Cardiac Sarcoidosis: A Comprehensive Clinical Review.

Sarcoidosis is an inflammatory multisystemic disease of unknown etiology characterized by the formation of non-caseating granulomas. Sarcoidosis can affect any organ, predominantly the lungs, lymphatic system, skin and eyes. While > 90% of patients with sarcoidosis have lung involvement, an estimated 5% of patients with sarcoidosis have clinically manifest cardiac sarcoidosis (CS), whereas approximately 25% have asymptomatic, clinically silent cardiac involvement verified by autopsy or imaging studies. CS can present with conduction disturbances, ventricular arrhythmias, heart failure or sudden cardiac death. Approximately 30% of < 60-year-old patients presenting with unexplained high degree atrioventricular (AV) block or ventricular tachycardia are diagnosed with CS, therefore CS should be strongly considered in such patients. CS is the second leading cause of death among patients affected by sarcoidosis after pulmonary sarcoidosis, therefore its early recognition is important, because early treatment may prevent death from cardiovascular involvement. The establishment of isolated CS diagnosis sometimes can be quite difficult, when extracardiac disease cannot be verified. The other reason for the difficulty to diagnose CS is that CS is a chameleon of cardiology and it can mimic (completely or almost completely) different cardiac diseases, such as arrhythmogenic cardiomyopathy, giant cell myocarditis, dilated, restrictive and hypertrophic cardiomyopathies. In this review article we will discuss the current diagnosis and management of CS and delineate the potential difficulties and pitfalls of establishing the diagnosis in atypical cases of isolated CS.

Coexistence of aortic valve stenosis and cardiac amyloidosis: echocardiographic and clinical significance.

BACKGROUND: Left ventricular hypertrophy and diastolic dysfunction are common echocardiographic features of both aortic valve stenosis (AS) and cardiac amyloidosis (CA). These two different entities therefore may mask each other. From recent years, there is a growing body of evidence about the relatively high incidence of wild-type transthyretin (wtTTR) amyloidosis in AS, but there are scarce data on the prevalence of AS in CA, particularly in AL-type amyloidosis. The echocardiographic approach to these patients is not obvious, and not evidence based. We aimed to study the prevalence, severity, and type of AS in patients with CA and also to evaluate the potential of echocardiography in the diagnostic process. METHODS: Between January 2009 and January 2019, we retrospectively analyzed the clinical and echocardiographic data, and the echocardiographic work up of 55 consecutive CA patients. RESULTS: 80% of our CA patients had AL amyloidosis. We identified 5 patients (9%) with moderate to severe AS: two with moderate AS and three with low-flow, low-grade AS (LFLG AS). Further analysis of the latter three patients with dobutamine stress echocardiography revealed pseudo-severe LFLG AS in two, and true-severe AS in one patient. CONCLUSION: The prevalence of moderate to severe AS is 9% in our population of CA patients, the majority of whom have AL amyloidosis. Dobutamine echocardiography seems to be appropriate for the further characterization of patients with LFLG AS, even with normal ejection fraction.

The timing of testing influences skill retention after basic life support training: a prospective quasi-experimental study.

BACKGROUND: Proper basic life support (BLS) is key in improving the survival of out-of-hospital cardiac arrest. BLS skills deteriorate in three to 6 months after training. One method to improve skill retention may be using the "testing effect" to test skills at the end of a BLS course. The aim of our study was to investigate whether either testing or the timing of such testing after BLS training have any influence on skill retention. METHODS: This was a post-test only, partial coverage, prospective quasi-experimental study designed to evaluate a BLS training course among 464 fifth year medical students at Semmelweis University in the first semester of 2013/2014. Groups were systematically but non-randomly assigned to either a control group that took no exam or one of two experimental groups that took an exam (N = 179, NoExam group; N = 165, EndExam group - exam at the end of the BLS training; N = 120, 3mExam group - exam 3 months after the BLS training). The ability to perform ten prescribed essential BLS steps was evaluated during a skill retention assessment 2 months after the course in the NoExam, 2 months after the course (and the exam) in the EndExam and 5 months after the course (2 months after the exam) in the 3mExam group to measure skill retention and the effect of our intervention. Scores were calculated for each BLS step, and also summed up as a total score. We used Kruskal-Wallis test to assess differences in skill retention. RESULTS: Overall, NoExam and EndExam groups showed similar skill retention. The mean total score (and many of the sub-scores) of students was significantly higher in the 3mExam group compared to both the NoExam and the EndExam groups, and there was no difference in the total score (and many of the sub-scores) of the latter two groups. The 3mExam group had less variability in total scores (and many of the sub-scores) than the other two groups. CONCLUSION: Our study provides evidence that testing these skills 3 months after BLS training may be more effective than either testing immediately at the end of the course or no testing at all.

