Assessment of longitudinal strain in acute ST-Elevation Myocardial Infarction.

INTRODUCTION : Coronary Artery Disease is the leading cause of death worldwide. Every year about 100,000 people in the United States suffer acute Myocardial Infarction (AMI)1. The AMI incidence though shows declining trend in the west it is on the rise in the developing world. Effective management of this increasing epidemic imposes a technical challenge as well as a socioeconomic burden to the third world countries. In addition to the routine clinical and Electrocardiographic (ECG) evaluation, Echocardiography is an integral part of AMI management. Assessment of overall Left ventricular (LV) function and the regional wall motion of individual myocardial segments is the essence of Echocardiography in the patients with AMI. Traditionally the regional wall motion is assessed subjectively by 2D imaging and objectively by calculation of wall motion score index. Global LV function is usually assessed by Teichzolts and Simpson`s methodologies. These modalities have their own limitations in patients with Acute myocardial infarction. Tissue Doppler imaging offsets some of the disadvantages of 2D echocardiography but by itself has several disadvantages in the assessment of regional and overall LV function. The introduction of Strain imaging has added substance to the imaging of patients with AMI. Strain and strain rate imaging has overcome the disadvantages of 2D as well as Tissue Doppler imaging and has stood the test of time since its introduction a decade ago. The modality of Strain imaging is fast advancing with the initial reports of Doppler based strain imaging now giving way to strain by 2D Speckle tracking. This study utilizes Longitudinal strain derived by 2D speckle tracking for assessment of regional and global LV function in patients with AMI and compares the same with traditional parameters like Wall motion score index and 2D derived Ejection Fraction (EF). AIM OF THE STUDY : To assess longitudinal strain of individual segments and global LV function by strain imaging in patients with acute ST‐elevation myocardial infarction and to compare them with wall motion score index and Simpson`s method respectively. CONCLUSION : Echocardiography, done using two methods‐ subjective assessment of wall motion as well as objective measurement of deformation (strain), in patients with acute myocardial infarction detected myocardial regions involved as well as the overall Left Ventricular function. These measurements, the WMSI and Strain correlated with each other with regards to the regional as well as global LV function. Analysis based on coefficient of correlation showed peak systolic longitudinal strain as good as WMSI in this prediction. Thus, advanced technological analysis of wall motion using strain imaging did contribute additional value compared with a conventional assessment such as wall motion score index and Simpson`s method

Hodnocení myokardiální energetiky pomocí strain echokardiografie

2nd Department of Medicine - Clinical Department of Cardiology and AngiologyII. interní klinika - klinika kardiologie a angiologie 1.LF a VFN v PrazeFirst Faculty of Medicine1. lékařská fakult

