Publications by authors named "Kasper Karmark Iversen"

38 Publications

Gestational Age and Neonatal Electrocardiograms.

Pediatrics 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.

Objectives: Interpretation of the neonatal electrocardiogram (ECG) is challenging due to the profound changes of the cardiovascular system in this period. We aimed to investigate the impact of gestational age (GA) on the neonatal ECG and create GA-specific reference values.

Methods: The Copenhagen Baby Heart Study is a prospective general population study that offered cardiac evaluation of neonates. ECGs and echocardiograms were obtained and systematically analyzed. GA, weight, height, and other baseline variables were registered.

Results: We included 16 462 neonates (52% boys) with normal echocardiograms. The median postnatal age was 11 days (range 0 to 30), and the median GA was 281 days (range 238 to 301). Analyzing the ECG parameters as a function of GA, we found an effect of GA on almost all investigated ECG parameters. The largest percentual effect of GA was on heart rate (HR; 147 vs 139 beats per minute), the QRS axis (103° vs 116°), and maximum R-wave amplitude in V1 (R-V1; 0.97 vs 1.19 mV) for GA ≤35 vs ≥42 weeks, respectively. Boys had longer PR and QRS intervals and a more right-shifted QRS axis within multiple GA intervals (all P < .01). The effect of GA generally persisted after multifactorial adjustment.

Conclusions: GA was associated with significant differences in multiple neonatal ECG parameters. The association generally persisted after multifactorial adjustment, indicating a direct effect of GA on the developing neonatal cardiac conduction system. For HR, the QRS axis, and R-V1, the use of GA-specific reference values may optimize clinical handling of neonates.
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http://dx.doi.org/10.1542/peds.2021-050942DOI Listing
November 2021

Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants.

Front Immunol 2021 7;12:757197. Epub 2021 Oct 7.

Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

The recent identification and rise to dominance of the P.1 and B.1.351 SARS-CoV-2 variants have brought international concern because they may confer fitness advantages. The same three positions in the receptor-binding domain (RBD) are affected in both variants, but where the 417 substitution differs, the E484K/N501Y have co-evolved by convergent evolution. Here we characterize the functional and immune evasive consequences of the P.1 and B.1.351 RBD mutations. E484K and N501Y result in gain-of-function with two different outcomes: The N501Y confers a ten-fold affinity increase towards ACE-2, but a modest antibody evasion potential of plasma from convalescent or vaccinated individuals, whereas the E484K displays a significant antibody evasion capacity without a major impact on affinity. On the other hand, the two different 417 substitutions severely impair the RBD/ACE-2 affinity, but in the combined P.1 and B.1.351 RBD variants, this effect is partly counterbalanced by the effect of the E484K and N501Y. Our results suggest that the combination of these three mutations is a two-step forward and one step back in terms of viral fitness.
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http://dx.doi.org/10.3389/fimmu.2021.757197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529273PMC
November 2021

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark.

Microbiol Spectr 2021 10 20;9(2):e0090421. Epub 2021 Oct 20.

Department of Clinical Research, Nordsjaellands Hospital, Hilleroed, Denmark.

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants' PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.
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http://dx.doi.org/10.1128/Spectrum.00904-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528102PMC
October 2021

"Global" cardiac atherosclerotic burden assessed by artificial intelligence-based versus manual segmentation in F-sodium fluoride PET/CT scans: Head-to-head comparison.

J Nucl Cardiol 2021 Aug 12. Epub 2021 Aug 12.

Department of Nuclear Medicine, Odense University Hospital, 5000, Odense C, Denmark.

Background: Artificial intelligence (AI) is known to provide effective means to accelerate and facilitate clinical and research processes. So in this study it was aimed to compare a AI-based method for cardiac segmentation in positron emission tomography/computed tomography (PET/CT) scans with manual segmentation to assess global cardiac atherosclerosis burden.

Methods: A trained convolutional neural network (CNN) was used for cardiac segmentation in F-sodium fluoride PET/CT scans of 29 healthy volunteers and 20 angina pectoris patients and compared with manual segmentation. Parameters for segmented volume (Vol) and mean, maximal, and total standardized uptake values (SUVmean, SUVmax, SUVtotal) were analyzed by Bland-Altman Limits of Agreement. Repeatability with AI-based assessment of the same scans is 100%. Repeatability (same conditions, same operator) and reproducibility (same conditions, two different operators) of manual segmentation was examined by re-segmentation in 25 randomly selected scans.

Results: Mean (± SD) values with manual vs. CNN-based segmentation were Vol 617.65 ± 154.99 mL vs 625.26 ± 153.55 mL (P = .21), SUVmean 0.69 ± 0.15 vs 0.69 ± 0.15 (P = .26), SUVmax 2.68 ± 0.86 vs 2.77 ± 1.05 (P = .34), and SUVtotal 425.51 ± 138.93 vs 427.91 ± 132.68 (P = .62). Limits of agreement were - 89.42 to 74.2, - 0.02 to 0.02, - 1.52 to 1.32, and - 68.02 to 63.21, respectively. Manual segmentation lasted typically 30 minutes vs about one minute with the CNN-based approach. The maximal deviation at manual re-segmentation was for the four parameters 0% to 0.5% with the same and 0% to 1% with different operators.

Conclusion: The CNN-based method was faster and provided values for Vol, SUVmean, SUVmax, and SUVtotal comparable to the manually obtained ones. This AI-based segmentation approach appears to offer a more reproducible and much faster substitute for slow and cumbersome manual segmentation of the heart.
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http://dx.doi.org/10.1007/s12350-021-02758-9DOI Listing
August 2021

Hemodialysis leads to plasma depletion of lectin complement pathway initiator molecule ficolin-2.

Hemodial Int 2021 Oct 16;25(4):479-488. Epub 2021 Jun 16.

Laboratory of Molecular Medicine, Department of Clinical Immunology, University of Copenhagen, Copenhagen, Denmark.

Introduction: This study aimed to investigate changes in complement system-related molecules in patients undergoing hemodialysis.

