Andrzej Wojtarowicz

Plasma concentrations of TNF-α and its soluble receptors sTNFR1 and sTNFR2 in patients with coronary artery disease

Tumour necrosis factor alpha (TNF-alpha) is implicated in post-ischemic myocardial dysfunction. Two distinct TNF-alpha receptors are shed from cell membranes and circulate in plasma as soluble sTNFR1 and sTNFR2 proteins. The aim of the study was to establish factors associated with plasma concentrations of TNF-alpha and its receptors in patients with coronary artery disease (CAD). Since adenosine inhibits the expression of TNF-alpha, two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism, i.e. AMP deaminase-1 (AMPD1, C34T) and adenosine deaminase (ADA, G22A), were analyzed. Plasma concentrations of TNF-alpha, sTNFR1, and sTNFR2 were measured using ELISA in 167 patients with CAD. Common factors significantly associated with higher TNF-alpha, sTNFR1, and sTNFR2 were lower glomerular filtration rate (GFR), older age, higher BNP, lower blood haemoglobin, and the presence of asthma or chronic obstructive pulmonary disease (COPD). Higher TNF-alpha and sTNFR1 concentrations were also associated with the presence of heart failure (HF), lower ejection and shortening fraction, the presence of diabetes or metabolic syndrome, lower serum HDL cholesterol, and higher uric acid. In multivariate analysis the common independent predictors of higher TNF-alpha, sTNFR1, and sTNFR2 were lower GFR, lower HDL cholesterol, higher BNP, and the presence of asthma or COPD. There were no associations between AMPD1 C34T or ADA G22A genotypes and TNF-alpha or its receptors. In conclusion, the concentrations of TNF-alpha, sTNFR1, and sTNFR2 reflect the impairment of cardiac and renal function in patients with CAD. Metabolic syndrome and diabetes are associated with higher plasma concentrations of TNF-alpha and its receptors.

Sudden death in hypertrophic cardiomyopathy: old risk factors re-assessed in a new model of maximalized follow-up.

AIMS in hypertrophic cardiomyopathy (HCM), the following five risk factors have a major role in the primary prevention of sudden death (SD): family history of SD (FHSD), syncope, massive wall thickness (MWTh) >30 mm, non-sustained ventricular tachycardia (nsVT) in Holter monitoring of electrocardiography, and abnormal blood pressure response to exercise (aBPRE). In HCM, as a genetic cardiac disease, the risk for SD may also exist from birth. The aim of the study was to compare the survival curves constructed for each of the five risk factors in a traditional follow-up model (started at the first presentation of a patient at the institution) and in a novel follow-up model (started at the date of birth). In an additional analysis, we compared the survival rate in three subgroups (without FHSD, with one SD, and with two or more SDs in a family). METHODS AND RESULTS a total of 1306 consecutive HCM patients (705 males, 601 females, mean age of 47 years, and 193 patients were <18 years) evaluated at 15 referral centres in Poland were enrolled in the study. In a novel method of follow-up, all the five risk factors confirmed its prognostic power (FHSD: P = 0.0007; nsVT: P < 0.0001; aBPRE: P = 0.0081; syncope: P < 0.0001; MWTh P> 0.0001), whereas in a traditional method, only four factors predicted SD (except aBPRE). In a novel model of follow-up, FHSD in a single episode starts to influence the prognosis with a delay to the fifth decade of life (P = 0.0007). Multiple FHSD appears to be a very powerful risk factor (P < 0.0001), predicting frequent SDs in childhood and adolescence. CONCLUSION the proposed concept of a lifelong calculated follow-up is a useful strategy in the risk stratification of SD. Multiple FHSD is a very ominous risk factor with strong impact, predicting frequent SD episodes in the early period of life.

