Pawel Petkow Dimitrow

The non-invasive documentation of coronary microcirculation impairment: role of transthoracic echocardiography

Transthoracic Doppler echocardiographic-derived coronary flow reserve is an useful hemodynamic index to assess dysfunction of coronary microcirculation. Isolated coronary microvascular abnormalities are overt by reduced coronary flow reserve despite normal epicardial coronary arteries. These abnormalities may occur in several diseases (arterial hypertension, diabetes mellitus, hypercholesterolemia, syndrome X, aortic valve disease, hypertrophic cardiomyopathy and idiopathic dilated cardiomyopathy). The prognostic role of impaired microvascular coronary flow reserve has been shown unfavourable especially in hypertrophic or idiopathic dilated cardiomyopathies. Coronary flow reserve reduction may be reversible, for instance after regression of left ventricular hypertrophy subsequent to valve replacement in patients with aortic stenosis, after anti-hypertensive treatment or using cholesterol lowering drugs. Coronary flow reserve may increase by 30% or more after pharmacological therapy and achieve normal level >3.0. In contrast to other non invasive tools as positron emission tomography, very expensive and associated with radiation exposure, transthoracic Doppler-derived coronary flow reserve is equally non invasive but cheaper, very accessible and prone to a reliable exploration of coronary microvascular territories, otherwise not detectable by invasive coronary angiography, able to visualize only large epicardial arteries.

Transthoracic Doppler echocardiography – noninvasive diagnostic window for coronary flow reserve assessment

This review focuses on transthoracic Doppler echocardiography as noninvasive method used to assess coronary flow reserve (CFR) in a wide spectrum of clinical settings. Transthoracic Doppler echocardiography is rapidly gaining appreciation as popular tool to measure CFR both in stenosed and normal epicardial coronary arteries (predominantly in left anterior descending coronary artery). Post-stenotic CFR measurement is helpful in: functional assessment of moderate stenosis, detection of significant or critical stenosis, monitoring of restenosis after revascularization. In the absence of stenosis in the epicardial coronary artery, decreased CFR enable to detect impaired microvascular vasodilatation in: reperfused myocardial infarct, arterial hypertension with or without left ventricular hypertrophy, diabetes mellitus, hypercholesterolemia, syndrome X, hypertrophic cardiomyopathy. In these diseases, noninvasive transthoracic Doppler echocardiography allows for serial CFR evaluations to explore the effect of various pharmacological therapies.

Left Ventricular Outflow Tract Gradient Provoked by Upright Position or Exercise in Treated Patients with Hypertrophic Cardiomyopathy without Obstruction at Rest

Objectives: The aim of the study was to assess inducibility of left ventricular outflow tract (LVOT) gradient by change of position from supine to upright and by treadmill exercise in treated patients with hypertrophic cardiomyopathy (HCM) without obstruction at rest. Methods: We studied 37 treated HCM patients (21 men and 16 women, mean age 44 ± 12 years) with LVOT gradient <30 mmHg at rest in supine position. The patients were then placed in upright position and the gradient was reexamined. The patients who developed LVOT gradient ≥30 mmHg during this maneuver were not exercised, whereas the remaining patients (nonobstructive in orthostatic position) performed moderate‐intensity exercise on a treadmill, with continuous monitoring of the LVOT gradient. For comparison with resting measurements, gradients at peak exercise (in upright position) and at recovery (in supine position) were used. The resting minimal distance between the mitral valve and ventricular septum at systole was used to assess the degree of narrowing of LVOT. Results: The orthostatic position provoked LVOT gradient ≥30 mmHg in 8 of 37 patients. At peak exercise, 10 of the remaining 29 patients developed significant LVOT gradient. At recovery in supine position, this significant gradient disappeared in 6 of 10 patients, despite only a short delay in measurement. Of resting echocardiographic parameters, only systolic mitral–septal distance differentiated between the provocable and nonprovocable subgroups. Patients with provocable gradient (either by changing position or by exercise) presented with lower values of this parameter than the nonprovacable subgroup. Conclusions: In nonobstructive HCM patients under treatment, the LVOT gradient was inducible by upright position in 21.6% and by upright moderate exercise in 34.5%. The minimal septal–mitral distance may be useful to identify patients with provocable obstruction.

Obstructive hypertrophic cardiomyopathy is associated with enhanced thrombin generation and platelet activation

