Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.

BACKGROUND: Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

Evaluation of the significance of cystatin C levels in patients suffering from coronary artery disease.

OBJECTIVES: Cystatin C is a novel marker used in the diagnosis of preclinical chronic kidney disease (CKD). The aim of the study was to assess the role of cystatin C in the diagnosis of coronary artery disease. MATERIAL AND METHODS: The study involved 63 patients of a mean age of 62.7 ± 9.5 years. The population was divided into two groups: Group I were patients with angiographically diagnosed coronary artery disease (CAD) with their first acute coronary syndrome (ACS, n = 45); Group II were patients who had clinically diagnosed coronary disease but were negative on angiography (n = 18). Cystatin C levels were measured before angiography in both groups; in Group I they were also measured 6 months after discharge. RESULTS: Cystatin C levels were significantly higher in Group I (p = 0.01), and this depended on the type of CAD: non-ACS, non-ST elevated myocardial infarction (NSTEMI) or ST elevated myocardial infarction (STEMI) (p = 0.01). Cystatin C levels correlated inversely with the left ventricular ejection fraction in the whole study population (p = 0.003) and in patients with NSTEMI (p = 0.03). A high cystatin C level was found to be a risk factor for ACS (OR: 1.002 95% CI [1.00029-1.004], p = 0.02) and STEMI (OR: 1.0009 95% CI [0.99-1.002], p = 0.04) but not for NSTEMI (OR: 0.99 95% CI [0.99-1.0], p = 0.21. A ROC analysis revealed that there is a significantly higher risk of ACS above a cystatin C level of 727.85 ng/mL (OR: 5.5 CI [1.65-18.3], p = 0.004) and a significantly higher risk of STEMI above 915.22 ng/mL (OR: 5.9 CI [1.7-19.7], p = 0.003). CONCLUSIONS: The available data suggest that a high cystatin C level is a risk factor for ACS and STEMI. This could play an important role in the early diagnosis and prevention of adverse cardiovascular events.

Left main aneurysm and what's next?

The purpose of the case report is to present a case of a 65-year-old male, referred for coronary angiography because of a typical chest pain. The coronary angiography showed an aneurysm of the left main coronary artery. Despite the absence of obvious ischemic symptoms and because of the potential complications of the aneurysm with a width of 15 mm, the patient underwent surgery.

The choice of surgical specialization by medical students and their syncopal history.

BACKGROUND: The aim of the study was to assess whether medical students' fainting outside the university or while witnessing surgical procedures and/or autopsies influenced their choice of a specialization. MATERIALS AND METHODS: The study group consisted of 605 medical students (from fourth to sixth year of study) from five medical universities in Poland (325 women, 212 men and 8 responders of an unspecified gender). The median age of subjects studied was 23 years, and the interquartile range was 23-24 years. The students at each university were chosen randomly by the author who worked there and had contact with them. An anonymous questionnaire was developed to gather information regarding demographics, the specialization which each student wanted to choose, the syncope occurrence in the medical history, the syncope and presyncope occurrence during surgery and autopsy as well as the syncopal events' characteristics. RESULTS: The group of 15% of women and 30% of men declared to have pursued the surgical specialization (P<0.001), 29% of women and 56% of men declared the intention to pursue an invasive specialization (P<0.001). As many as 36.0% of women studied and 13.1% of men studied reported syncopal spells outside university (P<0.001). Only 41 students (6.8%) reported that syncope or presyncope in any studied circumstances had an impact on their specialization choice. The multivariate analysis showed that the choice of surgical specialization is related to the male gender and the absence of syncopal spells outside the university. CONCLUSIONS: Syncopal and presyncopal spells may affect the professional choices of the medical students. The male gender and a lack of syncope occurrence outside operating room are related to the choice of surgical specialization.

Cardiotoxicity of oncological treatment in children.

The incidence of complications after antineoplastic therapy is increasing in relation to the incidence of cancer and prolonged survival rate. Cardiotoxicity is one of the major complications, and it may occur during the therapy or many years after its termination, often leading to heart failure. Cardiotoxicity has been attributed particularly to cytostatics from the group of anthracycline antibiotics and radiotherapy, which are widely used in oncological treatment. The risk of developing cardiac complications depends on the cumulative dose of anthracyclines and the dose of chest irradiation, accompanying heart disorders, patient's age and sex. Acute myocardial damage occurs in the form of myocarditis and pericarditis. Late cardiotoxicity of anthracyclines manifests itself in the form of congestive cardiomyopathy, and late complications after radiotherapy also as valvular damage or restrictive cardiomyopathy. The incidence of asymptomatic myocardial dysfunction has been described in literature to range from 18 to 57% on long-term follow up of children after oncological treatment, and about 5% of children develop heart failure. For these reasons, attempts to develop schemes for monitoring patients after termination of antineoplastic treatment have been undertaken. The standards should include ECG, chest X-ray and echocardiography performed prior to, during and after oncological therapy. Biochemical markers, such as troponin or natriuretic peptide, may prove helpful. The frequency of cardiac function monitoring depends on the underlying risk. Long-term follow up of patients who have undergone antineoplastic therapy in childhood is recommended, with special attention paid to individual risk factors. The follow-up should also consider additional, well-known risk factors for cardiovascular diseases.

