Agnieszka Pawlak

The role of invasive diagnostics and its impact on the treatment of dilated cardiomyopathy: A systematic review

BACKGROUND Dilated cardiomyopathy is one of the most frequent causes of non-ischemic heart failure. Many factors including genetic disorders, infectious agents, toxins, drugs and autoimmune disorders might take part in the development of dilated cardiomyopathy. Diagnosis of left ventricular dilatation is most often limited to performing echocardiography and excluding ischemic etiology (coronary angiography). Since many pathologies take place at the cellular and subcellular level the only way to clarify the etiology of the disease is to examine the myocardium itself (endomyocardial biopsy). METHODS A systematic literature search was conducted for studies published between September 2000 and September 2015 using the PubMed database. RESULTS Of 7104 studies identified, 73 studies were included in this review. Controversies raised by opponents of the endomyocardial biopsy collide with the low percentage of serious complications confirmed in several single-center registries. Based on the available data the overall complication rate varies from 1% to about 3%, with 0.5% risk of serious complications. According to the current recommendations of the European and American scientific societies endomyocardial biopsy should be performed in most cases of left ventricular dilatation and heart failure of non-ischemic etiology. Endomyocardial biopsy allows for making the diagnosis and providing prognostic information especially in patients with familial dilated cardiomyopathy, diabetic cardiomyopathy with dilated phenotype, alcoholic cardiomyopathy, peripartum cardiomyopathy, iron overload cardiomyopathy, as well as inflammatory and viral cardiomyopathy. Iron overload cardiomyopathy, peripartum cardiomyopathy, inflammatory and viral cardiomyopathy are potentially treatable and reversible. CONCLUSIONS Targeted therapies are more effective when started early before myocardial injury becomes irreversible. Unfortunately, non-invasive techniques are not precise enough to decide if and which targeted therapy is required. Therefore endomyocardial biopsy should be mainly recognized as the essential diagnostic tool and should not be postponed.

Relations between circulating microRNAs (miR-21, miR-26, miR-29, miR-30 and miR-133a), extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy

Relations between circulating microRNAs (miR-21, miR-26, miR-29, miR-30 and miR-133a), extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy Paweł Rubiś ⁎, Justyna Totoń-Żurańska , Sylwia Wiśniowska-Śmiałek , Katarzyna Holcman , Maria Kołton-Wróż , Paweł Wołkow , Ewa Wypasek , Joanna Natorska , Lucyna Rudnicka-Sosin , Agnieszka Pawlak , Artur Kozanecki , Piotr Podolec a,g,1

Initial clinical experience with the first drug (sacubitril/valsartan) in a new class — angiotensin receptor neprilysin inhibitors in patients with heart failure with reduced left ventricular ejection fraction in Poland

BACKGROUND Sacubitril/valsartan is the first drug from a new class of angiotensin receptor neprilysin inhibitors (ARNIs) recommended in the new European Society of Cardiology guidelines instead of angiotensin converting enzyme inhibitors (ACEI), or angiotensin receptor blockers (ARB) that are used if ACEI are not tolerated. Sacubitril/valsartan is recommended for further reduction in the risk of hospitalisation or death in outpatients with heart failure with reduced ejection fraction (HFrEF) if symptoms continue despite optimal treatment with ACEI/ARB, beta-blockers, and mineralocorticoid antagonists. AIM The aim of this study is to present the initial experience with regard to the effectiveness, tolerance, and safety of sacubitril/valsartan in the outpatient cardiology practice in Poland. METHODS The study is a retrospective analysis of data obtained through a questionnaire filled in by the physicians who initiated the sacubitril/valsartan treatment in patients with HFrEF between 1 June 2016 and 30 September 2016. Patients were followed-up for three months. RESULTS The analysis included data on 28 patients aged 61 ± 16 years, of whom 85.7% were males. The drug was used in patients in New York Heart Association (NYHA) class I-III. In 25 (89.2%) patients sacubitril/valsartan was started at the lowest dose (24/26 mg BID). During follow-up the sacubitril/valsartan-treated patients had a reduction in HF symptoms assessed using the NYHA functional class (p = 0.001), a significant drop in N-terminal-pro B-type natriuretic peptide levels (mean, from 2900 to 2270 pg/mL; p = 0.008), and improved exercise tolerance, which occurred shortly after treatment initiation - after a mean of 28 days. CONCLUSIONS It was demonstrated that the use of sacubitril/valsartan in outpatients with HFrEF is safe and is associated with a significant clinical improvement.