ADA*2 Allele of the Adenosine Deaminase Gene May Protect against Coronary Artery Disease

Background/Aims: The common G22A polymorphism in the adenosine deaminase (ADA) gene leads to substitution Asp8Asn. The lower activity of the enzyme encoded by A22 (ADA*2) allele may increase tissue concentrations of adenosine, a potent cardioprotective agent. In a case-control study, we investigated the association between ADA polymorphism and coronary artery disease (CAD). Methods: A hundred and seventy-one CAD patients from the north-western part of Poland and 200 consecutive newborns from the same population were genotyped by PCR-RFLP. Results: Twenty-five ADA*1/*2 heterozygotes (12.5%) and 2 ADA*2/*2 homozygotes (1%) were found in the control group, while only 10 *1/*2 heterozygotes (5.9%) and no *2/*2 homozygotes were found in the CAD group. Frequencies of ADA*2 carriers (5.9% vs. 13.5%, p = 0.015) and ADA*2 allele (2.9% vs. 7.3%, p = 0.0083) were lower in CAD patients than in controls. Among CAD patients, a significantly lower proportion of *2 allele carriers was treated with diuretics and ACE inhibitors when compared to *1/*1 wild-type homozygotes. Conclusion: ADA*2 allele may decrease genetic susceptibility to CAD. ADA should be added to the list of candidate genes modifying the risk of cardiovascular diseases.

Association of C34T AMPD1 gene polymorphism with features of metabolic syndrome in patients with coronary artery disease or heart failure.

Objective. The common C34T polymorphism in the AMP deaminase‐1 (AMPD1) gene results in an inactive enzyme in homozygotes for the mutated T allele. Some studies have shown an association of T allele with longer survival in heart failure (HF) and/or coronary artery disease (CAD). The aim of this study was to assess genotype–phenotype correlations in such patients, with emphasis on components of the metabolic syndrome. Methods. Ninety‐seven patients with CAD without HF (CAD+ HF–) and 104 with HF (HF+) were genotyped by PCR‐RFLP. The genetic control group comprised 200 newborns. Results. No significant differences were found in the frequency of AMPD1 genotypes between the groups. In the CAD+ HF– group, the carriers of T allele compared to CC homozygotes had significantly lower values of waist circumference (89.5±8.5 versus 97.7±11.2 cm; p = 0.00029), waist/hip ratio (p = 0.0059) and BMI (p = 0.045). There was no diabetes or fasting glycaemia ⩾126 mg/dL in T carriers, while these features were present in 25 % of CC homozygotes (p = 0.0024). In the HF+ group, a tendency towards a lower prevalence of diabetes (20 % versus 41 %; p = 0.068) and significantly lower systolic blood pressure (p = 0.048) were observed in T allele carriers. Conclusions. C34T AMPD1 polymorphism may be associated with reduced frequency of obesity in CAD patients and of hyperglycaemia and diabetes in both CAD and HF patients. Morphometric parameters associated with adipose tissue distribution and parameters of glucose metabolism should be analysed as potential confounders in further studies on the role of polymorphisms of AMPD1 and other genes associated with AMP and adenosine metabolism in cardiovascular disease.

Atrial Epicardial Pacing with Long Stimulus to P Wave Interval in a Patient with Arrhythmogenic Right Ventricular Dysplasia Complicated by Right Atrial Thrombosis

Atrial epicardial pacing with a long stimulus to P wave interval in a patient with arrhythmogenic right ventricular dysplasia complicated by right atrial thrombosis is discussed. Arrhythmogenic right ventricular dysplasia (ARVD) is associated with a high incidence of malignant ventricular arrhythmias. Most patients with ARVD need antiarrhythmic drugs, catheter ablation, or an implantable cardioverter defibrillator. We report a patient with ARVD in whom effective treatment with sotalol caused severe, symptomatic sinus bradycardia requiring permanent pacing. Due to leftward displacement of the right ventricle and the presence of two thrombi in the right atrium, an epicardial atrial lead and AAI pacemaker were implanted. A long stimulus to P wave interval caused by severe dilatation of the right atrium was recorded. During a 6 months of follow‐up on sotalol treatment there were neither ventricular tachycardia (VT) attacks nor pacing problems.

