Troponin as ischemic biomarker is related with all three echocardiographic risk factors for sudden death in hypertrophic cardiomyopathy (ESC Guidelines 2014).

BACKGROUND: Sudden cardiac death (SCD) risk stratification is the most important preventive action in patients with hypertrophic cardiomyopathy (HCM). The identification of the ischemia biomarker high sensitive troponin I (hs-TnI) role for this arrhythmic disease may provide additional information for SCD risk stratification. The aim of the study was to compare echocardiographic parameters (prognostic for risk stratification of SCD in HCM) among two subgroups of HCM patients: with elevated hs-TnI versus non-elevated hs-TnI level. METHODS: In 51 HCM patients (mean age 39 ± 8 years, 31 males and 20 females) an echocardiographic examination, including the stimulating maneuvers to provoke maximized LVOT gradient, was performed. The hs-TnI was measured 24 h later. RESULTS: By comparing two subgroups of patients, 26 members with hs-TnI positive versus 25 with hs-TnI negative, the study showed that the values of all three parameters were greater: provocable left ventricular outflow tract gradient (LVOTG) - 49.1 ± 45.9 vs 25.5 ± 24.8 mmHg, p = 0.019; left atrial diameter - 50.1 ± 9.6 vs 43.9 ± 9.8 mmHg, p = 0.041; maximal LV thickness - 22.1 ± 5.3 vs 19.9 ± 34 mm, p = 0.029. CONCLUSION: The increased value of all three echocardiographic parameters used as risk factors for SCD (ESC Guidelines) is related to the elevated level of hs-TnI in HCM. Due to the high LVOTG - great hs-TnI relationship, exercise stress, both diagnostic and even rehabilitation/training, should be monitored by biomarker control.

Patient after renal transplantation with syncope: Role of echocardiography in upright position.

In Doppler echocardiography, testing left ventricular outflow tract (LVOT) gradient in the supine position (as is done in everyday practice) does not reflect the pathophysiology of this dynamic abnormality during the daily activities that trigger the symptoms (eg, syncope). LVOT obstruction is a dynamic phenomenon, strongly dependent on the left ventricular cavity size, geometric configuration of hypertrophy, load variability, contractility, and mitral apparatus abnormalities. LVOT gradient may develop not only in hypertrophic cardiomyopathy but also in various heart diseases. Recent investigations show that LVOT gradient should be measured also in the standing position. Here, we report the case of patient after renal transplantation, who developed LVOT gradient during orthostatic test. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:616-620, 2017.

Orthostatic stress echocardiography as a useful test to measure variability of transvalvular pressure gradients in aortic stenosis.

UNLABELLED: The aim of the study was to assess the influence of the orthostatic stress test on changes in aortic pressure gradients in patients with aortic stenosis (AS). METHODS: The orthostatic stress test was performed in 56 AS patients. The maximum aortic gradient was compared between the supine and the upright position (using Doppler echocardiography from the apical window). The left hand of each patient was kept on top of their head for both readings. 21 patients were excluded from the study for three reasons: 1) atrial fibrillation (significant beat-to-beat variability of measured gradient), 2) suboptimal Doppler signal during the orthostatic test, and 3) aortic gradient significantly higher in suprasternal or right parasternal windows than in apical window (different direction of stenosed blood jets) in the supine examination. The last limitation (#3) is methodologically important because during the orthostatic examination, only the transapical measurement was used. We were able to analyze 35 AS patients (20 males, 15 females, mean age 74.8 ± 9.2 years). RESULTS: The wide range of severity of AS was examined (maximal aortic gradient in the supine position from 30 to 146 mmHg). With regard to statistical trends, the mean value of the maximum aortic gradient significantly decreased after orthostatic stress (from 87.5 ± 28.6 to 75.8 ± 23.7 mmHg), p > 0.01). In 7 patients (increasing responders) the peak aortic gradient slightly increased during the stress test. Five of the seven only increased by a few percent. The other two patients increased by nearly 10%. In contrast, the remaining 28 AS patients' gradient decreased by as much as 40% (decreasing responders). CONCLUSIONS: The orthostatic position test frequently generated a decrease of "theoretically fixed at rest" valvular gradient in AS. The combination of the stiffened stenotic valve apparatus and a reduced LV preload may be responsible for this decreasing response.