Objectives: To investigate the association of left ventricular outflow tract (LVOT) obstruction with blood coagulation, platelet activity and inflammatory response in patients with hypertrophic cardiomyopathy (HCM) and sinus rhythm. Patients and main outcome measures: In 42 patients with HCM with sinus rhythm, including 16 patients with resting LVOT obstruction (gradient ⩾30 mm Hg) and 29 age- and sex-matched controls, markers of thrombin generation (thrombin–antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2)), platelet activation (soluble CD40 ligand (sCD40L), β-thromboglobulin (β-TG), P-selectin) and inflammation (C-reactive protein (CRP), interleukin (IL)6, tumour necrosis factor-α (TNFα)) were determined. Results: Thrombin, platelet and inflammatory markers were higher in the entire HCM group than in controls (p<0.005 for all compared parameters). Compared with non-obstructive HCM, obstructive HCM was associated with increased thrombin formation (TAT, F1+2), platelet activation (sCD40L, β-TG, P-selectin) and both CRP and IL6 levels. Only the level of TNFα was similar in both forms of HCM. In contrast, a comparison of non-obstructive HCM with controls showed that all these variables (except for P-selectin) were similar; P-selectin was higher in non-obstructive HCM. The LVOT gradient correlated positively with all the raised blood markers (r from 0.39 to 0.73; p<0.05), except for TNFα. In multiple regression analysis models, the LVOT gradient was the only independent predictor of TAT (R2 = 0.61; p<0.001), sCD40L (R2 = 0.59; p<0.001), F1+2 (R2 = 0.55; p = 0.002), P-selectin (R2 = 0.49; p = 0.004) and β-TG (R2 = 0.38; p = 0.005) in patients with HCM. Conclusions: LVOT obstruction is independently associated with enhanced thrombin generation and platelet activity in patients with HCM with sinus rhythm.

Imaging of all three coronary arteries by transthoracic echocardiography. an illustrated guide

BackgroundImprovements in ultrasound technology has enabled direct, transthoracic visualization of long portions of coronary arteries : the left anterior descending (LAD), circumflex (Cx) and right coronary artery (RCA). Transthoracic measurements of coronary flow velocity were proved to be highly reproducible and correlated with invasive measurements. While clinical applications of transthoracic echocardiography (TTE) of principal coronary arteries are still very limited they will likely grow. The echocardiographers may therefore be interested to know the ultrasonic views, technique of examination and be aware where to look for coronary arteries and how to optimize the images.MethodsA step-by-step approach to direct, transthoracic visualization of the LAD, Cx and RCA is presented. The technique of examination is discussed, correlations with basic coronary angiography views and heart anatomy are shown and extensively illustrated with photographs and movie-pictures. Hints concerning optimization of ultrasound images are presented and artifacts of imaging are discussed.ConclusionsDirect, transthoracic examination of the LAD, Cx and RCA in adults is possible and may become a useful adjunct to other methods of coronary artery examination but studies are needed to establish its role.

Sudden death in hypertrophic cardiomyopathy: old risk factors re-assessed in a new model of maximalized follow-up.

AIMS in hypertrophic cardiomyopathy (HCM), the following five risk factors have a major role in the primary prevention of sudden death (SD): family history of SD (FHSD), syncope, massive wall thickness (MWTh) >30 mm, non-sustained ventricular tachycardia (nsVT) in Holter monitoring of electrocardiography, and abnormal blood pressure response to exercise (aBPRE). In HCM, as a genetic cardiac disease, the risk for SD may also exist from birth. The aim of the study was to compare the survival curves constructed for each of the five risk factors in a traditional follow-up model (started at the first presentation of a patient at the institution) and in a novel follow-up model (started at the date of birth). In an additional analysis, we compared the survival rate in three subgroups (without FHSD, with one SD, and with two or more SDs in a family). METHODS AND RESULTS a total of 1306 consecutive HCM patients (705 males, 601 females, mean age of 47 years, and 193 patients were <18 years) evaluated at 15 referral centres in Poland were enrolled in the study. In a novel method of follow-up, all the five risk factors confirmed its prognostic power (FHSD: P = 0.0007; nsVT: P < 0.0001; aBPRE: P = 0.0081; syncope: P < 0.0001; MWTh P> 0.0001), whereas in a traditional method, only four factors predicted SD (except aBPRE). In a novel model of follow-up, FHSD in a single episode starts to influence the prognosis with a delay to the fifth decade of life (P = 0.0007). Multiple FHSD appears to be a very powerful risk factor (P < 0.0001), predicting frequent SDs in childhood and adolescence. CONCLUSION the proposed concept of a lifelong calculated follow-up is a useful strategy in the risk stratification of SD. Multiple FHSD is a very ominous risk factor with strong impact, predicting frequent SD episodes in the early period of life.

Effect of aortic valve stenosis on haemostasis is independent from vascular atherosclerotic burden

OBJECTIVE The aim of study was to assess whether activation of blood coagulation and platelets is enhanced in aortic stenosis (AS) and if so, to determine factors that might modulate these processes. PATIENTS/METHODS Seventy-five patients with AS (48 males, 27 females, aged 65+/-10 years) were enrolled in the study. A control group comprised 75 age- and sex-matched subjects. We determined markers of thrombin generation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1+2]), platelet activation (soluble CD40 ligand [sCD40L], beta-thromboglobulin [beta-TG], P-selectin) in peripheral blood plasma. The extent of atherosclerosis in the carotid and coronary arteries was assessed as a potential confounding factor. RESULTS Mean concentrations of thrombin and platelet markers were higher approximately two-fold in the AS group than in controls (p<0.005 for all comparisons). Maximal gradient was positively associated with TAT (r=0.61, p<0.001), F1+2 (r=0.60, p<0.001), sCD40L (r=0.52, p<0.01) and beta-TG (r=0.70, p<0.001). Aortic valve area (AVA) negatively associated only with one platelet marker, beta-TG (r=-0.30, p<0.05). The presence of concomitant atherosclerotic plaque in the carotid (in 65% of patients) or coronary arteries (in 43% of patients) did not influence thrombin generation and platelet activation in patients with AS. CONCLUSIONS AS predisposes to prothrombotic state. Maximal gradient as an index of turbulent flow associated with activation of coagulation and platelets. In contrast, the small aortic valve area was not closely related to these parameters.

