Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials.

AIM: The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. METHODS AND RESULTS: The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. CONCLUSION: Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.

The effects of P2Y12 adenosine receptors' inhibitors on central and peripheral chemoreflexes.

Introduction: The most common side effect of ticagrelor is dyspnea, which leads to premature withdrawal of this life-saving medication in 6.5% of patients. Increased chemoreceptors' sensitivity was suggested as a possible pathophysiological explanation of this phenomenon; however, the link between oversensitization of peripheral and/or central chemosensory areas and ticagrelor intake has not been conclusively proved. Methods: We measured peripheral chemoreceptors' sensitivity using hypoxic ventilatory response (HVR), central chemoreceptors' sensitivity using hypercapnic hyperoxic ventilatory response (HCVR), and dyspnea severity before and 4 ± 1 weeks following ticagrelor initiation in 11 subjects with chronic coronary syndrome undergoing percutaneous coronary intervention (PCI). The same tests were performed in 11 age-, sex-, and BMI-matched patients treated with clopidogrel. The study is registered at ClinicalTrials.com at NCT05080478. Results: Ticagrelor significantly increased both HVR (0.52 ± 0.46 vs. 0.84 ± 0.69 L min-1 %-1; p < 0.01) and HCVR (1.05 ± 0.64 vs. 1.75 ± 1.04 L min-1 mmHg-1; p < 0.01). The absolute change in HVR correlated with the change in HCVR. Clopidogrel administration did not significantly influence HVR (0.63 ± 0.32 vs. 0.58 ± 0.33 L min-1%-1; p = 0.53) and HCVR (1.22 ± 0.67 vs. 1.2 ± 0.64 L min-1 mmHg-1; p = 0.79). Drug-related dyspnea was reported by three subjects in the ticagrelor group and by none in the clopidogrel group. These patients were characterized by either high baseline HVR and HCVR or excessive increase in HVR following ticagrelor initiation. Discussion: Ticagrelor, contrary to clopidogrel, sensitizes both peripheral and central facets of chemodetection. Two potential mechanisms of ticagrelor-induced dyspnea have been identified: 1) high baseline HVR and HCVR or 2) excessive increase in HVR or HVR and HCVR. Whether other patterns of changes in chemosensitivities play a role in the pathogenesis of this phenomenon needs to be further investigated.

Inflammatory activation biomarker profile after marathon running and its impact on cardiovascular stress in amateur middle-aged male runners.

BACKGROUND: Cardiovascular safety of marathon running middle-aged amateurs remains unclear. We previously hypothesized that transient release of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in addition to an acute inflammatory response to exercise, may be the cause. OBJECTIVES: To evaluate the effects of running a marathon on inflammatory biomarkers, and its impact on cardiovascular function. MATERIAL AND METHODS: Thirty-three healthy male amateur runners aged ≥50 (mean age: 57 ±7 years) were enrolled in the study. Venous blood samples were obtained before the marathon, just after the race, and 2-4 days and 7 days after the marathon. Using novel single molecule counting (SMC) technology, we measured plasma concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). White blood cell (WBC) count was measured using a certified hematology analyzer. The results were related to previous analyses on cardiovascular stress and endothelial function biomarkers. Transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) were used to determine myocardial function. RESULTS: We observed a sharp rise of all studied biomarkers after the race, which subsequently normalized after 2-4 days and stayed within the normal range 7 days after the race. We found no correlation between inflammatory and cardiovascular stress biomarkers. Transthoracic echocardiography and CMR did not show ischemic or inflammatory myocardial damage. CONCLUSIONS: Marathon running is associated with a sharp and significant rise in inflammatory and cardiovascular stress biomarkers. We found no connection between immune activation and cardiac biomarker release. Cardiovascular imaging showed no myocardial damage due to ischemia or inflammation.

The how and why of assessing frailty syndrome in cardiac surgery.

