Cardiovascular phenotype of long-term anabolic-androgenic steroid abusers compared with strength-trained athletes.

INTRODUCTION: Abuse of anabolic-androgenic steroids (AAS) has been linked to a variety of different cardiovascular (CV) side effects, but still the clinical effects of AAS abuse on CV risk are not clear. The aim of this study was to assess the CV phenotype of a large cohort of men with long-term AAS use compared with strength-trained athletes without AAS use. METHODS: Fifty one strength-trained men with ≥3 years of AAS use was compared with twenty one strength-trained competing athletes. We verified substance abuse and non-abuse by blood and urine analyses. The participants underwent comprehensive CV evaluation including laboratory analyses, 12-lead ECG with measurement of QT dispersion, exercise ECG, 24 h ECG with analyses of heart rate variability, signal averaged ECG, basic transthoracic echocardiography, and coronary computed tomography angiography (CCTA). RESULTS: Hemoglobin levels and hematocrit were higher among the AAS users compared with non-users (16.8 vs. 15.0 g/dl, and 0.50% vs. 0.44%, respectively, both p < 0.01) and HDL cholesterol significantly lower (0.69 vs. 1.25 mmol/L, p < 0.01). Maximal exercise capacity was 270 and 280 W in the AAS and the non-user group, respectively (p = 0.04). Echocardiography showed thicker intraventricular septum and left ventricular (LV) posterior wall among AAS users (p < 0.01 for both), while LV ejection fraction was lower (50 vs. 54%, p = 0.02). Seven AAS users (17%) had evidence of coronary artery disease on CCTA. There were no differences in ECG measures between the groups. CONCLUSIONS: A divergent CV phenotype dominated by increased CV risk, accelerated coronary artery disease, and concentric myocardial hypertrophy was revealed among the AAS users.

Cardiovascular rEmodelling in living kidNey donorS with reduced glomerular filtration rate: rationale and design of the CENS study.

Purpose: Until recently, it has been believed that donating a kidney not represents any risk for development of cardiovascular disease. However, a recent Norwegian epidemiological study suggests that kidney donors have an increased long-term risk of cardiovascular mortality. The pathophysiological mechanisms linking reduced kidney function to cardiovascular disease are not known. Living kidney donors are screened for cardiovascular morbidity before unilateral nephrectomy, and are left with mildly reduced glomerular filtration rate (GFR) after donation. Therefore, they represent an unique model for investigating the pathogenesis linking reduced GFR to cardiovascular disease and cardiovascular remodelling. We present the study design of Cardiovascular rEmodelling in living kidNey donorS with reduced glomerular filtration rate (CENS), which is an investigator-initiated prospective observational study on living kidney donors. The hypothesis is that living kidney donors develop cardiovascular remodelling due to a reduction of GFR.Materials and methods: 60 living kidney donors and 60 age and sex matched healthy controls will be recruited. The controls will be evaluated to fulfil the Norwegian transplantation protocol for living kidney donors. Investigations will be performed at baseline and after 1, 3, 6 and 10 years in both groups. The investigations include cardiac magnetic resonance imaging, echocardiography, bone density scan, flow mediated dilatation, laser Doppler flowmetry, nailfold capillaroscopy, office blood pressure, 24-h ambulatory blood pressure, heart rate variability and investigation of microbiota and biomarkers for inflammation, cardiovascular risk and the calcium-phosphate metabolism.Conclusions: The present study seeks to provide new insight in the pathophysiological mechanisms linking reduced kidney function to cardiovascular disease. In addition, we aim to enlighten predictors of adverse cardiovascular outcome in living kidney donors. The study is registered at Clinical-Trials.gov (identifier: NCT03729557).

Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease.

BACKGROUND: Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life. METHODS: We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life. RESULTS: At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P<0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups. CONCLUSIONS: In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).

Catheter-based left atrial appendage closure. / Kateterbasert lukking av venstre atriums aurikkel.

