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Razlike u fibrozi atrija po dobi i spolu među pacijentima s atrijskom fibrilacijom
Aim: Age and female sex are associated with a higher risk of stroke in atrial fibrillation (AF).
We sought to determine whether advancing age and female sex are associated with higher atrial
fibrosis.
Methods and results: We conducted an observational cohort study of patients with AF enrolled
in the University of Utah AF Database and a non-AF control group who underwent lategadolinium enhancement magnetic resonance imaging (LGE-MRI) for atrial fibrosis
quantification. Participants with contraindications for contrast MRI scanning were excluded.
Nine hundred and eight consecutive men and women with AF and 15 non-AF controls were
included in this study. Left atrial fibrosis increased with age in both men and women with AF.
Women with AF (n = 316) were older than men (n = 592): mean age 68.7±11.6 vs. 64.9±11.7
years; P < 0.01, and had higher left atrial fibrosis compared with men 17.5 ± 10.1% vs. 15.3 ±
8.9%; P < 0.001. Women also had a higher prevalence of prior stroke than men (15.8% vs.
6.5%; P < 0.001). Age and sex relationships with atrial fibrosis remained significant in
multivariate analysis. Compared with the non-AF control group, patients with AF they had
significantly higher atrial fibrosis: 16.0 ± 9.4 vs. 5.5 ± 5.8%; P < 0.001.
Conclusions: Advancing age and female sex are associated with a higher burden of atrial
fibrosis in patients with AF. Women with a prior history of stroke also have higher fibrosis
than women and men without a history of stroke. Advanced fibrosis may explain the female
and age association with stroke in AF.Cilj: Dob i ženski spol povezani su s većim rizikom za moždani udar u osoba s atrijskom
fibrilacijom (AF). Željeli smo utvrditi jesu li starija životna dob i ženski spol povezani s višom
razinom fibroze atrija.
Metode i rezultati: Proveli smo kohortnu studiju u koju smo uključili pacijente s AF koji su
bili upisani u bazu podataka na Sveučilištu Utah i kontrolnu skupinu bez AF, koja je
podvrgnuta magnetskoj rezonanciji s kasnim gadolinijskim kontrastnim pojačanjem prikaza
(engl. late-gadolinium enhancement magnetic resonance imaging, LGE-MRI) radi određivanja
atrijske fibroze. Osobe s kontraindikacijama za LGE-MRI pretragu su bile isključene. Devet
stotina i osam uzastopnih ispitanika muškog i ženskog spola s AF i 15 kontrola bez AF-a bilo
je uključeno u ovo istraživanje. Fibroza lijevog atrija se povećavala s dobi i kod muškaraca i
kod žena s AF. Žene s AF (n=316) bile su starije od muškaraca (n=592), s prosječnom dobi od
68,7 godina ± 11,6 u odnosu na 64,9 ± 11,7 godina u muškaraca (P<0,001) te su imale višu
razinu fibroze lijevog atrija u usporedbi s muškarcima (17,5 ± 10,1% nasuprot 15,3 ± 8,9%;
P<0,001). Žene su također imale veću prevalenciju prethodnog moždanog udara u usporedbi s
muškarcima (15,8% nasuprot 6,5%; P<0,001). Dob i spol bili su prediktori atrijske fibroze u
multivarijatnoj analizi. U usporedbi s kontrolnom skupinom koja nema AF, pacijenti s AF imali
su značajno višu razinu atrijske fibroze (16,0 ± 9,4 naspram 5,5 ± 5,8%; P<0,001).
Zaključci: Starija životna dob i ženski spol povezani su s većim teretom atrijske fibroze kod
pacijenata s AF. Žene koje imaju prethodni moždani udar također imaju i veću razinu atrijske
fibroze u usporedbi sa ženama i muškarcima koji nisu imali moždani udar. Uznapredovala
fibroza može objasniti povezanost između ženskog spola i starije životne dobi s moždanim
udarom kod AF
Kliničke koristi i prognostička vrijednost proteina koji veže masne kiseline srčanog tipa, miokardijalne kreatin kinaze i specifičnih ehokardiografskih parametara desne klijetke za stratifikaciju rizika normotenzivnih bolesnika s plućnom embolijom
The treatment of acute pulmonary artery embolism remains a challenge for modern medicine.
While the risk-adapted treatment strategies for the groups with high and low mortality risk are
essentially uncontroversial, uncertainty remains in patients with intermediate risk PE about the
appropriate risk stratification and management. Despite therapy, the mortality rate of this form
of pulmonary embolism is about 5-16%. It is possible that current concepts for risk
stratification, based on the use and combination of troponin I (TnI) with imaging techniques
such as echocardiography, only transfer to this patient group in limited capacity. Therefore,
clinical research is increasingly focusing on other cardiac-specific biomarkers, such as cardiac
muscle-specific fatty acid binding protein (H-FABP), which is already being used successfully
in early-stage cardiac infarction diagnostics.
Aim of the study
The present study investigates the prognostic value of new myocardial laboratory markers as
well as specific right ventricular echo parameters and contributes to risk stratification in PE
with intermediate mortality risk.
Material and Methods
Between 2005 and 2010, 161 patients with proven PE and an initial systolic blood pressure
above 90 mmHg were enrolled. All patients underwent TnI, creatine kinase isoenzyme MB
(CK-MB), CK and D-dimers determination at the routine cardiology laboratory. All patients
continued to receive a commercially available qualitative H-FABP rapid test (threshold 7
ng/ml). The routine echocardiographic examination with measurement of ventricular size ratios
(RV/LV index), the mTDI parameters, the TAPSE and other standard parameters took place on
the admission day. An intermediate mortality risk was based on the guidelines for
echocardiographic signs of right ventricular dysfunction (RVD) or elevated cardiac muscle
specific laboratory parameters. The primary endpoint was the 30-day mortality due to PE. The
secondary endpoint was the occurrence of a complicated clinical course, defined by therapy
escalation in the form of catecholamine administration, thrombolysis or embolectomy or
resuscitation.
