The Curious Role of PAI-1 in Severe Obstructive Sleep Apnea.

Plasminogen activator inhibitor-1 (PAI-1) has a significant role in fibrinolysis, atherogenesis, cellular senescence, and chronic inflammation. OSA (obstructive sleep apnea) leads to increased PAI-1 levels and the development of cardiovascular disease (CVD). The aim of this study was to determine the effects of CPAP therapy on coagulation parameters and PAI-1 in patients with severe OSA. This prospective, controlled study enrolled 57 patients who were newly diagnosed with severe OSA, 37 of whom had had good CPAP adherence after 6 months of therapy (usage of the device for at least 4 h per night), and their data were analyzed. The analysis showed a statistically significant increase in D-dimer values before CPAP therapy (415 (316.5-537.5)) vs. after therapy (499 (327-652)), p = 0.0282, and a decrease in fibrinogen values (3.665 ± 0.752 before CPAP therapy vs. 3.365 ± 0.771 after therapy, p = 0.0075)). PAI-1 concentration values before and after CPAP therapy did not differ significantly (17.35 ± 7.01 ng/mL before CPAP therapy vs. 17.42 ± 6.99 ng/mL after therapy, p = 0.9367). This study shows a tendency for fibrinolytic capacity to improve in patients with OSA after CPAP therapy, although PAI-1 levels did not differ significantly.

Impact of CPAP Therapy on the Autonomic Nervous System.

Obstructive sleep apnea (OSA) is a significant risk factor for cardiovascular disease (CVD) with increasing prevalence. An important mechanism of CVD development is a dysregulation of the autonomic nervous system (ANS). This prospective and controlled cohort study aimed to investigate ANS function in OSA including the response to long-term continuous positive airway pressure (CPAP) therapy by analyzing 24 h Holter electrocardiogram and 24 h Holter ambulatory blood pressure recording parameters. The study enrolled 57 patients who were newly diagnosed with severe OSA. After 6 months of CPAP therapy, 37 patients had a good therapy adherence (usage of CPAP device >4 h per night), and their data were analyzed. The difference in nocturnal diastolic blood pressure values before and after CPAP therapy reached statistical significance (76 (68-84) vs. 74 (63-80) mmHg, p = 0.0439). Lower nocturnal values after CPAP therapy of SDNN (101.5 vs. 95 ms, p = 0.0492) and RMSSD (29.5 vs. 26 ms, p = 0.0193) were found. An increase in diurnal spectral power (1742 vs. 2112 ms2, p = 0.0282) and a decrease in nocturnal spectral power (3256 vs. 2124 ms2, p = 0.0097), nocturnal VLF band (2493 vs. 1485.4 ms2, p = 0.0176), nocturnal LF band (638.7 vs. 473 ms2, p = 0.0097), and nocturnal HF band (234.9 vs. 135.7 ms2, p = 0.0319) was found. The results showed an imbalance of the ANS with a sympathetic predominance, especially during the night hours and in those with arterial hypertension. The impact of CPAP therapy on the improvement in ANS parameters was more pronounced at night, in men, and those with arterial hypertension.

The impact of earthquakes on the frequency and prognosis of the most common emergency cardiac conditions.