BAKGRUNN: Atrieflimmer er en vanlig tilstand i befolkningen og gir økt risiko for hjerneslag. Antikoagulasjonsbehandling er effektivt for å forebygge tromboembolisme ved atrieflimmer, men av ulike grunner blir mange atrieflimmerpasienter med indikasjon for antikoagulasjonsbehandling ikke behandlet. Kateterbasert lukking av venstre atriums aurikkel er en ny metode for å forebygge hjerneslag ved atrieflimmer. MATERIALE OG METODE: I perioden september 2014-april 2016 gjennomgikk 27 pasienter med atrieflimmer og høy risiko for hjerneslag forsøk på kateterbasert lukking av venstre atriums aurikkel ved Oslo universitetssykehus. Antikoagulasjonsbehandling var vurdert som kontraindisert hos 26 av pasientene. Vi presenterer resultater fra prosedyre, ekkokardiografikontroller og kliniske hendelser i oppfølgingsperioden på ett år. RESULTATER: Aurikkelplugg ble vellykket implantert hos 26 pasienter. To pasienter fikk komplikasjoner i forbindelse med prosedyren: En fikk hjerneslag og en fikk transfusjonskrevende lyskeblødning. En pasient fikk hjertetamponade fem måneder etter prosedyren. En pasient som grunnet anatomisk vanskelige forhold ikke fikk implantert aurikkelplugg, døde av hjerneslag i oppfølgingsperioden. Tre pasienter hadde klinisk transitorisk iskemisk anfall (TIA). Det var ingen forekomst av intrakranial eller gastrointestinal blødning. FORTOLKNING: Kateterbasert lukking av venstre atriums aurikkel er gjennomførbart, men innebærer risiko for komplikasjoner og bør forbeholdes pasienter med høy risiko for hjerneslag og kontraindikasjon mot antikoagulasjonsbehandling.

Cardiac output estimation using ballistocardiography: a feasibility study in healthy subjects.

There is no reliable automated non-invasive solution for monitoring circulation and guiding treatment in prehospital emergency medicine. Cardiac output (CO) monitoring might provide a solution, but CO monitors are not feasible/practical in the prehospital setting. Non-invasive ballistocardiography (BCG) measures heart contractility and tracks CO changes. This study analyzed the feasibility of estimating CO using morphological features extracted from BCG signals. In 20 healthy subjects ECG, carotid/abdominal BCG, and invasive arterial blood pressure based CO were recorded. BCG signals were adaptively processed to isolate the circulatory component from carotid (CCc) and abdominal (CCa) BCG. Then, 66 features were computed on a beat-to-beat basis to characterize amplitude/duration/area/length of the fluctuation in CCc and CCa. Subjects' data were split into development set (75%) to select the best feature subset with which to build a machine learning model to estimate CO and validation set (25%) to evaluate model's performance. The model showed a mean absolute error, percentage error and 95% limits of agreement of 0.83 L/min, 30.2% and - 2.18-1.89 L/min respectively in the validation set. BCG showed potential to reliably estimate/track CO. This method is a promising first step towards an automated, non-invasive and reliable CO estimator that may be tested in prehospital emergencies.

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels 3 months after myocardial infarction are more strongly associated with magnetic resonance-determined ejection fraction than NTproBNP levels in the acute phase.

BACKGROUND: The relationship between levels of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular function determined by magnetic resonance imaging (MRI) in ST-segment-elevation myocardial infarction (STEMI) is largely unknown. METHODS AND RESULTS: This was a substudy of the Norwegian Study on District Treatment of STEMI, in which patients received thrombolysis followed by early or late invasive strategy. NT-proBNP was measured at 3 days and 3 months after the myocardial infarction, and magnetic resonance imaging was performed after 3 months (n = 160). Log NT-proBNP levels at both time points were significantly associated with ejection fraction (EF) (r(2) values 0.25 and 0.42, respectively) as well as infarct size (r(2) values 0.38 and 0.47, respectively; P < .0001 for all, adjusted for confounders). Furthermore, receiver operating characteristic (ROC) curves used to analyze the ability of NT-proBNP to discriminate long-term low EF (≤40%) and large infarct size (≥15.7%), were significant at both time points (P < .001 for all). Pairwise comparison of the ROC curves showed a significantly better performance of NT-proBNP at 3 months compared with 3 days for discrimination of low EF (P = .023). CONCLUSION: Repeated measurements of NT-proBNP in STEMI patients showed that NT-proBNP levels at 3 months were more strongly associated with long-term EF and infarct size than NT-pro BNP levels after 3 days. Our data suggest that measurement of NT-proBNP 3 months after myocardial infarction is a better indicator of left ventricular function compared with NT-proBNP in the acute phase.