Standing position alone or in combination with exercise as a stress test to provoke left ventricular outflow tract gradient in hypertrophic cardiomyopathy and other conditions

Measuring left ventricular outflow tract (LVOT) gradient by echocardiography in decubitus position, which is used in routine clinical practice, does not reflect the pathophysiology of this dynamic abnormality during daily activities, which trigger the symptoms. LVOT obstruction is dynamic and greatly dependent upon the left ventricular cavity size, geometric configuration of hypertrophy, load, contractility and mitral apparatus abnormalities, including systolic anterior motion of mitral leaflet. Importantly, LVOT gradient may develop not only in hypertrophic cardiomyopathy, but also in other heart diseases. Recent studies show that LVOT gradient should be measured both in a standing position and during exercise.

Pleiotropic, cardioprotective effects of omega-3 polyunsaturated fatty acids.

The cardioprotective effects of food rich in omega-3 (omega-3) polyunsaturated fatty acids (PUFA) on cardiovascular risk has been of interest from the moment when a low rate of coronary heart disease was documented in the Eskimo population. The aim of the present review is to discuss recent studies documenting multidirectional action of omega-3 PUFA due to its pleiotropic properties. Experimental studies in cellular and animal models have extensively documented the favorable effects of omega-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) on: inflammatory processes, endothelial dysfunction, platelet aggregation and arrhythmogenesis. It was reported that antiarrhythmic effects of omega-3 PUFA resulted from stabilization of cardiomyocyte membrane and inhibition of ion channels. Moreover, PUFA possess several pleiotropic properties i.e. anti-inflammatory, anti-atherogenic and antithrombotic. Anti-atherogenic effects (plaque stabilization) of omega-3 PUFA have recently been demonstrated. It was documented (OCEAN study) that eicosapentaenoic acid from a source of highly purified ethyl esters is incorporated into plaques in a relatively short period of time and these higher concentrations of omega-3 PUFA may stabilize vulnerable atherosclerotic plaques. The anti-inflammatory effect of omega-3 PUFA is associated with reduction of levels of TNF-alpha and interleukin-6. Eicosapentaenoic acid and docosahexaenoic acid inhibit arachidonic acid metabolism to inflammatory eicosanoids.

The influence of age on gender-specific differences in the left ventricular cavity size and contractility in patients with hypertrophic cardiomyopathy

BACKGROUND The aim of the study was to assess gender-specific differences in left ventricular cavity size, contractility and left ventricular outflow tract obstruction in younger and older subgroups of patients with hypertrophic cardiomyopathy. METHODS We studied retrospectively 153 referred patients with hypertrophic cardiomyopathy (89 males and 64 females). The echocardiographically measured left ventricular end-systolic, end-diastolic dimensions, fractional shortening and occurrence of left ventricular outflow tract gradient were compared between sexes in subgroups of patients </=50 and >50 years of age. RESULTS In younger patients with hypertrophic cardiomyopathy, left ventricular end-diastolic and end-systolic dimensions were significantly smaller in females than males (41.9+/-5.8 vs. 44.7+/-5 mm P<0.01 23.4+/-5 vs. 25.2+/-5.4 mm P<0.05, respectively). Fractional shortening was comparable in both sexes (44.7+/-7.5 vs. 43.7+/-8.2% P>0.05). The left ventricular outflow tract gradient occurred in females as frequently as in males (13.3 vs. 17.6% P>0.05). In older patients with hypertrophic cardiomyopathy, left ventricular end-diastolic and end-systolic dimensions were also significantly smaller in females than males (42.5+/-6 vs. 46.3+/-3.2 mm P<0.02; 25.7+/-4.8 vs. 28.6+/-3.7 mm P<0.01, respectively). In contrast to the younger group, the fractional shortening was significantly higher in females than males (44.4+/-6.8 vs. 38.2+/-7.3% P<0.02). The left ventricular outflow tract gradient occurred in females more frequently than in males (63.2 vs. 20.8% P<0.02). CONCLUSIONS In patients with hypertrophic cardiomyopathy, the gender-based differences in the absolute value of left ventricular cavity size persisted with aging. In older females left ventricular contractility was higher and left ventricular outflow tract gradient occurred more frequently than in males. In younger patients with hypertophic cardiomyopathy these sex-based differences were absent. The gender-specific differences in the parameters of left ventricular systolic function became apparent with increasing age.