The influence of statins on levels of calcification biomarkers in patients with aortic sclerosis or mild aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Following the SEAS and SALTIRE studies in moderate-to-severe aortic stenosis (AS), it was postulated that the statin treatment had been initiated far too late during the disease course. Thus, the study aim was to assess the effect of four-week atorvastatin treatment (20 mg/day) on levels of calcification biomarkers in patients with early-stage disease (i.e., aortic sclerosis or mild AS). METHODS: In total, 33 patients (18 males, 15 females; mean age 70 +/- 8 years) with aortic sclerosis or mild AS, who had never received statin treatment, were enrolled into the study. According to their baseline lipid levels, 17 patients were hypercholesterolemic and 16 normocholesterolemic. Hence, rather than apply randomization, all patients were administered atorvastatin at a moderate dose level. Plasma levels of three biomarkers of calcification were measured, namely osteoprotegerin (OPG), osteopontin (OPN), and soluble receptor activator of nuclear factor (NF)-kappaB ligand (sRANKL). RESULTS: Plasma levels of all three biomarkers were decreased after atorvastatin treatment. OPG levels fell from 13.23 +/- 5.33 to 10.92 +/- 5.34 pmol/l (p < 0.05), sRANKL from 105.36 +/- 69.47 to 86.74 +/- 71.36 ng/ml (p < 0.05), and OPN from 31.60 +/- 20.29 to 28.45 +/- 15.98 ng/ml (p = NS). When comparing patients with no/mild valvular calcification to those with moderate valvular calcification, only the OPG level before atorvastatin was statistically higher in patients from the latter group: 11.44 +/- 4.51 versus 16.09 +/- 5.67 pmol/l (p < 0.05). CONCLUSION: Atorvastatin, at a dose level of 20 mg per day, reduced the plasma levels of calcification biomarkers in patients with aortic sclerosis and mild AS. The pre-atorvastatin OPG level was significantly higher when the aortic valve was moderately calcified, despite a persistent low transvalvular gradient.

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.

The effect of hemodialysis on left ventricular outflow tract gradient.

BACKGROUND: The aim of the study was to assess the effect of hemodialysis (HD) on left ventricular outflow tract gradient (LVOTG) measured both in supine and upright position (provocative maneuver to unload LV cavity by rapid preload reduction). Supine/standing echocardiography was performed immediately before and immediately after HD. For additional verification of the hypothesis about preload-dependence of LVOTG, the echocardiograms after long (2-day delay HD due to weekend) versus short (usual 1-day) pause between HDs were compared. METHODS: Forty-one patients on chronic HD (mean age 44 +/- 11 years) were examined using a portable hand-carried echocardiograph. In accordance with the prestudy assumption the ultrafiltration volume was significantly greater during HD after a long pause in comparison to HD after a short pause (3707 +/- 2826 mL vs. 2665 +/- 1152 mL P < 0.05). RESULTS: After a long pause, the mean value of LVOTG at the pre-HD was mildly increased in the supine position and remained at a similar level in the upright position (13.1 +/- 6.1 vs. 13.6 +/- 9.1 mmHg). Mean LVOTG at the post-HD in the supine position was similar to pre-HD, however the orthostatic stress test induced a significant increase of LVOTG (13.9 +/- 15.2 vs. 18.2 +/- 19.9 mmHg P < 0.05). After a short pause at the pre-HD the LVOTG in the supine position and after the orthostatic provocation was very similar to measurements after long pause (13.3 +/- 9.1 vs. 13.3 +/- 10.8 mmHg). At the post-HD the mean value of LVOTG increased during upright posture but the differences were of borderline significance (13.2 +/- 6.6 vs. 17.9 +/- 18.6 mmHg P = 0.052). CONCLUSIONS: HD predisposed to standing-provoked LVOTG especially when a long pause (2 days) between HDs induced a greater weight gain and subsequently a larger volume of ultrafiltration was needed to reduce hypervolemia.

Reversed Septal Curvature Is Associated with Elevated Troponin Level in Hypertrophic Cardiomyopathy.