Results
In total, 16 out of 161 (9.9%) patients died within 30 days after hospital admission. The
deceased had significantly higher plasma levels of TnI, and CK-MB compared to survivors. A positive H-FABP test was found in 26 patients, of whom 15 (57.7%) died. In contrast, one of
135 H-FABP-negative patients died (0.7%, H-FABP positive vs. negative P <0.001).
Stratification according to TnI resulted in a mortality rate of 19.7% (13 out of 66) among TnIpositive patients and 3.2% among those that were TnI-negative (3 out of 95, P = 0.001). In
echocardiography, H-FABP positives exhibited significantly greater RV/LV indices (1.02 ±
0.21 vs. 0.86 ± 0.22, P = 0.001) compared to H-FABP negatives, and a significantly lower
TAPSE (13.7 ± 4.0 mm vs. 19.1 ± 4.7 mm, P <0.001). There were no significant differences
for the mTDI parameters. Multivariate logistic regression analysis identified H-FABP (OR 27.1
95% CI 2.1 - 352.3), CK-MB (OR 5.3 95% CI 1.3 - 23.3) and the systolic blood pressure on
admisson (OR 1.2 95% CI 1.1 - 1.3) as independent predictors of 30-day mortality. The
combination of positive H-FABP test and increased CK-MB resulted in a particularly high
mortality risk: 14 of 16 patients with this laboratory constellation (87.5%) died. Conversely,
the survival probability of H-FABP-negative patients was over 99%.
There was an increased risk of a complicated clinical course with a positive H-FABP test
(OR 4.8 95% CI 1.1 - 21.1) and reduced TAPSE (OR 1.3 95% CI 1.2 - 1.5). TAPSE values
above 17.5mm made a complicated course unlikely in 98% of the cases.
Conclusion
Our data support the hypothesis that H-FABP could be a promising prognostic marker in
intermediate risk PE being highly associated with an unfavorable short-term outcome. Its
clinical value in risk stratification seems to be superior to that of cardiac troponins. The
combination of elevated H-FABP and CK-MB plasma levels indicates a particularly high risk
of mortality. The clinical value of CK-MB in risk stratification of PE is unclear and might be
underestimated and further studies are required. Increased H-FABP values correlate with
echocardiographic markers of RVD. MTDI is not suitable for risk stratification in this patient
group. Additional studies are necessary to identify which specific echocardiographic
parameters are the most useful in risk assessment in acute PE with intermediate risk mortality.Liječenje akutne embolije plućne arterije i dalje ostaje izazov za suvremenu medicinu. Iako su
strategije liječenja prilagođene riziku za skupine s visokim i niskim rizikom od smrtnosti u
osnovi nesporne, kod bolesnika sa srednjim rizikom za plućnu emboliju ostaje neizvjesnost o
odgovarajućoj stratifikaciji rizika i zbrinjavanja pacijenta. Unatoč terapiji, stopa smrtnosti od
ovog oblika plućne embolije je oko 5-16%. Moguće je da se trenutni koncepti za stratifikaciju
rizika, temeljeni na upotrebi i kombinaciji troponina I (TnI) s tehnikama slikovnog prikaza,
poput ehokardiografije, prenose na ovu grupu bolesnika u ograničenom kapacitetu. Stoga se
klinička istraživanja sve više fokusiraju na druge specifične srčane biomarkere, poput srčanomišićnog proteina koji veže masne kiseline (H-FABP), koji se već uspješno koristi u ranoj fazi
dijagnostičkog postupka srčanog infarkta.
Cilj studije
Ova studija istražuje prognostičku vrijednost novih laboratorijskih markera miokarda, kao i
specifične parametre ultrazvuka desnog ventrikula te doprinosi stratifikaciji rizika u pacijenata
s plućnom embolijom sa srednjim rizikom smrtnosti.
Materijali i metode
Između 2005. i 2010. godine u istraživanje je uključeno 161 pacijenta s dokazanom plućnom
ebmolijom i početnim sistoličkim krvnim tlakom većim od 90 mmHg. Za sve pacijente
provedeno je mjerenje TnI, kreatin kinaze MB (CK-MB), CK i D-dimera u laboratoriju za
rutinsku kardiologiju. Kod svih bolesnika učinjen je komercijalno dostupan kvalitativni brzi
test H-FABP (prag osjetljivosti od 7 ng/ml). Rutinski ultrazvučni pregled s mjerenjem omjera
veličine ventrikula (RV/LV indeks), mTDI parametrima, TAPSE i drugim standardnim
parametrima obavljen je na dan prijema. Definicija srednje razine rizika od smrtnog ishoda
zasnovana je na smjernicama za ultrazvučne znakove disfunkcije desne klijetke (RVD) ili na
povišenim vrijednostima specifičnih laboratorijskih parametara za srčani mišić. Primarni
promatrani ishod bila je smrtnost unutar 30 dana zbog plućne embolije. Sekundarni promatrani
ishod bila je pojava kompliciranog kliničkog tijeka, definiranog eskalacijom terapije u obliku
primjene kateholamina, trombolize ili embolektomije ili reanimacije.
Rezultati
Ukupno je 16 od 161 (9,9%) bolesnika umrlo u roku od 30 dana nakon prijema u bolnicu.