Intracavitary mass as the initial manifestation of primary pericardial mesothelioma: a case report.

A 31-year-old woman presented with a 3-month history of progressing fatigue and effort dyspnea. Echocardiography depicted a tumor within the free wall of the right ventricle and right atrium, located on both sides of the tricuspid annulus. Computed tomography showed disseminated circular shadows sized up to 7 mm—most likely metastatic lesions—in both lungs. The diagnosis of low-grade mesothelioma bifasicum was confirmed with histopathologic and immunohistochemical studies of the samples taken by thoracoscopy from parietal pleura, lung tumor, and diaphragm region. Chemotherapy, which included gemcitabine and carboplatin, resulted in transient improvement of the clinical status of the patient and reduction of the tumor mass lasting several months followed by progression of the disease. Significant amounts of pleural fluid and huge tumors within both pleural cavities emerged. The patient died due to respiratory and circulatory insufficiency 11 months following the diagnosis.

Effect of cardiac resynchronisation therapy on coronary blood flow in patients with non-ischaemic dilated cardiomyopathy

BACKGROUND Cardiac resynchronisation therapy (CRT) has beneficial effects on cardiac function, exercise tolerance, symptoms, and prognosis. Coronary blood flow impairment has been observed in patients with non-ischaemic dilated cardiomyopathy (DCM) despite angiographically normal coronary arteries. No data are available on coronary blood flow and coronary flow reserve (CFR) measured by intracoronary Doppler in different coronary arteries in patients with DCM and left bundle branch block (LBBB) before and during treatment with CRT. AIM Thus, the major aim of our study was to assess the effect of CRT on coronary blood flow in patients with non-ischaemic DCM and to compare coronary blood flow and CFR measured in the 3 major coronary arteries (left anterior descending [LAD], left circumflex [LCX], and right coronary artery [RCA]). METHODS Twenty one patients with DCM and LBBB (mean left ventricular ejection fraction 26 ± 7%, 5 females, mean age 57.8 ± 8.1 years) were studied. Average peak velocity, diastolic/systolic velocity ratio and CFR were measured using intracoronary Doppler before and 6-9 months after implantation of CRT-D or CRT-P. RESULTS In patients with a clinical improvement (71.4%), CFR increased in LAD. CFR measured in LCX and RCA did not improve either in the overall study group or in patients with a clinical improvement. The observed increase in CFR in LAD correlated only with reduction of QRS duration. CONCLUSIONS In non-ischaemic DCM, CFR is reduced only in LAD. A significant improvement of CFR in LAD after CRT correlates with reduction of QRS duration.

Alcohol septal ablation in hypertrophic cardiomyopathy utilizing a longitudinal 17-year study (mean 10.8). Observation follow-ups taken at a single medical centre.

BACKGROUND Alcohol septal ablation (ASA) is a method of treatment in obstructive hypertrophic car-diomyopathy (HOCM), but there is little data on the long-term results of ASA and the natural course after treatment. The aim of the study was to evaluate the results of ASA in HOCM in multiannual observation, and its impact on patient survival, exercise capacity, electrical complications, and changes in the anatomy and function of the heart. METHODS The study evaluated 47 patients with HOCM with a high left ventricular outflow tract (LVOT gradient) treated between 1997 and 2014 with ASA. Annual examinations evaluated the clinical condi-tion, at rest and with exercise electrocardiogram, Holter monitoring, echocardiography, the evolution of HOCM towards the dilated form, and the frequency of pacemaker implantation. RESULTS The analysis included data from 34 patients under observation for 3 to 17 (mean 10.8) years. Their age at procedure was 21-65, a mean of 47 years. All patients had permanently reduced LVOT gradient with a mean of 77.36 ± 35.46 to 11.40 ± 10.85 and showed improvement in the performance I to II New York Heart Association. Two out of five deaths had possible cardiac etiology. Fifteen patients received a pacemaker or cardioverter implants. In 4 subjects the long-term observation revealed new wall contractility abnormalities, interpreted as a shift of HOCM to the dilated form. CONCLUSIONS Alcohol septal ablation permanently eliminated the gradient in LVOT and improved the performance of patients, however it did not prevent a shift of HOCM to the dilated form. Pacemaker implantations are relatively frequent. (Cardiol J 2017; 24, 2: 125-130).