The aim of study was to compare patients with hypertrophic cardiomyopathy divided according to septal configuration assessed in a 4-chamber apical window. The study group consisted of 56 consecutive patients. Reversed septal curvature (RSC) and non-RSC were diagnosed in 17 (30.4%) and 39 (69.6%) patients, respectively. Both RSC and non-RSC groups were compared in terms of the level of high-sensitivity troponin I (hs-TnI), NT-proBNP (absolute value), NT-proBNP/ULN (value normalized for sex and age), and echocardiographic parameters, including left ventricular outflow tract gradient (LVOTG). A higher level of hs-TnI was observed in RSC patients as compared to the non-RSC group (102 (29.2-214.7) vs. 8.7 (5.3-18) (ng/l), p = 0.001). A trend toward increased NT-proBNP value was reported in RSC patients (1279 (367.3-1186) vs. 551.7 (273-969) (pg/ml), p = 0.056). However, no difference in the NT-proBNP/ULN level between both groups was observed. Provocable LVOTG was higher in RSC as compared to non-RSC patients (51 (9.5-105) vs. 13.6 (7.5-31) (mmHg), p = 0.04). Furthermore, more patients with RSC had prognostically unfavourable increased septal thickness to left LV diameter at the end diastole ratio. Patients with RSC were associated with an increased level of hs-TnI, and the only trend observed in this group was for the higher NT-proBNP levels. RSC seems to be an alerting factor for the risk of ischemic events. Not resting but only provocable LVOTG was higher in RSC as compared to non-RSC patients.

Predictors of syncope in patients with severe aortic stenosis: The role of orthostatic unload test.

BACKGROUND: There is a paucity of data regarding response of cerebral blood flow to the postural unloading maneuver and its impact on the risk of syncope in patients with aortic stenosis (AS). The aim of the present study was to assess effects of orthostatic stress test on changes in carotid and vertebral artery blood flow and its association with syncope in patients with severe AS. METHODS: 108 patients were enrolled (72 with and 36 patients without syncope) with severe isolated severe AS. Peak systolic blood-flow velocity (PSV) and end-diastolic velocity in the carotid arteries and vertebral arteries were measured by duplex ultrasound in the supine position and at 1-2 min after the assumption of the standing position. RESULTS: The orthostatic stress test induced a significant decrease in carotid and vertebral arterial flow velocities in all examined arteries (p < 0.001). The median (interquartile range) of mean change in PSV for carotid arteries was higher for patients with syncope (syncope [-] vs. syncope [+]: -0.6 cm/s [-1.8, 1.0] vs. -7.3 cm/s [-9.5, -2.0]; p < 0.001) and similarly for vertebral arteries (-0.5 cm/s [-2.0, 0.5] vs. -4.8 cm/s [-6.5, -1.3]; p < 0.001, respectively). Age, aortic valve area, and mean change in PSV for carotid arteries were independently associated with syncope. CONCLUSIONS: In patients with AS, a decrease in carotid and vertebral arterial flow velocities in the standing position was observed and was associated with syncope. The present findings may support the value of an orthostatic test in identifying patients with severe AS and a high risk of syncope.

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.

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 >or= 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 >or= 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 nonprovocable 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.

Hypertrophic Cardiomyopathy: The Time-Synchronized Relationship between Ischemia and Left Ventricular Dysfunction Assessed by Highly Sensitive Troponin I and NT-proBNP.

The aim of this study was to compare NT-proBNP using the absolute values and NT-proBNP/ULN values that were standardized by age and gender between three subgroups: those without ischemia (negative hs-troponin I and no anginal pain (hsTnI-/AP-)), those with painless ischemia (hsTnI+/AP-), and those with painful ischemia (hsTnI+/AP+). Additionally, echocardiographic parameters were compared in these three subgroups. The absolute value of NT-proBNP was significantly higher in the painful ischemia subgroup (hsTnI-/AP- vs. hsTnI+/AP- vs. hsTnI+/AP+: 502 (174-833) vs. 969 (363-1346) vs. 2053 (323-3283) pg/ml; p = 0.018 for the whole-model analysis). The standardized value of NT-proBNP/ULN was gradually increased (hsTnI-/AP- vs. hsTnI+/AP- vs. hsTnI+/AP+: 3.61 + 0.63 vs. 6.90 + 1.31 vs. 9.35 + 1.87; p = 0.001 for the whole-model analysis). In the comparison between subgroups (hsTnI-/AP- vs. hsTnI+/AP- vs. hsTnI+/AP+), two echocardiographic parameters increased significantly. The left ventricular maximum wall thickness (LVMWT) at diastole was 1.99 ± 0.08 cm vs. 2.28 ± 0.13 cm vs. 2.49 ± 0.15 cm (p = 0.004 for the whole-model analysis). The maximal gradient of the provoked left ventricular outflow tract (LVOT) gradient increased significantly in only the painful-ischemia subgroup (11 (7-30) mmHg vs. 12 (9.35-31.5) mmHg vs. 100 (43-120) mmHg). In conclusion, both painless ischemia and painful ischemia are associated with a gradual, significant increase in NT-proBNP/ULN in comparison to the double-negative hsTnI/AP subgroup. In contrast, NT-proBNP is significantly higher in only the subgroup with painful ischemia.

