A genetic variant of the atrial natriuretic peptide gene is associated with left ventricular hypertrophy in a non-diabetic population - the Malmo preventive project study

Background: Epidemiological studies have shown considerable heritability of blood pressure, thus suggesting a role for genetic factors. Previous studies have shown an association of a single nucleotide polymorphism rs5068 in the NPPA locus gene with higher levels of circulating atrial natriuretic peptide as well as with lower intra individual blood pressure, but up to date, no association between rs5068 and cardiac organ damage, i.e. left ventricular hypertrophy, has been accounted for in humans. We sought to explore if rs5068 is associated with left ventricular hypertrophy as measured by echocardiographic examination in a non-diabetic population. Methods: 968 non-diabetic individuals from the Malmo Preventive Project (mean age 67 years; 31% women) were genotyped and examined with echocardiography. Logistic regression was used to adjust for covariates. Results: The minor allele of rs5068 was associated with decreased prevalence of left ventricular hypertrophy (p = 0.021) after adjustment for sex and age. In the multivariate logistic analysis including; age, sex, systolic blood pressure, antihypertensive and/or cardioprotective treatment, body mass index and fasting plasma glucose, the association of rs5068 with left ventricular hypertrophy was, as expected, attenuated (p = 0.061). Conclusion: In a non-diabetic population, the minor allele of rs5068 was associated with lower left ventricular mass. These findings suggest that rs5068, or genetic variants in linkage disequilibrium, might affect susceptibility to left ventricular hypertrophy and support the possible protective role of natriuretic peptides

Assessing left ventricular systolic function in shock: evaluation of echocardiographic parameters in intensive care

Introduction: Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE). Methods: Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI). Results: EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively), and worst for the Simpson method (8.2% and 10.6%, respectively). Conclusions: EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction

Visually estimated ejection fraction by two dimensional and triplane echocardiography is closely correlated with quantitative ejection fraction by real-time three dimensional echocardiography

<p>Abstract</p> <p>Background</p> <p>Visual assessment of left ventricular ejection fraction (LVEF) is often used in clinical routine despite general recommendations to use quantitative biplane Simpsons (BPS) measurements. Even thou quantitative methods are well validated and from many reasons preferable, the feasibility of visual assessment (eyeballing) is superior. There is to date only sparse data comparing visual EF assessment in comparison to quantitative methods available. The aim of this study was to compare visual EF assessment by two-dimensional echocardiography (2DE) and triplane echocardiography (TPE) using quantitative real-time three-dimensional echocardiography (RT3DE) as the reference method.</p> <p>Methods</p> <p>Thirty patients were enrolled in the study. Eyeballing EF was assessed using apical 4-and 2 chamber views and TP mode by two experienced readers blinded to all clinical data. The measurements were compared to quantitative RT3DE.</p> <p>Results</p> <p>There were an excellent correlation between eyeballing EF by 2D and TP vs 3DE (r = 0.91 and 0.95 respectively) without any significant bias (-0.5 ± 3.7% and -0.2 ± 2.9% respectively). Intraobserver variability was 3.8% for eyeballing 2DE, 3.2% for eyeballing TP and 2.3% for quantitative 3D-EF. Interobserver variability was 7.5% for eyeballing 2D and 8.4% for eyeballing TP.</p> <p>Conclusion</p> <p>Visual estimation of LVEF both using 2D and TP by an experienced reader correlates well with quantitative EF determined by RT3DE. There is an apparent trend towards a smaller variability using TP in comparison to 2D, this was however not statistically significant.</p

Quantitative detection of myocardial ischaemia by stress echocardiography; a comparison with SPECT