Myocardial perfusion and resistive vessel function in coronary artery disease

Myocardial blood flow (MBF) is regulated by the coronary resistive vessels which continuously adapt the coronary blood flow he myocardial metabolic requirements, modulated by neural and humoral mechanisms, and this adaptation can compensate for increased resistance of an epicardial stenosis to a considerable extent. In patients with coronary artery disease, we postulate t dysfunction of the coronary resistive vessels may cause or contribute to myocardial ischaemia. Thus, impaired myocardial fusion maybe due to the abnormal behaviour of collateral and resistive vessels rather than to epicardial disease alone. We ipose that this alteration in resistive vessel function occurs, not only in regions subtended by epicardial disease, but is present in rote myocardium and may be altered by coronary intervention such as coronary angioplasty (PTCA) and after myocardial irction (MI). To investigate coronary resistive vessel function, positron emission tomography (PET) may be used to evaluate ional MBF using the flow tracer lsO-labelled water. Using vasodilator (or vasoconstrictor) stimuli, the coronary vasodilator ponse (CVR=maximal/basal coronary [myocardial] blood flow), an index of coronary resistive vessel function, may be measured 1 compared in regions of interest and in remote myocardium.Recovery of Resistive Vessel Dysfunction After Successful PTCA. To investigate the frequency and the time course of abnormal onary resistive vessel function after successful PTCA, patients with single vessel coronary disease and normal left ventricular ction underwent intracoronary (IC) Doppler measurement of coronary flow velocity, before and after successful PTCA, at basal I after intravenous (IV) dipyridamole. PET was performed on 3 occasions after PTCA. There was no change in CVR at Doppler ;r PTCA. In patients without restenosis, the CVR was reduced in the PTCA region for >7 days, but returned to normal at 3 nths, due to increased basal MBF for >7 days in the PTCA region, with a reduction in the dipyridamole-induced maximal MBF > 24 hours.Altered Nitric Oxide Synthesis/Release and Resistive Vessel Dysfunction After PTCA. Impaired production or release of nitric de (NO) in the from resistive vessel endothelium may cause this alteration in the CVR after PTCA. As the CVR to exogenous rates is enhanced by the endothelial dysfunction, large doses of IC sodium nitroprusside, an NO donor, were infused at the peak ?ct of IV dipyridamole to test this hypothesis using Doppler catheterisation in patients with single vessel disease, roprusside in doses sufficient to cause ultimately a fall in blood pressure did not augment the dipyridamole-induced increase in onary blood flow velocity.Altered Flow and Metabolism in Regions Subtended by Angiographically Normal Arteries in Coronary Artery Disease. The ional CVR was measured using PET in patients with stable single vessel disease. In a second group of patients and controls, [ultaneous arterial and great cardiac vein catheterisation was done at rest and during atrial pacing to measure myocardial tabolism in regions subtended by a diseased artery or by an angiographically normal artery with epicardial disease elsewhere. ; CVR was reduced in remote regions compared to controls. In the second group, at maximal pacing, there was net lactate duction in the diseased region compared to net extraction in both the remote and control.Resistive Vessel Dysfunction in Infarcted and Remote Myocardium After MI. To investigate acute resistive vessel dysfunction, ients were studied after thrombolysis for MI. Regional MBF and the CVR in infarct and remote regions was assessed, after a an of 8 days and 6 months after MI by PET. At early scanning^ the CVR was markedly reduced in the infarct region, and was tted to the amount of residual viable tissue. There was no correlation between the CVR and residual stenosis area. The remote R was less than that in remote regions, subtended by a normal artery, in controls with stable single vessel disease without MI. late scanning, the CVR improved in the infarct region, but the CVR in the remote region still remained lower than in controls.Impaired Flow Response to Cold Pressor in Collateral-Dependent Myocardium. To investigate the response of collateralpendent myocardium to reflex sympathetic stimulation (cold pressor stress), patients with stable angina and normal left itricular function were studied, in whom one coronary artery was occluded (without previous MI), and the other arteries were ;iographically normal supplying collaterals. Regional MBF and glucose uptake (using 18F-deoxyglucose) was measured using r at basal and at cold pressor. With cold pressor, no patients developed ECG changes. The cold pressor response (cold ssor/basal MBF) was low in the collateralised region, compared to remote regions, due to vasoconstriction in the majority, but in absence of demonstrable ischaemia.In summary, there is coronary resistive vessel dysfunction after PTCA which recovers over 3 months due to acute impairment of response to dipyridamole and a longer increase in basal flow, possibly due to the previous stenosis. This impairment is not due iltered production or release of NO in the microcirculation. In stable disease, there is both an impaired CVR and altered tabolism during pacing in regions subtended by a normal artery. This remote alteration is impaired acutely by myocardial irction elsewhere, with only incomplete recovery over at least 6 months. In addition to reduced vasodilator function, resistive sels in patients with atherosclerosis, have an increased tendency to vasoconstrict to a sympathetic stimulus. Thus, the erosclerotic process and the sympathetic nervous system may both play a role in determining the degree of resistive vessel function, which may cause or contribute to myocardial ischaemia in patients with coronary artery disease

Diagnostic and prognostic value of free PAPP-A in coronary artery disease – clinical studies with novel immunoassay