Methods: Patients >18 years of age on maintenance hemodialysis were included. Using enzyme-linked immunosorbent assays (ELISA) methods complement related molecules ficolin-1, ficolin-2, ficolin-3 mannose-binding lectin, long pentraxin 3, complement activation products C3c, and complement activation potentials were measured before and after a single hemodialysis treatment. All patients were dialyzed with synthetic high flux filters >1.6 m , respectively, Polyamix and Polysulfone, and the Kt/V was maintained >1.3.

Findings: Three hundred and four patients were included. There was a modest decrease in plasma level of ficolin-1 (p < 0.001). Ficolin-2 was virtually depleted with median 3.9 (interquartile range [IQR]: 2.6-6.1, range 0.3-13.5) μg/ml before dialysis to median 0.0 (IQR: 0.0-0.5, range 0.0-5.5) μg/ml after dialysis (p < 0.001). No significant difference before and after hemodialysis was seen for mannose-binding lectin and long pentraxin 3 (p > 0.05). In a random subgroup of 160 patients ficolin-2-binding, ficolin-3-mediated lectin pathway capacity and classical pathway capacity were significantly decreased due to hemodialysis. The complement capacity of the alternative pathway was increased after hemodialysis (p = 0.0101), while mannose-binding lectin-mediated lectin pathway capacity was unaltered (p = 0.79). There was an increase in the complement activation product C3c (p < 0.0001), while the concentration of total C4 and C3 did not change (p > 0.158). Multivariate Cox proportional hazard analyses showed an increased risk for all-cause mortality with increasing ficolin-2 (p = 0.002) after hemodialysis.

Discussion: Plasma ficolin-2 was virtually depleted from the circulation after hemodialysis. However, elevated plasma ficolin-2 levels after hemodialysis was independently associated with increased mortality.
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http://dx.doi.org/10.1111/hdi.12948DOI Listing
October 2021

Mid-regional pro-atrial natriuretic peptide levels before and after hemodialysis predict long-term prognosis.

Clin Biochem 2021 Aug 15;94:20-26. Epub 2021 Apr 15.

Department of Emergency Medicine, Herlev and Gentofte Hospital, Copenhagen, Denmark.

Background: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a strong prognostic biomarker in cardiovascular disease but there is limited data for its use among patients undergoing dialysis.

Methods: This was a cohort study of patients receiving maintenance hemodialysis from two Danish centers. Blood sampling and echocardiography were performed before and after a dialysis session. We calculated the area under the curve (AUC) for the receiver operating characteristics for diagnosing heart failure and Cox regressions for cardiovascular events and all-cause mortality.

Results: Of the 306 patients, 284 (93%) had MR-proANP measurements both before and after dialysis. Median concentration was 642 pmol/L (IQR 419-858) before and 351 pmol/L (IQR 197-537) after dialysis, a mean decrease of 330 pmol/L (43%, CI 296-364, P < 0.001). MR-proANP concentration both before and after dialysis was negatively correlated to left ventricular ejection fraction with no difference in predictive ability for heart failure, AUC before and after dialysis were 0.60 (CI 0.50-0.70) and 0.61 (CI 0.51-0.71) (P = 0.40). Median follow-up was 32 months (IQR 31-33), during which 99 patients (32%) had a cardiovascular event and 110 (36%) died. A doubling of MR-proANP concentration was associated with a hazard ratio (HR) of 1.6 (CI 1.3-1.9) before and 1.7 (CI 1.4-2.0) after dialysis for mortality and a HR of 1.5 (CI 1.2-1.9) before and 1.4 (CI 1.2-1.7) after dialysis for cardiovascular events (all P < 0.001).

Conclusion: The MR-proANP concentration is elevated among patients undergoing hemodialysis and decreases during dialysis. MR-proANP concentration both before, after and intra-dialysis change strongly predicted cardiovascular events and all-cause mortality.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.04.010DOI Listing
August 2021

The Evolution of the Neonatal QRS Axis during the First Four Weeks of Life.

Neonatology 2021 10;118(2):155-162. Epub 2021 Mar 10.

Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark,

Background: The QRS axis represents the sum and orientation of the ventricular depolarization. Accurate interpretation of abnormalities in the QRS axis may facilitate early diagnosis of heart disease in newborns. We aimed at describing the evolution of the QRS axis during the first 4 weeks of life and provide reference values from healthy newborns.

Methods: The Copenhagen Baby Heart Study is a prospective general population study that offered cardiac evaluation during the first month of life to all newborns delivered in the Copenhagen area.

Results: Electrocardiograms from 12,317 newborns (52% boys; mean age 12 days) with normal echocardiograms were included. The median QRS axis was 119° at the ages 0-7 days and shifted leftward to 102° at the ages 22-28 days (p < 0.001). We found that girls had a significantly less pronounced right-shifted axis than boys (p < 0.001) and that increasing gestational age (GA) was associated with a more pronounced right-shifted axis (p < 0.05). Infant size did not affect the axis (p > 0.05). Only 0.5% had an axis within the interval 0 to -90° and 1.1% in the interval +240 to +30°.

Conclusions: The QRS axis showed a gradual leftward-shift during the first 4 weeks of life and was affected by sex and GA but unaffected by infant size. Less than 1% of the newborns had a QRS axis between 0 and -90°. This study represents updated reference values, which may facilitate the clinical handling of newborns.
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http://dx.doi.org/10.1159/000513526DOI Listing
August 2021

Precordial ECG Amplitudes in the Days After Birth: Electrocardiographic Changes During Transition from Fetal to Neonatal Circulation.

Pediatr Cardiol 2021 Apr 28;42(4):832-839. Epub 2021 Jan 28.

Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Danmark.

