Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

The Impact of Hypertension and Atrial Fibrillation on Cognitive Decline and Subclinical Atherosclerosis

Background: Assessment of cognitive impairment and the presence of subclinical atherosclerosis are very important especially in patients with cardiovascular risk factors. Methods: We included 155 hypertensive patients (84 with AF versus 71 without AF) to identify the premature cognitive impairment, the earliest signs of subclinical atherosclerosis and onset of myocardial dysfunction and to evaluate the type of anticoagulation used, the importance of CHA₂DS₂-VASc score (</>3), age (</>65 years) in hypertensive patients with AF. Results: Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), Left Ventricular Ejection Fraction (LVEF) were significantly decreased, and Activities of Daily Living Score (ADL), Geriatric Depression Scale(GDS-15), and intima–media thickness (IMT) were significantly increased in hypertensive patients with AF vs. without AF (p < 0.05). MMSE was significantly decreased, ADL and IMT were significant increased in patients with AF and CHA₂DS₂-VASc>3 and non-vitamin K antagonists oral anticoagulants therapy (NOACs)(p < 0.05). Patients with age >65 with AF had higher rates of cognitive impairment (MMSE significant decrease) and a larger IMT (significant increase) versus patients with AF and age <65 (p < 0.05). Conclusions: Cognitive impairment is encountered in hypertensive patients having AF. Our conclusions suggest a direct link between cognitive impairment, depression, hypertension, AF, age, CHA₂DS₂-VASc score, type of anticoagulants used, LVEF, cognitive parameters, and IMT. We acknowledge the importance of identifying and preventing cognitive changes

Connections between Cognitive Impairment and Atrial Fibrillation in Patients with Diabetes Mellitus Type 2

(1) Background: Cognitive decline (CD), considered a precursory state of dementia, is frequently encountered in patients with diabetes mellitus type 2 (DM-2) and might even have a higher prevalence in those with associated atrial fibrillation (AF). In this study, we aimed to research if the association of DM-2 and AF favors a precocious onset of CD. (2) Methods: This study was conducted on 160 patients, featuring 50 with DM-2, 54 with DM-2 and AF, and 56 subjects without DM-2 and AF, all evaluated clinically and with five neuropsychiatric scales. (3) Results: The Mini-Mental-State-Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living Score (ADL), Instrumental Activities of Daily Living Score (IADL), and Geriatric Depression Scale (GDS-15) were significantly altered in patients with DM-2 and AF in comparison to patients without these diseases. The logistic regression model indicated that, in patients with DM-2 and AF, an increase of one year in age is associated with a 7.3% augmentation of the risk of a precocious onset of CD (MMSE < 27). (4) Conclusions: CD is more frequent in patients with DM-2, especially when associated with AF, versus those without DM-2 and AF. Our findings suggest that an older age and associated dyslipidemia represent risk factors for CD in patients with DM-2

Correlation between sleep apnea syndrome and heart failure depending on ejection fraction

OBJECTIVES The aim of this study was to analyze the correlations between sleep apnea syndrome(SAS) and heart failure(HF) in patients with preserved or reduced ejection fraction(EF). MATERIALS AND METHODS We evaluated 51 patients with suspected SAS and HF in sleep lab in Timișoara. General data was collected using sleep questionnaires, anthropometric measurements, somnography for apnea-hypopnea index, oxygen desaturation index, echocardiographic data, comorbidities and lab tests. RESULTS Creatinine -1.1±0.2 vs 1.4±0.7, p=0.05; stroke-23% vs 4%, p=0.04; aortic insufficiency-11.5% vs 36%, p=0.04; tricuspid insufficiency-46.1% vs 80%, p=0.01. Differences between groups regarding anthropometric measurements, somnographic index, lipidic profile were not statistically significant.. CONCLUSIONS Patients with SAS-IC with preserved EF have a higher risk of stroke events. Patients with IC with EF<50% had a significantly increased risk of developing a life-long chronic kidney disease. The SAS-IC population with low EF is at a higher risk of developing aortic and tricuspid insufficiency. REFERENCES 1. Douglas T. Sleep Apnea and Heart Failure. Part1: Obstructive Sleep Apnea. Circulation.2003.107:1671-1678. 2. Takatoshi K, Douglas TB. Obstructive Sleep Apnea and Heart Failure-Pathophysiologic and Therapeutic Implication. Journal of the American College of Cardiology. 2011; 57:doi: 10.1016/j.jacc.2010.08.627 3. Ferrier K, Campbell A, Yee B et al. Sleepdisordered breathing occurs frequently in stable outpatients with congestive heart failure. Chest. 2005;128:2116–2122

