Zastosowanie leczenia przeciwpłytkowego i rewaskularyzacji u pacjentów z ostrym zespołem wieńcowym. Dane z polskiego rejestru EPICOR

Background: Cardiovascular disease is the leading cause of mortality and morbidity in developed countries, including Poland. Antithrom­botic drugs play a crucial role in the management of acute coronary syndromes (ACS). Recent clinical trials have demonstrated the efficacy and safety profiles of new antiplatelet and anticoagulant agents, which may be used as add-on therapy or replacements for older drugs. The long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients (EPICOR) is a prospective international observational study (NCT01171404) designed to describe the use of antithrombotic management strategies for the treatment of ACS during the acute phase and over a follow-up period of up to two years from the index event. A total of 608 patients from 26 hospitals in Poland were enrolled into the registry between September 2010 and March 2011. Aim: The aim of this work was to summarise data on pre-hospital and in-hospital and revascularisation therapy in 608 patients enrolled into the registry in Poland. Methods: The registry collected the records of patients who were hospitalised for ACS within 24 h of symptom onset and who had a final diagnosis of unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), or ST-segment elevation myocardial infarction (STEMI), and survived to discharge. Results: Among 608 enrolled patients, 291 had a final diagnosis of STEMI and 317 had a final diagnosis of NSTEMI/UA. Patients with NSTEMI/UA were generally at higher cardiovascular risk than patients with STEMI. Before admission to the hospital antiplatelet drugs (acetylsalicylic acid [ASA] and/or clopidogrel) were administered more frequently to STEMI than to NSTEMI/UA patients. Glycoprotein (GP) IIb/IIIa inhibitors were used in almost half of the STEMI patients and in nearly 10% of NSTEMI/UA patients. The combinations of antiplatelet drugs included ASA + clopidogrel (predominantly in NSTEMI/UA) or ASA + clopidogrel + GPIIb/IIIa inhibitor (predominantly in STEMI), while other possible combinations were not used. Almost all STEMI patients (96.2%) and the clear majority of NSTEMI/UA patients (73.8%) were subjected to percutaneous coronary intervention (PCI), while coronary artery bypass grafting was performed in only 2.5% of the NSTEMI/UA patients. At the time of discharge from hospital almost all patients with STEMI received ASA together with clopidogrel, but this strategy was used only in 91.5% of patients with NSTEMI/UA (p < 0.05). Unfractionated heparin was used in 62% of patients, low-molecular weight heparin in 35%, fondaparinux in 0.7%, and bivalirudin in none of the studied patients. Conclusions: Among patients with ACS enrolled to the EPICOR study in Poland, antiplatelet therapy was started in the pre-hospital phase in approximately one-third of the STEMI patients and in one out of ten of the NSTEMI/UA patients. The initial antiplatelet therapy was mostly based on ASA + clopidogrel and was followed by a combination of ASA + clopidogrel + GPIIb/IIIa inhibitor. Other drugs or combinations, as well as novel antiplatelet drugs, were only used exceptionally. Almost 