During the first month of life, the relation between right and left ventricular function is markedly altered. We aimed at describing the electrocardiographic transition from fetal to neonatal circulation by investigating changes in R- and S-wave amplitudes in V1 and V6 during the first 4 weeks of life. This study is part of the prospective, population-based Copenhagen Baby Heart Study offering cardiac evaluation to newborns within 28 days from birth. ECGs were obtained and analyzed using a computerized algorithm. A total of 14,577 newborns (52% boys), median age of 11.0 days, were included. All had normal echocardiograms. Within 28 days from birth, the amplitudes in V1 decreased: R-V1 (1262 µV day0; 947 µV day28, p < 0.001) and S-V1 (1240 µV day0; 473 µV day28, p < 0.001). An increase was observed for R-V6 (825 µV day0; 1196 µV day28, p = 0.002), while S-V6 decreased (830 µV day0; 634 µV day28, p = 0.003). For all amplitudes, interindividual variation was large (up to 20 times). The amplitudes were not affected by sex (p > 0.05), but R-V1, R-V6, and S-V6 positively correlated with newborn weight (p < 0.01). R-V1 and S-V6 showed positive correlation with gestational age (p < 0.05). In conclusion, systematic analyses of ECGs from healthy newborns showed significant decreases in R-V1, S-V1, and S-V6 amplitudes, while R-V6 increased. Interindividual variation was large, making ECGs unlikely as a sensitive tool for diagnosing congenital heart diseases. Our data may serve as updated, digitalized reference values in newborns.
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http://dx.doi.org/10.1007/s00246-021-02547-8DOI Listing
April 2021

Atherosclerosis Imaging with F-Sodium Fluoride PET.

Diagnostics (Basel) 2020 Oct 20;10(10). Epub 2020 Oct 20.

Department of Nuclear Medicine, Odense University Hospital, 5000 Odense, Denmark.

The evidence on atherosclerosis imaging with F-sodium-fluoride (NaF) positron emission tomography (PET) is hotly debated because of the different patient characteristics, methodology, vascular beds, etc. in reported studies. This review is a continuation of a previous review on this topic, which covered the period 2010-2018. The purpose was to examine whether some of the most important questions that the previous review had left open had been elucidated by the most recent literature. Using principles of a systematic review, we ended analyzing 25 articles dealing with the carotids, coronary arteries, aorta, femoral, intracranial, renal, and penile arteries. The knowledge thus far can be summarized as follows: by targeting active arterial microcalcification, NaF uptake is considered a marker of early stage atherosclerosis, is age-dependent, and consistently associated with cardiovascular risk. Longitudinal studies on NaF uptake, conducted in the abdominal aorta only, showed unchanged uptake in postmenopausal women for nearly four years and varying uptake in prostate cancer patients over 1.5 years, despite constant or increasing calcium volume detected by computed tomography (CT). Thus, uncertainty remains about the transition from active arterial wall calcification marked by increased NaF uptake to less active or consolidated calcification detected by CT. The question of whether early-phase atherosclerosis and calcification can be modified remains also unanswered due to lack of intervention studies.
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http://dx.doi.org/10.3390/diagnostics10100852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590213PMC
October 2020

Defining the normal QT interval in newborns: the natural history and reference values for the first 4 weeks of life.

Europace 2021 02;23(2):278-286

Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, DK-2730 Herlev, Copenhagen, Denmark.

Aims: Evaluation of the neonatal QT interval is important to diagnose arrhythmia syndromes and evaluate side effects of drugs. We aimed at describing the natural history of the QT interval duration during the first 4 weeks of life and to provide reference values from a large general population sample.

Methods And Results: The Copenhagen Baby Heart Study is a prospective general population study that offered cardiac evaluation of newborns. Eight-lead electrocardiograms were obtained and analysed with a computerized algorithm with manual validation. We included 14 164 newborns (52% boys), aged 0-28 days, with normal echocardiograms. The median values (ms, 2-98%ile) for the corrected intervals QTc (Bazett), QTc (Hodges), QTc (Fridericia), and QTc (Framingham) were 419 (373-474), 419 (373-472), 364 (320-414), and 363 (327-405). During the 4 weeks, we observed a small decrease of QTcFramingham, and an increase of QTcHodges (both P < 0.01), while QTcBazett and QTcFridericia did not change (P > 0.05). Applying published QT interval cut-off values resulted in 5-25% of the newborns having QT prolongation. Uncorrected QT intervals decreased linearly with increasing heart rate (HR). Sex and infant size did not affect the QT interval and the gestational age (GA) only showed an effect when comparing the extreme low- vs. high GA groups (≤34 vs. ≥42 weeks, P = 0.021).

Conclusion: During the 4 weeks QTcFramingham and QTcHodges showed minor changes, whereas QTcBazett and QTcFridericia were stable. The QT interval was unaffected by sex and infant size and GA only showed an effect in very premature newborns. Reference values for HR-specific uncorrected QT intervals may facilitate a more accurate diagnosis of newborns with abnormal QT intervals.
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http://dx.doi.org/10.1093/europace/euaa143DOI Listing
February 2021

Risk for infective endocarditis in bacteremia with Gram positive cocci.

Infection 2020 Dec 25;48(6):905-912. Epub 2020 Aug 25.

Department of Cardiology, Herlev-Gentofte hospital, University of Copenhagen, Herlev Ringvej 75, Herlev, 2730, Copenhagen, Denmark.

Purpose: Infective endocarditis (IE) is a serious complication of bacteremia and is most often caused by Gram positive cocci. We investigated the prevalence of IE in patients where echocardiography was encouraged when bacteremia with Gram positive cocci was present.

Methods: The study included patients with Gram positive cocci bacteremia hospitalized at two Danish hospitals between March and December 2016. Information concerning echocardiography, demographics and bacterial species was collected from the patients' medical files. Patients without echocardiography were followed for 6 months in order to confirm or reject possible IE.

Results: The study included 585 patients with Gram positive cocci bacteremia, and echocardiography was performed in 414 (71%) of them. The prevalence of IE in patients with high risk bacteremia, i.e. Staphylococcus aureus, non-beta-hemolytic streptococci, Enterococcus faecalis, and coagulase-negative staphylococci was 16%. Patients with Enterococcus faecalis had the highest prevalence of IE (33%) followed by non-beta-hemolytic streptococci (23%) and Staphylococcus aureus (12%). Among low risk bacteremia the prevalence of IE was 1%. The mean age of patients with IE was 74 years (SD 12.9) and 71% were male.

Conclusion: These findings strongly support routine echocardiography in patients with high risk bacteremia and non-performance of echocardiography in patients with low risk bacteremia.
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http://dx.doi.org/10.1007/s15010-020-01504-6DOI Listing
December 2020

Prognostic value of 12 novel cardiological biomarkers in stable coronary artery disease. A 10-year follow-up of the placebo group of the Copenhagen CLARICOR trial.