Viral heart disease — treatment

Agnieszka Pawlak, MD, PhD, FESC graduated with honours from the Medical University in Warsaw. Doctor Pawlak is currently Chief of the Heart Failure Unit and Echocardiography Lab in the Department of Invasive Cardiology of the Central Clinical Hospital of the Ministry of Interior in Warsaw. She is also a researcher in the Mossakowski Medical Research Centre of the Polish Academy of Sciences in Warsaw. Her main interests include heart failure, myocarditis, echocardiography, molecular biology, and ultrastructure of heart tissue. She is author or co-author many publications in peer-reviewed journals, abstracts, and chapters of books. Doctor Pawlak is a member of the Polish Society of Cardiology, the European Society of Cardiology (ESC), the European Heart Failure Association, and a member of the Working Group of Myocardial and Pericardial Diseases of ESC. She was trained in Allgemeines Krankenhaus (AKH) in Vienna, the Heart Centre in Leizpig, Kerckhoff-Klinik in Bad Nauheim, and on Columbia University in New York.

Viral Nucleic Acids in the Serum Are Dependent on Blood Sampling Site in Patients with Clinical Suspicion of Myocarditis

Background: The meaning of viral nucleic acids in the myocardium in many cases is difficult for clinical interpretation, whereas the presence of viral nucleic acids in the serum is a marker of active infection. We determined the diagnostic value of viral nucleic acids in ventricular serum and peripheral serum samples in comparison with endomyocardial biopsy (EMB) specimens in patients with clinically suspected myocarditis. Methods: The viral nucleic acid evaluation was performed in serum samples and EMB specimens by real-time PCR in 70 patients (age: 47 ± 16 years). The biopsy specimens were examined by histo- and immunohistochemistry to detect inflammatory response. Results: The viral nucleic acids were detected in ventricular and peripheral serum, and EMB samples of 10 (14%), 14 (20%), and 32 (46%) patients, respectively. Notably, viral nucleic acids of the same virus as in the EMB sample were present more often in ventricular than in peripheral serum (60 vs. 7%, p = 0.01). A significant concurrence was observed between the positive and the negative results of viral nucleic acids present in EMB and ventricular serum (p = 0.0001). Conclusions: The detection of the same viral nucleic acid type in the myocardium and in ventricular serum being significantly more frequent than in the peripheral serum may suggest that the site of the blood collection is important for more precise and reliable confirmation of the active viral replication in the heart.

Patterns of desmin expression in idiopathic dilated cardiomyopathy are related to the desmin mRNA and ubiquitin expression

Desmin expression depends on desmin messenger RNA (mRNA) and ubiquitin proteasome system. This process is poorly understood in dilated cardiomyopathy. The aim of the study was to investigate whether changes of desmin mRNA and ubiquitin expression correlate with types of desmin expression in cardiomyocytes. Endomyocardial biopsy was performed in 60 patients (85% men, mean age 46±14 years) with heart failure (HF; left ventricular ejection fraction <45%). Desmin and ubiquitin expression were analysed in histological sections by immunohistochemistry and in Western blot. Desmin mRNA expression was determined by fluorescent in situ hybridization methods. In patients with weak/even desmin expression, weak/even expression of ubiquitin in the cytosol and low desmin mRNA expression in the cytosol and nuclei of cardiomyocytes were observed. Expression of ubiquitin and desmin mRNA increased along with the progression of desmin cytoskeleton remodeling. Desmin mRNA and ubiquitin were weakly expressed/absent in cardiomyocytes with low/lack of desmin expression. Variations in desmin mRNA, desmin and ubiquitin expression were associated with gradual changes in myocardial structure and clinical parameters. To conclude, changes in ubiquitin and desmin mRNA expression are related to patterns of desmin expression. An increase in the expression of ubiquitin and desmin mRNA may be a protective feature against unfavorable cell remodeling. This may reduce the adverse effects of cytoskeleton damage in the early stages of HF. Low/lack ubiquitin and/or desmin mRNA expression may be markers of end-stage HF.

Viral Infection of the Heart: Pathogenesis and Diagnosis

Viral infections of the heart cause serious clinical problems, either as infectious myocarditis, which usually is a consequence of acute infection or as idiopathic dilated cardiomyopathy, resulting rather from a chronic infection. This minireview presents an up-to-date view on pathomechanisms of viral infection of the heart tissues, the role of immune system in controlling infectious process at its various stages and current possibilities of recognizing viral infection of the heart with use of both cardiological and virological methods. Our goal was to present the variety of known viral agents causing heart infection, level of complexity in mutual virus-cell interactions, and consequent clinical scenarios.