Complications of coronary artery disease are the number one cause of death worldwide, so identification of high-risk individuals is crucial. Pregnancy-associated plasma protein A (PAPP-A) is a candidate cardiac-risk related biomarker, which has been linked to poorer outcome in various cardiovascular patients. Especially, the free form of PAPP-A (fPAPP-A) is linked to cardiovascular events, but thus far no direct assay detecting fPAPP-A has been published. Most available assays measure total PAPP-A and are widely used in prenatal screening where high concentration changes occur. Thus, cardiac-related slight fPAPP-A changes might be undetectable with total PAPP-A assays. Also, PAPP-A is released to circulation after heparin treatment, which is a common anticoagulant used in dissolving thrombus. This might question the ability of PAPP-A to be used as a marker for haparinized patients. I n this thesis, first direct immunoassay targeting fPAPP-A was created and its analytical and clinical performance as cardiac-risk related biomarker was evaluated. The analytical performance of the fPAPP-A assay was evaluated against current guidelines. The risk of death or myocardial infarction in patients admitted to hospital due to chest pain was studied and compared to tPAPP-A and indirect fPAPP-A assays. The developed assay was also used in predicting obstructive CAD in suspected chronic CAD patients. The disease extent and severity was determined with hybrid computed tomography and positron emission tomography myocardial perfusion imaging. Correlation of heparin-induced release of fPAPP-A and atherosclerotic burden was studied in suspected chronic CAD patients. The developed assay sensitively measured fPAPP-A. The risk of death or myocardial infarction correlated with increasing circulating fPAPP-A concentration. Also, fPAPP-A in combination with contemporary cTnI further improved the riskpredictive capability. Accordingly, the fPAPP-A level was elevated in chronic CAD patients who were diagnosed with obstructive CAD. As a biomarker, fPAPP-A outperformed traditional risk factors and other evaluated biomarkers in predicting obstructive CAD. Heparin-induced release of fPAPP-A to circulation was not associated with clinical coronary atherosclerotic characteristristics observed with coronary computed tomography angiography.Suoralla menetelmällä mitattu vapaa PAPP-A diagnostisena ja ennustavana merkkiaineena sepelvaltimotaudissa Sepelvaltimotautiin liittyvät komplikaatiot ovat yleisin kuolinsyy maailmassa, jonka vuoksi korkean riskin potilaiden tunnistaminen ajoissa on tärkeää. Raskauteen liittyvä plasmaproteiini A (PAPP-A) on lupaava merkkiaine, joka on yhdistetty erilaisilla sydänpotilailla heikompaan selviytymiseen ilman sydäntapahtumia. Erityisesti PAPP-A:n vapaa muoto (fPAPP-A) on liitetty sydäntapahtumiin, mutta suoraa määritysmenetelmää fPAPP-A:lle ei ole vielä kehitetty. Useimmat määritykset mittaavat kaikkia PAPP-A:n muotoja ja niitä käytetään raskaudenaikaiseen seulontaan, jolloin pitoisuusmuutokset ovat suuria. Tällaisella määrityksellä mitattuna sydäntapahtumien yhteydessä tapahtuvat pienet fPAPP-A -muutokset saattavat jäädä huomioimatta. PAPP-A:ta vapautuu verenkiertoon myös verihyytymien liuottamiseen käytetyn hepariinilääkityksen vuoksi. Tämä saattaa kyseenalaistaa PAPP-A:n käytön merkkiaineena hepariinilääkityillä potilailla. Väitöskirjatyössä kehitettiin ensimmäinen suora fPAPP-A:ta mittaava immunomääritys. Määrityksen analyyttista toimivuutta evaluoitiin kliinisen kemian ohjeistusten mukaisesti. FPAPP-A:n käyttöä sydänkohtaukseen tai kuolemaan liitettynä merkkiaineena tutkittiin rintakivun vuoksi sairaalaan saapuneilta potilailta ja tuloksia verrattiin epäsuoralla menetelmällä mitattuun fPAPP-A:han sekä kaikkia PAPP-A:n muotoja mittaavaan määritykseen. Lisäksi, fPAPP-A:n yhteyttä ahtauttavaan sepelvaltimotautiin tarkasteltiin epäillyillä vakaaoireisilla sepelvaltimotautipotilailla. Sepelvaltimotaudin vakavuuden ja laajuuden määrittäimiseen käytettiin hybridikuvantamista, jossa hyödynnetään tietokonetomografiaa ja isotooppitutkimusta. Samoilla potilailla tutkittiin myös hepariinin vapauttaman fPAPPA:n yhteyttä sepelvaltimotaudin vaikeusasteeseen. Kehitetty määritys oli herkkä mittaamaan fPAPP-A:ta. Kohonnut fPAPP-A oli yhteydessä suurentuneeseen sydänkohtauksen tai kuoleman riskiin. Yhdistettynä sydänperäisen troponiini I:n kanssa, kyky ennustaa riskä parani entisestään. Lisäksi, ahtauttavaa sepelvaltimotautia sairastavilla potilailla oli kohonnut fPAPP-A - pitoisuus ja fPAPP-A toimi paremmin kuin perinteiset riskitekijät tai muut mitatut merkkiaineet. Hepariinin vuoksi verenkiertoon vapautunut fPAPP-A ei ollut yhteydessä selvaltimotaudin vakavuuteen tai laajuuteen