Particularities of Older Patients with Obstructive Sleep Apnea and Heart Failure with Mid-Range Ejection Fraction

Background and objectives: Obstructive sleep apnea syndrome (OSAS) and heart failure (HF) are increasing in prevalence with a greater impact on the health system. The aim of this study was to assess the particularities of patients with OSAS and HF, focusing on the new class of HF with mid-range ejection fraction (HFmrEF, EF = 40%&ndash;49%), and comparing it with reduced EF (HFrEF, EF &lt; 40%) and preserved EF (HFpEF, EF &ge; 50%). Materials and Methods: A total of 143 patients with OSAS and HF were evaluated in three sleep labs of &ldquo;Victor Babes&rdquo; Hospital and Cardiovascular Institute, Timisoara, Western Romania. We collected socio-demographic data, anthropometric sleep-related measurements, symptoms through sleep questionnaires and comorbidity-related data. We performed blood tests, cardio-respiratory polygraphy and echocardiographic measurements. Patients were divided into three groups depending on ejection fraction. Results: Patients with HFmrEF were older (p = 0.0358), with higher values of the highest systolic blood pressure (mmHg) (p = 0.0016), higher serum creatinine (p = 0.0013), a lower glomerular filtration rate (p = 0.0003), higher glycemic levels (p = 0.008) and a larger left atrial diameter (p = 0.0002). Regarding comorbidities, data were presented as percentage, HFrEF vs. HFmrEF vs. HFpEF. Higher prevalence of diabetes mellitus (52.9 vs. 72.7 vs. 40.2, p = 0.006), chronic kidney disease (17.6 vs. 57.6 vs. 21.5, p &lt; 0.001), tricuspid insufficiency (76.5 vs. 84.8 vs.59.1, p = 0.018) and aortic insufficiency (35.3 vs.42.4 vs. 20.4, p = 0.038) were observed in patients with HFmrEF, whereas chronic obstructive pulmonary disease(COPD) (52.9 vs. 24.2 vs.18.3, p = 0.009), coronary artery disease(CAD) (82.4 vs. 6.7 vs. 49.5, p = 0.026), myocardial infarction (35.3 vs. 24.2 vs. 5.4, p &lt; 0.001) and impaired parietal heart kinetics (70.6 vs. 68.8 vs. 15.2, p &lt; 0.001) were more prevalent in patients with HFrEF. Conclusions: Patients with OSAS and HF with mid-range EF may represent a new group with increased risk of developing life-long chronic kidney disease, diabetes mellitus, tricuspid and aortic insufficiency. COPD, myocardial infarction, impaired parietal kinetics and CAD are most prevalent comorbidities in HFrEF patients but they are closer in prevalence to HFmrEF than HFpEF

Prevalence of Cardio-Embolic Brain Complications in Permanent and Paroxysmal Atrial Fibrillation Patients

Background: Atrial fibrillation (AF) is the most frequent of all cardiac arrhythmias, with an increasing prevalence in the last 20 years. Cardio-embolic brain complications (CEBC) related to AF often occur or recur, even following appropriate treatment. Method: We conducted a retrospective study and analyzed the presence of stroke, dementia, and Parkinson’s disease (PD) in both paroxysmal and permanent AF patients. The records of 1111 consecutive admitted patients with primary diagnosis of AF at the Municipal Emergency University Hospital, Timisoara, between 2015 and 2016 were examined. Statistical analysis was performed on the patients included in the study based on the inclusion and exclusion criteria. Results: A significant statistical difference was noted among the permanent AF group for stroke (48.75% vs. 26.74%, p p < 0.001) compared to paroxysmal AF patients. Permanent AF patients presented a higher risk of developing stroke, dementia, and PD compared to patients with paroxysmal AF. Meanwhile, male gender and an increase in age showed an increase in the odds of having cardio-embolic brain complications in patients with paroxysmal AF. Conclusion: Based on the results obtained, it can be concluded that the risk of cardio-cerebral embolic complications is greater in permanent AF patients compared to paroxysmal AF cases. Ischemic stroke and dementia are more frequent in the permanent AF group, but analyzing the data regarding the age of onset paroxysmal AF is critical due to the fact that it involves a younger population. Prompt diagnosis and treatment can help significantly in saving stroke patients

What to Do When There Is Something Unexpected?