BMJ Open 2020 08 20;10(8):e033720. Epub 2020 Aug 20.

The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Objective: To assess if 12 novel circulating biomarkers, when added to 'standard predictors' available in general practice, could improve the 10-year prediction of cardiovascular events and mortality in patients with stable coronary heart disease.

Design: The patients participated as placebo receiving patients in the randomised clarithromycin for patients with stable coronary artery disease (CLARICOR) trial at a random time in their disease trajectory.

Setting: Five Copenhagen University cardiology departments and a coordinating centre.

Participants: 1998 participants with stable coronary artery disease.

Outcomes: Death and composite of myocardial infarction, unstable angina pectoris, cerebrovascular disease and death.

Results: When only 'standard predictors' were included, 83.4% of all-cause death predictions and 68.4% of composite outcome predictions were correct. Log(calprotectin) and log(cathepsin-S) were not associated (p≥0.01) with the outcomes, not even as single predictors. Adding the remaining 10 biomarkers (high-sensitive assay cardiac troponin T; neutrophil gelatinase-associated lipocalin; osteoprotegerin; N-terminal pro-B-type natriuretic peptide; tumour necrosis factor receptor 1 and 2; pregnancy-associated plasma protein A; endostatin; YKL40; cathepsin-B), which were all individually significantly associated with the prediction of the two outcomes, increased the figures to 84.7% and 69.7%.

Conclusion: When 'standard predictors' routinely available in general practices are used for risk assessment in consecutively sampled patients with stable coronary artery disease, the addition of 10 novel biomarkers to the prediction model improved the correct prediction of all-cause death and the composite outcome by <1.5%.

Trial Registration Number: NCT00121550.
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http://dx.doi.org/10.1136/bmjopen-2019-033720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443269PMC
August 2020

Low-Dose Radiation to COVID-19 Patients to Ease the Disease Course and Reduce the Need of Intensive Care.

J Nucl Med 2020 12 3;61(12):1724-1725. Epub 2020 Jul 3.

Odense University Hospital Sdr. Boulevard 29 Odense C, 5000, Denmark E-mail:

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http://dx.doi.org/10.2967/jnumed.120.251892DOI Listing
December 2020

[First Danish case of Mycobacteriumchimaerainfection from cardiac surgery with contaminated heater-cooler unit].

Ugeskr Laeger 2020 06;182(26)

Infection with Mycobacterium chimaera has globally been linked to cardiac surgery using cardiopulmonary bypass devices with contaminated heater-cooler units (HCU). This is a case report of M. chimaera infection linked to HCU in Denmark in which we show, how difficult the diagnosis can be. A 67-year-old man had an aortic graft and valvular replacement using HCU. Post-operatively he developed progressing symptoms of intermittent fever, malaise and endocarditis with septic embolic events, and despite extensive diagnostic work-up, he remained undiagnosed for 16 months following surgery.
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June 2020

Clinical usefulness of FDG-PET/CT for identification of abnormal extra-cardiac foci in patients with infective endocarditis.

Int J Cardiovasc Imaging 2020 May 14;36(5):939-946. Epub 2020 Feb 14.

Department of Cardiology, Herlev Gentofte Hospital, Herlev Ringvej 75, 2730, Herlev, Denmark.

The aim of the study was to evaluate the ability to detect extra-cardiac foci by means of whole-body F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with definite endocarditis (IE) according to the modified Duke criteria and investigate the clinical impact of the findings. From January 2011 to December 2015 we included 178 patients (mean age 66 ± 14 years, 25% female) with IE in this multicentre study. FDG-PET/CT was part of the work-up for extra-cardiac foci in the including hospitals and was performed at a median of 9 days (IQR 10) after IE was diagnosed. In 114 patients FDG-PET/CT identified 166 lesions: 52 (31%) infectious lesions, 21 (13%) cases of cancer, 7 (4%) cases of embolism, 60 (36%) reactive findings, and 26 (16%) other types of lesions. A total of 74 new extra-cardiac findings, not previously discovered by other modalities, were identified in 62 patients and resulted in additional investigations in 29 patients and a change in treatment in 18 patients (10%). The most frequent diagnoses discovered by FDG-PET/CT were colon polyps, cancer, and spondylodiscitis. There was a higher rate of findings leading to a change in treatment in patients above 67 years of age infected with other bacterial aetiologies than streptococci. FDG-PET/CT was useful to detect extra-cardiac foci. FDG-PET/CT findings may lead to unnecessary investigations. One out of 10 the patients with definite endocarditis had underwent a change in treatment regimen based on the FDG-PET/CT findings.
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http://dx.doi.org/10.1007/s10554-020-01787-8DOI Listing
May 2020

Adjusting Early Warning Score by clinical assessment: a study protocol for a Danish cluster-randomised, multicentre study of an Individual Early Warning Score (I-EWS).

BMJ Open 2020 01 7;10(1):e033676. Epub 2020 Jan 7.

Department of Emergency Medicine, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.

Introduction: Track and trigger systems (TTSs) based on vital signs are implemented in hospitals worldwide to identify patients with clinical deterioration. TTSs may provide prognostic information but do not actively include clinical assessment, and their impact on severe adverse events remain uncertain. The demand for prospective, multicentre studies to demonstrate the effectiveness of TTSs has grown the last decade. Individual Early Warning Score (I-EWS) is a newly developed TTS with an aggregated score based on vital signs that can be adjusted according to the clinical assessment of the patient. The objective is to compare I-EWS with the existing National Early Warning Score (NEWS) algorithm regarding clinical outcomes and use of resources.

Method And Analysis: In a prospective, multicentre, cluster-randomised, crossover, non-inferiority study. Eight hospitals are randomised to use either NEWS in combination with the Capital Region of Denmark NEWS Override System (CROS) or implement I-EWS for 6.5 months, followed by a crossover. Based on their clinical assessment, the nursing staff can adjust the aggregated score with a maximum of -4 or +6 points. We expect to include 150 000 unique patients. The primary endpoint is all-cause mortality at 30 days. Coprimary endpoint is the average number of times per day a patient is NEWS/I-EWS-scored, and secondary outcomes are all-cause mortality at 48 hours and at 7 days as well as length of stay.

