D. Bartos

Midkine proteins in cardio-vascular disease.: Where do we come from and where are we heading to?

Midkine is a recently identified new growth factor/cytokine with pleiotropic functions in the human organism. First discovered in the late eighties, midkines have now become the subject of numerous studies in cardiovascular, neurologic, renal diseases and also various types of cancers. We summarize here the most important functions of midkine in cardiovascular diseases, emphasizing its role in inflammation and its antiapoptotic and proangiogenetic effects. Midkine has multiple roles in the organism, with the specific feature of being either beneficial or harmful depending on which tissue it acts on. Even though midkine has been shown to have cardiac protective effects against acute ischemia/reperfusion injury and to inhibit cardiac remodeling, it also promotes intimal hyperplasia and vascular stenosis. As such, different therapeutic strategies are currently being evaluated, consisting of administering either midkine proteins or midkine inhibitors depending on the desired outcome. More data is gathering to suggest that these novel therapies could become an adjunctive to standard cardiovascular therapy. Nonetheless, much is still to be learned about midkine. The encouraging results up till now require further studying in order to fully understand the complete profile of its mechanism of action and the clinical safety and efficacy of novel therapeutic opportunities offered by midkine molecular targeting.

Cardiovascular risk factors in a Roma sample population from Romania

Abstract Background. The Roma population has a high prevalence of cardiovascular risk factors, higher mortality, and shorter life expectancy. It is found in the largest number in Romania, but published data are still scarce here. We studied cardiovascular risk factors and disease along with target organ damage on a population of Roma inhabitants from Bucharest, Romania. Methods. This cross-sectional study enrolled 806 Roma subjects (18-83 years), in a community-based participatory research manner. Demographics included anthropometric data, a questionnaire on social status, education, medical history, and health deleterious behaviors. Medical evaluation included clinical examination, blood pressure, ankle-brachial index, pulse wave velocity measurements, blood tests (complete blood count, lipid profile, glucose, creatinine, uric acid), dip-stick microalbuminuria, dilated fundoscopy, ECG, and echocardiography. Results. Prevalence of all cardiovascular risk factors was high, peaking in abnormal lipid metabolism (82.13%), heavy smoking (63.02% including ex-smokers) and obesity (50.99%). The first and the latter were actually similar to the general population in Romania. Almost half of subjects were at high or very high risk for fatal cardiovascular disease. Conclusions. The study shows that the Roma population in a more affluent region in Romania shares a similarly high cardiovascular burden to their surrounding community.

Pulmonary thromboembolism in an emergency hospital: Are our patients different?

Abstract Introduction. Pulmonary thromboembolism (PTE) represents a medical emergency and is the third most common cause of mortality after myocardial infarction and stroke. The purpose of this study was to describe the characteristics and management of patients with PTE admitted in a referral emergency hospital in Romania. Material and methods. We retrospectively reviewed all cases of PTE diagnosed in one of the largest emergency hospitals in Bucharest during a 2-year period (January 2014 – December 2016). Patients with acute PTE were identified by a database search of the diagnostic codes of all discharge diagnoses. Demographic, clinical and paraclinical tests data was retrieved from medical records. Results. 221 patients (48.87% male, mean age 61.76 years (range 21-94 years)) were diagnosed with PTE in our hospital (0.31% of all hospitalizations). Dyspnea was the most frequent symptom reported (78.9%), followed by pleuritic chest pain (23.9%) and unilateral leg pain (15.8%). Upon presentation, 12.6% of patients had high-risk PTE. Up to 72.8% of patients had at least one thrombotic risk factor, while cancer (14%) was the most frequent amongst them. The mean length of hospitalization was 10.3 ± 4.6 days. Unfractioned heparin (UFH) was the preferred anticoagulant during hospital stay (73.7%, p < 0.001). Vitamin K antagonists (AVK) were the preferred anticoagulant (71.7%, p < 0.001) after discharge, whereas non-antivitamin K oral anticoagulants (NOAC) were recommended in 26.3% of patients. Thrombolysis was used in 18 (8.4%) cases. Mortality was 0.9%. Younger patients more frequently associated thrombophilia or a previous thromboembolic event and clinical signs of DVT at presentation. Older patients associated more frequently a history of hospitalization for heart failure or atrial fibrillation during the previous 3 months and a history of cancer. The clinical presentation in older patients was more severe, with higher PESI scores (103.6 ± 33.4 vs. 55.5 ± 17.9, p<0.001) and a longer hospital stay (10.7 ± 4.7 vs. 9.2 ± 3.9, p = 0.03). The type of anticoagulant treatment did not differ depending on age. Conclusion. In our emergency hospital, PTE is a relatively rare cause of hospitalization; the rate is, however, comparable with other major hospitals. Dyspnea and pleuritic chest pain was the clinical presentation dyad. UFH was the preferred anticoagulant for in-hospital treatment while AVK was the preferred option for long term treatment and recurrence prophylaxis; however an increasing number of patients are prescribed NOAC. In older patients clinical severity was higher upon presentation, hospitalization duration was increased and cancer was more frequently associated. Younger patients associated more frequently a primary hypercoagulable state and recurrent thromboembolism. Mortality rate was low during hospitalization, comparable with that seen in other studied populations.