Frailty syndrome (FS) is one of the most important variables that have a proven impact on the increased risk of morbidity and mortality in cardiac surgery. However, FS assessment is not routinely incorporated into daily clinical practice or included in commonly used risk assessment models. The inclusion of FS in perioperative risk prediction models in cardiac surgery would not only allow for a more accurate assessment but could also assist in the selection of an appropriate treatment strategy while favoring the appropriate use of clinical resources. The identification of FS in the qualification process must not be seen as an absolute contraindication to cardiac surgery but as an opportunity to adequately prepare the patient for the procedure. However, the literature is heterogeneous in terms of the selection of an appropriate tool for identifying FS. Selected tools commonly used in the assessment of FS in patients with cardiovascular disease, including those of greatest relevance in cardiac surgery, are presented in this editorial.

Stand-Alone Left Atrial appendage occlusion for throMboembolism prevention in nonvalvular Atrial fibrillatioN DiseasE Registry (SALAMANDER): protocol for a prospective observational nationwide study.

INTRODUCTION: Atrial fibrillation (AF) is a prevalent disease considerably contributing to the worldwide cardiovascular burden. For patients at high thromboembolic risk (CHA2DS2-VASc ≥3) and not suitable for chronic oral anticoagulation, owing to history of major bleeding or other contraindications, left atrial appendage occlusion (LAAO) is indicated for stroke prevention, as it lowers patient's ischaemic burden without augmentation in their anticoagulation profile. METHODS AND ANALYSIS: Stand-Alone Left Atrial appendage occlusion for throMboembolism prevention in nonvalvular Atrial fibrillatioN DiseasE Registry (SALAMANDER) will be conducted in 10 heart surgery and cardiology centres across Poland to assess the outcomes of LAAO performed by fully thoracoscopic-epicardial, percutaneous-endocardial or hybrid endo-epicardial approach. The registry will include patients with nonvalvular AF at a high risk of thromboembolic and bleeding complications (CHA2DS2-VASc Score ≥2 for males, ≥3 for females, HASBLED score ≥2) referred for LAAO. The first primary outcome is composite procedure-related complications, all-cause death or major bleeding at 12 months. The second primary outcome is a composite of ischaemic stroke or systemic embolism at 12 months. The third primary outcome is the device-specific success assessed by an independent core laboratory at 3-6 weeks. The quality of life (QoL) will be assessed as well based on the QoL EQ-5D-5L questionnaire. Medication and drug adherence will be assessed as well. ETHICS AND DISSEMINATION: Before enrolment, a detailed explanation is provided by the investigator and patients are given time to make an informed decision. The patient's data will be protected according to the requirements of Polish law, General Data Protection Regulation (GDPR) and hospital Standard Operating Procedures. The study will be conducted in accordance with the Declaration of Helsinki. Ethical approval was granted by the local Bioethics Committee of the Upper-Silesian Medical Centre of the Silesian Medical University in Katowice (decision number KNW/0022/KB/284/19). The results will be published in peer-reviewed journals and presented during national and international conferences. TRIAL REGISTRATION NUMBER: NCT05144958.

Optimal medical therapy in patients with stable coronary artery disease in Poland: the ISCHEMIA trial experience.

Introduction: Optimal medical therapy (OMT) is the cornerstone of treatment for stable coronary disease with the ISCHEMIA trial showing similar outcomes using OMT with or without an initial invasive approach. Objectives: To describe OMT goal attainment in Polish ISCHEMIA participants compared with other countries. Patients and methods: Among 5179 trial participants, 333 were randomized in Poland. The median follow-up was 3.2 years. OMT targets were: not smoking, high-intensity statin therapy, low-density lipoprotein cholesterol (LDL-C) of less than 70 mg/dl, systolic blood pressure of less than 140 mm Hg, aspirin therapy, and ACEI / ARB, and ß-blocker therapy if indicated. Results: Compared with 36 other countries, at randomization, patients in Poland were older (67 [62­75] y vs 65 [58­71] y); P <⁠0.001), more often female (30% vs 22%; P = 0.002), with a longer history of angina (3 [1­9] y vs 1 [0­3] y; P <⁠0.001), and there were more cases of prior myocardial infarction (32% vs 18%; P <⁠0.01) and revascularization (PCI, 40% vs 19%; CABG, 11% vs 3%; P <⁠0.001 for both). The number of OMT goals attained increased from baseline to follow-up visits (5 [4­5] vs 6 [5­6]; P <⁠0.001) in Poland and other countries alike (P = 0.89 vs P = 0.14). In Poland, significant improvements were achieved regarding high-intensity statin therapy (27% vs 50%), LDL-C <⁠70 mg/dl (29% vs 65%), and systolic blood pressure of less than 140 mm Hg (63% vs 81%) (P <⁠0.001 for all), whereas not-smoking (89% vs 89%), aspirin (90% vs 88%), ACEI / ARB (93% vs 95%), and ß-blocker therapy (94% vs 90%) remained high. Conclusions: With regular surveillance and contemporary medical therapy, high OMT goal attainment was achievable among the participants of the ISCHEMIA trial in Poland relative to other countries. There is still room for improvement in LDL-C and blood pressure management.

