Michał Marchel

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.

Progeroid syndrome with scleroderma-like skin changes associated with homozygous R435C LMNA mutation†

Hutchinson–Gilford progeria is a rare genetic disorder resulting from mutations in the LMNA gene encoding lamin A/C. In addition to the classical phenotype usually caused by the 1824C>T mutation of LMNA, a number of atypical progeroid syndromes have been described. They have some distinct features, such as skeletal deformities or scleroderma‐like skin changes. The underlying defect is usually a homozygous mutation of LMNA, or a combined defect of LMNA and another gene, for example, ZMPSTE‐24. We present a 2‐year‐old girl born to consanguineous parents affected by progeroid syndrome with scleroderma‐like skin changes. Genetic analysis revealed the homozygous LMNA mutation 1303C>T (R435C). The same heterozygous mutation was found in the patients parents and 11 other family members. The progeroid syndrome in our patient shares the signs of two laminopathies: progeria and restrictive dermatopathy. Two other children in the family died at the age of 2 due to a disease similar to that in the proposita. On the basis of the family pedigree we presume that these children probably had the same homozygous LMNA mutation. Scleroderma‐like skin changes in infants, associated with growth retardation and dysmorphic features, suggest premature aging syndrome, requiring genetic testing and counseling of asymptomatic carriers of LMNA mutations.

Clinical characteristics and predictors of one-year outcome of heart failure patients with atrial fibrillation compared to heart failure patients in sinus rhythm

BACKGROUND Atrial fibrillation (AF) frequently coexists with heart failure (HF). AIM To assess clinical characteristics and to identify predictors of one-year outcome of patients hospitalised for HF, depending on whether they were in sinus rhythm (SR) or had AF. METHODS The study included Polish patients hospitalised for HF, participating in the Heart Failure Pilot Survey of the European Society of Cardiology, who were followed for 12 months after discharge. Patients with paced heart rhythm were excluded from the study. The primary endpoint was all-cause death at 12 months. RESULTS The final analysis included 587 patients. AF occurred in 215 (36.6%) patients. Compared to patients in SR, patients with AF were older, more often had a history of previous HF hospitalisation, were characterised by a higher New York Heart Association (NYHA) class, higher heart rate, and lower diastolic blood pressure at hospital admission, and had higher serum creatinine and lower haemoglobin concentration at admission. In-hospital mortality was higher in AF patients compared to SR patients (5.1% vs. 2.4%, respectively), but the difference did not reach statistical significance (p = 0.1). The primary endpoint occurred in 41 of 215 AF patients (19.1%) and in 40 of 372 SR patients (10.8%; p = 0.006). In a multivariate analysis, predictors of the primary endpoint in AF patients were: higher NYHA class at hospital admission (p = 0.02), higher admission heart rate (p = 0.04), lower admission serum sodium concentration (p = 0.0001), and higher heart rate at discharge (p = 0.01). In patients with SR, independent predictors of the primary endpoint included: older age (p = 0.007), lower serum sodium concentration at admission (p = 0.0006), and higher heart rate at discharge (p = 0.008). CONCLUSIONS Patients with HF and concomitant AF differ significantly from HF patients in SR. In the studied group of real-world HF patients, serum sodium concentration at hospital admission and heart rate at hospital discharge were independent prognostic factors in patients with AF and in patients in SR. In contrast to SR patients, heart rate at hospital admission in AF patients was also predictive of long-term mortality.

Common carotid artery access for transcatheter aortic valve implantation

Transcatheter aortic valve implantation (TAVI) is an alternative method of treatment for severe symptomatic aortic stenosis in patients who are at high risk of surgical aortic valve replacement (AVR). In randomised clinical trials TAVI was shown to be superior to standard medical therapy in a cohort of inoperable patients and non-inferior to AVR in high-risk operable patients. Additionally, in a recent trial with self-expandable prosthesis use, TAVI was associated with lower mortality compared with surgery. Usually, femoral arteries are the most common vascular access to deliver the bioprosthesis; however, in some cases (up to 20%) this route may not be applied because of significant peripheral artery disease or tortuosity. In this article, we present the first two TAVI procedures in Poland performed via the left common carotid artery.