Complement C3a predicts outcome in cardiac resynchronization therapy of heart failure.

BACKGROUND: The chronic inflammation plays an important role in heart failure and complement components might be useful markers of the prognosis. We set out to evaluate their predictive value in the clinical outcomes of patients with cardiac resynchronization therapy (CRT). METHODS: We determined the complement levels C3, C3a, sC5b-9 and also the N-terminus of the prohormone brain natriuretic peptide (NT-proBNP) of 126 heart failure patients in a prospective, single-center observational study before and 6 months after CRT implantation. RESULTS: CRT reduced the C3a [212.5 (148.2-283.6) vs. 153 (119.8-218.3) ng/mL, p < 0.0001] and the sC5b-9 levels [296.9 (234.2-358.8) vs. 255.1 (210.1-319.0) ng/mL, p = 0.0006], but not the total C3 levels [1.43 (1.26-1.61) vs. 1.38 (1.23-1.57) g/L, p = 0.57]. C3a predicted the 5-year mortality of the patients [C3a > 165 ng/mL hazard ratio = 4.21 (1.65-10.72), p = 0.003] independent of the NT-proBNP and other factors. After reclassification, we observed a significant net reclassification improvement [NRI = 0.71 (0.43-0.98), p < 0.0001] and integrated discrimination improvement [IDI = 0.08 (0.03-0.12), p = 0.0002]. CONCLUSIONS: In patients with CRT, elevated C3a levels increase the risk of mortality independent of the NT-proBNP levels or other factors. CRT exerts anti-inflammatory effect by reducing the complement activation.

The ratio of the neutrophil leucocytes to the lymphocytes predicts the outcome after cardiac resynchronization therapy.

AIMS: The low lymphocyte counts and high neutrophil leucocyte fractions have been associated with poor prognosis in chronic heart failure. We hypothesized that the baseline ratio of the neutrophil leucocytes to the lymphocytes (NL ratio) would predict the outcome of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). METHODS AND RESULTS: The qualitative blood counts and the serum levels of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) of 122 chronic heart failure patients and 122 healthy controls were analysed prospectively in this observational study. The 2-year mortality was considered as primary endpoint and the 6-month reverse remodelling (≥15% decrease in the end-systolic volume) as secondary endpoint. Multivariable regression analyses were applied and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. The NL ratio was elevated in chronic heart failure patients when compared with the healthy controls [2.93 (2.12-4.05) vs. 2.21 (1.64-2.81), P < 0.0001]. The baseline NL ratio exceeding 2.95 predicted the lack of the 6-month reverse remodelling [n = 63, odds ratio = 0.38 (0.17-0.85), P = 0.01; NRI = 0.49 (0.14-0.83), P = 0.005; IDI = 0.04 (0.00-0.07), P = 0.02] and the 2-year mortality [n = 29, hazard ratio = 2.44 (1.04-5.71), P = 0.03; NRI = 0.63 (0.24-1.01), P = 0.001; IDI = 0.04 (0.00-0.08), P = 0.02] independently of the NT-proBNP levels or other factors. CONCLUSION: The NL ratio is elevated in chronic heart failure and predicts outcome after CRT. According to the reclassification analysis, 4% of the patients would have been better categorized in the prediction models by combining the NT-proBNP with the NL ratio. Thus, a single blood count measurement could facilitate the optimal patient selection for the CRT.

[The role of therapeutic hypothermia in post-resuscitation care - review of the literature and personal experience]. / A terápiás hypothermia szerepe a postresuscitatiós ellátásban - irodalmi áttekintés és saját tapasztalatok.

In the last fifteen years mild therapeutic hypothermia became an accepted and widespread therapeutic method in the treatment of successfully resuscitated patients due to sudden cardiac death. Based on the available evidence therapeutic hypothermia is part of the resuscitation guidelines, however, many aspects of its therapeutic use are based on empirical facts. In particular, the subjects of intense debate are the ideal target temperature and the benefit of hypothermia in patients found with non-shockable rhythm. Hypothermia affects almost all organ systems and, therefore, early detection and treatment of side effects are essential. The aim of the authors is to summarize the clinical role and pathophysiologic effects of therapeutic hypothermia in the treatment of resuscitated patients based on current evidence and their practical experience.

[Useful tests to assess the clinical usefulness of new prognostic markers: the example of heart failure]. / Hasznos tesztek az új prognosztikai markerek klinikai értékének felmérésére: a szívelégtelenség példája.