RELATIONS BETWEEN FIBROSIS-LINKED MICRORNAS (MIR-21, MIR-26, MIR-29, MIR-30 AND MIR-133A) AND RIGHT VENTRICULAR MORPHOLOGY AND FUNCTION IN DILATED CARDIOMYOPATHY

Background: Relations between right ventricle (RV) and microRNAs in dilated cardiomyopathy (DCM) are poorly understood. Methods: We studied 70 DCM patients (pts) (48 ± 12.1 years, EF 24.4 ± 7.4%). Basal RV (RVd1) > 41 mm and/or mid-cavity RV dimension (RVd2) > 35 mm was diagnostic for RV

A large symptomatic pericardial cyst

Pacjentka w wieku 26 lat z niedowidzeniem oka prawego po witrektomii z powodu retinopatii wcześniaczej została przyjęta do Kliniki Kardiologii Inwazyjnej z powodu nawracających od ok. 2 lat epizodów kołatania serca. Jednocześnie negowała omdlenia, zasłabnięcia, stenokardię. Pacjentka o budowie astenicznej, ze wskaźnikiem masy ciała wynoszącym 18 kg/m2 i ciśnieniem tętniczym 100/70 mm Hg. W 24-godzinnej analizie elektrokardiograficznej metodą Holtera zarejestrowano 16 epizodów tachykardii zatokowej o maksymalnej częstości 120 uderzeń/min, bez arytmii komorowej i nadkomorowej. W badaniu echokardiograficznym swierdzono prawidłową wielkość jam serca i grubość ścian lewej komory, małą niedomykalność zastawki trójdzielnej, prawidłową kurczliwość lewej i prawej komory oraz strukturę na wysokości koniuszka i drogi odpływu prawej komory z widocznymi w świetle linijnymi strukturami oraz ruchomymi, drobnymi, hiperechogenicznymi echami (ryc. 1). Nie zaobserwowano cech jej ucisku na jamy serca. W badaniu radiologicznym klatki piersiowej w okolicy koniuszka uwidoczniono zacienienie o wymiarach ok. 4,0 × 5,3 cm (ryc. 2). W celu poszerzenia diagnostyki wykonano rezonans magnetyczny serca, w którym w obrębie śródpiersia dolnego przedniego po stronie lewej i centralnie uwidoczniono zmianę torbielowatą o wymiarach 105 × 60 × 31 mm, otorebkowaną, zawierającą przegrody, o niejednorodnym sygnale, przemawiającym za zawartością płynową. W świetle zmiany była możliwa obecność produktów przemiany hemoglobiny. Nie uwidoczniono naciekania struktur przyległych (ryc. 3A, B). W rozpoznaniu różnicowym uwzględniono torbiel okołoosierdziową lub naczyniak limfatyczny. Pacjentkę konsultowano z torakochirurgiem i zakwalifikowano do leczenia operacyjnego. Przez torakotomię lewostronną wykonano zabieg wycięcia torbieli. Przebieg pooperacyjny był niepowikłany, pacjentkę w stanie dobrym wypisano do domu. W badaniu histopatologicznym stwierdzono torbiel wysłaną pojedynczą warstwą nabłonka mezotelialnego, ścianę torbieli stanowiły luźna tkanka łączna i tkanka tłuszczowa z licznymi drobnymi naczyniami krwionośnymi. Wokół torbieli uwidoczniono rozrost tkanki tłuszczowej. Obraz mikroskopowy odpowiadał zmianie łagodnej o charakterze torbieli okołoosierdziwoej, celomicznej. W kontrolnej ocenie klinicznej wykonanej po 6 miesiącach od zabiegu pacjentka negowała poczucie arytmii, zgłaszała znaczną poprawę samopoczucia. W badaniu echokardiograficznym serca i rezonansie magnetycznym nie wykazano dodatkowych patologicznych stuktur wokól serca (ryc. 4A, B). Rycina 1. Echokardiografia przezklatkowa; w okolicy koniuszka serca struktura z licznymi drobnymi, ruchomymi hiperechogenicznymi echami (strzałka) Rycina 2. Badanie radiologiczne klatki piersiowej (PA); zacienienie w okolicy koniuszka serca (strzałka)

Impella LD microaxial pump supporting combined mitral and coronary surgery in a patient with dilated cardiomyopathy. A short bridge to recovery

Cardiac surgeons have to face the problem of impaired left ventricle function in patients undergoing routine valve or coronary procedures. The intra-aortic balloon pump is not always effective in preventing cardiac failure. The idea of using a microaxial rotating pump as a short-term perioperative support seems to be a convenient solution. The case of a patient with dilated cardiomyopathy undergoing combined mitral and coronary surgery with elective use of the Impella LD pump is presented. Various options of applying the Impella device are discussed, especially as a bridge to transplant or bridge to recovery.