Osteopontin – a fibrosis-related marker – in dilated cardiomyopathy in patients with Emery-Dreifuss muscular dystrophy

Abstract Background: As osteopontin (OPN) may be assumed to have diagnostic/prognostic value in heart diseases, it is worth assessing whether it is also involved in the pathogenesis and can be applied in the diagnosis of the dilated cardiomyopathy (DCM) in Emery-Dreifuss muscular dystrophy (EDMD). Methods: Serum levels of osteopontin were quantified by means of sandwich immunoassay in 25 EDMD patients (10 laminopathies AD-EDMD and 15 emerinopathies – X-EDMD), eight carriers of X-EDMD, nine disease controls (patients with dystrophinopathy) and 20 age-matched healthy controls. Results: The levels of circulating OPN were elevated in all AD-EDMD and X-linked EDMD patients, as well as in X-EDMD carriers and patients suffering progressive muscular dystrophy. There was no correlation between the osteopontin level and different cardiac parameters, including left-ventricular end-diastolic diameter, left atrial diameter, the left ventricular ejection fraction and the CK-MB level. There was a slight negative correlation with the ages of the patients. Conclusions: The presented results indicate that assessments of circulating OPN levels may help to identify EDMD patients at risk of dilated cardiomyopathy and might be therefore included among the set of biomarkers referred to with a view to appropriate early cardiologic diagnosis and therapy being commenced with in time.

Predictors of one-year outcome in patients hospitalised for heart failure: results from the Polish part of the Heart Failure Pilot Survey of the European Society of Cardiology.

BACKGROUND Over the last few decades, the incidence and prevalence of chronic heart failure (HF) have been constantly increasing. AIM To identify predictors of one-year mortality and hospital readmissions in patients discharged after hospitalisation for HF. METHODS The study included Polish patients who agreed to participate in the Heart Failure Pilot Survey of the European Society of Cardiology and were followed for 12 months. The primary endpoint was all-cause death at 12 months. The secondary endpoint was a composite of all-cause death and readmission for cardiac causes at 12 months. RESULTS The final analysis included 629 patients. The primary end point occurred in 68 of 629 patients (10.8%). In multivariate analysis, independent predictors of one-year mortality were: higher New York Heart Association (NYHA) class at admission (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.01-3.59; p = 0.0478), inotropic support during hospitalisation (OR 3.95; 95% CI 1.49-10.47; p = 0.0056), and lower glomerular filtration rate at discharge (OR 0.978; 95% CI 0.961-0.995; p = 0.0117). The secondary endpoint occurred in 278 of 503 patients (55.3%). In multivariate analysis, predictors of secondary endpoint were a history of previous coronary revascularisation (OR 2.403; 95% CI 1.221-4.701; p = 0.002) and inotropic support during hospitalisation (OR 2.521; 95% CI 1.062-5.651; p = 0.009). CONCLUSIONS Patients discharged after hospitalisation for HF remained at high risk of death and hospital readmission. A previous history of coronary revascularisation, decreased renal function, and worse clinical status at admission with the need for inotropic support were predictors of one-year outcome in Polish patients hospitalised for HF.

Limb-girdle muscular dystrophy with severe heart failure overlapping with lipodystrophy in a patient with LMNA mutation p.Ser334del

Laminopathies, a group of heterogeneous disorders associated with lamin A/C gene (LMNA) mutations, encompass a wide spectrum of clinical phenotypes, which may present as separate disease or as overlapping syndromes. We describe a 35-year-old female in whom a novel sporadic heterozygous mutation c.1001_1003delGCC (p.Ser334del) of the LMNA gene was found. The patient presented with overlapping syndrome of heart failure secondary to dilated cardiomyopathy, limb-girdle dystrophy and partial lipodystrophy. Endomyocardial biopsy revealed strong up-regulation of HLA classes I and II antigens on microvessels and induction of the class I antigens on cardiomyocytes. On muscle biopsy, a wide range of fiber sizes and small clusters of inflammatory infiltrations were found. In the rapid progression of heart failure with arrhythmias or conduction defect, accompanied with muscle atrophy and lipodystrophy, the genetic disease should be taken into consideration. In addition, undefined inflammatory response and fibrosis in the heart or skeletal muscle might further justify screening of the lamin A/C gene.