Procedural and 1-year outcomes following large vessel coronary artery perforation treated by covered stents implantation: Multicentre CRACK registry.

BACKGROUND: Data regarding the clinical outcomes of covered stents (CSs) used to seal coronary artery perforations (CAPs) in the all-comer population are scarce. The aim of the CRACK Registry was to evaluate the procedural, 30-days and 1-year outcomes after CAP treated by CS implantation. METHODS: This multicenter all-comer registry included data of consecutive patients with CAP treated by CS implantation. The primary endpoint was the composite of major adverse cardiac events (MACEs), defined as cardiac death, target lesion revascularization (TLR), and myocardial infarction (MI). RESULTS: The registry included 119 patients (mean age: 68.9 ± 9.7 years, 55.5% men). Acute coronary syndrome, including: unstable angina 21 (17.6%), NSTEMI 26 (21.8%), and STEMI 26 (21.8%), was the presenting diagnosis in 61.3%, and chronic coronary syndromes in 38.7% of patients. The most common lesion type, according to ACC/AHA classification, was type C lesion in 47 (39.5%) of cases. A total of 52 patients (43.7%) had type 3 Ellis classification, 28 patients (23.5%) had type 2 followed by 39 patients (32.8%) with type 1 perforation. Complex PCI was performed in 73 (61.3%) of patients. Periprocedural death occurred in eight patients (6.7%), of which two patients had emergency cardiac surgery. Those patients were excluded from the one-year analysis. Successful sealing of the perforation was achieved in 99 (83.2%) patients. During the follow-up, 26 (26.2%) patients experienced MACE [7 (7.1%) cardiac deaths, 13 (13.1%) TLR, 11 (11.0%) MIs]. Stent thrombosis (ST) occurred in 6 (6.1%) patients [4(4.0%) acute ST, 1(1.0%) subacute ST and 1(1.0%) late ST]. CONCLUSIONS: The use of covered stents is an effective treatment of CAP. The procedural and 1-year outcomes of CAP treated by CS implantation showed that such patients should remain under follow-up due to relatively high risk of MACE.

Effect of Sex on Outcomes of Coronary Rotational Atherectomy Percutaneous Coronary Intervention (From the European Multicenter Euro4C Registry).

Data regarding the potential influence of gender on outcomes of rotational atherectomy (RA) percutaneous coronary intervention (PCI) are scarce and conflicting. Using the Euro4C registry, an international prospective multicentric registry of RA PCI, we evaluated the influence of gender on clinical outcomes of RA PCI. Between October 2016 and July 2018, 966 patients were included. In them, 267 (27.6%) were females. Female patients were older than males (77.7 years old ± 9.8 vs 73.3 ± 9.5 years old respectively, p < 0.001) had a poorer renal function (43,1% of females had a GFR < 60 ml/min:1.73m² vs 30.4% of males, p < 0.001) and were more frequently admitted for an acute coronary syndrome (32.2% vs 22.3% p = 0.002). During RA procedure, women were less likely to be treated by radial approach (65.0% vs 74.4%, p = 0.004). In-hospital major adverse cardiac event rate-defined as cardiovascular death, myocardial infarction, stroke/transient ischemic attack, target lesion revascularization, and coronary artery bypass grafting surgery-was higher in the female group (7.1% vs 3.7%, p = 0.043). However, coronary perforation, dissection, slow/low flow and tamponade did not significantly differ in gender, neither did cardiovascular medications at discharge. At 1 year follow-up, rate of major adverse cardiac event was 18.4% in the female group vs 11.2% in the male group (adjusted Hazard Ratio 1.82 [1.24 to 2.67], p = 0.002). No significant bleeding differences were observed in gender, neither in hospital, nor during follow-up. In conclusion women had worse clinical outcomes following RA PCI during hospitalization and at 1 year follow-up than did men.