Assessment of left ventricular function in ST-elevation myocardial infarction by global longitudinal strain: a comparison with ejection fraction, infarct size, and wall motion score index measured by non-invasive imaging modalities.

AIMS: We aimed to compare two-dimensional global longitudinal strain (GS) with different non-invasive imaging modalities for the assessment of left ventricular function in an ST-elevation myocardial infarction population. METHODS AND RESULTS: GS was compared with ejection fraction (EF) determined by magnetic resonance imaging (MRI), standard echocardiography (echo), contrast echo, and electrocardiography-gated single-photon emission computed tomography (SPECT), as well as with MRI-determined relative infarct size and echo-determined wall motion score index (WMSI), in 163 patients participating in the NORwegian Study on District Treatment of ST-Elevation Myocardial Infarction (NORDISTEMI). The linear relation between GS and standard echo (r(2)= 0.43, P <0.001), contrast echo (r(2)= 0.38, P <0.001), and SPECT-determined EF (r(2)= 0.52, P <0.001) was almost identical as that between GS and the gold standard MRI-determined EF (r(2)= 0.47, P <0.001). GS was best associated with WMSI by echo (r(2)= 0.55, P <0.001), while the associations between GS and relative infarct size were weaker (r = 0.43, P <0.001). Receiver operator characteristics curves, used to analyse the ability of GS to discriminate low EF (≤ 40%) measured by the four different modalities, large myocardial infarction (MI ≥ 15.7%), and high WMSI (≥ 1.5), were significant for all. GS was shown to be the best predictor of low EF measured by MRI [area under the curve (AUC) 0.965], while the lowest AUC was found between GS and large MI (0.814). CONCLUSION: Global strain is associated well with EF measured by all modalities. Global strain was found to be the best predictor of low EF measured by the gold standard MRI. Since global strain is an inexpensive test, these data may be of health economic interest.

Left ventricular function in acute myocardial infarction treated with thrombolysis followed by early versus late invasive strategy.

BACKGROUND: Thrombolysis remains the treatment of choice in acute ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be performed within 90 to 120 minutes. The optimal treatment after thrombolysis is still debated, but several studies have shown improved clinical outcomes with early transfer for PCI. The aim of this study was to investigate whether an early invasive strategy after thrombolysis preserved left ventricular function better than a late invasive strategy. METHODS: This was a substudy of the NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction. Patients with STEMI of <6 hours of duration and >90 minutes of expected transfer delays to PCI were treated with aspirin, tenecteplase, enoxaparin, and clopidogrel and randomized to early or late invasive strategy (N = 266). Left ventricular volumes and ejection fraction were assessed by single-photon emission computed tomography, echocardiography, and magnetic resonance imaging 3 months after the index infarction. RESULTS: Noninvasive imaging was completed in 241 patients (91%). Median end-diastolic and end-systolic volumes after 3 months did not differ between groups. Median ejection fraction was well preserved and also without differences: 63% (interquartile range 51-70) in the early invasive versus 65% (interquartile range 55-71) in the late invasive group when assessed by single-photon emission computed tomography (P = .30), 55% versus 55% when assessed by echocardiography (P = .88), and 57% versus 57% when assessed by magnetic resonance imaging (P = .99). CONCLUSION: In this group of STEMI patients treated with thrombolysis, no difference in left ventricular function after 3 months was found between patients treated with early versus late invasive strategy.

Assessment of left ventricular function with magnetic resonance imaging vs. echocardiography, contrast echocardiography, and single-photon emission computed tomography in patients with recent ST-elevation myocardial infarction.

AIMS: Magnetic resonance imaging (MRI) is often considered to be the gold standard in measuring left ventricular function and volumes. The aim of this study was to assess the agreements between standard echocardiography (standard echo), contrast echocardiography (contrast echo), single-photon emission computed tomography (SPECT), and MRI in the determination of left ventricular ejection fraction (EF) and end-diastolic volumes (EDV) in patients treated for acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Standard echo, contrast echo, SPECT and MRI were performed on the same day, 3 months after STEMI in 150 patients participating in the NORwegian Study on District Treatment of ST-Elevation Myocardial Infarction (NORDISTEMI). Bland-Altman analysis of EF measured by all four imaging modalities showed generally low mean differences but wide limits of agreement. The mean EDV difference, however, was consistently higher when MRI was compared with standard echo (54.9 mL), contrast echo (41.7 mL) and SPECT (54.6 mL), and the limits of agreement were wider. The mean EDV differences between contrast echo vs. standard echo, SPECT vs. standard echo and contrast echo vs. SPECT were small. CONCLUSION: Our data suggest that all four imaging modalities measured EF closely similar after STEMI as demonstrated by a very small bias. The limits of agreement were however wide. EDV measured by MRI was consistently higher when compared with the other methods which may be caused by different tracing-methods and imaging principles. As echocardiography is preferable from a cost-benefit point of view, further analysis would be needed to clarify the nature of such differences.

Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction.

BACKGROUND: Previous studies have shown improvement in left ventricular function after intracoronary injection of autologous cells derived from bone marrow (BMC) in the acute phase of myocardial infarction. We designed a randomized, controlled trial to further investigate the effects of this treatment. METHODS: Patients with acute ST-elevation myocardial infarction of the anterior wall treated with percutaneous coronary intervention were randomly assigned to the group that underwent intracoronary injection of autologous mononuclear BMC or to the control group, in which neither aspiration nor sham injection was performed. Left ventricular function was assessed with the use of electrocardiogram-gated single-photon-emission computed tomography (SPECT) and echocardiography at baseline and magnetic resonance imaging (MRI) 2 to 3 weeks after the infarction. These procedures were repeated 6 months after the infarction. End points were changes in the left ventricular ejection fraction (LVEF), end-diastolic volume, and infarct size. RESULTS: Of the 50 patients assigned to treatment with mononuclear BMC, 47 underwent intracoronary injection of the cells at a median of 6 days after myocardial infarction. There were 50 patients in the control group. The mean (+/-SD) change in LVEF, measured with the use of SPECT, between baseline and 6 months after infarction for all patients was 7.6+/-10.4 percentage points. The effect of BMC treatment on the change in LVEF was an increase of 0.6 percentage point (95% confidence interval [CI], -3.4 to 4.6; P=0.77) on SPECT, an increase of 0.6 percentage point (95% CI, -2.6 to 3.8; P=0.70) on echocardiography, and a decrease of 3.0 percentage points (95% CI, 0.1 to -6.1; P=0.054) on MRI. The two groups did not differ significantly in changes in left ventricular end-diastolic volume or infarct size and had similar rates of adverse events. CONCLUSIONS: With the methods used, we found no effects of intracoronary injection of autologous mononuclear BMC on global left ventricular function.

Gender differences in management and outcome of acute myocardial infarctions treated in 2006-2007.

OBJECTIVES: Women with acute myocardial infarction (AMI) previously received less invasive evaluation and experienced higher mortality than men. After improvements in AMI care it is unclear whether gender differences still exist in management and outcome of AMI. METHODS: All patients admitted to Ullevål University Hospital for AMI during 2006 and 2007 were included in this cohort study. Predefined data were recorded during the hospital stay, and the survival status of the patients was ascertained on June 30, 2008. RESULTS: A total of 931 women and 2,174 men were included. No gender differences were observed in treatment delay or age-adjusted odds ratio (OR) of invasive evaluation in ST-elevation myocardial infarction (STEMI). In non-ST-elevation myocardial infarction (NSTEMI), women were less likely than men to undergo coronary angiography (adjusted OR 0.72, 95% CI 0.53-0.99, p = 0.044) and percutaneous coronary intervention (adjusted OR 0.60, 95% CI 0.47-0.76, p = 0.0001). Age-adjusted in-hospital mortality and long-term survival were similar between men and women. CONCLUSIONS: Women with STEMI experienced similar treatment delays and odds of invasive evaluation as men. However, gender differences in invasive evaluation were still observed in NSTEMI patients. No sex differences were observed in age-adjusted early and long-term mortality.

[Musculoskeletal pain in ultrasound operators]. / Muskel- og skjelettplager hos ultralydoperatører.