Natriuretic Peptides Assessment in Dilated Cardiomyopathy in Patients with Emery-Dreifuss Muscular Dystrophy

Introduction: Levels of natriuretic peptides in blood are often tested for as screening for heart disease and their progress assessed. Dilated cardiomyopathy (DCM) with conduction disturbances is one of the leading serious manifestations in genetically transmitted Emery-Dreifuss muscular dystrophy (EDMD). However, the potential significance of and variability to brain-natriuretic peptides (BNP) and atrial-natriuretic peptides (ANP) in this disease has not been tested hitherto. It seemed worth considering whether estimation of natriuretic peptides might help in defining cardiac dysfunction in the early stages of the disease, prior to the appearance of echocardiographic changes. This is perceived especially important in cardiologically asymptomatic patients, who are still at risk of cardiac sudden death. Patients and Methods: Serum levels of BNP, NT-proBNP, ANP and NT-proANP were quantified by ELISA sandwich immunoassay in 25 EDMD patients (10 autosomal-dominant AD-EDMD, 15 X-linked EDMD), 8 X-EDMD carriers, 9 patients with dystrophinopathy as disease controls, and 20 age-matched healthy controls. Results: Serum levels of BNP, NT-pro-BNP, ANP, and NT-proANP were elevated in the blood of about 50% of patients with both the AD-EDMD and the X-EDMD form. Values were distributed from normal through to highly elevated. In the X-EDMD group there was a marked increase in the ANP and NT-proANP values. The X-EDMD group also manifested a correlation between level of atrial natriuretic peptides, echocardiographic parameters and severity of cardiac symptoms. Conclusions: The presented results indicate that assessment of circulating natriuretic peptides is of limited value in identifying cardiac involvement in EDMD. However, when included to the panel of other cardiologic biomarkers the estimation of natriuretic peptides may offer additional information in respect of proper diagnosis, prognosis, monitoring of appropriate treatment, prediction of outcome. and help to prevent cardiac decompensation and sudden death.

Chronic heart failure management in primary healthcare in Poland: Results of a nationwide cross-sectional study

Abstract Background: Organizational and educational activities in primary care in Poland have been introduced to improve the chronic heart failure (CHF) management. Objectives: To assess the use of diagnostic procedures, pharmacotherapy and referrals of CHF in primary care in Poland. Methods: The cross-sectional survey was conducted in 2013, involving 390 primary care centres randomly selected from a national database. Trained nurses contacted primary care physicians who retrospectively filled out the study questionnaires on the previous year’s CHF management in the last five patients who had recently visited their office. The data on diagnostic and treatment procedures were collected. Results: The mean age ± SD of the 2006 patients was 72 ± 11 years, 45% were female, and 56% had left ventricular ejection fraction <50%. The percentage of the CHF patients diagnosed based on echocardiography was 67% and significantly increased during the last decade. Echocardiography was still less frequently performed in older patients (≥80 years) than in the younger ones (respectively 50% versus 72%, Ρ <0.001) and in women than in men (62% versus 71%, P <0.001). The percentage of the patients treated with β-blocker alone was 88%, but those with a combination of angiotensin inhibition 71%. The decade before, these percentages were 68% and 57%, respectively. Moreover, an age-related gap observed in the use of the above-mentioned therapy has disappeared. Conclusion: The use of echocardiography in CHF diagnostics has significantly improved in primary care in Poland but a noticeable inequality in the geriatric patients and women remains. Most CHF patients received drug classes in accordance with guidelines.

Low-symptomatic skeletal muscle disease in patients with a cardiac disease – Diagnostic approach in skeletal muscle laminopathies

Mild skeletal muscle symptoms might be accompanied with severe cardiac disease, sometimes indicating a serious inherited disorder. Very often it is a cardiologist who refers a patient with cardiomyopathy and/or cardiac arrhythmia and discrete muscle disease for neurological consultation, which helps to establish a proper diagnosis. Here we present three families in which a diagnosis of skeletal muscle laminopathy was made after careful examination of the members, who presented with cardiac arrhythmia and/or heart failure and a mild skeletal muscle disease, which together with positive family history allowed to direct the molecular diagnostics and then provide appropriate treatment and counseling.