Ispitanici koji su preminuli imali su značajno više razine TnI i CK-MB u plazmi, u usporedbi s preživjelima. Pozitivan test H-FABP pronađen je kod 26 bolesnika, od kojih je njih 15 (57,7%)
umrlo. Suprotno tome, jedan od 135 bolesnika s negativnim H-FABP je umro (0,7%, pozitivan
H-FABP u odnosu na negativan P<0,001). Stratifikacija prema TnI rezultirala je pojavom
smrtnosti od 19,7% (13 od 66) među TnI-pozitivnim pacijentima i 3,2% među onima koji su
bili TnI-negativni (3 od 95; P=0,001). U ehokardiografiji, ispitanici s pozitivnim H-FABP
pokazali su značajno veće RV/LV indekse u usporedbi s H-FABP negativnima (1,02 ± 0,21 u
odnosu na 0,86 ± 0,22; P=0,001) i značajno niži TAPSE (13,7 ± 4,0 mm nasuprot 19,1 ± 4,7
mm; P<0,001). Nije bilo značajnih razlika za mTDI parametre. Multivarijantnom logističkom
regresijskom analizom utvrđeni su H-FABP (OR=27,1; 95% CI 2,1 - 352,3), CK-MB (OR=5,3;
95% CI 1,3 - 23,3) i sistolički krvni tlak pri prijemu (OR=1,2 95% CI 1,1 - 1.3) kao neovisni
prediktori 30-dnevne smrtnosti. Kombinacija pozitivnog H-FABP testa i povišenog CK-MB
rezultirala je s posebno visokim rizikom od smrtnosti: umrlo je 14 od 16 bolesnika s ovom
kombinacijom laboratorijskih nalaza (87,5%). Suprotno tome, vjerojatnost preživljavanja
bolesnika s negativnim H-FABP testom iznosila je preko 99%.
Zabilježen je povećan rizik od kompliciranog kliničkog tijeka u bolesnika s pozitivnim HFABP testom (OR=4,8; 95% CI 1,1- 21,1) i smanjenim TAPSE (OR=1,3; 95% CI 1,2 - 1,5).
Bolesnici s vrijednostima TAPSE iznad 17,5 mm imali su nekompliciran tijek bolesti u 98%
slučajeva.
Zaključak
Naši podaci podržavaju hipotezu da bi H-FABP mogao biti obećavajući prognostički biljeg za
plućnu emboliju s intermedijarnim rizikom jer je snažno povezan s nepovoljnim kratkoročnim
ishodom. Čini se da je njegova klinička vrijednost u stratifikaciji rizika veća od srčanih
troponina. Kombinacija povišene razine H-FABP i CK-MB u plazmi ukazuje na posebno visok
rizik od smrtnog ishoda. Klinička vrijednost CK-MB u stratifikaciji rizika od plućne embolije
je nejasna i moguće podcijenjena te su potrebne daljnje studije. Povećane vrijednosti H-FABP
koreliraju s ultrazvučnim markerima disfunkcije desne klijetke. MTDI nije pogodan za
stratifikaciju rizika u ovoj skupini bolesnika. Potrebne su dodatne studije kako bi se utvrdilo
koji su ultrazvučni parametri najkorisniji za procjenu rizika za smrtni ishod u bolesnika s
akutnom plućnom embolijom srednjeg rizika
Razlike u fibrozi atrija po dobi i spolu među pacijentima s atrijskom fibrilacijom
Aim: Age and female sex are associated with a higher risk of stroke in atrial fibrillation (AF).
We sought to determine whether advancing age and female sex are associated with higher atrial
fibrosis.
Methods and results: We conducted an observational cohort study of patients with AF enrolled
in the University of Utah AF Database and a non-AF control group who underwent lategadolinium enhancement magnetic resonance imaging (LGE-MRI) for atrial fibrosis
quantification. Participants with contraindications for contrast MRI scanning were excluded.
Nine hundred and eight consecutive men and women with AF and 15 non-AF controls were
included in this study. Left atrial fibrosis increased with age in both men and women with AF.
Women with AF (n = 316) were older than men (n = 592): mean age 68.7±11.6 vs. 64.9±11.7
years; P < 0.01, and had higher left atrial fibrosis compared with men 17.5 ± 10.1% vs. 15.3 ±
8.9%; P < 0.001. Women also had a higher prevalence of prior stroke than men (15.8% vs.
6.5%; P < 0.001). Age and sex relationships with atrial fibrosis remained significant in
multivariate analysis. Compared with the non-AF control group, patients with AF they had
significantly higher atrial fibrosis: 16.0 ± 9.4 vs. 5.5 ± 5.8%; P < 0.001.
Conclusions: Advancing age and female sex are associated with a higher burden of atrial
fibrosis in patients with AF. Women with a prior history of stroke also have higher fibrosis
than women and men without a history of stroke. Advanced fibrosis may explain the female
and age association with stroke in AF.Cilj: Dob i ženski spol povezani su s većim rizikom za moždani udar u osoba s atrijskom
fibrilacijom (AF). Željeli smo utvrditi jesu li starija životna dob i ženski spol povezani s višom
razinom fibroze atrija.
Metode i rezultati: Proveli smo kohortnu studiju u koju smo uključili pacijente s AF koji su
bili upisani u bazu podataka na Sveučilištu Utah i kontrolnu skupinu bez AF, koja je
podvrgnuta magnetskoj rezonanciji s kasnim gadolinijskim kontrastnim pojačanjem prikaza
(engl. late-gadolinium enhancement magnetic resonance imaging, LGE-MRI) radi određivanja
atrijske fibroze. Osobe s kontraindikacijama za LGE-MRI pretragu su bile isključene. Devet
stotina i osam uzastopnih ispitanika muškog i ženskog spola s AF i 15 kontrola bez AF-a bilo
je uključeno u ovo istraživanje. Fibroza lijevog atrija se povećavala s dobi i kod muškaraca i
kod žena s AF. Žene s AF (n=316) bile su starije od muškaraca (n=592), s prosječnom dobi od
68,7 godina ± 11,6 u odnosu na 64,9 ± 11,7 godina u muškaraca (P<0,001) te su imale višu
razinu fibroze lijevog atrija u usporedbi s muškarcima (17,5 ± 10,1% nasuprot 15,3 ± 8,9%;
P<0,001). Žene su također imale veću prevalenciju prethodnog moždanog udara u usporedbi s
muškarcima (15,8% nasuprot 6,5%; P<0,001). Dob i spol bili su prediktori atrijske fibroze u
multivarijatnoj analizi. U usporedbi s kontrolnom skupinom koja nema AF, pacijenti s AF imali
su značajno višu razinu atrijske fibroze (16,0 ± 9,4 naspram 5,5 ± 5,8%; P<0,001).