Background: Myocardial infarction is currently the leading cause of death worldwide, followed by malignant neoplasms. The presence of both within the same patient obviously increases the risk of death, as many coronary events are detected in patients diagnosed with cancer. Diagnosis of an occult digestive cancer in the acute phase of myocardial infarction is most frequently prompted by a hemorrhagic complication. Case summary: This case features an 81-year-old male patient diagnosed with acute myocardial infarction, treated with primary percutaneous intervention (PCI), who developed post-stenting hemorrhagic complications in the first 24 h due to the presence of two different concomitant malignant neoplasms. The outcome was favorable in the acute phase, even if de-escalation therapy was given immediately post-stenting, and intrastent residual thrombotic risk was high. Conclusions: The presence of bleeding complications in patients with acute myocardial infarction should mobilize resources in search of a neoplastic cause, especially a digestive one. However, other locations should be looked for, depending on the source of bleeding

Rhythm Disturbances in Post-Acute COVID-19 Syndrome in Young Men without Pre-Existing Known Cardiovascular Disease—A Case Series

Current data indicate the existence of post-acute COVID-19 syndrome frequently expressing as cardiovascular and respiratory health issues. The long-term evolution of these complications is not yet fully known or predictable. Among the most common clinical manifestations of post-acute COVID-19 syndrome are dyspnea, palpitations, and fatigue, in most cases being transient and without underlying any morphological or functional changes. A single-center retrospective observational study was performed on cases that had presented with new-onset cardiac symptoms post-COVID-19 infection. Records of three male patients without pre-existing chronic cardiovascular pathology who had presented for dyspnea, fatigue, and palpitations around four weeks post-COVID-19 acute phase were studied in detail. The three post-COVID-19 cases exhibited arrhythmic complications after completely healing from the acute phase of the infection. Palpitations, along with chest pain, and possible aggravation or appearance of dyspnea, with syncopal episodes, were found to be present. All the three cases were non-vaccinated against COVID-19 infection. Isolated case reports showing arrhythmic complications such as atrial fibrillation and ventricular tachycardia on a small number of patients with these complications indicate the need for arrhythmic evaluation of large groups of patients in the post-acute stage of the COVID-19 syndrome for a better understanding of the phenomenon and implicitly better care of these patients. It would also be useful to evaluate large groups of patients divided into vaccinated/non-vaccinated against COVID-19 categories to determine whether vaccination per se can provide protection in the occurrence of these types of complications

Cholesterol Gallstones and Long-Term Use of Statins: Is Gut Microbiota Dysbiosis Bridging over Uncertainties?

A total of 300 research participants—200 consecutive patients diagnosed with dyslipidemia (100 statin (+), treated for at least five years, and 100 statin (−)) and 100 healthy controls—were included in this observational study. The aim of the study was to deliver insights into the relationship between the long-term use of statins for dyslipidemia and gallstone disease (GSD), as well as insights into the background particularities of the gut microbiota. All study participants underwent clinical examination, laboratory workups, stool microbiology/stool 16S r RNA, next-generation sequencing, and abdominal ultrasound/CT exams. Results: The research participants presented with similarities related to age, gender, and location. Patients displayed comparable heredity for GSs, metabolic issues, and related co-morbidities. Gut dysbiosis (DB) was present in 54% of the statin (−) patients vs. 35% of the statin (+) patients (p = 0.0070). GSs were present in 14% of patients in the statin (−) group vs. 5% of patients in the statin (+) group (p = 0.0304). Severe dysbiosis, with a significant reduction in biodiversity, an increase in LPS (+) bacteria, and a notable decrease in mucin-degrading bacteria, mucosa-protective bacteria, and butyrate-producing bacteria were observed in the statin (−) group. Strong positive correlations between GSD and diabetes/impaired glucose tolerance (r = 0.3368, p = 0.0006), obesity (r = 0.3923, p p = 0.0011), and DB (r = 0.7343, p p = 0.0211), were observed. The multiple regression equation demonstrated that only DB (95% CI: 0.3163 to 0.5670; p p = 0.0289) were independent risk factors predicting GSD in the group of patients treated with statins. Conclusion: The long-term use of statins in dyslipidemic patients was associated with a low risk of developing GSs. The gut microbiota associated with a long-term use of statins in dyslipidemic patients was characterized by a low risk of developing an imbalance of various functional bacteria and alterations in the metabolic microbiota. DB and obesity were found to be independent risk factors predicting GSD in statin (+) patients

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)