AIM: To assess whether the number of patients with a cardiac chief complaint and their characteristics differed between before and after two major earthquakes that struck Croatia in 2020. METHODS: We collected data on all visits of patients with a cardiac chief complaint examined in the emergency departments of six hospitals nearest to the epicenters. Patients seen during the 7 days before the earthquake were compared with those seen on the day and during the 6 days after the earthquake. RESULTS: Patients seen after the earthquake were younger (68 [59-79] vs 72.5 [65-80]; P<0.001) and less frequently had cardiovascular disease (32.9% vs 42.8%; P<0.001). This group less frequently had the primary diagnosis of acute myocardial infarction (AMI) (15.6% vs 21.9%; P=0.005), heart failure (9.3% vs 19.4%; P<0.001), dysregulated hypertension (13.9% vs 19.4%; P=0.01), but more frequently had non-anginal chest discomfort (28.8% vs 18.0%; P<0.001). In a subgroup analysis of patients seen in hospitals located within 20 km from the epicenter, significantly more patients seen after the earthquake compared with those seen before the earthquake presented with AMI (14.5% vs 22.8%; P=0.028), acute elevation of blood pressure (10% vs 21.8%, P=0.001), and paroxysmal arrhythmias treated with electrocardioversion (0.9% vs 4.5%, P=0.022). CONCLUSION: After two moderately strong earthquakes, hospitals within 20 km from the epicenter saw a significant increase in acute cardiac conditions such as elevated blood pressure, AMI, and cardioverted arrhythmias. Eventually, these earthquakes had no impact on the outcomes of the studied population.

Perimyocarditis as First Manifestation of Systemic Lupus Erythematosus Successfully Treated with Heart Failure and Immunosuppressive Therapy.

Systemic lupus erythematosus (SLE) myocarditis is presumed to be rare, but associated with adverse outcomes. If SLE diagnosis has not previously been established, its clinical presentation is often unspecific and difficult to recognize. Furthermore, there is a lack of data in the scientific literature regarding myocarditis and its treatment in systemic immune-mediated diseases, leading to its late recognition and undertreatment. We present the case of a young woman whose first lupus manifestations included acute perimyocarditis, among other symptoms and signs that provided clues to the diagnosis of SLE. Transthoracic and speckle tracking echocardiography were helpful in detecting early abnormalities in the myocardial wall thickness and contractility while waiting for cardiac magnetic resonance. Since the patient presented with acute decompensated heart failure (HF), HF treatment was promptly started in parallel with immunosuppressive therapy, with a good response. In the treatment of myocarditis with heart failure, we were guided by the clinical signs, echocardiographic findings, biomarkers of myocardial stress, necrosis, and systemic inflammation, as well as markers of SLE disease activity.

Rituximab, Intravitreal Bevacizumab and Laser Photocoagulation for Treatment of Macrophage Activation Syndrome and Retinal Vasculitis in Lupus: A Case Report.

Systemic lupus erythematosus (SLE) most commonly manifests as mild to moderate disease with severe manifestations such as diffuse alveolar hemorrhage, central nervous system vasculitis, macrophage activation syndrome (MAS) or retinal vasculitis (RV) with visual disturbances occurring in a significantly smaller proportion of patients, most of whom have a poor outcome. Macrophage activation syndrome and RV are insufficiently early and rarely recognized presentations of lupus-consequently there are still no treatment recommendations. Here we present the course of diagnosis and treatment of a patient with an SLE flare that resulted in both life-threatening disease (MAS) and vision-threatening disease (RV). The patient was successfully treated with systemic immunosuppressives, a high dose of glucocorticoids and rituximab (RTX), in parallel with intraocular therapy, intravitreal bevacizumab (BEV) and laser photocoagulation.

Impact of CPAP Therapy on New Inflammation Biomarkers.

Obstructive sleep apnea (OSA) is a common sleep disorder leading to increased risk of developing cardiovascular diseases (CVDs) by supporting a low-grade chronic inflammation as one of the pathological mechanisms. The continuous positive airway pressure (CPAP) device is used as an effective treatment for moderate and severe OSA. Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), white blood cell-mean platelet volume ratio (WMR), C-reactive protein-albumin ratio (CAR) and fibrinogen-albumin ratio (FAR) are new potential inflammatory biomarkers that are widely available and were shown to be possibly favorable screening or follow-up tools for moderate- or severe-grade OSA, as well as indirect indicators for cardiovascular risk. Our study evaluated the impact of CPAP therapy in patients with severe OSA and acceptable therapy adherence on NLR, PLR, WMR, FAR and CAR. Of 57 patients who were initially enrolled and had no exclusion criteria, 37 had a satisfactory CPAP adherence (usage of ≥4 h per night) after a minimum of 6 months of therapy. There was a statistically significant difference in NLR (2.122 ± 0.745 before therapy vs. 1.888 ± 0.735 after therapy) and FAR (86.445 ± 18.763 before therapy vs. 77.321 ± 19.133 after therapy) suggesting a positive effect of the CPAP therapy on chronic inflammatory states, thereby possibly reducing cardiovascular risk.