Acute coronary syndrome - Still a valid contraindication to perform rotational atherectomy? Early and one-year outcomes.

BACKGROUND: Rotational atherectomy (RA) is an acknowledged method of percutaneous treatment of highly calcified or fibrotic coronary lesions. However, using the rotablator system in patients presenting with acute coronary syndromes (ACS) remains controversial and is considered as a relative contraindication. The aim of our study was to assess in-hospital and 1-year outcomes in patients undergoing RA presenting with ACS, in comparison to elective RA procedures. METHODS: This single-center observational study included all consecutive patients who underwent RA and PCI in our institution from April 2008 to October 2015. All patients were subsequently divided into two groups based on clinical presentation: stable angina group (SA) and ACS group. Primary endpoints were in-hospital and 1-year all-cause mortality and 1-year major adverse cardiac events (MACE). Secondary endpoints were procedural success and in-hospital complications. RESULTS: The study included 207 patients, 164 (79%) in SA group and 43 (21%) in ACS group. In-hospital mortality was higher in patients with ACS (4.7% vs. 0%, p=0.01). Procedural success was similar in both groups, 93% in ACS groups vs. 92.7% in SA group, p=0.94. There were no significant differences in the rate of periprocedural complications (4.7% vs. 10.4%, p=0.25), however postprocedural complications were more frequent in ACS group. At 1-year follow-up MACE rate and mortality were numerically higher, however statistically not significant (25.6% vs. 16.5%, p=0.17 and 16.3% vs. 7.9%, p=0.10; respectively). CONCLUSIONS: Despite higher mortality and complication rate in ACS group observed in postprocedural period, we found no significant difference in 1-year outcomes in comparison to elective patients. Procedural success of RA in ACS patients is similar to elective patients with SA and this procedure should be considered in case of urgent indications, if no other options of treatment exist.

Effects of selective carotid body stimulation with adenosine in conscious humans.

KEY POINTS: In humans, excitation of peripheral chemoreceptors with systemic hypoxia causes hyperventilation, hypertension and tachycardia. However, the contribution of particular chemosensory areas (carotid vs. aortic bodies) to this response is unclear. We showed that selective stimulation of the carotid body by the injection of adenosine into the carotid artery causes a dose-dependent increase in minute ventilation and blood pressure with a concomitant decrease in heart rate in conscious humans. The ventilatory response was abolished and the haemodynamic response was diminished following carotid body ablation. We found that the magnitude of adenosine evoked responses in minute ventilation and blood pressure was analogous to the responses evoked by hypoxia. By contrast, opposing heart rate responses were evoked by adenosine (bradycardia) vs. hypoxia (tachycardia). Intra-carotid adenosine administration may provide a novel method for perioperative assessment of the effectiveness of carotid body ablation, which has been recently proposed as a treatment strategy for sympathetically-mediated diseases. ABSTRACT: Stimulation of peripheral chemoreceptors by acute hypoxia causes an increase in minute ventilation (VI), heart rate (HR) and arterial blood pressure (BP). However, the contribution of particular chemosensory areas, such as carotid (CB) vs. aortic bodies, to this response in humans remains unknown. We performed a blinded, randomized and placebo-controlled study in 11 conscious patients (nine men, two women) undergoing common carotid artery angiography. Doses of adenosine ranging from 4 to 512 µg or placebo solution of a matching volume were administered in randomized order via a diagnostic catheter located in a common carotid artery. Separately, ventilatory and haemodynamic responses to systemic hypoxia were also assessed. Direct excitation of a CB with intra-arterial adenosine increased VI, systolic BP, mean BP and decreased HR. No responses in these variables were seen after injections of placebo. The magnitude of the ventilatory and haemodynamic responses depended on both the dose of adenosine used and on the level of chemosensitivity as determined by the ventilatory response to hypoxia. Percutaneous radiofrequency ablation of the CB abolished the adenosine evoked respiratory response and partially depressed the cardiovascular response in one participant. The results of the present study confirm the excitatory role of purines in CB physiology in humans and suggest that adenosine may be used for selective stimulation and assessment of CB activity. The trial is registered at ClinicalTrials.gov NCT01939912.