Ethics And Dissemination: The study was presented for the Regional Ethics committee who decided that no formal approval was needed according to Danish law (J.no. 1701733). The I-EWS study is a large prospective, randomised multicentre study that investigates the effect of integrating a clinical assessment performed by the nursing staff in a TTS, in a head-to-head comparison with the internationally used NEWS with the opportunity to use CROS.

Trial Registration Number: NCT03690128.
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http://dx.doi.org/10.1136/bmjopen-2019-033676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955532PMC
January 2020

Coronary risk stratification of patients with newly diagnosed heart failure.

Open Heart 2019;6(2):e001074. Epub 2019 Oct 3.

Department of Cardiology, Herlev og Gentofte Hospital, Herlev, Denmark.

Objective: Coronary artery disease (CAD) is frequent in patients with newly diagnosed heart failure (HF). Multislice CT (MSCT) is a non-invasive alternative to coronary angiography (CAG) suggested for patients with a low-to-intermediate risk of CAD. No established definition of such patients exists. Our purpose was to develop a simple score to identify as large a group as possible with a suitable pretest risk of CAD.

Methods: Retrospective study of patients in Denmark undergoing CAG due to newly diagnosed HF from 2010 to 2014. All Danish patients were registered in two databases according to geographical location. We used data from one registry and multiple logistic regression with backwards elimination to find predictors of CAD and used the derived OR to develop a clinical risk score called the CT-HF score, which was subsequently validated in the other database.

Results: The main cohort consisted of 2171 patients and the validation cohort consisted of 2795 patients with 24% and 27% of patients having significant CAD, respectively. Among significant predictor, the strongest was extracardiac arteriopathy (OR 2.84). Other significant factors were male sex, smoking, hyperlipidaemia, diabetes mellitus, angina and age. A proposed cut-off of 9 points identified 61% of patients with a 15% risk of having CAD, resulting in an estimated savings of 15% of the cost and 21% of the radiation.

Conclusions: A simple score based on clinical risk factors could identify HF patients with a low risk of CAD; these patients may have benefitted from MSCT as a gatekeeper for CAG.
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http://dx.doi.org/10.1136/openhrt-2019-001074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802977PMC
February 2021

External validation of the HANDOC score - high sensitivity to identify patients with non-beta-haemolytic streptococcal endocarditis.

Infect Dis (Lond) 2020 01 17;52(1):54-57. Epub 2019 Oct 17.

Division for Infection Medicine, Department of Clinical Sciences, Medical Faculty, Lund University, Lund, Sweden.

Invasive infections with non-beta-haemolytic streptococci (NBHS) is quite common and presents the clinicians with difficulties regarding which patients are at risk for infective endocarditis (IE). The HANDOC score was developed to identify patients with NBHS bacteraemia who are at low risk of IE. This study was conducted to validate HANDOC in an external cohort. Patients with NBHS in blood cultures between March and September 2016 in a Danish centre were included as part of an on-going study. Patient characteristics were collected to classify bacteria according to Dukés criteria and the components of the HANDOC score were collected retrospectively from the patients' medical records. 68 patients were included in the cohort, of which 16 fulfilled Dukés criteria for IE. All patients with IE (16 of 16) had a HANDOC score above the predefined cut-off. Cases of IE were found in patients with. , , , and group streptococci. The HANDOC score thus had a sensitivity of 100% and a specificity of 62% in this cohort. HANDOC has a sensitivity of 100% and a relatively high specificity (62%) also in a prospectively enrolled cohort of patients from another country than its origin. This indicates that HANDOC can be implemented in clinical practice to identify patients with a low risk of IE in whom echocardiography can be omitted.
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http://dx.doi.org/10.1080/23744235.2019.1679388DOI Listing
January 2020

Increased Risk of Ischemic Stroke After Treatment of Infective Endocarditis: A Danish, Nationwide, Propensity Score-Matched Cohort Study.

Clin Infect Dis 2020 03;70(6):1186-1192

Department of Cardiology, Herlev Gentofte Hospital, Denmark.

Background: Several studies have reported a high risk of ischemic stroke (IS) during the acute phase of infective endocarditis (IE). The long-term risk of IS after IE, however, is not fully illuminated.

Methods: This Danish, nationwide, register-based, propensity score-matched cohort study used Cox regression to estimate hazard ratios (HRs) of IS for persons with vs without a history of left-sided IE, from 1977 to 2015.

Results: We followed 9312 patients exposed to a first-time IE and 91 996 nonexposed, matched control persons. Compared to persons without IE, patients with a history of IE had a significantly increased risk of IS; the risk was highest during the first 4 weeks after IE diagnosis (HR 57.20, 95% confidence interval [CI] 45.58-71.78; P < .0001) and a moderately elevated risk persisted until 2 years after IE (4 weeks to 3 months after IE, HR 5.40, 95% CI 4.11-7.19; 3 months to 2 years after IE, HR 1.73, 95% CI 1.48-2.01). Mediation analyses showed that the higher risk of IS the first 2 years after IE could not be explained by atrial fibrillation (AF) or inserted mechanical valves in IE patients. In the period from 4 weeks to 3 months after IE diagnosis, patients treated with anticoagulative therapy had a lower risk of IS (HR 0.30, 95% CI .10-0.96; P = .04).

Conclusions: Patients with a history of IE had an increased risk of IS for up to 2 years after IE diagnosis. The increased risk was unrelated to AF and inserted mechanical valves. During the initial phase after IE, patients taking an anticoagulative medication had a lower risk of IS.
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http://dx.doi.org/10.1093/cid/ciz320DOI Listing
March 2020

In-hospital metabolite changes in infective endocarditis-a longitudinal H NMR-based study.

Eur J Clin Microbiol Infect Dis 2019 Aug 22;38(8):1553-1560. Epub 2019 May 22.

Department of Chemistry, Lund University, P.O. Box 124, SE-22100, Lund, Sweden.