INTRODUCTION: Identification of risk factors is one of the most frequent questions in medical research currently. Several reports showed "significant" and "independent" prognostic factors in a variety of human conditions, however, those were not tested about predictive information in addition to standard risk markers. Recently novel statistical approaches (reclassification) have been developed to test the performance and usefulness of new risk factors and prognostic markers. There are several established methods to test the prognostic models. AIM: The aim of this work was to present the application of these novel statistical approaches by re-analyzing previously reported results of the authors. METHOD: The authors analyzed the prognostic role of two markers: red cell distribution width and heat shock protein 70 in patients with heart failure. Using Cox regression analyses the authors have reported previously that both markers are independent predictors. In the present study they re-analyzed the role of red cell distribution width and heat shock protein 70 by reclassification tests. RESULTS: Incorporating red cell distribution width to the reference model the authors found a significant improvement in discrimination . However, the reclassification analysis provided ambiguous results with heat shock protein 70. CONCLUSIONS: Interpretation of results on new prognostic factors has to be done carefully, and appropriate reclassification approaches may help to confirm clinical usefulness only.

[Physiologic effects of hypothermia]. / A hypothermia élettani hatásai.

Therapeutic use of hypothermia has come to the frontline in the past decade again in the prevention and in mitigation of neurologic impairment. The application of hypothermia is considered as a successful therapeutic measure not just in neuro- or cardiac surgery, but also in states causing brain injury or damage. According to our present knowledge this is the only proven therapeutic tool, which improves the neurologic outcome after cardiac arrest, decreasing the oxygen demand of the brain. Besides influencing the nervous system, hypothermia influences the function of the whole organ system. Beside its beneficial effects, it has many side-effects, which may be harmful to the patient. Before using it for a therapeutic purpose, it is very important to be familiar with the physiology and complications of hypothermia, to know, how to prevent and treat its side-effects. The purpose of this article is to summarize the physiologic and pathophysiologic effects of hypothermia.

Pilot analysis of the usefulness of mortality risk score systems at resuscitated patients / Halálozásikockázat-becslo pontrendszerek alkalmazhatóságának elozetes vizsgálata újraélesztett betegek körében.

Összefoglaló. Bevezetés: A cardiovascularis halálokok közül világszerte nagy jelentoségu a hirtelen szívhalál. Annak ellenére, hogy a cardiopulmonalis resuscitatio és a postresuscitatiós intenzív osztályos kezelés is komoly metodikai és technikai fejlodésen ment keresztül az elmúlt idoszakban, kevés az olyan validált pontrendszer, amely jól becsülné a beteg intenzív osztályra kerülésekor a mortalitási rizikót. Célkituzés: A sikeres újraélesztést követo intenzív osztályos kezelés kezdetekor felmért, a cardiogen shock rizikóstratifikációjára alkalmazott CardShock Risk Score (CSRS) és az általunk hozzáadott, specifikus súlyozófaktorokkal (iniciális ritmus, inotropigény) módosított CardShock Risk Score (mCSRS) összevetése a mortalitás elorejelzésében post-cardiac arrest szindrómás betegeknél. Módszerek: Retrospektív vizsgálatunk során 172, kórházon kívül sikeresen újraélesztett és klinikánkon ellátott consecutiv betegbol a CSRS- és mCSRS-pontrendszerek segítségével végül 123 beteg adatait elemeztük. A CSRS- és mCSRS-változók és a korai/késoi mortalitás közötti összefüggést Cox-regressziós analízissel vizsgáltuk. A pontszámok alapján 3 csoportba (1-3, 4-6, 7+) soroltuk a betegeket. Az összevont csoportok túlélését log-rank teszttel hasonlítottuk össze. Eredmények: A betegpopuláció átlagéletkora 63,6 év volt (69% férfi), és a hirtelen szívhalál hátterében 80%-ban akut coronaria szindróma állt. A korai/késoi mortalitást leginkább a felvétel utáni neurológiai állapot, a szérumlaktátszint, a vesefunkció, az iniciális ritmus és a beteg katecholaminigénye határozta meg. A mCSRS alkalmazását követoen mind az "1-3" és a "4-6" (p≤0,001), mind a "4-6" és a "7+" (p = 0,006) csoportok között szignifikáns különbséget találtunk a túlélésben. Következtetés: A felvételkori pontok alapján a mCSRS pontosabban definiálja és differenciálja egymástól az általunk beválasztott két extra súlyozófaktorral az enyhe, a közepes és a magas mortalitási rizikóval bíró betegpopulációkat, mint a CSRS. Orv Hetil. 2021; 162(2): 52-60. INTRODUCTION: Sudden cardiac death is one of the most significant cardiovascular causes of death worldwide. Although there have been immense methodological and technical advances in the field of cardiopulmonary resuscitation and following intensive care in the last decade, currently there are only a few validated risk-stratification scoring systems for the quick and reliable estimation of the mortality risk of these patients at the time of admission to the intensive care unit. OBJECTIVE: Our aim was to correlate the mortality prediction risk points calculated by CardShock Risk Score (CSRS) and modified (m) CSRS based on the admission data of the post-cardiac arrest syndrome (PCAS) patients. METHODS: The medical records of 172 out-of-hospital resuscitated cardiac arrest patients, who were admitted at the Heart and Vascular Centre of Semmelweis University, were screened retrospectively. Out of the 172 selected patients, 123 were eligible for inclusion to calculate CSRS and mCSRS. Based on CSRS score, we generated three different groups of patients, with scores 1 to 3, 4 to 6, and 7+, respectively. Mortality data of the groups were compared by log-rank test. RESULTS: Mean age of the patients was 63.6 years (69% male), the cause of sudden cardiac death was acut coronary syndrome in 80% of the cases. The early and late mortality was predicted by neurological status, serum lactate level, renal function, initial rhythm, and the need of catecholamines. Using mCSRS, a significant survival difference was proven in between the groups "1-3" vs "4-6" (p≤0.001), "4-6" vs "7+" (p = 0.006). CONCLUSION: Compared to the CSRS, the mCSRS expanded with the 2 additional weighting points differentiates more specifically the low-moderate and high survival groups in the PCAS patient population treated in our institute. Orv Hetil. 2021; 162(2): 52-60.