<p>Abstract</p> <p>Aims</p> <p>Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique angio-mode (AM), provides images for off-line perfusion quantification using Qontrast^®software, generating values of peak signal intensity (A), myocardial blood flow velocity (β) and myocardial blood flow (Axβ). By comparing rest and stress values, their respective reserve values (A-r, β-r, Axβ-r) are generated. We evaluated myocardial ischaemia by RTP-ASE Qontrast^®quantification, compared to visual perfusion evaluation with ^99mTc-tetrofosmin single-photon emission computed tomography (SPECT).</p> <p>Methods and Results</p> <p>Patients admitted to SPECT underwent RTP-ASE (SONOS 5500) using AM during Sonovue^®infusion, before and throughout adenosine stress, also used for SPECT. Visual myocardial perfusion and wall motion analysis, and Qontrast^®quantification, were blindly compared to one another and to SPECT, at different time points off-line.</p> <p>We analyzed 201 coronary territories (left anterior descendent [LAD], left circumflex [LCx] and right coronary [RCA] artery territories) in 67 patients. SPECT showed ischaemia in 18 patients and 19 territories. Receiver operator characteristics and kappa values showed significant agreement with SPECT only for β-r and Axβ-r in all segments: area under the curve 0.678 and 0.665; P < 0.001 and < 0.01, respectively. The closest agreements were seen in the LAD territory: kappa 0.442 for both β-r and Axβ-r; P < 0.01. Visual evaluation of ischaemia showed good agreement with SPECT: accuracy 93%; kappa 0.67; P < 0.001; without non-interpretable territories.</p> <p>Conclusion</p> <p>In this agreement study with SPECT, RTP-ASE Qontrast^®quantification of myocardial ischaemia was less accurate and less feasible than visual evaluation and needs further development to be clinically useful.</p

Head to head comparisons of two modalities of perfusion adenosine stress echocardiography with simultaneous SPECT

<p>Abstract</p> <p>Background</p> <p>Real-time perfusion (RTP) contrast echocardiography can be used during adenosine stress echocardiography (ASE) to evaluate myocardial ischemia. We compared two different types of RTP power modulation techniques, angiomode (AM) and high-resolution grayscale (HR), with ^99mTc-tetrofosmin single-photon emission computed tomography (SPECT) for the detection of myocardial ischemia.</p> <p>Methods</p> <p>Patients with known or suspected coronary artery disease (CAD), admitted to SPECT, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using AM and HR during Sonovue^®infusion, before and throughout the adenosine stress, also used for SPECT. Analysis of myocardial perfusion and wall motion by RTP-ASE were done for AM and HR at different time points, blinded to one another and to SPECT. Each segment was attributed to one of the three main coronary vessel areas of interest.</p> <p>Results</p> <p>In 50 patients, 150 coronary areas were analyzed by SPECT and RTP-ASE AM and HR. SPECT showed evidence of ischemia in 13 out of 50 patients. There was no significant difference between AM and HR in detecting ischemia (p = 0.08). The agreement for AM and HR, compared to SPECT, was 93% and 96%, with Kappa values of 0.67 and 0.75, respectively (p < 0.001).</p> <p>Conclusion</p> <p>There was no significant difference between AM and HR in correctly detecting myocardial ischemia as judged by SPECT. This suggests that different types of RTP modalities give comparable data during RTP-ASE in patients with known or suspected CAD.</p

Flow-volume loops derived from three-dimensional echocardiography: a novel approach to the assessment of left ventricular hemodynamics

BACKGROUND: This study explores the feasibility of non-invasive evaluation of left ventricular (LV) flow-volume dynamics using 3-dimensional (3D) echocardiography, and the capacity of such an approach to identify altered LV hemodynamic states caused by valvular abnormalities. METHODS: Thirty-one patients with moderate-severe aortic (AS) and mitral (MS) stenoses (21 and 10 patients, respectively) and 10 healthy volunteers underwent 3D echocardiography with full volume acquisition using Philips Sonos 7500 equipment. The digital 3D data were post- processed using TomTec software. LV flow-volume loops were subsequently constructed for each subject by plotting instantaneous LV volume data sampled throughout the cardiac cycle vs. their first derivative representing LV flow. After correction for body surface area, an average flow-volume loop was calculated for each subject group. RESULTS: Flow-volume loops were obtainable in all subjects, except 3 patients with AS. The flow-volume diagrams displayed clear differences in the form and position of the loops between normal individuals and the respective patient groups. In patients with AS, an "obstructive" pattern was observed, with lower flow values during early systole and larger end-systolic volume. On the other hand, patients with MS displayed a "restrictive" flow-volume pattern, with reduced diastolic filling and smaller end-diastolic volume. CONCLUSION: Non-invasive evaluation of LV flow-volume dynamics using 3D-echocardiographic data is technically possible and the approach has a capacity to identify certain specific types of alteration of LV flow-volume pattern caused by valvular abnormalities, thus reflecting underlying hemodynamic states specific for these abnormalities

Three-dimensional echocardiography using single-heartbeat modality decreases variability in measuring left ventricular volumes and function in comparison to four-beat technique in atrial fibrillation