10% of NSTEMI/UA patients did not receive dual antiplatelet therapy at discharge. PCI plays a dominating role in the first-line treatment for the patients enrolled to this registry in Poland.Wstęp: Choroby układu sercowo-naczyniowego stanowią główną przyczynę zgonów w krajach rozwiniętych, w tym w Polsce. Leki przeciwpłytkowe odgrywają zasadniczą rolę w leczeniu ostrych zespołów wieńcowych (ACS). Wyniki ostatnio prze­prowadzonych badań wykazały skuteczność i bezpieczeństwo nowych leków przeciwpłytkowych i przeciwzakrzepowych, które mogą być dodawane do terapii lub mogą zastępować starsze preparaty. Rejestr EPICOR (long-tErm follow-uP of antit­hrombotic management patterns In acute CORonary syndrome patients) był prospektywnym, międzynarodowym badaniem (NCT01171404), które przedstawiło strategię postępowania u osób z ACS, zarówno w ostrej fazie choroby, jak i 2 lata później. Do badania włączono 608 chorych z 26 szpitali w Polsce między wrześniem 2010 a marcem 2011 r. Cel: Celem badania było przedstawienie strategii postępowania w fazie przedszpitalnej i szpitalnej oraz rewaskularyzacji u pacjentów z ACS w Polsce. Metody: Do rejestru włączono chorych z ACS w ciągu 24 godzin od początku wystąpienia bólu, u których ostatecznie rozpoznano dławicę niestabilną (UA), zawał serca bez uniesienia odcinka ST (NSTEMI) i zawał serca z uniesieniem odcinka ST (STEMI), i którzy przeżyli do momentu wypisania ze szpitala. Wyniki: Spośród 608 włączonych pacjentów u 291 stwierdzono STEMI, u 317 — NSTEMI/UA. Pacjenci z NSTEMI/UA należeli do grupy wyższego ryzyka chorób sercowo-naczyniowych niż osoby ze STEMI. Przed wypisaniem ze szpitala leki przeciwpłytkowe (kwas acetylosalicylowy [ASA] i/lub klopidogrel) były częściej przyjmowane przez chorych ze STEMI niż z NSTEMI/UA. Inhibitory glikoproteiny (GPIIa/IIIb) były stosowane w połowie przypadków w STEMI i prawie w 10% w NSTEMI/UA. Wykorzystywano połączenia leków przeciwpłytkowych, w tym ASA + klopidogrel (szczególnie u osób z NSTEMI/UA) lub ASA + klopidogrel + inhibitor GPIIa/IIIb (szczególnie u osób ze STEMI); inne możliwe połączenia nie były stosowane. W momencie wypisania ze szpitala prawie wszyscy pacjenci ze STEMI otrzymywali ASA razem z klopidogrelem, ale ta strategia była stosowana tylko u 91,5% chorych z NSTEMI/UA (p < 0,05). Wnioski: Spośród pacjentów z ACS włączonych do rejestru EPICOR w Polsce leczenie przeciwpłytkowe było rozpoczęte już w fazie przedszpitalnej u 1/3 osób ze STEMI i u co 10. chorego z NSTEMI. Prawie u wszystkich pacjentów ze STEMI i u zna­miennej większości z NSTEMI/UA przeprowadzono przezskórną interwencję wieńcową (96,2% i 73,8%). Pomostowanie aortalno-wieńcowe wykonano tylko u 2,5% chorych z NSTEMI i u żadnego pacjenta ze STEMI. Początkowo w ramach terapii przeciwpłytkowej wykorzystywano: ASA + klopidogrel, a następnie stosowano połączenie leków: ASA + klopidogrel + inhibitor GPIIb/IIIa. Inne połączenia leków i preparaty przeciwpłytkowe nowszej generacji stosowano jedynie w wyjątkowych przypadkach. Prawie 10% chorych z NSTEMI/UA nie otrzymało podwójnej terapii przeciwpłytkowej przy wypisaniu ze szpitala. Angioplastyka wieńcowa odgrywała dominującą rolę w leczeniu pacjentów z ACS włączonych do polskiego rejestru EPICOR

