Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Invasive hemodynamic assessment of patients with cardiomyopathies

Инвазивната хемодинамична оценка на сърдечните заболявания придобива все по-голяма роля през последни- те десетилетия. Поради по-широката си достъпност и безопасност неинвазивните техники са основните методи, използващи се за оценка на сърдечната функция. Хемодинамичната оценка чрез сърдечна катетеризация се при- лага за решаване на диагностични проблеми, които не могат да бъдат решени чрез рутинните методики. Този тип изследване трябва да бъде индивидуализирано спрямо конкретните проблеми на всеки пациент и базирано на получените от неинвазивните изследвания резултати. Инвазивната диагностика се използва широко при оценка- та на пациентите с различни сърдечно-съдови заболявания, включително и кардиомиопатии. В настоящия обзор разглеждаме ролята на сърдечната катетеризация, нейните предимства и недостатъци като част от цялостната оценка на пациентите с кардиомиопатии.  Invasive hemodynamic assessment of cardiac diseases has become an important diagnostic tool in recent decades. Non-invasive methods are the main techniques used to assess cardiac function, due to their wider availability. Cardiac catheterization is useful when there are diagnostic problems that cannot be solved with routine methods. Cardiac catheterization should be individualized according to the specific problems of the patient and based on the results from non-invasive methods. Invasive diagnostics is used in the assessment of patients with various cardiovascular diseases, including cardiomyopathies. In this review, we consider the role of cardiac catheterization, its advantages and disadvantages as part of the overall assessment of patients with cardiomyopathies.

Survival of patients with cardiomyopathies

Кардиомиопатиите са хетерогенна група заболявания. Основният патогенетичен механизъм е миокардна увреда, резултат най-често на генетични мутации. Те са една от водещите причини за развитие на сърдечна недостатъч- ност, внезапна сърдечна смърт и животозастрашаващи аритмии. Прогнозата при пациентите с кардиомиопатии се определя основно от наличието или липсата на определени фактори, асоциирани с неблагоприятно протичане, както и от етапа на диагностицирането им. Преживяемостта при отделните видове кардиомиопатии е различна, като водеща причина за повишена смъртност е късното откриване на заболяването и съответно забавеното за- почване на лечение. Основните кардиомиопатии, разгледани в настоящия обзор, са хипертрофична, дилативна, рестриктивна, ЛК некомпактност и аритмогенна деснокамерна кардиомиопатия. Cardiomyopathies are a heterogeneous group of diseases. The main pathogenetic mechanism is myocardial damage due to genetic mutations. Cardiomyopathies are one of the leading causes of heart failure, sudden cardiac death, and life-threatening arrhythmias. Certain factors associated with poor prognosis determined the prognosis in this group of patients. Survival in different types of cardiomyopathies depends on the time of diagnosis and initial treatment. The types of cardiomyopathies discussed in this review are hypertrophic cardiomyopathy, dilative cardiomyopathy, restrictive cardiomyopathy, left ventricle non-compaction, and arrhythmogenic right ventricular cardiomyopathy

Clinical effect of carotid stenting on cognitive abilities – possible evaluation using candidates for biomarkers

Micro- and macrovascular consequences of atherosclerosis, arterial hypertension, dyslipidemia, and smoking can affect neurotransmission and markers for neuronal activity. The potential direction and specifics are under study. It is also known that optimal control of hypertension, diabetes, and dyslipidemia in midlife may positively affect cognitive functioning later in life. However, the role of hemodynamically significant carotid stenoses in neuronal activity markers and cognitive functioning is still being debated. With the increased use of interventional treatment for extracranial carotid disease, the question of whether it might affect neuronal activity indicators and whether we can stop or even reverse the path of cognitive deterioration in patients with hemodynamically severe carotid stenoses naturally emerges. The existing state of knowledge provides us with ambiguous answers. We sought the literature for possible markers of neuronal activity that can explain any potential difference in cognitive outcomes and guide us in the assessment of patients throughout carotid stenting. The combination of biochemical markers for neuronal activity with neuropsychological assessment and neuroimaging may be important from practical point of view and may provide the answer to the question for the consequences of carotid stenting for long-term cognitive prognosis

Intracoronary electrocardiogram to guide percutaneous interventions in coronary bifurcations - a proof of concept: The FIESTA (Ffr vs. IcEcgSTA) study

Aims: The aim of this study was to determine the accuracy of the intracoronary electrocardiogram (icECG) to detect ischaemia during bifurcation lesion percutaneous coronary intervention (PCI) with fractional flow reserve (FFR) as a reference. Methods and results: Patients with significant bifurcation lesions defined as FFR ≤0.80 were included. FFR and icECG were performed in the main vessel (MV) and side branch (SB) before and after provisional stenting. icECG was recorded with an uninsulated proximal wire end connected to a unipolar lead. The diagnostic accuracy of the icECG for the detection of ischaemia in the SB after MV stenting was determined with FFR as a reference. Overall, 37 patients were included. Seventeen bifurcations had an SB FFR ≤0.80 after MV stenting and 20 patients had an ST-segment elevation on the icECG. There was significant correlation between SB FFR and ST-segment elevation on the icECG (r=-0.533, p<0.001). The diagnostic accuracy of icECG ST-elevation to detect functionally significant SB stenosis revealed an AUC of 0.71 (95% CI: 0.64-0.80) with a sensitivity of 88% and specificity of 75% with a positive predictive value of 75% and negative predictive value of 88%. Neither SB FFR nor icECG correlated with SB percent diameter stenosis after MV stenting. Conclusions: Intracoronary ECG has a good ability to predict functionally significant stenosis at the SB after MV stenting during bifurcation PCI. This method provides a novel strategy to assess the significance of an SB lesion without the need of a pressure wire

Widely Split P Waves After Pharmacologic Cardioversion in a Patient With Atrial Fibrillation

We report a case of a clinically asymptomatic patient with extreme P-wave separation on the electrocardiogram mimicking atrial tachycardia with atrioventricular block. The accurate examination of the patient, analysis of the electrocardiogram, and echocardiographic findings led to proper diagnosis, management, and treatment. (Level of Difficulty: Intermediate.