BACKGROUND: Three dimensional echocardiography (3DE) approaches the accuracy of cardiac magnetic resonance in measuring left ventricular (LV) volumes and ejection fraction (EF). The multibeat modality in comparison to single-beat (SB) requires breath-hold technique and regular heart rhythm which could limit the use of this technique in patients with atrial fibrillation (AF) due to stitching artifact. The study aimed to investigate whether SB full volume 3DE acquisition reduces inter- and intraobserver variability in assessment of LV volumes and EF in comparison to four-beat (4B) ECG-gated full volume 3DE recording in patients with AF. METHODS: A total of 78 patients were included in this study. Fifty-five with sinus rhythm (group A) and 23 having AF (group B). 4B and SB 3DE was performed in all patients. LV volumes and EF was determined by these two modalities and inter- and intraobserver variability was analyzed. RESULTS: SB modality showed significantly lower inter- and intraobserver variability in group B in comparison to 4B when measuring LV volumes and EF, except for end-systolic volume (ESV) in intraobserver analysis. There were significant differences when calculating the LV volumes (p<0.001) and EF (p<0.05) with SB in comparison to 4B in group B. CONCLUSION: Single-beat three-dimensional full volume acquisition seems to be superior to four-beat ECG-gated acquisition in measuring left ventricular volumes and ejection fraction in patients having atrial fibrillation. The variability is significantly lower both for ejection fraction and left ventricular volumes

Detection of Myocardial Ischemia using Real-Time Myocardial Contrast Echocardiography