A Novel DSP Truncating Variant in a Family with Episodic Myocardial Injury in the Course of Arrhythmogenic Cardiomyopathy—A Possible Role of a Low Penetrance NLRP3 Variant

Mono-allelic dominant mutations in the desmoplakin gene (DSP) have been linked to known cardiac disorders, such as arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy. During the course of DSP cardiomyopathy, episodes of acute myocardial injury may occur. While their mechanisms remain unclear, myocarditis has been postulated as an underlying cause. We report on an adolescent girl with arrhythmogenic biventricular cardiomyopathy and three acute myocarditis-like episodes in whom we found a novel truncating DSP variant accompanied by a known low penetrance R490K variant in the NLRP3. Upon family screening, other carriers of the DSP variant have been identified in whom only mild cardiac abnormalities were found. We hypothesized that the uncommon course of cardiomyopathy in the proband as well as striking discrepancies in the phenotype observed in her family may be explained by the co-existence of her low penetrance genetic autoinflammatory predisposition

Titin-Related Dilated Cardiomyopathy: The Clinical Trajectory and the Role of Circulating Biomarkers in the Clinical Assessment

Titin truncating variants (TTNtv) are known as the leading cause of inherited dilated cardiomyopathy (DCM). Nevertheless, it is unclear whether circulating cardiac biomarkers are helpful in detection and risk assessment. We sought to assess 1) early indicators of cardiotitinopathy including the serum biomarkers high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in clinically stable patients, and 2) predictors of outcome among TTNtv carriers. Our single-center cohort consisted of 108 TTNtv carriers (including 70 DCM patients) from 43 families. Clinical, laboratory and follow-up data were analyzed. The earliest abnormality was left ventricular dysfunction, present in 8, 26 and 47% of patients in the second, third and fourth decade of life, respectively. It was followed by symptoms of heart failure, linked to NT-proBNP elevation and severe left ventricular systolic dysfunction, and later by arrhythmias. Hs-cTnT serum levels were increased in the late stage of the disease only. During the median follow-up of 5.2 years, both malignant ventricular arrhythmia (MVA) and end-stage heart failure (esHF) occurred in 12% of TTNtv carriers. In multivariable analysis, NT-proBNP level ≥650 pg/mL was the best predictor of both composite endpoints (MVA and esHF) and of MVA alone. In conclusion, echocardiographic abnormalities are the first detectable anomalies in the course of cardiotitinopathies. The assessment of circulating cardiac biomarkers is not useful in the detection of the disease onset but may be helpful in risk assessment

Transthyretin-related familial amyloid polyneuropathy (ATTR-FAP) in Poland — genetic and clinical presentation

Background. Transthyretin-related familial amyloid polyneuropathy (ATTR-FAP) is a rare, progressive, hereditary, highly disabling multisystem disorder. ATTR-FAP phenotypes differ according to the type of TTR mutation, geographic region and other as yet unidentified factors. The aim of this study was to establish the clinical and genetic characteristics of Polish patients.Methods and patients. Clinical data and necessary examinations were collected from patients diagnosed with ATTR-FAP at the Department of Neurology of Medical University of Warsaw between 1970 and 2019.Results. 16 patients from eight unrelated families with five different TTR mutations were identified. The family with Val71Ala TTR mutation presented with early onset severe progressive polyneuropathy, with marked visual symptoms in a few patients. The next family with Ile73Val TTR mutation developed symptoms in middle age, and presented with mixed neuropathic and cardiologic phenotype. Four unrelated families were found to have the Phe33Leu TTR mutation with mixed neuropathic and cardiologic phenotype and late onset of symptoms. Other TTR mutations identified were: Val30Met and Asp38Val, both with late onset sensory, motor and autonomic neuropathy.Conclusion. Polish ATTR-FAP cases presented with heterogeneity typical for non-endemic areas. Phe33Leu TTR mutation was the most common, found in four unrelated families

A novel risk model for predicting potentially life-threatening arrhythmias in non-ischemic dilated cardiomyopathy (DCM-SVA risk)

BACKGROUND: Non-ischemic dilated cardiomyopathy (DCM) can be complicated by sustained ventricular arrhythmias (SVA) and sudden cardiac death (SCD). By now, left-ventricular ejection fraction (LV-EF) is the main guideline criterion for primary prophylactic ICD implantation, potentially leading either to overtreatment or failed detection of patients at risk without severely impaired LV-EF. The aim of the European multi-center study DETECTIN-HF was to establish a clinical risk calculator for individualized risk stratification of DCM patients. METHODS: 1393 patients (68% male, mean age 50.7 ± 14.3y) from four European countries were included. The outcome was occurrence of first potentially life-threatening ventricular arrhythmia. The model was developed using Cox proportional hazards, and internally validated using cross validation. The model included seven independent and easily accessible clinical parameters sex, history of non-sustained ventricular tachycardia, history of syncope, family history of cardiomyopathy, QRS duration, LV-EF, and history of atrial fibrillation. The model was also expanded to account for presence of LGE as the eight8h parameter for cases with available cMRI and scar information. RESULTS: During a mean follow-up period of 57.0 months, 193 (13.8%) patients experienced an arrhythmic event. The calibration slope of the developed model was 00.97 (95% CI 0.90-1.03) and the C-index was 0.72 (95% CI 0.71-0.73). Compared to current guidelines, the model was able to protect the same number of patients (5-year risk ≥8.5%) with 15% fewer ICD implantations. CONCLUSIONS: This DCM-SVA risk model could improve decision making in primary prevention of SCD in non-ischemic DCM using easily accessible clinical information and will likely reduce overtreatment