Familial predisposition to vasovagal syncope.

OBJECTIVE: A handful of studies suggest a familial predisposition to vasovagal syncope (WS) but the scope of information available to date is poor. The aim of our study was to evaluate the prevalence of vasovagal syncope and its familial occurrence in the young. METHODS AND RESULTS: The studied group consisted of 281 women and 111 men, aged 18-32 years. Forty-seven percent of the population had one brother or sister, and the mean number of individuals per family was 4.4 +/- 1.0. The questionnaire consisted of 30 questions regarding syncopal history. Syncope was reported in 32.1% of the patients studied (36.7% in women vs. 20.7% in men; P < 0.05), 29.1% of mothers, 16.8% of fathers, 30.9% of sisters and 14.2% of brothers. Logistic regression analysis revealed that positive history regarding the syncope in the whole group of students was related to the female gender (OR 2.17; CI: 1.28-3.7), the history of a syncope in mother (OR 1.74; CI: 1.09-2.78) and the history of a syncope in father (OR 2.22; CI: 1.28-3.86; P < 0.001). CONCLUSIONS: A positive history of syncope in male relatives increases the risk of syncope in men and women, whereas a positive history of syncope in female relatives increases the risk of syncope in women only. Female gender independently of the family history increases the risk of syncope. The genetics of the vasovagal syncope could be polygenic but the mechanisms of a transmission remain unclear to date.

[Life saving angioplasty of left main coronary artery in a high risk patient]. / Ratujaca zycie angioplastyka pnia lewej tetnicy wiencowej u chorego wysokiego ryzyka.

A case a of a life-saving angioplasty of left main coronary artery (LMCA) is presented. A 75 year old patient with a history of diabetes, previous CABG and carotid surgery was admitted to our hospital with symptoms of early post-infarct angina. Coronary angiography revealed significant stenosis of LMCA, in addition to previously known multi-vessel diffuse CAD. Taking into consideration a very high risk of repeat CABG surgery a decision was made to perform an angioplasty. The intervention was carried out with good angiographic effect and the patient was discharged home few days later, free from angina. In 9 month follow-up angiography there was no restenosis in LMCA. In patients to whom cardiac surgery presents very high risk, an angioplasty of LMCA can be life-saving, with good long term effects.

[The influence of deterioration of clinical condition on the change of revascularisation method in coronary artery disease]. / Wplyw zaostrzenia stanu klinicznego na zmiane metody rewaskularyzacji w chorobie wiencowej. Omówienie metod postepowania na podstawie opisywanego przypadku.

A case of a 52-year old woman with diabetes mellitus and symptomatic, multivessel coronary disease is presented. The patient underwent coronary angiography. Taking in consideration the intensity of atherosclerotic lesions and vessels diameter, she was initially selected for cardiovascular surgery. However, because of sudden deterioration of clinical condition caused by myocardial infarction the strategy of cardiac revascularisation was changed. The patient underwent multivessel percutaneous coronary intervention with good result in short- and 6-month observation.

[The role of TNF-alpha in the etiopathogenesis of heart failure]. / Udzial TNF-alpha w etiopatogenezie niewydolnosci serca.

Clinical evidence demonstrates participation of several cytokines in cardiac heart failure pathogenesis, in particular tumor necrosis factor-alpha (TNF-alpha), which induces left ventricular dysfunction, acute pulmonary edema and congestive cardiomyopathy. Increased levels of TNF-alpha in patients with heart failure were proved and may have prognostic significance. Absent in normal myocardium, produced in the myocardium in response to volume overload, TNF-alpha can depress cardiac function directly and indirectly by induction of nitric oxide synthase produced by macrophages, cardiac myocytes and other cells. The most of TNF-alpha effects are performed by two receptors termed as TNF-RI and TNF-RII identified on the surface of many cells. The extracellular domain fragments of both receptors shed from cell surface can be detected as soluble forms sTNF-RI and sTNF-RII in the urine and blood, and their blood levels in patients with severe heart failure are elevated. There are various pharmacological agents that block the biological effects of TNF-alpha, however only two of them have been used in patients with heart failure: pentoxifylline and etanercept. Encouraging effects of this studies must be regarded as provisional because of relatively small numbers of treated patients. Preliminary results of other randomized, multicenter and in large patients populations trials, planned till 2002 year indicate the possibility of novel anti-TNF strategies in heart failure; treatment is well tolerated and can be effective. It is thought, that recombinantly produced TNF-alpha soluble receptor being now evaluated clinically can determine the progress in heart failure treatment.