Tamás Forster

Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC).

Non-thrombotic PE does not represent a distinct clinical syndrome. It may be due to a variety of embolic materials and result in a wide spectrum of clinical presentations, making the diagnosis difficult. With the exception of severe air and fat embolism, the haemodynamic consequences of non-thrombotic emboli are usually mild. Treatment is mostly supportive but may differ according to the type of embolic material and clinical severity.

High-fat diet-induced obesity leads to increased NO sensitivity of rat coronary arterioles: role of soluble guanylate cyclase activation

The impact of obesity on nitric oxide (NO)-mediated coronary microvascular responses is poorly understood. Thus NO-mediated vasomotor responses were investigated in pressurized coronary arterioles ( approximately 100 microm) isolated from lean (on normal diet) and obese (fed with 60% of saturated fat) rats. We found that dilations to acetylcholine (ACh) were not significantly different in obese and lean rats (lean, 83 +/- 4%; and obese, 85 +/- 3% at 1 microM), yet the inhibition of NO synthesis with N(omega)-nitro-l-arginine methyl ester reduced ACh-induced dilations only in vessels of lean controls. The presence of the soluble guanylate cyclase (sGC) inhibitor oxadiazolo-quinoxaline (ODQ) elicited a similar reduction in ACh-induced dilations in the two groups of vessels (lean, 60 +/- 11%; and obese, 57 +/- 3%). Dilations to NO donors, sodium nitroprusside (SNP), and diethylenetriamine (DETA)-NONOate were enhanced in coronary arterioles of obese compared with lean control rats (lean, 63 +/- 6% and 51 +/- 5%; and obese, 78 +/- 5% and 70 +/- 5%, respectively, at 1 microM), whereas dilations to 8-bromo-cGMP were not different in the two groups. In the presence of ODQ, both SNP and DETA-NONOate-induced dilations were reduced to a similar level in lean and obese rats. Moreover, SNP-stimulated cGMP immunoreactivity in coronary arterioles and also cGMP levels in carotid arteries were enhanced in obese rats, whereas the protein expression of endothelial NOS and the sGC beta1-subunit were not different in the two groups. Collectively, these findings suggest that in coronary arterioles of obese rats, the increased activity of sGC leads to an enhanced sensitivity to NO, which may contribute to the maintenance of NO-mediated dilations and coronary perfusion in obesity.

Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial

AIMS Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). METHODS AND RESULTS A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed. CONCLUSIONS Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury.

Three-dimensional speckle-tracking echocardiography – a further step in the non-invasive three-dimensional cardiac imaging

Three-dimensional speckle-tracking echocardiography is a new cardiac imaging methodology, which allows three-dimensional non-invasive evaluation of the myocardial mechanics. The aim of this review is to present this new tool emphasizing its diagnostic potentials and demonstrating its limitations, as well.

Reduced aortic distensibility and coronary flow velocity reserve in diabetes mellitus patients with a negative coronary angiogram

BACKGROUND Structural and functional abnormalities of the aortic wall and disturbances of the coronary circulation with presumed microvascular complications have been reported in patients with diabetes mellitus. OBJECTIVES To simultaneously establish the coronary flow velocity reserve (CFVR) and aortic distensibility indexes in type 2 diabetes mellitus patients who have normal epicardial coronary arteries by stress transesophageal echocardiography (STEE). METHODS The elastic properties of the descending aorta and the CFVR were evaluated simultaneously in 18 type 2 diabetes mellitus patients who had negative coronary angiograms. These results were compared with those of 21 nondiabetic subjects with normal epicardial coronary arteries and 24 patients with left anterior descending coronary artery (LAD) stenosis. STEE was used for the evaluation of elastic moduli of the descending aorta. The CFVR was calculated as the ratio of the average peak diastolic flow velocity during hyperemia to that at rest. RESULTS The CFVR of diabetic patients with normal epicardial coronary arteries and those with LAD stenosis was similarly decreased compared with the controls (2.10+/-0.63 and 1.78+/-0.47 versus 2.76+/-1.25, P<0.05 and P<0.001, respectively). The elastic modulus (in 103 mmHg) was similarly increased in patients with diabetes mellitus and normal epicardial coronary arteries, and in those with LAD stenosis, compared with the control subjects (0.94+/-0.82 and 0.91+/-0.59 versus 0.49+/-0.19, P<0.05 and P<0.05, respectively). CONCLUSIONS It may be stated that reduced aortic distensibility (increased elastic modulus) and the CFVR were demonstrated simultaneously during STEE in diabetic patients compared with nondiabetic subjects with negative coronary angiograms.