Zaključci: Starija životna dob i ženski spol povezani su s većim teretom atrijske fibroze kod
pacijenata s AF. Žene koje imaju prethodni moždani udar također imaju i veću razinu atrijske
fibroze u usporedbi sa ženama i muškarcima koji nisu imali moždani udar. Uznapredovala
fibroza može objasniti povezanost između ženskog spola i starije životne dobi s moždanim
udarom kod AF
Transkriptom-Analyse zirkulierender Monozyten zur Erforschung neuer Marker/Mediatoren akzelerierter Atherosklerose bei Hämodialyse-Patienten
INTRODUCTION AND AIMS: Traditional risk factors of atherosclerosis inadequately explain the increased cardiovascular mortality in hemodialysis (HD) patients. Observations in humans and animal experiments underscore the pivotal role of the monocyte/macrophage system in the pathogenesis of atherosclerosis. Since circulating monocytes may serve as easily accessible reporters of vascular disease, we compared the transcriptomes of purified monocytes in HD patients and controls to search for new markers and potential mediators of atherosclerosis in HD patients.METHODS: Sequential monocyte purification via lymphoflot gradient centrifugation and CD14 bead separation was performed in 39 HD-patients (age: 65+13 years, HD-duration: 3,5 + 2,7 years, coronary artery disease (CAD): present: 21; absent 18) at the beginning of a HD session following a long interval and after 3h of hemodialysis. 30 age-matched healthy individuals served as controls (no coronary or peripheral artery disease, no diabetes, no continuous medication). To avoid pleiotropic effects of erythropoietin on monocytes all HD patients were off erythropoietin for more than 3 month. The amount and integrity of isolated RNA was checked using Agilentcapillary electrophoresis. 5 g of pooled RNA were hybridized on a GeneChip(U133 Plus 2.0). Differentially expressed genes were validated using absolute quantitative realtime PCR on the individual level. Serum clinical chemistry included serum levels of CRP, calcium, phosphate, PTH, ferritin, albumin, creatinine and a differential blood count.RESULTS: GeneChip-based analysis revealed about 33.000 transcripts expressed in circulating monocytes. Focussing on altered gene expression by a factor greater +/- 3 we detected 105 differentially regulated transcripts between controls and HD patients at the start of a hemodialysis session. This number increased to 469 genes after 3 hours of hemodialysis. Hitherto, we validated the pooled array results on the individual patient level focussing on differentially regulated genes between controls and patients at the start of hemodialysis with known function. Up to now we screened 16 differentially regulated transcripts on the individual patient level and identified 6 candidate genes discriminating between HD patients with CAD and controls: (HD-CAD vs. control, median [copies/1Mio18S; *T-test): cyclooxygenase2 (72 vs. 163; *<0.01); cannabinoid receptor 1 (1.1 vs. 0.27; *<0.01); interleukin-7 receptor (19 vs. 9; *<0.05); retinoic acid receptor-alpha (518 vs. 397; *<0.05); tissue factor (0.47 vs. 0.16; +<0.05); toll-like receptor 4 (1271 vs. 876; *<0.05).CONCLUSIONS: Our results suggest that transcriptome analysis of gene expression in circulating monocytes may provide a tool to detect new markers of atherosclerosis in HD patients. The potential pathomechanistic relevance in the context of accelerated atherosclerosis in the HD population is currently explored using functional in vitro studies
Fetuin-A-Serum-Spiegel und kardiovaskuläre Mortalität bei Dialysepatienten : eine Querschnittsuntersuchung
Fetuin-A als Risikomarker bei Patienten mit Niereninsuffizienz : Nephelometrie als neues Nachweisverfahren bei Risikokollektiven
The cardiovascular mortality rate in the dialysis population is dramatically increased compared to the population without renal failure. This increased mortality rate occurs because of so called "accelerated artherosclerosis", which is partially attributed to the increased calcium-phosphate-product and hyperphosphatemia in the serum. The calcification inhibiting protein ahsg/fetuin-a accounts for 50% of the precipitation inhibitory effect in serum and acts in vivo and in vitro. Additionally ahsg/fetuin-a is a negative acute phase protein whose concentration is downregulated during acute or chronic inflammation. In this context it has recently been shown that the ashg/fetuin-a concentration is significantly decreased in the dialysis population in contrast to non-renal patients correlating with a higher risk of cardiovascular and overall mortality. A decreased ahsg/fetuin-a concentration in serum is now considered to be a new important cardiovascular risk factor in the dialysis population.In the past the detection of ahsg/fetiun-a was achieved via ELISA (enzyme linked immuno sorbent assay), which due to the high dilution factors involved has been shown to be very inaccurate. By developing nepholomerty to measure ahsg/fetuin-a as outlined in this paper we have successeded to establish a robust risk factor screening methodology.Nephelometry was established in the following steps:1.determination of an appropriate antibody2.setting the optimal level of dilution3.selection of the appropiate standard serum4.vertification of the results with westenblot analysis5.exemplarly measurement of control groupsNephelometry has been proven to be a very stable measuring technique, which can be performed with a significantly higher accuracy than the previously used ELISA test. It is less time consuming (one sample can be measured in 5 minutes) and due to the much lower level of dilutions it is also less susceptible to inaccuracy. In the future it would be useful to transform the nepholometry test to an automized machine that can measure multiple samples at once instead of doing single sample measurements as undertaken in this study
Kliničke koristi i prognostička vrijednost proteina koji veže masne kiseline srčanog tipa, miokardijalne kreatin kinaze i specifičnih ehokardiografskih parametara desne klijetke za stratifikaciju rizika normotenzivnih bolesnika s plućnom embolijom
The treatment of acute pulmonary artery embolism remains a challenge for modern medicine.