Treatment of infective endocarditis (IE) is a 4-6-week provided course of intravenously administered antibiotics. The aim of this study was to investigate how serum metabolites as measured by proton nuclear magnetic resonance (H NMR) spectroscopy are changing over time during the active phase of IE, and to see whether these metabolite changes might be used to monitor recovery in these patients. Patients hospitalized with first-time IE at Herlev Hospital, Denmark, from September 2015 to June 2017 were included. Longitudinal blood sampling was performed and serum was analyzed using H NMR. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was used to separate sample groups and analyze differences in metabolite profiles. Thirteen patients were included in the study (77% men, median age 62 years (IQR 53-77)). All patients were cured during the hospitalization without any relapse during 6 months of follow-up. We analyzed 61 serum samples (median 5 samples, range 2-8 per person) drawn in the treatment period after IE diagnosis. The main changes during the in-hospital period were decreased levels of glucose, mannose, leucine, isoleucine, phenylalanine, tyrosine, and signals from polyols and N-acetylated protein. The metabolomic changes could in contrast to the routinely used parameters CRP and leucocyte levels distinguish between the early and late stages of disease treatment. We present the first longitudinal study of H NMR metabolomics in patients with infective endocarditis. The metabolomic changes show a promising strength compared to routinely used clinical parameters.
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http://dx.doi.org/10.1007/s10096-019-03586-zDOI Listing
August 2019

Risk assessment models for potential use in the emergency department have lower predictive ability in older patients compared to the middle-aged for short-term mortality - a retrospective cohort study.

BMC Geriatr 2019 05 16;19(1):134. Epub 2019 May 16.

Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730, Herlev, Denmark.

Background: Older patients is a complex group at increased risk of adverse outcomes compared to younger patients, which should be considered in the risk assessment performed in emergency departments. We evaluated whether the predictive ability of different risk assessment models for acutely admitted patients is affected by age.

Methods: Cohort study of middle-aged and older patients. We investigated the accuracy in discriminating between survivors and non-survivors within 7 days of different risk assessment models; a traditional triage algorithm, a triage algorithm with clinical assessment, vital signs, routine biomarkers, and the prognostic biomarker soluble urokinase plasminogen activator receptor (suPAR).

Results: The cohort included 22,653 (53.2%) middle-aged patients (age 40-69 years), and 19,889 (46.8%) older patients (aged 70+ years). Death within 7 days occurred in 139 patients (0.6%) in middle-aged patients and 596 (3.0%) of the older patients. The models based on vital signs and routine biomarkers had the highest area under the curve (AUC), and both were significantly better at discriminating 7-day mortality in middle-aged patients compared to older patients; AUC (95% CI): 0.88 (0.84-0.91), 0.75 (0.72-0.78), P < 0.01, and 0.86 (0.82-0.90), 0.76 (0.73-0.78), P < 0.001. In a subgroup of the total cohort (6.400 patients, 15.0%), the suPAR level was available. suPAR had the highest AUC of all individual predictors with no significant difference between the age groups, but further research in this biomarker is required before it can be used.

Conclusion: The predictive value was lower in older patients compared to middle-aged patients for all investigated models. Vital signs or routine biomarkers constituted the best models for predicting 7-day mortality and were better than the traditional triage model. Hence, the current risk assessment for short-term mortality can be strengthened, but modifications for age should be considered when constructing new risk assessment models in the emergency department.
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http://dx.doi.org/10.1186/s12877-019-1154-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521424PMC
May 2019

Prevalence of early stages of heart failure in an elderly risk population: the Copenhagen Heart Failure Risk Study.

Open Heart 2019;6(1):e000840. Epub 2019 Feb 27.

Department of Cardiology, Herlev and Gentofte University Hospital, Herlev, Denmark.

Aims: To describe the prevalence of heart failure (HF) stages in elderly outpatients with risk factors for HF but without known HF, and characterise the clinical, biochemical and echocardiographic findings in each stage.

Background: Early stages of HF are underdiagnosed; nevertheless, they are associated with an increased risk of hospitalisation and increased mortality. The prevalence of HF stages in elderly high-risk patients is unknown.

Methods: A total of 400 patients were consecutively included: ≥60 years old, ≥1 risk factor for HF (diabetes, chronic kidney disease, cardiovascular disease, atrial fibrillation, hypertension), and without known or suspected HF. HF stages were defined as the following: stage A (risk factor for HF, normal echocardiography), stage B (abnormal echocardiography, without symptoms of HF) and stage C (abnormal echocardiography, symptoms of HF, clinical signs/increased plasma aminoterminal pro-B-type natriuretic peptide [NT-proBNP] concentrations).

Results: After thorough examination 44.25% of patients were categorised as HF stage A, 37.5% were HF stage B and 18.25% HF stage C. Those with higher stages of HF were older (p<0.001) and more often had atrial fibrillation (p=0.006). The median plasma NT-proBNP concentrations (pg/mL) were 132.5 for HF stage A, 275.5 for HF stage B and 400.0 for HF stage C (p<0.001). Detectable plasma troponin-I was more frequent with abnormal echocardiography: HF stage A 9.7%, HF stage B 27.3% and HF stage C 30.1% (p<0.001). HF stage C reported higher score on the Minnesota Living with Heart Failure Questionnaire (p<0.001).

Conclusions: In an elderly high-risk population without known or suspected HF, more than half were HF stage B or C. Higher stages of HF had increased plasma concentrations of NT-proBNP and troponin-I, besides a reduced quality of life. Focus on symptoms and signs of HF in this population are warranted.
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http://dx.doi.org/10.1136/openhrt-2018-000840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443139PMC
February 2021

FGF23 in hemodialysis patients is associated with left ventricular hypertrophy and reduced ejection fraction.

Nefrologia (Engl Ed) 2019 May - Jun;39(3):258-268. Epub 2019 Feb 2.

Department of Medicine, Zealand University Hospital, Roskilde, Denmark.

Background: Fibroblast growth factor 23 (FGF23) is known to cause left ventricular hypertrophy (LVH), but controversy exists concerning its effect in dialysis. This study evaluated associations between FGF23 levels, echocardiography and prognosis in patients on hemodialysis (HD).

Methods: Patients >18 years on chronic HD were included in this cross-sectional study. Plasma C-terminal FGF23 concentration was measured with ELISA and transthoracic echocardiography was performed, both before and after HD treatment.