Evaluation of Macrophage-Targeting PET Tracers for Imaging Inflammation in Atherosclerosis

Atherosclerosis is an inflammatory disease which is characterized by accumulation of lipids in the vascular wall. The rupture of atherosclerotic plaque is often behind the leading causes of death in the Western world: myocardial infarction and stroke. Plaques prone to rupture are often inflamed and contain large numbers of immune cells, especially macrophages. The detection of inflammation has been studied by new imaging techniques, such as positron emission tomography (PET). The aim of this thesis was to evaluate macrophage-targeting PET tracers for the imaging of inflammation in atherosclerosis and to evaluate responses to interventions using an established PET tracer. The studies were conducted in two mouse models. In vivo imaging, ex vivo biodistribution and aortic autoradiography were utilized to assess the tracer uptake in atherosclerotic arteries. Plasma biomarker measurements and histological stainings were conducted to assess the inflammation and the presence of tracer targets. The effects of dietary and atorvastatin interventions on aortic inflammation and uptake of an established tracer, 18F-FDG, were studied. Of the studied tracers, 18F-FMCH showed the highest potential. 18F-FEMPA, 68Ga-DOTANOC, and 68 Ga-DOTATATE also showed suitable characteristics for in vivo imaging with certain limitations, whereas 18F-FDR-NOC was not suitable. Compared to mice on high-fat food, dietary intervention led to attenuated aortic inflammation and lower 18F-FDG uptake, whereas atorvastatin alone had no effect. In conclusion, the macrophage-targeting tracers showed potential for the imaging of inflammation in atherosclerosis, especially 18F-FMCH, which will be further studied in a clinical setting. The therapy responses could be assessed in a mouse model with 18F-FDG.Siirretty Doriast

Usefulness of Tissue Doppler Imaging for the Diagnosis of Coronary Artery Disease in patients with Left Bundle Branch Block.