Multiple cardiovascular complications in a patient with missed small apical myocardial infarction caused by a coronary artery thrombus of uncertain origin

An 82 year-old hypertensive male with no concomitant diseases was admitted because of missed myocardial infarction (MI), 3 days after chest pain onset. On admission, the patient was pain free with stable haemodynamics and normal physical examination. The ECG (Fig. 1) showed atrial fibrillation (AF) and ischaemic changes with its resolution at follow-up. During coronarography (Fig. 2), the presence of a thrombus in the apical part of the left anterior descending (LAD) artery, atherosclerotic plaques with lack of culprit lesion clearly connected to the thrombus, and insignificant myocardial bridging (MB) were demonstrated. The patient was followed conservatively. Troponin and CK-MB elevation with decreasing consecutive values was observed. Transthoracic echocardiography (TTE) delineated left atrial (LA) enlargement, akinesia limited to the left ventricular apex with preserved global ejection fraction of 60% as well as a recent, partially movable, apical left ventricular mural thrombus (LVMT) (Fig. 3A). Warfarin therapy was introduced. On day 2, he developed acute ischaemic stroke (AIS). Carotid artery disease was excluded. On day 6, a systolic murmur demonstrated by echocardiography as an apical ventricular septal rupture (VSR) with left-to-right shunt and a thrombus partially occluding the defect which was smaller and less movable was diagnosed (Fig. 3B). The cardiothoracic surgeon recommended delaying surgical treatment. The patient’s haemodynamic status worsened gradually with signs of exclusive right ventricular failure. An intra-aortic balloon pump was not used due to lack of patient co-operation. On day 18, the family requested that he be discharged home where he finally died. It is most likely that atherosclerotic plaque was involved in the thrombus formation and coronary occlusion, although an AF related embolism is quite possible. These hypotheses could not be verified because there was no culprit lesion and no LA thrombus confirmation. Less probably, MB could have given rise to coronary thrombosis with subsequent MI. Finally, tako-tsubo cardiomyopathy, coronary vasospasm or MB can be a primary cause of apical akinesia, blood stagnation, LVMT development and secondary coronary embolism. LVMT and VSR are strongly associated with extensive anterior MI. In this case it was small and limited to the apex, but proximal LAD occlusion with downstream thrombus migration is possible. Moreover, we speculate that ST elevation in inferior leads might be related to dominant LAD and that ST depression in precordial leads might be a reciprocal change. A coincidence of LVMT and VSR has rarely been documented. Moreover, we observed the partial occlusion of the defect by the thrombus which might delay its recognition and slow the natural evolution. The most probable explanation for AIS is embolisation related to recent LVMT or AF.

Heart rate variability during and after chemotherapy with anthracycline in patients with breast cancer

INTRODUCTION Breast cancer is one of the most common types of cancer. Fortunately, the survival rate of breast cancer patients is quite high. However, cardiotoxicity after breast cancer treatment is a potentially life-threatening complication. Cardiac function can be assessed with echocardiography and biological markers [1]. However, there are few studies on heart rate variability (HRV) in patients with cancer, especially breast cancer, assessed with 24-h Holter electrocardiography (ECG). To our knowledge, no study has assessed HRV parameters immediately after chemotherapy infusion cessation. Low HRV has been shown to be a risk factor for cardiovascular diseases and a marker for all-cause mortality [2]. The present study aimed to assess early HRV changes during chemotherapy, assessed with 24-h Holter ECG in breast cancer patients.