BACKGROUND: Ultrasound-based techniques are frequently used in cardiology, gynecology and radiology. Work-related symptoms are reported for ultrasound operators, but controlled studies have not been published. We wanted to map symptoms and clinical diagnoses in ultrasound operators, compare them to matched controls and evaluate a possible relation between symptoms and exposure. MATERIAL AND METHODS: All ultrasound operators working at Rikshospitalet and Ullevaal University hospitals and matched controls who had other work at the hospitals were invited to participate. They answered questions about pain, well-being at the workplace, physical activity, smoking and validated function scores for the back (Oswestry Disability Index-ODI), shoulder and arm (Quick-DASH), and health- related quality of life (EQ-5D and EQ-VAS, as well as exposure time for ultrasound examinations. All participants underwent a blinded, systematic clinical examination. RESULTS: 81 persons participated (43 women, 38 men); 44 operators and 37 controls. The ultrasound operators reported significantly more work-related pain from the wrist, elbow and shoulder and scored significantly worse on Quick-DASH (difference 6.1 [95 % CI 2.0 to 10.2, p < 0.001) and health-related function (EQ-5D). There was no difference in health-related quality of life (EQ-VAS) or back function (ODI). The number of persons with one or more clinical diagnosis was significantly higher for ultrasound operators (26/44 [59 %]) than controls (7/37 [19 %]), odds ratio 5.2; 95 % CI 2,0 to 14.0, p < 0.001. For subacromial pain the numbers were 11/44 (25 %) and 2/37 (5 %), odds ratio 5,8; CI 1.2 to 28.3, p = 0.034. For the ultrasound operators there was a significant association between exposure > 1000 min/week and Quick-DASH, subacromial pain and lateral epicondylagia. INTERPRETATION: Ultrasound operators reported significantly more shoulder and arm complaints and clinical diagnosis than controls.

Systolic mitral annulus velocity is a sensitive index for changes in left ventricular systolic function during inotropic therapy in patients with acute heart failure.

BACKGROUND: Echocardiography is recommended for assessment of left ventricular systolic function in patients with acute heart failure but few randomised trials have validated techniques like tissue Doppler (TDI) and speckle tracking (STE) in patients with acute heart failure following ST-elevation myocardial infarction. METHODS: This was a substudy from the LEAF (LEvosimendan in Acute heart Failure following myocardial infarction) trial (NCT00324766 ), which randomised 61 patients developing acute heart failure, including cardiogenic shock, within 48 hours after ST-elevation myocardial infarction, double-blind to a 25-hour infusion of levosimendan or placebo. TDI-derived systolic mitral annulus velocity (S'), STE-derived global longitudinal strain (Sl) and strain rate (SRl) were measured at baseline, day 1, day 5 and after 42 days. RESULTS: Datasets rejected for analyses were 2% (TDI) and 17% (STE). S' increased by 23% in the levosimendan group versus 8% in the placebo group from baseline to day 1 ( p= 0.011) and by 30% vs. 3% from baseline to day 5 ( p <0.0005). Significant, but less pronounced, improvements in global Sl ( p = 0.025 and p = 0.032) and in global SRl ( p = 0.046 and p = 0.001) in favour of levosimendan were also present. CONCLUSION: S' by TDI and STE-derived Sl and SRl were sensitive indices for changes in left ventricular systolic function related to treatment with levosimendan. However, S' by TDI was more feasible and sensitive and might be preferred for assessment of changes in left ventricular systolic function in critically ill patients with acute heart failure receiving inotropic therapy.

Arterial plasma vasopressin and aldosterone predict left ventricular mass in men who develop hypertension over 20 years.

Left ventricular (LV) hypertrophy is related to blood pressure level and neurohormonal factors. The authors previously demonstrated that arterial norepinephrine levels predict LV mass in middle-aged men who developed hypertension through 20 years. The aim of this 20-year prospective study was to investigate arterial vasopressin, aldosterone, and renin as long-term predictors of LV mass. Normotensives (n=17), subjects who developed hypertension (n=17), and sustained hypertensives (n=22) were compared at baseline (42 years) and at follow-up (62 years). There were no significant differences in baseline vasopressin, aldosterone, or renin levels. The group with sustained hypertension had more LV hypertrophy (P=.025) at follow-up. Among new hypertensives, multiple regression analysis demonstrated that baseline arterial vasopressin (beta-0.53; P=.041) and aldosterone (beta-0.56;P=.032) independently explained LV mass index (R(2)=0.85; P=.035). In conclusion, baseline arterial vasopressin and aldosterone, but not renin, appear to predict LV mass in middle-aged men who developed hypertension over a 20-year period.

Arterial plasma noradrenaline predicts left ventricular mass independently of blood pressure and body build in men who develop hypertension over 20 years.