Could an analysis of mean corpuscular volume help to improve risk stratification in non-anemic patients with acute myocardial infarction?

BACKGROUND: Nowadays, when the majority of patients with acute myocardial infarction (AMI) are treated with primary percutaneous coronary intervention and modern pharmacotherapy, risk stratification becomes a challenge. Simple and easily accessible parameters that would help in a better determination of prognosis are needed. The aim of the study was to estimate the prevalence of high mean corpuscular volume (MCV, defined as MCV > 92 fL) and to establish its prognostic value in non-anemic patients with AMI. METHODS: We retrospectively analyzed the data of 248 consecutive non-anemic patients hospitalized due to AMI (median age: 65 [59-76] years, men: 63%, ST segment elevation myocardial infarction: 31%, and median left ventricular ejection fraction [LVEF]: 50%). RESULTS: The prevalence of high MCV was 39 ± 6% (± 95% confidence interval) in the entire AMI population. High MCV was more prevalent in males, patients with low body mass index, non-diabetics and cigarette smokers (all p < 0.05). During the 180-day follow-up, there were 38 (15%) events, defined as another AMI or death. In a multivariable Cox proportional hazard model, female gender (p < 0.01), low LVEF (p < 0.001), previous AMI (p < 0.05), arterial hypertension (p < 0.05), and high MCV (p < 0.001) were prognosticators of pre-defined events. CONCLUSIONS: In non-anemic patients with AMI, high MCV is an independent prognostic factor of poor outcome defined as another AMI or death.

Iron status and survival in diabetic patients with coronary artery disease.

OBJECTIVE: To investigate the impact of iron status on survival in patients with type 2 diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: Serum ferritin, transferrin saturation (Tsat), and soluble transferrin receptor (sTfR) were measured in 287 patients with type 2 diabetes and stable CAD (65 ± 9 years of age, 78% men). RESULTS: During a mean follow-up of 45 ± 19 months, there were 59 (21%) deaths and 60 (21%) cardiovascular hospitalizations. Both serum ferritin and sTfR strongly predicted 5-year all-cause mortality rates, independently of other variables (including hemoglobin, measures of renal function, inflammation, and neurohormonal activation). There was an exponential relationship between sTfR and mortality (adjusted hazard ratio [HR] per 1 log mg/L: 4.24 [95% CI 1.43-12.58], P = 0.01), whereas the relationship between ferritin and mortality was U-shaped (for the lowest and the highest quintiles vs. the middle quintile [reference group], respectively: adjusted HR 7.18 [95% CI 2.03-25.46], P = 0.002, and adjusted HR 5.12 [1.48-17.73], P = 0.01). Similar patterns were observed for the composite outcome of all-cause mortality or cardiovascular hospitalization, and in these multivariable models, low Tsat was related to unfavorable outcome. CONCLUSIONS: Both low and high serum ferritin (possibly reflecting depleted and excessive iron stores, respectively) along with high serum sTfR (reflecting reduced metabolically available iron) identify patients with type 2 diabetes and CAD who have a poor prognosis.

Percutaneous reduction of mitral valve regurgitation using the MitraClip system - immediate and 90-day follow-up of 3 cases.

Treatment of hemodynamically significant valvular heart diseases has been the domain of cardiac surgery for decades. However, a promising novel method is the MitraClip system, involving percutaneous connection of insufficient valve leaflets with special cobalt-chrome clips. Our study presents clinical characteristics, course of treatment with the MitraClip system, and immediate and 90-day clinical and echocardiographic follow-up of the first 3 patients treated in our institution. Subsequently, based on data from the literature and our own experience, the current position around the world, and the target group of patients who are most likely to benefit from treatment using the MitraClip system, are discussed.

Self-expanding versus balloon-expandable stents in acute myocardial infarction: results from the APPOSITION II study: self-expanding stents in ST-segment elevation myocardial infarction.