The Mystery of Diabetic Cardiomyopathy: From Early Concepts and Underlying Mechanisms to Novel Therapeutic Possibilities.

Diabetic patients are predisposed to diabetic cardiomyopathy, a specific form of cardiomyopathy which is characterized by the development of myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis that develops independently of concomitant macrovascular and microvascular diabetic complications. Its pathophysiology is multifactorial and poorly understood and no specific therapeutic guideline has yet been established. Diabetic cardiomyopathy is a challenging diagnosis, made after excluding other potential entities, treated with different pharmacotherapeutic agents targeting various pathophysiological pathways that need yet to be unraveled. It has great clinical importance as diabetes is a disease with pandemic proportions. This review focuses on the potential mechanisms contributing to this entity, diagnostic options, as well as on potential therapeutic interventions taking in consideration their clinical feasibility and limitations in everyday practice. Besides conventional therapies, we discuss novel therapeutic possibilities that have not yet been translated into clinical practice.

CONGENITAL LONG QT SYNDROME: A SYSTEMATIC REVIEW.

Congenital long QT syndrome (LQTS) is a disorder of myocardial repolarization defined by a prolonged QT interval on electrocardiogram (ECG) that can cause ventricular arrhythmias and lead to sudden cardiac death. LQTS was first described in 1957 and since then its genetic etiology has been researched in many studies, but it is still not fully understood. Depending on the type of monogenic mutation, LQTS is currently divided into 17 subtypes, with LQT1, LQT2, and LQT3 being the most common forms. Based on the results of a prospective study, it is suggested that the real prevalence of congenital LQTS is around 1:2000. Clinical manifestations of congenital LQTS include LQTS-attributable syncope, aborted cardiac arrest, and sudden cardiac death. Many patients with congenital LQTS will remain asymptomatic for life. The initial diagnostic evaluation of congenital LQTS includes obtaining detailed personal and multi-generation family history, physical examination, series of 12-lead ECG recordings, and calculation of the LQTS diagnostic score, called Schwartz score. Patients are also advised to undertake 24-hour ambulatory monitoring, treadmill/cycle stress testing, and LQTS genetic testing for definitive confirmation of the diagnosis. Currently available treatment options include lifestyle modifications, medication therapy with emphasis on beta-blockers, device therapy and surgical therapy, with beta-blockers being the first-line treatment option, both in symptomatic and asymptomatic patients.

Impact of troponin I on outcome of ischemic stroke patients.

INTRODUCTION: Stroke is one of the leading causes of morbidity and mortality. Cardiac troponins have been found to be increased in other conditions apart from the cardiac diseases, such as stroke. The aim of the study was to assess the correlation between elevated troponin I levels and stroke outcome. METHODS: This retrospective study included 198 acute ischemic stroke patients in whom troponin I levels have been obtained at admission. Exclusion criteria were concomitant acute coronary syndrome, congestive heart failure, pulmonary embolism, renal failure, rhabdomyolysis and septic conditions. RESULTS: There was a statistically significant difference in the proportion of deaths during hospitalization (p = 0.041) and modified Rankin Scale scores (p = 0.016) between the group of patients with elevated troponin I levels and the control group. Prior ischemic strokes were more common in the group with elevated troponin I levels (p = 0.032). No other differences were observed. CONCLUSIONS: Our study showed that patients with elevated initial troponin I levels are associated with unfavorable outcome or death. Stroke may be associated with mild elevation of troponin levels, contrary to higher levels which are usually related to other conditions.