Back ground: Non-invasive diagnosis of LAD stenosis in patients with LBBB is particularly difficult because of the well known ECG limitations, echocardiographic abnormal septal wall motion and possible myocardial scintigraphic antero-septal perfusion defect artifacts. Recent reports show that Tissue Doppler derived Post-systolic motion, an asynchronous contraction occurring during an isovolumetric relaxation period is a sensitive and specific marker for LAD occlusion. Aim: The aim of this study was to analyze the usefulness of TDI and to characterize PSM in LBBB with or without stenosis of the left anterior descending coronary artery (LAD). Methods and Materials: 28 patients with chest pain with out prior myocardial infarction and complete LBBB were included for the study. Standard Doppler echocardiography and tissue Doppler of both the middle posterior septum and lateral mitral annulus were performed in the apical 4-chamber view. Tissue Doppler-derived septal PSM were measured and all patients underwent coronary angiography within 1 month. Results: Angiographically the study populations were divided into two groups. 13 without LAD stenosis and 15 with LAD stenosis.[ LAD stenosis > 50% ]. The Clinical, ECG and standard doppler diastolic indexes were comparable between the two groups. Septal tissue Doppler showed lower myocardial systolic (Sm) and atrial peak velocities (both p 2cm/sec; p < 0.005), in patients with LAD stenosis. A Sm/PSM ratio < 1 was detected in 93.3 % of patients [14/15] with LAD stenosis (sensitivity 93.3%, specificity 100%). 30 %[4/13] patients without LAD stenosis also had PSM but with a Sm/PSM ratio <1. Conclusion: Pulsed Tissue Doppler derived high amplitude Post Systolic Motion and reduced systolic myocardial velocity are simple, non invasive markers with high sensitivity and specificity to diagnose LAD disease in the presence of LBBB

Hybrid Imaging for the Detection of Obstructive Coronary Artery Disease

ABSTRACT Coronary artery disease (CAD) is globally one of the leading causes of morbidity and mortality. CAD develops over decades when coronary arteries obstruct, typically causing chest pain symptoms and, in the worst case, death. Nowadays, obstructive CAD can be prevented and treated with modern and potent therapies; hence, accurate diagnostic tools have become more important. The aim of this thesis was to evaluate hybrid imaging techniques, i.e., combinations of two imaging techniques, for use in the detection of obstructive CAD. We evaluated the feasibility and accuracy of combined coronary computed tomography angiography (CTA) and either positron emission tomography (PET) myocardial perfusion imaging or coronary Doppler ultrasound to detect obstructive CAD in 107 symptomatic patents with an intermediate (30–70%) pretest probability of disease. Techniques were compared with invasive coronary angiography combined with physiological evaluation by fractional flow reserve. Our results showed that hybrid PET-CTA was highly accurate for detecting obstructive CAD and more accurate than either technique alone. Furthermore, measurement of myocardial blood flow by PET during vasodilator stress only was sufficient to evaluate the hemodynamic significance of coronary stenosis. We found that assessment of the coronary flow velocity profile at rest by Doppler ultrasound provides information on the hemodynamic significance of coronary stenosis identified by coronary CTA and may aid in detecting obstructive CAD. These results show the feasibility of hybrid imaging and demonstrate that it provides improved accuracy in detecting obstructive CAD as compared with standalone coronary CTA.TIIVISTELMÄ Sepelvaltimotauti on yksi yleisimmista kuolemaan johtavista sairauksista maailmassa. Tauti kehittyy vuosikymmenten aikana, jolloin sepelvaltimot ahtautuvat aiheuttaen taudille tyypilliset oireet. Nykyisilla, tehokkailla hoitomuodoilla tautia voidaan ennaltaehkaista ja hoitaa, minka vuoksi sairauden tasmallinen diagnostiikka on muodostunut entista tarkeammaksi. Taman vaitoskirjan tavoite oli tutkia hybridikuvantamisen, eli kahden eri kuvantamistutkimuksen yhdistelman diagnostista osuvuutta ahtauttavan sepelvaltimotaudin toteamisessa oireisilla potilailla, joilla taudin todennakoisyys oli keskisuuri. Tutkimme sepelvaltimoiden tietokonetomografian (TT) ja joko positroniemissiotomografia (PET) -menetelmalla mitatun sydanlihaksen verenvirtauksen tai ultraaanella mitatun sepelvaltimovirtausprofiilin yhdistelmaa 107 potilaan aineistossa. Kuvantamismenetelmia verrattiin perinteiseen katetriangiografiaan, jota taydennettiin tarvittaessa sepelvaltimon sisaisella painemittauksella. Tulokset osoittavat, etta sepelvaltimoiden TT:n ja PET-kuvauksen yhdistelma on tarkka menetelma ahtauttavan sepelvaltimotaudin toteamisessa ja yhdistelma on tarkempi kuin kumpikaan menetelma yksin. Sydanlihaksen verenvirtauksen mittaaminen PET kameralla pelkan adenosiinirasituksen aikana ilman levossa tehtavaa mittausta riittaa ahtauttavan sepelvaltimotaudin toteamiseen. Lisaksi havaitsimme, etta sepelvaltimon virtausprofiilin mittaaminen levossa Dopplerultraaanella auttaa sepelvaltimoiden TT -kuvauksessa todetun ahtauman vaikeusasteen arvioinnissa ja voi auttaa taudin diagnostiikassa. Hybridikuvantaminen parantaa ahtauttavan sepelvaltimotaudin diagnostiikkaa verrattuna pelkkaan sepelvaltimoiden TT-kuvaukseen. Hybridikuvantaminen on toteutettavissa kliinisessa diagnostiikassa