BACKGROUND: Increased sympathetic activity may be an underlying mechanism in cardiovascular disease. It has been hypothesized that the degree of left ventricular (LV) hypertrophy is partly related to the blood pressure level, and partly to neurohormonal factors. The aim of this study was to investigate predictors of LV mass, including arterial plasma noradrenaline as an index of sympathetic activity, with particular emphasis on subjects who developed hypertension over a period of 20 years. METHODS: In a 20-year prospective study of middle-aged men, sustained hypertensives (n = 22), new hypertensives (crossovers) (n = 17) and sustained normotensives (controls) (n = 17) were examined both at baseline and after 20 years of follow-up (at ages 42.1 +/- 0.5 and 62.3 +/- 0.6 years, respectively). Relationships between arterial plasma catecholamines, blood pressure and body mass index at baseline to left ventricular parameters by echocardiography at follow-up were investigated. RESULTS: Groups were homogeneous regarding age, gender, race and body build. The group of sustained hypertensives had significantly more LV hypertrophy (P = 0.025) and diastolic dysfunction (P = 0.010). Among the crossovers, LV mass index was positively correlated to arterial plasma noradrenaline (r = 0.50, P = 0.043) and body mass index (BMI) (r = 0.51, P = 0.039) and showed a positive trend with systolic blood pressure (SBP) at baseline. Arterial plasma noradrenaline (beta = 0.47) was found to predict LV mass index after 20 years independently of BMI (beta = 0.45) and SBP (beta = 0.22) at baseline (R adjusted = 0.345, P = 0.037). Such a relationship was not found in the controls or in the sustained hypertensives, of which 16 were treated with antihypertensive drugs. CONCLUSIONS: Arterial plasma noradrenaline at baseline, as an index of sympathetic activity, predicts LV mass at follow-up independently of systolic blood pressure and body build in middle-aged men who developed hypertension over a period of 20 years.

Thalidomide attenuates the development of fibrosis during post-infarction myocardial remodelling in rats.

BACKGROUND: Inflammation plays a pathogenic role in the development of heart failure (HF). The aim of this study was to examine the effect of treatment with the immunomodulating drug thalidomide in a rat model for post-myocardial infarction (MI) HF. METHODS: Rats were subjected to MI by left coronary artery ligation or sham-operated. Seven days after surgical intervention rats were randomised to treatment with thalidomide or vehicle for 8 weeks. RESULTS: Our main findings were: (i) thalidomide treatment did not affect cardiac function or the hypertrophic response, as determined by haemodynamic measurements and heart chamber weights, respectively. (ii) HF rats treated with thalidomide had a minor reduction in septum and relative wall thickness (p<0.05), indicating an anti-remodelling effect. (iii) Thalidomide appeared to have immunostimulatory effects on the myocardium as evident by increased MIP-1alpha gene expression (p<0.05). (iv) Treating HF rats with thalidomide reduced myocardial collagen content, as assessed by markedly decreased levels of hydroxyproline ( approximately 40% reduction; p<0.05), accompanied by lower TGF-beta(1) gene expression (p<0.05). CONCLUSION: Although thalidomide had no effect on cardiac function, our results suggest that intervention with thalidomide may have beneficial effects in post-MI HF by attenuating collagen accumulation and development of myocardial fibrosis.

[Cardiogenic shock-- new therapeutic strategies]. / Kardiogent sjokk--nye behandlingsmuligheter.

BACKGROUND: Cardiogenic shock is a condition associated with high mortality. The evidence base for choice of treatment is insufficient, but new therapeutic options and new understanding have lead to some improvement in the prognosis. A new class of heart failure medication is now approved in Norway (calcium sensitizers). METHODS: We present a case history that illustrates new options in the treatment of cardiogenic shock complicating acute myocardial infarction. We have searched available literature and give a review of the treatment of cardiogenic shock with special emphasis on the role of inotropic drug therapy. RESULTS AND INTERPRETATION: A 46-year-old man with cardiogenic shock complicating myocardial infarction because of occlusion of the left-main coronary artery was treated with acute revascularization, intra-aortic balloon counterpulsation (IABP) and levosimendan. Early revascularization is a key factor in the treatment of cardiogenic shock; rapid transfer of patients to a revascularization centre is recommended. IABP should be considered after successful revascularization because of post-ischaemic dysfunction that persists despite restoration of epicardial blood flow. Beta-adrenergic stimulation of the heart should, if possible, be avoided, because of increased myocardial oxygen requirement, calcium overload of the cardiomyocytes, and increased mortality. Drug therapy using calcium sensitizers is promising, but more controlled clinical trials are needed.