Hypersensitivity Eosinophilic Myocarditis in a Patient Receiving Multiple Drug Therapy: Challenges in Diagnosis and Defining the Aetiology.

Eosinophilic myocarditis (EM) is a rare and potentially fatal disease if left untreated. Because the disease can have a delayed presentation and can appear even after 2 years, its underlying causes often remain unknown. We report the case of a 63-year-old man with an atypical clinical presentation of hypersensitive EM and significant coronary artery disease, which was confirmed through coronary angiography. The patient was treated with hydrochlorothiazide (12.5 mg once daily for 2 years) and budesonide/formoterol (160/4.5 µg once daily for 2 years). Amoxicillin/clavulanic acid (1000/200 mg three times daily for 2 days) and azithromycin (500 mg once daily for 2 days) were used to treat pneumonia, while ibuprofen (600 mg three times daily for 2 days) was used to treat pericarditis. Extremely high levels of eosinophils led to clinical suspicion of non-acute coronary syndrome as the cause of chest pain and myocardial necrosis. In addition, early pulse doses of methylprednisolone (500 mg intravenously once daily) were administered. Complete clinical recovery and a fast decrease in eosinophils and troponin levels were observed after a few hours on the same day. No signs of recurrent myocarditis were noticed after 3 days of administering the same pulse doses of methylprednisolone, which was then replaced by oral methylprednisolone administered for the next 2 months (step-down regimen, starting from 64 mg/day). Despite causality assessment being difficult, prompt therapy must be given as soon as possible to prevent fatal outcomes. Delayed corticosteroid treatment, which is necessary regardless of the underlying cause, can result in heart failure and death.

P2RY12 gene polymorphisms and effect of clopidogrel on platelet aggregation.

Objective of this study was to assess platelet response to clopidogrel and its association with certain single nucleotide polymorphisms (SNPs) of the P2RY12 gene. Several studies have shown that patients with poor in vitro response to clopidogrel have worse outcomes after coronary interventions. Pharmacological response to clopidogrel is mediated by the P2Y12 platelet receptor, therefore, SNPs of the P2RY12 gene may account for some of the observed variability in the cardiovascular risk. Fifty patients with stable coronary heart disease, undergoing percutaneous coronary intervention were included in this study. Response to clopidogrel was analysed using light transmitted aggregometry before, and 5 days after the initation of therapy. SNPs analysed: c.-15+742C > T, c.-180+2739T > C and c.18C > T. A higher proportion of non-responders to clopidogrel were noted in carriers of 18C > T[T/T] (p = 0.05), and lower prevalence in carriers of 742C > T[T/T] (p = 0.05). Participants with 742C > T[T/T] had significantly higher change in aggregation compared to other 742C > T variants ([C/C] = 20.5 +/- 21.9%; [C/T] = 20.0 +/- 31.2%; [T/T] = 48.6 +/- 21.3%; p = 0.03). Those carrying 18C > T[T/T] had smaller change in aggregation (7.6 +/- 15.0%) compared to other variants, but the difference was not statistically significant (p = 0.15). Analysis of variance showed 18C > T[T/T] was a statistically significant predictor of poor response to antiaggregation therapy, independent from other clinical and demographic variables. There was no relation between poor response to clopidogrel and any other genetic variant. Our results suggest that 18C > T SNP of the P2RY12 gene may be an independent predictor of pharmacological response to clopidogrel. Larger prospective studies are needed to confirm this link and assess its possible clinical consequences.

Secondary hypertension due to isolated interrupted aortic arch in a 60-year-old person--one-year follow up.