Measurement of the Red Blood Cell Distribution Width Improves the Risk Prediction in Cardiac Resynchronization Therapy.

OBJECTIVES: Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction. DESIGN: The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed. RESULTS: After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n = 57). In the final model including all variables, the RDW [HR = 2.49 (1.27-4.86); p = 0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93-3.51); p = 0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model. CONCLUSIONS: Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT.

Persistently elevated extracellular HSP70 (HSPA1A) level as an independent prognostic marker in post-cardiac-arrest patients.

Predicting the prognosis of comatose, post-cardiac-arrest patients is a complex problem in clinical practice. There are several established methods to foretell neurological outcome; however, further prognostic markers are needed. HSP70 (HSPA1A), which increases rapidly in response to severe stress (among others after ischemic or hypoxic events), is a biomarker of cell damage in the ischemic brain and spinal cord. We hypothesized that HSP70 might be a reliable predictor of mortality in post-cardiac-arrest patients. The aim of this study was to analyze the role of extracellular HSP70 in the systemic inflammatory response over time, as well as the predictive value in cardiac arrest patients. Here, we show that the elevation of HSP70 levels in resuscitated patients and their persistence is an independent predictor of 30-day mortality after a cardiac arrest. Forty-six cardiac arrest patients were successfully cooled to 32-34 °C for 24 h, and followed up for 30 days. Twenty-four patients (52.2 %) were alive by the end of follow-up, and 22 patients (47.8 %) died. Forty-six patients with stable cardiovascular disease served as controls. Extracellular HSP70 (measured by ELISA in blood samples) was elevated in all resuscitated patients (1.31 [0.76-2.73] and 1.70 [1.20-2.37] ng/ml for survivors and non-survivors, respectively), compared with the controls (0.59 [0.44-0.83] ng/ml). HSP70 level decreased significantly in survivors, but persisted in non-survivors, and predicted 30-day mortality regardless of age, sex, complications, and the APACHE II score. Extracellular HSP70 could prove useful for estimating prognosis in comatose post-cardiac-arrest patients.

Elevated extracellular HSP70 (HSPA1A) level as an independent prognostic marker of mortality in patients with heart failure.

Predicting the survival of a patient with heart failure (HF) is a complex problem in clinical practice. Our previous study reported that extracellular HSP70 (HSPA1A) correlates with markers of heart function and disease severity in HF, but the predictive value of HSP70 is unclear. The goal of this study was to analyze extracellular HSP70 as predictive marker of mortality in HF. One hundred ninety-five patients with systolic heart failure were enrolled and followed up for 60 months. By the end of follow-up, 85 patients were alive (survivors) and 110 died (nonsurvivors). HSP70 (measured by ELISA in the serum) was elevated in nonsurvivors, compared with survivors (0.39 [0.27-0.59] vs. 0.30 [0.24-0.43] ng/ml, respectively, p = 0.0101). In Kaplan-Meier survival analysis higher HSP70 levels above median were associated with a significantly increased mortality. In multivariable survival models, we show that HSP70 level above the median is an age-, sex-, body mass index-, creatinine-, and NT-proBNP-independent predictor of 5-year mortality in HF. Extracellular HSP70 could prove useful for estimating survival in patients with HF.