Elevated Level of Troponin but Not N-Terminal Probrain Natriuretic Peptide Is Associated with Increased Risk of Sudden Cardiac Death in Hypertrophic Cardiomyopathy Calculated According to the ESC Guidelines 2014.

The aim of this study was to assess the relationship between biomarkers (high-sensitive troponin I [hs-TnI], N-Terminal probrain natriuretic peptide [NT-proBNP]) and calculated 5-year percentage risk score of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). Methods. In 46 HCM patients (mean age 39 ± 7 years, 24 males and 22 females), echocardiographic examination, including the stimulating maneuvers to provoke maximized LVOT gradient, had been performed and next ECG Holter was immediately started. After 24 hours, the ECG Holter was finished and the hs-TnI and NT-proBNP have been measured. Patients were divided according to 1/value of both biomarkers (hs-TnI-positive and hs-TnI-negative subgroups) and 2/(NT-proBNP lower and higher subgroup divided by median). Results. In comparison between 19 patients (hs-TnI positive) versus 27 patients (hs-TnI negative), the calculated 5-year percentage risk of SCD in HCM was significantly greater (6.38 ± 4.17% versus 3.81 ± 3.23%, P < 0.05). In comparison between higher NT-proBNP versus lower NT-proBNP subgroups, the calculated 5-year percentage risk of SCD in HCM was not significantly greater (5.18 ± 3.63% versus 4.14 ± 4.18%, P > 0.05). Conclusions. Patients with HCM and positive hs-TnI test have a higher risk of SCD estimated according to SCD calculator recommended by the ESC Guidelines 2014 than patients with negative hs-TnI test.

[Autoregulation of cerebral circulation: adaptation to hypertension and re-adaptation in response to antihypertensive treatment]. / Adaptacja autoregulacji krazenia mózgowego w przebiegu nadcisnienia tetniczego oraz readaptacja po zastosowaniu leków hipotensyjnych.

In chronic hypertension, autoregulation of cerebral blood flow (CBF) is adapted to high blood pressure. Thus in untreated hypertensive patients, the autoregulation curve is shifted towards higher pressure. With antihypertensive treatment autoregulation curve may be shifted back to the normal position or shift upward to the beneficially higher level of CBF. The effect of various antihypertensive drugs on CBF has been discussed.

Obstructive Form of Hypertrophic Cardiomyopathy-Left Ventricular Outflow Tract Gradient: Novel Methods of Provocation, Monitoring of Biomarkers, and Recent Advances in the Treatment.

Dynamic (latent or/and labile) obstruction of left ventricular outflow (LVOT) was recognized from the earliest clinical descriptions of hypertrophic cardiomyopathy (HCM) and has proved to be a complex phenomenon, as well as arguably the most audible ("visible") pathophysiological hallmark of this heterogeneous disease. The aim of the current review is focused on two novel issues in a subgroup of obstructive HCM. Firstly, the important methodological problem in HCM is the examination of a subgroup of patients with nonobstructive hypertrophy in resting conditions and hard, but possible provoking obstruction. Recently, investigators have proposed physiological stress test (with double combined stimuli) to disclose such type of patients. The upright exercise is described in the ESC guideline on hypertrophic cardiomyopathy from 2014 and may appear as a candidate for gold standard provocation test. The second novel area of interest is associated with elevated level of signaling biomarkers: hypercoagulation, hemolysis, acquired von Willebrand 2A disease, and enhanced oxidative stress. The accelerated and turbulent flow within narrow LVOT may be responsible for these biochemical disturbances. The most recent advances in the treatment of obstructive HCM are related to nonpharmacological methods of LVOT gradient reduction. This report extensively discusses novel methods.

Reduced coronary flow reserve in Anderson-Fabry disease measured by transthoracic Doppler echocardiography.

Coronary flow reserve was assessed in a patient with Anderson-Fabry disease complicated by symmetric left ventricular hypertrophy. Coronary flow reserve was measurable in all three major coronary arteries providing an opportunity to compare regional coronary flow reserve from different vascular beds. In this patient all the three vascular beds supplied diffusely hypertrophied myocardium. Coronary flow disturbances in small intramyocardial perforating arteries were visible. The coronary flow reserve was reduced to a similar level (around to 2.0) in all three major arteries. In our patient with Anderson-Fabry disease, the coronary vasodilatation was blunted in a diffuse pattern corresponding to the myocardial hypertrophy distribution. In small intramyocardial arteries coronary flow was also disturbed. Accordingly, retrograde systolic flow and accelerated anterograde diastolic flow were documented.

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.