While the risk-adapted treatment strategies for the groups with high and low mortality risk are
essentially uncontroversial, uncertainty remains in patients with intermediate risk PE about the
appropriate risk stratification and management. Despite therapy, the mortality rate of this form
of pulmonary embolism is about 5-16%. It is possible that current concepts for risk
stratification, based on the use and combination of troponin I (TnI) with imaging techniques
such as echocardiography, only transfer to this patient group in limited capacity. Therefore,
clinical research is increasingly focusing on other cardiac-specific biomarkers, such as cardiac
muscle-specific fatty acid binding protein (H-FABP), which is already being used successfully
in early-stage cardiac infarction diagnostics.
Aim of the study
The present study investigates the prognostic value of new myocardial laboratory markers as
well as specific right ventricular echo parameters and contributes to risk stratification in PE
with intermediate mortality risk.
Material and Methods
Between 2005 and 2010, 161 patients with proven PE and an initial systolic blood pressure
above 90 mmHg were enrolled. All patients underwent TnI, creatine kinase isoenzyme MB
(CK-MB), CK and D-dimers determination at the routine cardiology laboratory. All patients
continued to receive a commercially available qualitative H-FABP rapid test (threshold 7
ng/ml). The routine echocardiographic examination with measurement of ventricular size ratios
(RV/LV index), the mTDI parameters, the TAPSE and other standard parameters took place on
the admission day. An intermediate mortality risk was based on the guidelines for
echocardiographic signs of right ventricular dysfunction (RVD) or elevated cardiac muscle
specific laboratory parameters. The primary endpoint was the 30-day mortality due to PE. The
secondary endpoint was the occurrence of a complicated clinical course, defined by therapy
escalation in the form of catecholamine administration, thrombolysis or embolectomy or
resuscitation.
Results
In total, 16 out of 161 (9.9%) patients died within 30 days after hospital admission. The
deceased had significantly higher plasma levels of TnI, and CK-MB compared to survivors. A positive H-FABP test was found in 26 patients, of whom 15 (57.7%) died. In contrast, one of
135 H-FABP-negative patients died (0.7%, H-FABP positive vs. negative P <0.001).
Stratification according to TnI resulted in a mortality rate of 19.7% (13 out of 66) among TnIpositive patients and 3.2% among those that were TnI-negative (3 out of 95, P = 0.001). In
echocardiography, H-FABP positives exhibited significantly greater RV/LV indices (1.02 ±
0.21 vs. 0.86 ± 0.22, P = 0.001) compared to H-FABP negatives, and a significantly lower
TAPSE (13.7 ± 4.0 mm vs. 19.1 ± 4.7 mm, P <0.001). There were no significant differences
for the mTDI parameters. Multivariate logistic regression analysis identified H-FABP (OR 27.1
95% CI 2.1 - 352.3), CK-MB (OR 5.3 95% CI 1.3 - 23.3) and the systolic blood pressure on
admisson (OR 1.2 95% CI 1.1 - 1.3) as independent predictors of 30-day mortality. The
combination of positive H-FABP test and increased CK-MB resulted in a particularly high
mortality risk: 14 of 16 patients with this laboratory constellation (87.5%) died. Conversely,
the survival probability of H-FABP-negative patients was over 99%.
There was an increased risk of a complicated clinical course with a positive H-FABP test
(OR 4.8 95% CI 1.1 - 21.1) and reduced TAPSE (OR 1.3 95% CI 1.2 - 1.5). TAPSE values
above 17.5mm made a complicated course unlikely in 98% of the cases.
Conclusion
Our data support the hypothesis that H-FABP could be a promising prognostic marker in
intermediate risk PE being highly associated with an unfavorable short-term outcome. Its
clinical value in risk stratification seems to be superior to that of cardiac troponins. The
combination of elevated H-FABP and CK-MB plasma levels indicates a particularly high risk
of mortality. The clinical value of CK-MB in risk stratification of PE is unclear and might be
underestimated and further studies are required. Increased H-FABP values correlate with
echocardiographic markers of RVD. MTDI is not suitable for risk stratification in this patient
group. Additional studies are necessary to identify which specific echocardiographic
parameters are the most useful in risk assessment in acute PE with intermediate risk mortality.Liječenje akutne embolije plućne arterije i dalje ostaje izazov za suvremenu medicinu. Iako su
strategije liječenja prilagođene riziku za skupine s visokim i niskim rizikom od smrtnosti u
osnovi nesporne, kod bolesnika sa srednjim rizikom za plućnu emboliju ostaje neizvjesnost o
odgovarajućoj stratifikaciji rizika i zbrinjavanja pacijenta. Unatoč terapiji, stopa smrtnosti od
ovog oblika plućne embolije je oko 5-16%. Moguće je da se trenutni koncepti za stratifikaciju
rizika, temeljeni na upotrebi i kombinaciji troponina I (TnI) s tehnikama slikovnog prikaza,
poput ehokardiografije, prenose na ovu grupu bolesnika u ograničenom kapacitetu. Stoga se
klinička istraživanja sve više fokusiraju na druge specifične srčane biomarkere, poput srčanomišićnog proteina koji veže masne kiseline (H-FABP), koji se već uspješno koristi u ranoj fazi
dijagnostičkog postupka srčanog infarkta.