Quantification of left ventricular diastolic pressure-volume relations during routine cardiac catheterization by two-dimensional digital echo quantification and left ventricular micromanometer.

BACKGROUND: Currently there is no simple clinical method for quantifying the left ventricular (LV) diastolic pressure-volume relation. Echocardiographic-automated endocardial border detection, however, may be combined with LV micromanometer to construct LV pressure-volume loops. We investigated the feasibility of on-line display and sampling of LV pressure-volume loops by such an approach. For this purpose we used a new echocardiographic digital echo quantification (DEQ) method in combination with LV pressures on-line and in real-time. METHODS: Eighteen patients were screened by conventional echocardiography and DEQ. Ten of the patients with high quality images were included in the study. Left ventricular pressures and volumes were recorded simultaneously and were displayed on-line as pressure-volume loops. Changes in LV volume were induced by intravenous saline. Left ventricular chamber compliance was estimated as change in volume divided by change in pressure from minimum diastolic pressure to end-diastolic pressure (average LV chamber compliance). RESULTS: Left ventricular pressure-volume loops were displayed on-line during the examination. When compared with the Simpson's method, DEQ underestimated end-diastolic volume (EDV) by 35% and overestimated end-systolic volume (ESV) by 14%. Beat-to-beat variability for ESV and EDV were 7.4% +/- 0.8% and 7.2% +/- 0.7 %, respectively. Volume loading increased LV end-diastolic pressure (LVEDP) from 14.0 +/- 1.6 to 24.7 +/- 2.0 mm Hg (P <.05) and EDV from 79 +/- 10 to 85 +/- 11 mL (NS), and decreased LV chamber compliance from 4.0 +/- 0.7 to 2.0 +/- 0.3 mL/mm Hg (P <.05). CONCLUSION: The current study demonstrates that LV pressure-volume loops can be displayed and evaluated in real-time during routine cardiac catheterization. This may represent a clinically useful method for identifying patients with reduced chamber compliance. The underestimation of the volumes by DEQ compared with the Simpson's method suggests that further refinements should be performed to improve the endocardial border detection algorithm.

The effect of aortic valve replacement on N-terminal natriuretic propeptides in patients with aortic stenosis.

BACKGROUND: Increased plasma concentrations of natriuretic peptides have been demonstrated to be associated with increased intracardiac pressure and left ventricular (LV) hypertrophy. After aortic valve replacement (AVR) in aortic stenosis patients, there is a relief of the left outflow obstruction with a substantial hemodynamic improvement. This is followed by a gradual regression of the LV hypertrophy. HYPOTHESIS: After AVR, reduction in LV filling pressure is expected to occur rapidly, while regression of LV hypertrophy will take place over a longer time period. On this basis we hypothesized that the plasma levels of N-terminal proatrial natriuretic peptide (NT-proANP) would be reduced early in the postoperative period, while N-terminal probrain natriuretic peptide (NT-proBNP), through its closer reflection of LV hypertrophy, would be sustained for a longer period. METHODS: Two groups of patients with aortic stenosis undergoing AVR were followed for 4 and 12 months, respectively. Plasma concentrations of NT-proANP and NT-proBNP were measured before and after AVR and related to preoperative findings and changes in the aortic valve area index. RESULTS: Before AVR, the patients had significantly increased plasma levels of NT-proANP and NT-proBNP. After AVR, NT- proANP was decreased at 4 and 12 months but remained elevated compared with controls. N-terminal-proBNP tended to decrease, but did not change significantly. When the patients were followed for 12 months, only those with elevated preoperative pulmonary capillary wedge pressure had decreased peptide levels (NT-proANP: p = 0.017, NT-proBNP: p = 0.058). There was no regression of LV hypertrophy. The patients with the largest postoperative valve area index [1.27 (1.10-1.55) cm2/m2] had the largest reduction of NT-proBNP (47%). Those with the smallest valve area index [0.67 (0.54-0.73) cm2/m2] had no decrease in NT-proBNP. CONCLUSIONS: Our study suggests that a reduction in left atrial pressure is the main factor causing the change of NT-proANP level after AVR. A small prosthetic valve orifice area with a high aortic valve gradient might prevent regression of LV hypertrophy, thus representing a stimulus for increased cardiac secretion of NT-proBNP.