Remote Ischemic Pre-Conditioning Attenuates Adverse Cardiac Remodeling and Mortality Following Doxorubicin Administration in Mice

Objectives Because of its multifaceted cardioprotective effects, remote ischemic pre-conditioning (RIPC) was examined as a strategy to attenuate doxorubicin (DOX) cardiotoxicity. Background The use of DOX is limited by dose-dependent cardiotoxicity and heart failure. Oxidative stress, mitochondrial dysfunction, inflammation, and autophagy modulation have been proposed as mediators of DOX cardiotoxicity. Methods After baseline echocardiography, adult male CD1 mice were randomized to either sham or RIPC protocol (3 cycles of 5 min femoral artery occlusion followed by 5 min reperfusion) 1 h before receiving DOX (20 mg/kg, intraperitoneal). The mice were observed primarily for survival over 85 days (86 mice). An additional cohort of 50 mice was randomized to either sham or RIPC 1 h before DOX treatment and was followed for 25 days, at which time cardiac fibrosis, apoptosis, and mitochondrial oxidative phosphorylation were assessed, as well as the expression profiles of apoptosis and autophagy markers. Results Survival was significantly improved in the RIPC cohort compared with the sham cohort (p = 0.007). DOX-induced cardiac fibrosis and apoptosis were significantly attenuated with RIPC compared with sham (p \u3c 0.05 and p \u3c 0.001, respectively). Although no mitochondrial dysfunction was detected at 25 days, there was a significant increase in autophagy markers with DOX that was attenuated with RIPC. Moreover, DOX caused a 49% decline in cardiac BCL2/BAX expression, which was restored with RIPC (p \u3c 0.05 vs. DOX). DOX also resulted in a 17% reduction in left ventricular mass at 25 days, which was prevented with RIPC (p \u3c 0.01), despite the lack of significant changes in left ventricular ejection fraction. Conclusions Our preclinical results suggested that RIPC before DOX administration might be a promising approach for attenuating DOX cardiotoxicity

Coronary Angiography

In the intervening 10 years tremendous advances in the field of cardiac computed tomography have occurred. We now can legitimately claim that computed tomography angiography (CTA) of the coronary arteries is available. In the evaluation of patients with suspected coronary artery disease (CAD), many guidelines today consider CTA an alternative to stress testing. The use of CTA in primary prevention patients is more controversial in considering diagnostic test interpretation in populations with a low prevalence to disease. However the nuclear technique most frequently used by cardiologists is myocardial perfusion imaging (MPI). The combination of a nuclear camera with CTA allows for the attainment of coronary anatomic, cardiac function and MPI from one piece of equipment. PET/SPECT cameras can now assess perfusion, function, and metabolism. Assessing cardiac viability is now fairly routine with these enhancements to cardiac imaging. This issue is full of important information that every cardiologist needs to now