Cilj studije
Ova studija istražuje prognostičku vrijednost novih laboratorijskih markera miokarda, kao i
specifične parametre ultrazvuka desnog ventrikula te doprinosi stratifikaciji rizika u pacijenata
s plućnom embolijom sa srednjim rizikom smrtnosti.
Materijali i metode
Između 2005. i 2010. godine u istraživanje je uključeno 161 pacijenta s dokazanom plućnom
ebmolijom i početnim sistoličkim krvnim tlakom većim od 90 mmHg. Za sve pacijente
provedeno je mjerenje TnI, kreatin kinaze MB (CK-MB), CK i D-dimera u laboratoriju za
rutinsku kardiologiju. Kod svih bolesnika učinjen je komercijalno dostupan kvalitativni brzi
test H-FABP (prag osjetljivosti od 7 ng/ml). Rutinski ultrazvučni pregled s mjerenjem omjera
veličine ventrikula (RV/LV indeks), mTDI parametrima, TAPSE i drugim standardnim
parametrima obavljen je na dan prijema. Definicija srednje razine rizika od smrtnog ishoda
zasnovana je na smjernicama za ultrazvučne znakove disfunkcije desne klijetke (RVD) ili na
povišenim vrijednostima specifičnih laboratorijskih parametara za srčani mišić. Primarni
promatrani ishod bila je smrtnost unutar 30 dana zbog plućne embolije. Sekundarni promatrani
ishod bila je pojava kompliciranog kliničkog tijeka, definiranog eskalacijom terapije u obliku
primjene kateholamina, trombolize ili embolektomije ili reanimacije.
Rezultati
Ukupno je 16 od 161 (9,9%) bolesnika umrlo u roku od 30 dana nakon prijema u bolnicu.
Ispitanici koji su preminuli imali su značajno više razine TnI i CK-MB u plazmi, u usporedbi s preživjelima. Pozitivan test H-FABP pronađen je kod 26 bolesnika, od kojih je njih 15 (57,7%)
umrlo. Suprotno tome, jedan od 135 bolesnika s negativnim H-FABP je umro (0,7%, pozitivan
H-FABP u odnosu na negativan P<0,001). Stratifikacija prema TnI rezultirala je pojavom
smrtnosti od 19,7% (13 od 66) među TnI-pozitivnim pacijentima i 3,2% među onima koji su
bili TnI-negativni (3 od 95; P=0,001). U ehokardiografiji, ispitanici s pozitivnim H-FABP
pokazali su značajno veće RV/LV indekse u usporedbi s H-FABP negativnima (1,02 ± 0,21 u
odnosu na 0,86 ± 0,22; P=0,001) i značajno niži TAPSE (13,7 ± 4,0 mm nasuprot 19,1 ± 4,7
mm; P<0,001). Nije bilo značajnih razlika za mTDI parametre. Multivarijantnom logističkom
regresijskom analizom utvrđeni su H-FABP (OR=27,1; 95% CI 2,1 - 352,3), CK-MB (OR=5,3;
95% CI 1,3 - 23,3) i sistolički krvni tlak pri prijemu (OR=1,2 95% CI 1,1 - 1.3) kao neovisni
prediktori 30-dnevne smrtnosti. Kombinacija pozitivnog H-FABP testa i povišenog CK-MB
rezultirala je s posebno visokim rizikom od smrtnosti: umrlo je 14 od 16 bolesnika s ovom
kombinacijom laboratorijskih nalaza (87,5%). Suprotno tome, vjerojatnost preživljavanja
bolesnika s negativnim H-FABP testom iznosila je preko 99%.
Zabilježen je povećan rizik od kompliciranog kliničkog tijeka u bolesnika s pozitivnim HFABP testom (OR=4,8; 95% CI 1,1- 21,1) i smanjenim TAPSE (OR=1,3; 95% CI 1,2 - 1,5).
Bolesnici s vrijednostima TAPSE iznad 17,5 mm imali su nekompliciran tijek bolesti u 98%
slučajeva.
Zaključak
Naši podaci podržavaju hipotezu da bi H-FABP mogao biti obećavajući prognostički biljeg za
plućnu emboliju s intermedijarnim rizikom jer je snažno povezan s nepovoljnim kratkoročnim
ishodom. Čini se da je njegova klinička vrijednost u stratifikaciji rizika veća od srčanih
troponina. Kombinacija povišene razine H-FABP i CK-MB u plazmi ukazuje na posebno visok
rizik od smrtnog ishoda. Klinička vrijednost CK-MB u stratifikaciji rizika od plućne embolije
je nejasna i moguće podcijenjena te su potrebne daljnje studije. Povećane vrijednosti H-FABP
koreliraju s ultrazvučnim markerima disfunkcije desne klijetke. MTDI nije pogodan za
stratifikaciju rizika u ovoj skupini bolesnika. Potrebne su dodatne studije kako bi se utvrdilo
koji su ultrazvučni parametri najkorisniji za procjenu rizika za smrtni ishod u bolesnika s
akutnom plućnom embolijom srednjeg rizika
Consensus-Based Recommendations for the Diagnosis, Treatment, and Monitoring of Hypoparathyroidism: Insights from the DACH Region
Abstract Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by low parathyroid hormone (PTH) levels, hypocalcemia, hyperphosphatemia, reduced active vitamin D (1,25-OH2 vitamin D), and hypercalciuria. Due to its rarity, non-specialized physicians often lack experience managing HypoPT. To address this, expert consensus statements were developed for the DACH region (Germany, Austria, Switzerland), considering regional differences and high HypoPT incidence. These statements aim to enhance adherence to guideline recommendations and improve non-specialist knowledge. From December 2023 to April 2024, three rounds of a Delphi consensus survey were conducted with seven DACH-region clinical experts. Consensus was defined as agreement among at least 6 of 7 participants (85%). Experts agreed surgery accounts for 90% of chronic HypoPT cases. Common symptoms include paresthesia, muscle cramps, and fatigue. Albumin-adjusted serum calcium should be measured 12–24 h post-surgically, within 2 weeks, and every 3–6 months thereafter. Key treatment goals are maintaining albumin-adjusted serum calcium in the lower normal range, symptom control, and quality of life. Long-term objectives include avoiding hypo- and hypercalcemia phases and disease-related complications. Failure of calcium and active vitamin D therapy is defined by persistent symptoms, hospitalization, laboratory values outside of the normal range, or medication intolerance. Experts emphasized using HypoPT-specific, validated quality-of-life questionnaires. This consensus provides practical guidance for non-specialists in diagnosing, treating, and monitoring HypoPT, improving care in German-speaking regions
Kliničke koristi i prognostička vrijednost proteina koji veže masne kiseline srčanog tipa, miokardijalne kreatin kinaze i specifičnih ehokardiografskih parametara desne klijetke za stratifikaciju rizika normotenzivnih bolesnika s plućnom embolijom
The treatment of acute pulmonary artery embolism remains a challenge for modern medicine.
