Spadaccio, Cristiano; On, Young Keun; Mannacio, Vito; Berkan, Ocal; Yilmaz, Mehmet B.; Katrancioglu, Nurkay; Ji, Qiang; Kourliouros, Antonios; Baran, Cagdas; Pasceri, Vincenzo; Akar, Ahmet Ruechan; Kaski, Juan Carlos; Di Sciascio, Germano; Ray, Kausik K.Aims Statin pretreatment in patients undergoing cardiac surgery is understood to prevent postoperative atrial fibrillation (AF). However, this is based on observational and limited randomized trial evidence, resulting in uncertainty about any genuine anti-arrhythmic benefits of these agents in this setting. We therefore aimed to quantify precisely the association between statin pretreatment and postoperative AF among patients undergoing cardiac surgery. Methods and results A detailed search of MEDLINE and PubMed databases (1st January 1996 to 31st July 2012) was conducted, followed by a review of the reference lists of published studies and correspondence with trial investigators to obtain individual-participant data for meta-analysis. Evidence was combined across prospective, randomized clinical trials that compared the risk of postoperative AF among individuals randomized to statin pretreatment or placebo/control medication before elective cardiac surgery. Postoperative AF was defined as episodes of AF lasting >= 5 min. Overall, 1105 participants from 11 trials were included; of them, 552 received statin therapy preoperatively. Postoperative AF occurred in 19% of these participants when compared with 36% of those not treated with statins (odds ratio 0.41, 95% confidence interval 0.31-0.54, P< 0.00001, using a random-effects model). Atrial fibrillation prevention by statin pretreatment was consistent across different subgroups. Conclusion Short-term statin pretreatment may reduce the risk of postoperative AF among patients undergoing cardiac surgery.Öğe Thorax deformity, joint hypermobility, and anxiety disorders(SAUDI MED J, 2007) Gulsun, Murat; Yilmaz, Mehmet B.; Pinar, Murat; Tonbul, Murat; Celik, Cemil; Ozdemir, Barbaros; Dumu, Kemal; Erbas, MevlutObjective: To evaluate the association between thorax deformities, panic disorder, and joint hypermobility. Method:The study includes 52 males diagnosed with thorax deformity, and 40 healthy male controls without thorax deformity, in Tatvan Bitlis and Isparta, Turkey. The study was carried out from 2004 to 2006. The teleradiographic and thoracic lateral images of the subjects were evaluated to obtain the Beighton scores; subjects' psychiatric conditions were evaluated using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-1), and the Hamilton Anxiety Scale (HAM-A) was applied in order to determine the anxiety levels. Both the subjects and controls were compared in sociodemographic, anxiety levels, and joint mobility levels. In addition, males with joint hypermobility and thorax deformity were compared to the group with thorax deformity without joint hypermobility. Results: A significant difference in HAM-A scores was found between the groups with thorax deformity and without. In addition, 21 subjects with thorax deformity met the joint hypermobility criteria in the group with thorax deformity, and 7 subjects without thorax deformity met the joint hypermobility criteria in the group without thorax deformity, according to Beighton scoring. The Beighton scores of the subjects with thorax deformity were significantly different from those of the group without deformity. Additionally, anxiety scores of the males with thorax deformity and joint hypermobility were found higher than males with thorax deformity without joint hypermobility. Conclusions: Anxiety disorders, particularly panic disorder, have a significantly higher distribution in male subjects with thorax deformity compared to the healthy control group. In addition, the anxiety level of males with thorax deformity and joint hypermobility is higher than males with thorax deformity without joint hypermobility.Öğe Treatment Strategies and Outcomes of Coronary Artery Fistulas in a Turkish Adult Population(ORTADOGU AD PRES & PUBL CO, 2011) Ozerdem, Gokhan; Unal, Orcun; Katrancioglu, Nurkay; Bakuy, Vedat; Ozdemir, Ozcan; Candemir, Basar; Yilmaz, Mehmet B.; Berkan, Ocal; Akgul, Ahmet; Kaya, BulentObjective: Congenital coronary artery fistulas (CAF) are uncommon abnormalities that are known as abnormal communications between a coronary artery and a cardiac chamber or a major vessel. Incidence of CAF ranges between 0.1% and 0.2% 2 in literature,howeyer, there is no detailed data on the incidence of CAF in a Turkish population. In this article, we evaluated the clinical manifestations, symptoms, chosen treatment strategies, and long term follow-up results of GAF in Turkish adult population. Material and Methods: In this multicenter study carried out between 2001 and 2009, a total of 25 400 angiograms which were taken for various reasons were evaluated retrospectively. Sex, age, clinical manifestations, symptoms, number of the fistulas, chosen treatment strategies, and long term follow up results of the study population were recorded and analyzed. Results: CAF were found in 32 of these cases (0.13%). Eighteen of the cases were males, and 14 were females with a median age of 57.6 years. Fifteen cases had surgery, graft-stent was applied to two cases and coil embolization was preferred in two cases. Thirteen cases were followed up under medical treatment. Graft stents were occluded after 4 and 6 months following implantation in left anterior descending artery in both cases, and hence, these patients required surgery. Mean follow-up period was 48 +/- 27 months. All cases were asymptomatic (at the end of the follow-up period) and were doing well. Conclusion: In conclusion, incidence of CAF was found as 0.13% in the study population, and surgical treatment and coil embolization were considerably successful compared to stent graft application in CAF patients.