The Etiology of Syncope in an Emergency Hospital.

Abstract Background. Syncope is a commonly encountered problem in an emergency hospital. Global cerebral hypoperfusion is the final pathway common to all presentations of syncope, but this symptom presentation has a broad differential diagnosis. It is important to identify patients for whom syncope is a symptom of a potentially life-threatening condition. Material and methods. We identified adult patients presenting with syncope to the Emergency Department of our hospital from January 2012 to June 2014. Of 590 patients found in the hospital database we further selected 217 patients who met our criteria, namely having a positive diagnosis of syncope (being clearly distinguished from other TLOCs) and an etiology of the disease. Thus, definite diagnosis was established retrospectively by reviewing medical records. Results. The demographics of our group shows a slightly different distribution between men and women (49% men and 51% women) and a majority of the urban population (67%). As for the age range, most of our patients were in the age group of 70-80 years (30%), 29% were > 80 years old, and the percentage decreases significantly in the 60-70 years range (17%). The most frequent causes of syncope were cardiac (32%), vasovagal (23%) and due to orthostatic hypotension (12%), but we have also found various cases of mixt or iatrogenic causes. Conclusions. The incidence of syncope increases sharply after 70 years of age and poses special consideration in light of multiple comorbid conditions, age-related changes, atypical presentation, and concomitant medication use. The most common causes of syncope in this population are cardiac causes, orthostatic hypotension and carotid sinus hypersensitivity. Often, root cause of syncope remains undiagnosed, despite exhaustive diagnostic testing.

Illicit drugs and their impact on cardiovascular pathology

Abstract The use of illicit drugs has dramatically increased during the past years. Consequently, the number of presentations at the emergency departments due to the adverse effects of the illicit drugs has also increased. This review discusses the cardiovascular effects of cocaine, opiates and opioids, cannabinoids, amphetamines, methamphetamines and hallucinogens as we consider that it is essential for a clinician to be aware of them and understand their mechanisms in order to optimize the therapeutic management.

Right Ventricular Normal Function

The evaluation of right ventricular (RV) morphology and function, although for many centuries forgotten or sidelined, is now recognized to be essential in cardiovascular diseases, as it can be involved in the physiopathology of many disorders. Therefore, appropriate knowledge of RV function in health and disease is mandatory for clinicians. In the present chapter we summarize the current available data on RV function starting with a brief description of anatomy as morphology is closely related to function. We then describe mechanical and haemodynamic aspects of RV contraction. Furtheremore, we discuss methods of assessing RV performance using end-systolic and end-diastolic pressure-volume relationships as well as RV haemodynamic coupling with the pulmonary circulation based on the concept of elastance. Regulatory mechanisms of RV function are also described.

Heart Embryology: Overview

Human heart has a complex embryological development process driven by genetic mechanisms that have successive and unitary progression in a global context together with other developments of organogenesis. The first elements of cardiogenesis occur prematurely from mesoderm where cellular differentiation at this level acquires cardiogenic specificity by creating the first heart field. From this stage, cellular multiplication is specific for myocardial, endothelial, and smooth muscle cells through the second heart field. Accordingly to up-to-date evidence, the mechanisms of this process are genetically coordinated mainly by NKX2.5, GATA4, Mef2, TBX5 and Hand which establish not only the structure of the embryonic cord but also the sequential evolution of the differentiation and completion of the cardiac structures including the inlet and outlet paths. First field and second field are the initial particular stages of cardiogenesis. In the primary heart tube, the differentiation into adult anatomical cardiac structures (the atrial and ventricular cavities) begins. The heart tube looping initiates the separation of the primitive atria, ventricle and outflow tract. The separation between these cavities is made by different but concordant mechanisms. Coronarogenesis is the last stage before embryonic heart becomes functional.