OBJECTIVES: This study sought to investigate whether self-expanding stents are more effective than balloon-expandable stents for reducing stent malapposition at 3 days after implantation in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. BACKGROUND: Acute myocardial infarction is associated with vasoconstriction and large thrombus burden. Resolution of vasoconstriction and thrombus load during the first hours to days after primary percutaneous coronary intervention may lead to stent undersizing and malapposition, which may subsequently lead to stent thrombosis or restenosis. In addition, aggressive stent deployment may cause distal embolization. METHODS: Eighty patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomized to receive a self-expanding stent (STENTYS, STENTYS SA, Paris, France) (n = 43) or a balloon-expandable stent (VISION, Abbott Vascular, Santa Clara, California; or Driver, Medtronic, Minneapolis, Minnesota) (n = 37) at 9 European centers. The primary endpoint was the proportion of stent strut malapposition at 3 days after implantation measured by optical coherence tomography. Secondary endpoints included major adverse cardiac events (cardiac death, recurrent myocardial infarction, emergent bypass surgery, or clinically driven target lesion revascularization). RESULTS: At 3 days after implantation, on a per-strut basis, a lower rate of malapposed stent struts was observed by optical coherence tomography in the self-expanding stent group than in the balloon-expandable group (0.58% vs. 5.46%, p < 0.001). On a per-patient basis, none of the patients in the self-expanding stent group versus 28% in the balloon-expandable group presented ≥5% malapposed struts (p < 0.001). At 6 months, major adverse cardiac events were 2.3% versus 0% in the self-expanding and balloon-expandable groups, respectively (p = NS). CONCLUSIONS: Strut malapposition at 3 days is significantly lower in ST-segment elevation myocardial infarction patients allocated to self-expanding stents when than in those allocated to balloon-expandable stents. The impact of this difference on clinical outcome and the risk of late stent thrombosis need to be evaluated further. (Randomized Comparison Between the STENTYS Self-expanding Coronary Stent and a Balloon-expandable Stent in Acute Myocardial Infarction [APPOSITION II]; NCT01008085).

Circulating estradiol and mortality in men with systolic chronic heart failure.

CONTEXT: Androgen deficiency is common in men with chronic heart failure (HF) and is associated with increased morbidity and mortality. Estrogens are formed by the aromatization of androgens; therefore, abnormal estrogen metabolism would be anticipated in HF. OBJECTIVE: To examine the relationship between serum concentration of estradiol and mortality in men with chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study at 2 tertiary cardiology centers (Wroclaw and Zabrze, Poland) of 501 men (mean [SD] age, 58 [12] years) with chronic HF, LVEF of 28% (SD, 8%), and New York Heart Association [NYHA] classes 1, 2, 3, and 4 of 52, 231, 181, and 37, respectively, who were recruited between January 1, 2002, and May 31, 2006. Cohort was divided into quintiles of serum estradiol (quintile 1, < 12.90 pg/mL; quintile 2, 12.90-21.79 pg/mL; quintile 3, 21.80-30.11 pg/mL; quintile 4, 30.12-37.39 pg/mL; and quintile 5, > or = 37.40 pg/mL). Quintile 3 was considered prospectively as the reference group. MAIN OUTCOME MEASURES: Serum concentrations of estradiol and androgens (total testosterone and dehydroepiandrosterone sulfate [DHEA-S]) were measured using immunoassays. RESULTS: Among 501 men with chronic HF, 171 deaths (34%) occurred during the 3-year follow-up. Compared with quintile 3, men in the lowest and highest estradiol quintiles had increased mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 2.33-7.45 and HR, 2.33; 95% CI, 1.30-4.18; respectively; P < .001). These 2 quintiles had different clinical characteristics (quintile 1: increased serum total testosterone, decreased serum DHEA-S, advanced NYHA class, impaired renal function, and decreased total fat tissue mass; and quintile 5: increased serum bilirubin and liver enzymes, and decreased serum sodium; all P < .05 vs quintile 3). For increasing estradiol quintiles, 3-year survival rates adjusted for clinical variables and androgens were 44.6% (95% CI, 24.4%-63.0%), 65.8% (95% CI, 47.3%-79.2%), 82.4% (95% CI, 69.4%-90.2%), 79.0% (95% CI, 65.5%-87.6%), and 63.6% (95% CI, 46.6%-76.5%); respectively (P < .001). CONCLUSION: Among men with chronic HF and reduced LVEF, high and low concentrations of estradiol compared with the middle quintile of estradiol are related to an increased mortality.