Results: 239 haemodialysis (HD) patients were included in the study. The FGF23 was median 3560RU/ml (IQR 1447-9952). The mean left ventricular mass index (LVMI) was 110.2±26.7g/m and the left ventricular ejection fraction (LVEF) was 52.7±9.9%. Defined by LVMI, LVH was found in 110 patients (46%), of which 92 (84%) had hypertension (p<0.01). Patients with LVH had FGF23 levels of 5319 RU/ml (IQR 1858-12,859) and those without 2496 RU/ml (IQR 1141-7028) (p<0.01). FGF23 was significant positive correlated with LVMI (p<0.01), and negatively to LVEF (p<0.01). In a multivariate analysis, FGF23 was correlated with LVEF (p<0.01), but only marginally to LVMI (p<0.01). Cardiovascular events in the follow up period was not correlated with FGF23. Furthermore, FGF23 was independently correlated with overall mortality (p<0.001).

Conclusion: FGF23 was positively correlated with LVH and negatively to LVEF. FGF23 was an independent predictor for overall mortality.
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http://dx.doi.org/10.1016/j.nefro.2018.10.007DOI Listing
May 2020

A simple clinical assessment is superior to systematic triage in prediction of mortality in the emergency department.

Emerg Med J 2019 Feb 16;36(2):66-71. Epub 2018 Oct 16.

Department of Cardiology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.

Objective: To compare the Danish Emergency Process Triage (DEPT) with a quick clinical assessment (Eyeball triage) as predictors of short-term mortality in patients in the emergency department (ED).

Methods: The investigation was designed as a prospective cohort study conducted at North Zealand University Hospital. All patient visits to the ED from September 2013 to December 2013 except minor injuries were included. DEPT was performed by nurses. Eyeball triage was a quick non-systematic clinical assessment based on patient appearance performed by phlebotomists. Both triage methods categorised patients as green (not urgent), yellow, orange or red (most urgent). Primary analysis assessed the association between triage level and 30-day mortality for each triage method. Secondary analyses investigated the relation between triage level and 48-hour mortality as well as the agreement between DEPT and Eyeball triage.

Results: A total of 6383 patient visits were included. DEPT was performed for 6290 (98.5%) and Eyeball triage for 6382 (~100%) of the patient visits. Only patients with both triage assessments were included. The hazard ratio (HR) for 48-hour mortality for patients categorised as yellow was 0.9 (95% CI 0.4 to 1.9) for DEPT compared with 4.2 (95% CI 1.2 to 14.6) for Eyeball triage (green is reference). For orange the HR for DEPT was 2.2 (95% CI 1.1 to 4.4) and 17.1 (95% CI 5.1 to 57.1) for Eyeball triage. For red the HR was 30.9 (95% CI 12.3 to 77.4) for DEPT and 128.7 (95% CI 37.9 to 436.8) for Eyeball triage. For 30-day mortality the HR for patients categorised as yellow was 1.7 (95% CI 1.2 to 2.4) for DEPT and 2.4 (95% CI 1.6 to 3.5) for Eyeball triage. For orange the HR was 2.6 (95% CI 1.8 to 3.6) for DEPT and 7.6 (95% CI 5.1 to 11.2) for Eyeball triage, and for red the HR was 19.1 (95% CI 10.4 to 35.2) for DEPT and 27.1 (95% CI 16.9 to 43.5) for Eyeball triage. Agreement between the two systems was poor (kappa 0.05).

Conclusion: Agreement between formalised triage and clinical assessment is poor. A simple clinical assessment by phlebotomists is superior to a formalised triage system to predict short-term mortality in ED patients.
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http://dx.doi.org/10.1136/emermed-2016-206382DOI Listing
February 2019

Use of the prognostic biomarker suPAR in the emergency department improves risk stratification but has no effect on mortality: a cluster-randomized clinical trial (TRIAGE III).

Scand J Trauma Resusc Emerg Med 2018 Aug 28;26(1):69. Epub 2018 Aug 28.

Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Ringvej 75, 2730, Herlev, Denmark.

Background: Risk stratification of patients in the emergency department can be strengthened using prognostic biomarkers, but the impact on patient prognosis is unknown. The aim of the TRIAGE III trial was to investigate whether the introduction of the prognostic and nonspecific biomarker: soluble urokinase plasminogen activator receptor (suPAR) for risk stratification in the emergency department reduces mortality in acutely admitted patients.

Methods: The TRIAGE III trial was a cluster-randomized interventional trial conducted at emergency departments in the Capitol Region of Denmark. Eligible hospitals were required to have an emergency department with an intake of acute medical and surgical patients and no previous access to suPAR measurement. Three emergency departments were randomized; one withdrew shortly after the trial began. The inclusion period was from January through June of 2016 consisting of twelve cluster-periods of 3-weeks alternating between intervention and control and a subsequent follow-up of ten months. Patients were allocated to the intervention if they arrived in interventional periods, where suPAR measurement was routinely analysed at arrival. In the control periods suPAR measurement was not performed. The main outcome was all-cause mortality 10 months after arrival of the last patient in the inclusion period. Secondary outcomes included 30-day mortality.

Results: The trial enrolled a consecutive cohort of 16,801 acutely admitted patients; all were included in the analyses. The intervention group consisted of 6 cluster periods with 8900 patients and the control group consisted of 6 cluster periods with 7901 patients. After a median follow-up of 362 days, death occurred in 1241 patients (13.9%) in the intervention group and in 1126 patients (14.3%) in the control group. The weighted Cox model found a hazard ratio of 0.97 (95% confidence interval, 0.89 to 1.07; p = 0.57). Analysis of all subgroups and of 30-day all-cause mortality showed similar results.

Conclusions: The TRIAGE III trial found no effect of introducing the nonspecific and prognostic biomarker suPAR in emergency departments on short- or long-term all-cause mortality among acutely admitted patients. Further research is required to evaluate how prognostic biomarkers can be implemented in routine clinical practice.

Trial Registration: clinicaltrials.gov, NCT02643459 . Registered 31 December 2015.
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http://dx.doi.org/10.1186/s13049-018-0539-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114851PMC
August 2018

YKL-40 in patients with end-stage renal disease receiving haemodialysis.

Biomarkers 2018 May - Jun;23(4):357-363. Epub 2018 Mar 8.

a Department of Cardiology , Herlev Hospital University of Copenhagen , Copenhagen , Denmark.