STROKE RECURRENCE AND COMPLIANCE TO ANTIHYPERTENSIVE TREATMENT

Objective: To evaluate whether hypertension awareness and compliance to antihypertensive treatment is associated with less recurrent stroke among stroke patients from an emergency hospital. Design and method: 595 adult subjects (age range 28–104 years) admitted to the neurology department of an emergency hospital in 2016 with stroke were included. We tested whether hypertension and lack of hypertension awareness were associated with recurrence of stroke, and whether compliance to antihypertensive treatment was less frequent in recurrent stroke patients. Results: Among those at first stroke (78.82%) 74.84% were hypertensives, with 93.44% awareness rate, but with 85.06% of cases compliant to treatment. Hypertension correlated with stroke recurrence (chi2 = 4.002, RR 1.510 CI95% 0.99–2.299, p 0.045). Both compliance to antihypertensive treatment and hypertension awareness were more frequent among those with recurrent stroke (Mann Whitney p = 0.001, respectively, p = 0.03). On logistic regression, hypertension was the only predictor of recurrent stroke. For results see table. Figure. No caption available. Conclusions: Stroke, as the most frequent neurologic complication of hypertension, is often followed by recurrence. Our results underline that even awareness and compliance to antihypertensive treatment cannot fully protect from such major events, pointing at the high residual risk patients often carry despite adequate therapy. Often the first to occur in the cardiovascular continuum of disease, hypertension may manifest its effects years before other pathologies ensue, and this may explain its larger influence on cardiovascular events.

PREDICTORS OF STROKE RECURRENCE IN HYPERTENSIVES IN AN EMERGENCY HOSPITAL

Objective: To evaluate cardiovascular (CV) risk factors and therapeutic management as predictors of recurrent stroke among hypertensives from an emergency hospital. Design and method: From 595 adult subjects (age range 28–104 years) admitted to the neurology department of an emergency hospital in 2016 with stroke, we selected hypertensives (n = 456). They were divided in two subgroups depending on history of previous stroke and propensity matched to control for age and sex. Logistic regression was used to evaluate CV risk factors and treatment strategy as predictors of recurrent stroke. Results: The prevalence of hypertension among stroke patients was 76.63%. Propensity matching resulted in 208 hypertensives. CV risk factors and antihypertensive medication did not significantly differ among those with recurrent stroke versus first-time stroke event. In-hospital mortality was significantly higher in those with recurrent stroke (chi2 = 4.837, RR 1.150 CI95% 1.014–1.305, p 0.028). For results see table. Figure. No caption available. Conclusions: When adjusting for age and sex CV risk factors and antihypertensive medication did not predict stroke recurrence in hypertensives, which may suggest either the lack of intensive risk control, or an important residual risk despite therapy in those who already suffered stroke. Recurrence of stroke is more likely to lead to higher in-hospital mortality.

[PP.27.06] TO SEARCH...OR NOT TO SEARCH FOR THE CAUSE OF ARTERIAL HYPERTENSION

Objective: Primary hyperaldosteronism was initially considered a rarity, but has proven to be, according to more recent data, a more common cause of secondary hypertension (HTN). When sought, it may occur in greater percentages among patients with resistant HTN. More recent epidemiological work showed that most cases are usually associated with bilateral adrenal hyperplasia in the absence of the classically reported adenoma. Design and method: We present the case of 55 years old male diabetic patient, presenting to the emergency department with frequent hypertensive urgencies during the past year. He had been diagnosed 5 years prior with HTN and received treatment with an ACE inhibitor, a calcium channel blocker and a low-dose diuretic. Despite proper life style changes and appropriate adherence to therapy, the 24 h ambulatory blood pressure measurement showed significantly elevated blood pressure (BP) levels – mean systolic BP 175/94 mmHg with a non-dipping profile. In the course of investigations for secondary causes of hypertension we performed nocturnal polysomnography, duplex ultrasound of renal arteries and tested for cortisol levels – all with negative findings. Remarkable findings were a persistent moderate hypokalemia (∼ 3 mmol/L), mild hypernatremia (143 mmol/L) despite low-sodium diet and urinary potassium excretion increased at 37 mmol/24 h. Further, the abdominal CT scan showed bilateral adrenal hyperplasia, with no adenomas. The patient was switched to high-dose verapamil and high-dose doxazosin for 4 weeks, and the endocrinology profile showed high plasma aldosterone levels (suppressed after oral 50 mg of captopril), high plasma aldosterone/plasma renin activity ratio, with a negative postural test, thus confirming primary hyperaldosteronism. The patient was switched to initial antihypertensive therapy adding 50 mg spironolactone, which conferred a better BP control confirmed at 1-month re-evaluation. Results: The diagnostic of primary hyperaldosteronism is challenging, but it presence significantly affects BP control, especially in selected populations, such as resistant HTN patients. Considering recent trials (PATHWAY) showed that adding spironolactone to the triple therapy in resistant HTN achieves BP control in most patients, it may remain an open debate whether cases without evidence of adenoma actually benefit from performing the full diagnostic algorithm.