Long-term outcome of conservatively treated patients with borderline coronary lesions--role of the fractional flow reserve measurement.

BACKGROUND: Coronary fractional flow reserve (FFR) has been recommended as one of the functional methods which can be used to establish indications for revascularisation in patients with borderline coronary lesions. AIM: To assess long-term outcome of patients with borderline coronary lesions in whom the decision to implement conservative treatment was based on the results of FFR. METHODS: The study group consisted of 41 patients (13 females, mean age 61+/-9 years) who had CCS class II angina, an isolated borderline (40-70%) coronary lesion and FFR >0.75. All patients received 40 mg of simvastatin, angiotensin converting enzyme inhibitor and aspirin. The follow-up duration ranged from 7 to 32 months (mean 15.2+/-7.1, median 14.5 months). The analysed end-points included cardiac death, myocardial infarction (MI) (with or without ST segment elevation) and revascularisation of the target coronary artery. RESULTS: The mean FFR value in the whole study group was 0.91+/-0.05. Three (7%) patients had complications during follow-up: one patient developed MI, and two had coronary artery stenosis progression, requiring angioplasty. These patients had similar clinical and angiographic characteristics as well as FFR values as patients without complications. Among patients with uneventful outcome, in 33 (87%) anginal symptoms improved whereas in the remaining 5 (13%) patients CCS class did not change. Patients with angina alleviation were older and had higher FFR values than patients without improvement (63+/-8 vs 48+/-6 years, p=0.0005; and 0.92+/-0.05 vs 0.86+/-0.08, p=0.04, respectively). CONCLUSIONS: In patients with borderline coronary lesions and stable angina, angioplasty can be delayed on the basis of the FFR results. This approach is safe and is associated with an asymptomatic long-term follow-up in more than 90% of patients.

Measurement of fractional flow reserve in patients with multi-vessel coronary artery disease and borderline lesions prevents unnecessary revascularisation procedures.

BACKGROUND: Patients with multi-vessel coronary artery disease (CAD) are selected for percutaneous coronary interventions (PCI) or surgical revascularisation. The appropriateness of "ad hoc" PCI of borderline lesions (<70% of lumen diameter) in patients with a multi-vessel CAD has not been proven. However, delayed PCI of another lesion and gaining additional information from non-invasive tests is not a widely accepted strategy. When left anterior descending (LAD) coronary artery is one of the affected vessels, selection for surgical revascularisation is most likely. AIM: To assess long-term outcome in patients with multi-vessel CAD and borderline lesions, including LAD, in whom fractional flow reserve (FFR) in all affected vessels was measured and used for selection for PCI or conservative treatment. METHODS: The study group consisted of 16 patients with stable angina (11 males, mean age 60+/-9 years) with 34 lesions localised in the main epicardial coronary arteries [LAD / left main (LM) / right coronary artery (RCA) / intermediate branch (IB) / circumflex artery (Cx) - 15/1/5/5/8] of which at least two were borderline stenoses. Each lesion underwent FFR measurement. "Ad hoc" PCI was performed when FFR was <0.75, and conservative therapy was instituted when FFR was >0.75. RESULTS: Of 34 lesions, in 8 (23%) the FFR value was <0.75 and these lesions were treated with PCI (LAD/IB/Cx - 3/2/3). In the remaining 26 (77%) lesions, FFR was >0.75 and conservative therapy was instituted. During the mean follow-up of 15+/-6 months (range 6-28 months, median 15 months) in 8 of 9 conservatively treated patients no aggravation of anginal symptoms nor other coronary events were observed. One patient developed acute myocardial infarction due to thrombus occluding a borderline LAD lesion. Of 8 lesions treated with PCI (baseline FFR = 0.63+/-0.10 vs post-PCI FFR = 0.92+/-0.08, p=0.0002), in one case an in-stent restenosis in LAD occurred 9 months after PCI. Of a total of 26 lesions which were conservatively treated (mean FFR 0.91+/-0.05), in 2 (7.7%) the progression of CAD was noted. CONCLUSIONS: In patients with multi-vessel CAD and borderline lesions, FFR measurement identifies those, who can be treated conservatively with a good long-term outcome, and prevents unnecessary PCI.