While the risk-adapted treatment strategies for the groups with high and low mortality risk are
essentially uncontroversial, uncertainty remains in patients with intermediate risk PE about the
appropriate risk stratification and management. Despite therapy, the mortality rate of this form
of pulmonary embolism is about 5-16%. It is possible that current concepts for risk
stratification, based on the use and combination of troponin I (TnI) with imaging techniques
such as echocardiography, only transfer to this patient group in limited capacity. Therefore,
clinical research is increasingly focusing on other cardiac-specific biomarkers, such as cardiac
muscle-specific fatty acid binding protein (H-FABP), which is already being used successfully
in early-stage cardiac infarction diagnostics.
Aim of the study
The present study investigates the prognostic value of new myocardial laboratory markers as
well as specific right ventricular echo parameters and contributes to risk stratification in PE
with intermediate mortality risk.
Material and Methods
Between 2005 and 2010, 161 patients with proven PE and an initial systolic blood pressure
above 90 mmHg were enrolled. All patients underwent TnI, creatine kinase isoenzyme MB
(CK-MB), CK and D-dimers determination at the routine cardiology laboratory. All patients
continued to receive a commercially available qualitative H-FABP rapid test (threshold 7
ng/ml). The routine echocardiographic examination with measurement of ventricular size ratios
(RV/LV index), the mTDI parameters, the TAPSE and other standard parameters took place on
the admission day. An intermediate mortality risk was based on the guidelines for
echocardiographic signs of right ventricular dysfunction (RVD) or elevated cardiac muscle
specific laboratory parameters. The primary endpoint was the 30-day mortality due to PE. The
secondary endpoint was the occurrence of a complicated clinical course, defined by therapy
escalation in the form of catecholamine administration, thrombolysis or embolectomy or
resuscitation.
Results
In total, 16 out of 161 (9.9%) patients died within 30 days after hospital admission. The
deceased had significantly higher plasma levels of TnI, and CK-MB compared to survivors. A positive H-FABP test was found in 26 patients, of whom 15 (57.7%) died. In contrast, one of
135 H-FABP-negative patients died (0.7%, H-FABP positive vs. negative P <0.001).
Stratification according to TnI resulted in a mortality rate of 19.7% (13 out of 66) among TnIpositive patients and 3.2% among those that were TnI-negative (3 out of 95, P = 0.001). In
echocardiography, H-FABP positives exhibited significantly greater RV/LV indices (1.02 ±
0.21 vs. 0.86 ± 0.22, P = 0.001) compared to H-FABP negatives, and a significantly lower
TAPSE (13.7 ± 4.0 mm vs. 19.1 ± 4.7 mm, P <0.001). There were no significant differences
for the mTDI parameters. Multivariate logistic regression analysis identified H-FABP (OR 27.1
95% CI 2.1 - 352.3), CK-MB (OR 5.3 95% CI 1.3 - 23.3) and the systolic blood pressure on
admisson (OR 1.2 95% CI 1.1 - 1.3) as independent predictors of 30-day mortality. The
combination of positive H-FABP test and increased CK-MB resulted in a particularly high
mortality risk: 14 of 16 patients with this laboratory constellation (87.5%) died. Conversely,
the survival probability of H-FABP-negative patients was over 99%.
There was an increased risk of a complicated clinical course with a positive H-FABP test
(OR 4.8 95% CI 1.1 - 21.1) and reduced TAPSE (OR 1.3 95% CI 1.2 - 1.5). TAPSE values
above 17.5mm made a complicated course unlikely in 98% of the cases.
Conclusion
Our data support the hypothesis that H-FABP could be a promising prognostic marker in
intermediate risk PE being highly associated with an unfavorable short-term outcome. Its
clinical value in risk stratification seems to be superior to that of cardiac troponins. The
combination of elevated H-FABP and CK-MB plasma levels indicates a particularly high risk
of mortality. The clinical value of CK-MB in risk stratification of PE is unclear and might be
underestimated and further studies are required. Increased H-FABP values correlate with
echocardiographic markers of RVD. MTDI is not suitable for risk stratification in this patient
group. Additional studies are necessary to identify which specific echocardiographic
parameters are the most useful in risk assessment in acute PE with intermediate risk mortality.Liječenje akutne embolije plućne arterije i dalje ostaje izazov za suvremenu medicinu. Iako su
strategije liječenja prilagođene riziku za skupine s visokim i niskim rizikom od smrtnosti u
osnovi nesporne, kod bolesnika sa srednjim rizikom za plućnu emboliju ostaje neizvjesnost o
odgovarajućoj stratifikaciji rizika i zbrinjavanja pacijenta. Unatoč terapiji, stopa smrtnosti od
ovog oblika plućne embolije je oko 5-16%. Moguće je da se trenutni koncepti za stratifikaciju
rizika, temeljeni na upotrebi i kombinaciji troponina I (TnI) s tehnikama slikovnog prikaza,
poput ehokardiografije, prenose na ovu grupu bolesnika u ograničenom kapacitetu. Stoga se
klinička istraživanja sve više fokusiraju na druge specifične srčane biomarkere, poput srčanomišićnog proteina koji veže masne kiseline (H-FABP), koji se već uspješno koristi u ranoj fazi
dijagnostičkog postupka srčanog infarkta.