Purpose: This study aimed to determine serum YKL-40 in patients with end-stage renal disease (ESRD) on haemodialysis (HD) and to evaluate the prognostic value of serum YKL-40.

Methods: Patients >18 years on maintenance HD were included. Serum YKL-40 was measured using ELISA before and after a single HD treatment.

Results: A total of 306 patients were included. Median serum YKL-40 concentration was 238 µgL (IQR: 193-291 µgL) before HD treatment and 198 µgL (IQR: 147-258 µgL) after HD treatment, which corresponded to age-corrected 93th percentile in healthy subjects. All-cause mortality after 2.8 years was 35.9%. Patients with serum YKL-40 in the highest quartile compared with the lowest quartile had a univariate HR of 4.0 (95% CI: 2.2-7.3, p < 0.001) for all-cause mortality which decreased to 2.4 (95% CI: 1.1-4.5, p = 0.01) in multivariate analysis. Time-dependent receiver operating characteristic curves showed that serum YKL-40 after HD treatment had significant higher area under the curves from 90 d (p = 0.004) and throughout the rest of the follow-up period when compared to serum YKL-40 before HD treatment.

Conclusion: YKL-40 was highly elevated in patients with ESRD on HD, and dialysis reduced serum YKL-40 concentrations approximately one-sixth. YKL-40 measured after dialysis was independently associated with mortality in HD patients.
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http://dx.doi.org/10.1080/1354750X.2018.1428359DOI Listing
September 2018

Takotsubo cardiomyopathy, a two-stage recovery of left ventricular systolic and diastolic function as determined by cardiac magnetic resonance imaging.

Eur Heart J Cardiovasc Imaging 2014 Aug 12;15(8):855-62. Epub 2014 Feb 12.

Department of Cardiology, Rigshospitalet, Blegdamsvej 9, Copenhagen 2100, Denmark.

Aims: Takotsubo cardiomyopathy (TTC) is an entity mimicking acute myocardial infarction, characterized by transient severe systolic heart failure. Echocardiographic studies suggest that diastolic dysfunction is present in TTC at presentation; however, no reports exist regarding the time course of left ventricular (LV) recovery. This study describes the recovery of LV systolic and diastolic function in TTC. We hypothesized that, in TTC, there is diastolic dysfunction at admission, and that recovery is delayed compared with systolic function.

Methods And Results: We enrolled (consecutively 2010-12) 16 patients (mean age 66, range 39-84 years) diagnosed with TTC and 20 healthy matched controls. We performed cardiac magnetic resonance imaging (CMR) at admission, pre-discharge, and 3-month follow-up. Diastolic function was assessed by LV peak filling rate (LVPFR) and left atrial (LA) emptying volumes. At admission, LV ejection fraction was low, increased at pre-discharge (37 ± 6 vs. 58 ± 6%, P < 0.001), and normalized at follow-up (to 65 ± 5%, P = 0.01). LVPFR did not increase during hospitalization (80 ± 3 vs. 89 ± 4 mL/s/m(2), P = 0.21), but was normalized at follow-up (to 206 ± 19, P < 0.001; controls, 214 ± 13, P = 0.23). During hospitalization, LA passive emptying volume remained low (6 ± 2 vs. 8 ± 3 mL/m(2), P = 0.05) and LA active emptying volume remained high (17 ± 3 vs. 16 ± 3 mL/m(2), P = 0.71), whereas LA conduit volume increased (7 ± 3 vs. 23 ± 4 mL/m(2), P < 0.001). T2-weighted imaging demonstrated non-coronary distributed apical oedema without contrast enhancement.

Conclusion: Patients with TTC undergo fast systolic recovery. However, at discharge, profound diastolic dysfunction is demonstrated by CMR. At follow-up, both LV systolic and diastolic function is normalized in patients with recovered TTC.
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http://dx.doi.org/10.1093/ehjci/jeu004DOI Listing
August 2014

Echocardiographic predictors of exercise capacity and mortality in chronic obstructive pulmonary disease.

BMC Cardiovasc Disord 2013 Oct 12;13:84. Epub 2013 Oct 12.

Department of Cardiology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.

Background: Chronic obstructive pulmonary disease (COPD) reduces exercise capacity, but lung function parameters do not fully explain functional class and lung-heart interaction could be the explanation. We evaluated echocardiographic predictors of mortality and six minutes walking distance (6MWD), a marker for quality of life and mortality in COPD.

Methods: Ninety COPD patients (GOLD criteria) were evaluated by body plethysmography, 6MWD and advanced echocardiography parameters (pulsed wave tissue Doppler and speckle tracking).

Results: Mean 6MWD was 403 (± 113) meters. All 90 subjects had preserved left ventricular (LV) ejection fraction 64.3% ± 8.6%. Stroke volume decreased while heart rate increased with COPD severity and hyperinflation. In 66% of patients, some degree of diastolic dysfunction was present. Mitral tissue Doppler data in COPD could be interpreted as a sign of low LV preload and not necessarily an intrinsic impairment in LV relaxation/compliance. Tricuspid regurgitation (TR) increased with COPD severity and hyperinflation. Age (p < 0.001), BMI (p < 0.001), DLCO SB (p < 0.001) and TR (p 0.005) were independent predictors of 6MWD and a multivariable model incorporating heart function parameters (adjusted r2 = .511) compared well to a model with lung function parameters alone (adjusted r2 = .475). LV global longitudinal strain (p = 0.034) was the only independent predictor of mortality among all baseline, body plethysmographic and echocardiographic variables.

Conclusions: Among subjects with moderate to severe COPD and normal LVEF, GLS independently predicted all-cause mortality. Exercise tolerance correlated with standard lung function parameters only in univariate models; in subsequent models including echocardiographic parameters, longer 6MWD correlated independently with milder TR, better DLCO SB, younger age and lower BMI. We extended the evidence on COPD affecting cardiac chamber volumes, LV preload, heart rate, as well as systolic and diastolic function. Our results highlight lung-heart interaction and the necessity of cardiac evaluation in COPD.
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http://dx.doi.org/10.1186/1471-2261-13-84DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852306PMC
October 2013
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