Interrupted aortic arch (IAA) is a congenital defect characterized by loss of luminal continuity between the ascending and descending aorta1. It is a rare malformation with an estimated incidence of perinatally diagnosed cases of 3 per million live births3. The condition is considered extremely rare in adults. However, its true prevalence in this population is unknown. We have found 30 case reports of IAA in adults in literature, 5 of whom were older than 50 years. Four of them had type A IAA. Arterial hypertension is a typical co-morbidity. In this report we describe a 60-year-old male patient who had a type A asymptomatic IAA. Although we initially suspected the aortic coarctation, further invasive procedures revealed complete interruption of the aortic arch just distal to the origin of the left subclavian artery. The patient underwent surgical repair, followed by full recovery and near-normalization of blood pressure.

Natural history of cardiovascular disease in patients with diabetes: role of hyperglycemia.

Atherosclerotic vascular disease is more common in diabetic than in nondiabetic individuals. Diabetic macrovascular disease also has a more severe course with greater prevalence of multiple-vessel coronary artery disease and more diffuse elongated atheromas in affected blood vessels. In this review, we discuss possible reasons for increased incidence of cardiovascular (CV) events in individuals with diabetes. Although an increased prevalence of standard CV risk factors has been clearly documented in association with diabetes, diabetes-related abnormalities, particularly hyperglycemia, also play an important role. Epidemiological studies suggest that the effect of hyperglycemia on CV risk is independent of other known risk factors, but no data from primary interventional trials are available yet. Analysis of datasets from populations that included individuals with impaired glucose tolerance and impaired fasting glucose suggest that the pathogenic role of hyperglycemia on the blood vessel wall already exists in the early stages of glucose intolerance. The effect of postprandial or postchallenge hyperglycemia seems to be greater than the effect of fasting blood glucose abnormalities. The relationship of postprandial glycemia, fasting blood glucose, and CV risk in individuals with diagnosed (or overt) diabetes is less clear, although most reports indicate a greater pathogenic potential of postprandial hyperglycemia rather than fasting hyperglycemia. Based on the results of epidemiological reports, the most appropriate targets in interventional trials are postprandial hyperglycemia or A1C.

Abnormal systolic blood pressure during treadmill test and brachial artery flow-mediated vasodilatation impairment.

The aim of the study was to assess the relationship between systolic blood pressure during maximal treadmill test (SBP9mtt)) and flow-mediated vasodilation (FMD). Abnormal rise of SBP(mtt) is the phenomenon more frequent in hypertensive persons but it could be found in normotensive subjects too. 199 subjects referred to treadmill test were enrolled in the study. Four groups were formed: hypertensives with abnormal SBP(mtt) (group A), hypertensives with normal SBP(mtt) (group B), normotensives with abnormal SBP(mtt) (group C) and normotensives with normal SBP(mtt) (group D). Rise of SBP(mtt) above 200 mmHg was considered abnormal reaction. Simple linear regression analysis showed significant inverse relationship between SBP(mtt) and FMD (F = 20.2036, p < 0.001, R2 = 0.0956). Mean FMD index was worst in hypertensive subjects with abnormal SBP(mtt) (group A), followed by normotensives with abnormal SBP(mtt) (group C), hypertensives with normal SBP(mtt) (group B) and the best was in normotensives with normal SBP(mtt) (3.56 +/- 5.17, 4.19 +/- 5.14, 6.81 +/- 8.43 and 10.92 +/- 7.48%, respectively). In multivariate regression analysis FMD showed significant association with abnormal SBP(mtt) (p < 0.001) along with brachial artery diameter (p < 0.001), male gender (p < 0.001), but not with hypertension (p = 0.073), BMI (p = 0.137) and total cholesterol (p = 0.23) (coefficients: -0.26, -0.40, -0.27, -0.13, -0.11 and -0.07, respectively). There was a significant inverse relationship between SBP(mtt) and FMD. An impairment of FMD exists in normotensive subjects with abnormal SBP(mtt). In hypertensives with abnormal SBP(mtt) an additional impairment of FMD exists when compared to hypertensives with normal SBP(mtt). Abnormal SBP(mtt) should be taken into account in global cardiovascular risk assessment.