Cilj studije
Ova studija istražuje prognostičku vrijednost novih laboratorijskih markera miokarda, kao i
specifične parametre ultrazvuka desnog ventrikula te doprinosi stratifikaciji rizika u pacijenata
s plućnom embolijom sa srednjim rizikom smrtnosti.
Materijali i metode
Između 2005. i 2010. godine u istraživanje je uključeno 161 pacijenta s dokazanom plućnom
ebmolijom i početnim sistoličkim krvnim tlakom većim od 90 mmHg. Za sve pacijente
provedeno je mjerenje TnI, kreatin kinaze MB (CK-MB), CK i D-dimera u laboratoriju za
rutinsku kardiologiju. Kod svih bolesnika učinjen je komercijalno dostupan kvalitativni brzi
test H-FABP (prag osjetljivosti od 7 ng/ml). Rutinski ultrazvučni pregled s mjerenjem omjera
veličine ventrikula (RV/LV indeks), mTDI parametrima, TAPSE i drugim standardnim
parametrima obavljen je na dan prijema. Definicija srednje razine rizika od smrtnog ishoda
zasnovana je na smjernicama za ultrazvučne znakove disfunkcije desne klijetke (RVD) ili na
povišenim vrijednostima specifičnih laboratorijskih parametara za srčani mišić. Primarni
promatrani ishod bila je smrtnost unutar 30 dana zbog plućne embolije. Sekundarni promatrani
ishod bila je pojava kompliciranog kliničkog tijeka, definiranog eskalacijom terapije u obliku
primjene kateholamina, trombolize ili embolektomije ili reanimacije.
Rezultati
Ukupno je 16 od 161 (9,9%) bolesnika umrlo u roku od 30 dana nakon prijema u bolnicu.
Ispitanici koji su preminuli imali su značajno više razine TnI i CK-MB u plazmi, u usporedbi s preživjelima. Pozitivan test H-FABP pronađen je kod 26 bolesnika, od kojih je njih 15 (57,7%)
umrlo. Suprotno tome, jedan od 135 bolesnika s negativnim H-FABP je umro (0,7%, pozitivan
H-FABP u odnosu na negativan P<0,001). Stratifikacija prema TnI rezultirala je pojavom
smrtnosti od 19,7% (13 od 66) među TnI-pozitivnim pacijentima i 3,2% među onima koji su
bili TnI-negativni (3 od 95; P=0,001). U ehokardiografiji, ispitanici s pozitivnim H-FABP
pokazali su značajno veće RV/LV indekse u usporedbi s H-FABP negativnima (1,02 ± 0,21 u
odnosu na 0,86 ± 0,22; P=0,001) i značajno niži TAPSE (13,7 ± 4,0 mm nasuprot 19,1 ± 4,7
mm; P<0,001). Nije bilo značajnih razlika za mTDI parametre. Multivarijantnom logističkom
regresijskom analizom utvrđeni su H-FABP (OR=27,1; 95% CI 2,1 - 352,3), CK-MB (OR=5,3;
95% CI 1,3 - 23,3) i sistolički krvni tlak pri prijemu (OR=1,2 95% CI 1,1 - 1.3) kao neovisni
prediktori 30-dnevne smrtnosti. Kombinacija pozitivnog H-FABP testa i povišenog CK-MB
rezultirala je s posebno visokim rizikom od smrtnosti: umrlo je 14 od 16 bolesnika s ovom
kombinacijom laboratorijskih nalaza (87,5%). Suprotno tome, vjerojatnost preživljavanja
bolesnika s negativnim H-FABP testom iznosila je preko 99%.
Zabilježen je povećan rizik od kompliciranog kliničkog tijeka u bolesnika s pozitivnim HFABP testom (OR=4,8; 95% CI 1,1- 21,1) i smanjenim TAPSE (OR=1,3; 95% CI 1,2 - 1,5).
Bolesnici s vrijednostima TAPSE iznad 17,5 mm imali su nekompliciran tijek bolesti u 98%
slučajeva.
Zaključak
Naši podaci podržavaju hipotezu da bi H-FABP mogao biti obećavajući prognostički biljeg za
plućnu emboliju s intermedijarnim rizikom jer je snažno povezan s nepovoljnim kratkoročnim
ishodom. Čini se da je njegova klinička vrijednost u stratifikaciji rizika veća od srčanih
troponina. Kombinacija povišene razine H-FABP i CK-MB u plazmi ukazuje na posebno visok
rizik od smrtnog ishoda. Klinička vrijednost CK-MB u stratifikaciji rizika od plućne embolije
je nejasna i moguće podcijenjena te su potrebne daljnje studije. Povećane vrijednosti H-FABP
koreliraju s ultrazvučnim markerima disfunkcije desne klijetke. MTDI nije pogodan za
stratifikaciju rizika u ovoj skupini bolesnika. Potrebne su dodatne studije kako bi se utvrdilo
koji su ultrazvučni parametri najkorisniji za procjenu rizika za smrtni ishod u bolesnika s
akutnom plućnom embolijom srednjeg rizika
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