Diagnostisering av syrebrist i hjärtmuskeln med hjälp av kontrastförstärkt ultraljudsundersökning av hjärtmuskelns genomblödning. Ultraljudsundersökning av hjärtat (ekokardiografi) används mycket inom hjärtsjukvården idag, oftast för att utreda hjärtats och hjärtklaffarnas anatomi och funktion. Ekokardiografi är en ofarlig och ganska enkel undersökning och apparaturen som används är förhållandevis billig och mobil om man jämför med andra bildgivande undersökningar av hjärtat, såsom röntgen, isotopundersökning eller magnetresonans tomografi. Syrebrist (ischemi) i hjärtmuskeln uppkommer genom att inte tillräckligt med syreförande blod når ett eller flera områden av hjärtmuskeln, vanligen pga. förträngningar i hjärtats kranskärl. Ischemi orsakar ofta, men inte alltid bröstsmärtor, vilket kallas "kärlkramp" i hjärtat. Utvärdering av ischemi i hjärtmuskeln rekommenderas för optimal behandling av patienter med misstänkt sjukdom i hjärtats kranskärl. Denna utvärdering kan göras med hjälp av olika typer av belastningstest. Metoder som finns att tillgå är arbets-EKG, isotopundersökning (99mTc-sestamibi single-photon emission computed tomography - SPECT) och stress-ekokardiografi. Liksom arbets-EKG utförs både SPECT och stress-ekokardiografi med olika typer av belastning. Belastning vid SPECT sker vanligen genom ergometercykling, men kan också utföras genom provokation med läkemedel (dobutamin, adenosin) som ger en belastning på hjärtmuskeln liknande den vid fysisk ansträngning. Vid stress-ekokardiografi görs belastningen vanligast med dobutamin (dobutamin-atropin stress-ekokardiografi - DSE) men kan också göras med ergometercykling eller adenosin. SPECT påvisar ischemi i hjärtmuskeln genom att jämföra genomblödningen (perfusionen) i hjärtmuskeln vid maximal belastning och vila. Minskad genomblödning under belastning är tecken på ischemi. Genomblödningen i hjärtmuskeln uppskattas vid SPECT genom att en radioaktiv isotop injiceras i patientens blod. Isotopen fördelas i hjärtmuskeln på samma sätt som blodet och strålarna från isotopen kan detekteras av en speciell detektor (gammakamera). Från områden utan eller med nedsatt genomblödning detekteras ingen eller nedsatt strålning och i dessa områden föreligger således ischemi. Vid DSE jämför man vanligen hjärtmuskelns förmåga att dra ihop sig (kontraktionsförmåga) i arbete och vila. Om kontraktionen minskar i någon del av hjärtmuskeln under belastning så talar det för ischemi i detta område. Både SPECT och DSE är väldokumenterade och bättre men dyrare än arbets-EKG. Att belasta hjärtat med dobutamin är ofta påtagligt obehagligt för patienten, medan belastning med adenosin ofta uppfattas som mindre obehaglig. Själva belastningen är dessutom oftast kortare än vid både ergometercykling och dobutamin-belastning. Till skillnad från sedvanlig stress-ekokardiografi räcker det dock inte att bedöma hjärtmuskelns kontraktion vid adenosin-belastning, utan det krävs även att genomblödningen bedöms. Genomblödningen i hjärtmuskeln har inte tidigare varit möjlig att värdera vid adenosin-stress-ekokardiografi (ASE). Det blev dock möjligt för några år sedan, då en typ av ny ultraljuds-kontrastmedel introducerades inom ekokardiografi. Kontrastmedlet för ultraljud som användes inom ramen för denna avhandling var Sonovue. En kombination av ny ultraljudsteknik (realtids perfusion - RTP) och kontrastmedel har gjort det möjligt att samtidigt bedöma genomblödningen i hjärtmuskeln och dess kontraktionsförmåga. Därigenom skulle RTP i kombination med ASE (RTP-ASE) kunna användas för att tillförlitligt detektera ischemi i hjärtmuskeln. Om RTP-ASE visar sig kunna detektera ischemi lika bra som en redan erkänd undersökning, exempelvis SPECT, kan RTP-ASE bli en bra alternativ undersökning. Jämfört med SPECT är RTP-ASE mer tillgänglig och utan radioaktiv strålning, jämfört med DSE är den snabbare och mindre obehaglig, och den är mera noggrann än arbets-EKG.Echocardiography is an ideal clinical method for obtaining information about morphology and function of the heart. Echocardiography is more accessible, mobile and inexpensive compared to other imaging techniques and has become the perhaps most used diagnostic method in cardiology during recent years. To assess myocardial ischemia, different types of stress echocardiography have been available, where mainly wall motion analysis at rest and stress has been used to evaluate the presence and extent of ischemia. During the last few years, second generation contrast agents have become clinically available. This has improved image quality in echocardiography, which, combined with new ultrasound technical developments, has made it possible to obtain echocardiographic images of myocardial perfusion. When this myocardial contrast echocardiography technique is carried out in real-time, as in the studies of this thesis, it is labelled real-time perfusion (RTP). RTP in combination of adenosine stress (RTP-ASE) has the potential to become a valuable clinical tool to evaluate myocardial ischemia. If proven as accurate as other clinically and scientifically accepted methods, such as 99mTc-sestamibi single-photon emission computed tomography (SPECT), RTP-ASE might become an alternative method. Compared to SPECT, it is more accessible, mobile, inexpensive, and without radiation, compared to dobutamine-atropine stress echocardiography (DSE) it is more tolerable and swifter, and it is more accurate than exercise ECG. In all studies of this thesis, we performed RTP-ASE in patients with known or suspected stable coronary artery disease (CAD), admitted to adenosine SPECT evaluation. Adenosine was infused to provoke relative regional hypo-perfusion in ischemic myocardial territories. Using a SONOS 5500 echocardiography machine, patients underwent RTP imaging during Sonovue infusion, before and throughout the adenosine stress, also used for SPECT. RTP images were stored for later, blinded, off-line analysis. In studies III and IV, the commercially available software Qontrast was used to generate parametric images of myocardial perfusion and quantitative values of perfusion replenishment from RTP-ASE image loops. Method of reference for the ischemia evaluation in the thesis was the presence or absence of reversible ischemia at SPECT. The left ventricular myocardium was divided into three territories corresponding to the distribution territories of the three main coronary arteries; left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA). In studies I and II, we investigated the feasibility of RTP-ASE for the detection of ischemia using visual interpretation of RTP-ASE loops acquired at rest and stress. Study III was carried out to examine the value of quantitatively generated parametric perfusion images from RTP-ASE loops, in detecting myocardial ischemia. In study IV, the usefulness of quantitative detection of myocardial ischemia from RTP-ASE loops was assessed. Data comparing quantitative measurements of perfusion replenishment from RTP-ASE images at rest and stress were used as markers of ischemia. The results from the studies in this thesis suggest that visual evaluation of ischemia from RTP-ASE images, using angio-mode as well as high resolution grey scale mode, is accurate and feasible. It is therefore a clinically useful method in patients with known or suspected stable CAD. Quantification of ischemia or parametric imaging for ischemia evaluation using Qontrast, are not yet suitable for clinical use, as judged by the findings of this thesis. However, since further technical development can be expected, quantitative assessment of myocardial perfusion may well be a clinically useful method in the near future