Indices of aortic distensibility and coronary flow velocity reserve in patients with different grades of aortic atherosclerosis.

Objective: The purpose of this study was to evaluate the correlation of the elastic properties of the descending aorta, the coronary flow velocity reserve (CFR) and the grade of aortic atherosclerosis (AA) in patients who have undergone coronary angiography. Methods: A total of 113 consecutive patients (77 men and 36 women, aged 31–80 years) underwent stress transoesophageal echocardiographic (STEE) assessment of the CFR. The grade of AA and the indices of aortic distensibility were evaluated during the same session of STEE. All patients had chest pain without previous myocardial infarction. Coronary angiography was performed in all cases. Results: The resting systolic and diastolic coronary flow velocities increased, while the coronary flow velocities measured at the peak of stress and the ratio Smax/Srest decreased in parallel with the aortic grade. The CFR and mean CFR were impaired in patients who exhibited aortic intimal thickening, but no further decrease was found in the event of aortic plaque. The elastic moduli E(p) and E(s) increased in parallel with the grade of AA. The occurance of a negative coronary angiogram was more common in patients without AA, but significant left anterior descending coronary artery disease or multivessel disease were more frequent at a higher grade of AA (in cases with aortic plaque). Conclusions: The CFR was decreased in patients with aortic intimal thickening, but no further decrease was observed in the presence of aortic plaque. The indices of aortic distensibility increased continuously in parallel with the aortic grade.

Adaptation of Vasomotor Function of Human Coronary Arterioles to the Simultaneous Presence of Obesity and Hypertension

Objectives—We hypothesized that simultaneous presence of obesity and hypertension activates adaptive vascular mechanisms affecting dilations of human coronary arterioles. Methods and Results—Agonist-induced dilations were assessed in isolated pressurized coronary arterioles from patients (n=38) who underwent cardiac surgery. Among normotensives we found that dilations to bradykinin (BK) and the NO-donor, sodium-nitroprusside (SNP) were reduced in obese subjects (BK, 10−7 mol/L, lean:90±4%, obese:64±7%; SNP, 10−6 mol/L, lean:89±7%, obese:76±5%). However, among hypertensives, both BK- and SNP-induced dilations were significantly enhanced in obese patients, when compared with lean individuals (BK, lean:71±7%, obese:85±3%; SNP, lean:60±6%, obese:83±2%). Correspondingly, in hypertensive patients, but not in those of normotensives, a positive correlation was found between body mass index (BMI) and BK-induced (P=0.036, r=0.46), and also SNP-evoked (P=0.031, r=0.44) coronary dilations. Moreover, in additional 55 hypertensive patients flow-mediated (FMD) and nitroglycerin (NTG)-induced dilations of the brachial artery were assessed. In obese hypertensive individuals, FMD- and NTG-induced dilations were greater (FMD:6.2±0.7%, NTG:17.2±0.9%), than in lean hypertensive patients (FMD:3.7±0.6%, NTG:13.6±1.1%). Correspondingly, FMD- and NTG-induced dilations were positively correlated with BMI (P=0.020, r=0.31 and P=0.033, r=0.29, respectively). Conclusions—These findings are the first to suggest that obesity may lead to activation of adaptive vascular mechanisms to enhance the dilator function of coronary and peripheral arterial vessels in hypertensive patients.

How Can Coronary Flow Reserve Be Altered by Severe Aortic Stenosis

The coronary flow reserve, a well‐known characteristic of the distensibility of the coronary arteries, can be measured by means of dipyridamole stress transesophageal echocardiography. This study compared the coronary flow reserve in patients with normal coronary arteries with aortic stenosis (Group 1), in patients with normal coronary arteries without aortic stenosis (Group 2), and in patients with significant left anterior descending coronary artery disease (Group 3). Patients and Methods: Groups 1 and 2 were comprised of 21 patients each, while Group 3 was comprised of 37 patients. Transesophageal stress echocardiography was carried out according to a standard protocol, with a vasodilator stimulus of dipyridamole in a dose of 0.56 mg/kg over 4 minutes. The coronary flow reserve was calculated as the ratio of posthyperemic to basal peak (CFR) and mean (mean CFR) diastolic flow velocities. Results: The left ventricular mass and left ventricular mass index were significantly higher in Group 1 than in Groups 2 and 3. The coronary flow reserve and the posthyperemic mean diastolic flow velocities were significantly lower, while the resting mean diastolic flow velocities were significantly higher in Groups 1 and 3 than in Group 2. Conclusions: In patients with aortic stenosis and a normal coronary angiogram, the coronary flow reserve is significantly lower, similarly as in the case of significant left anterior descending coronary artery disease. In severe aortic stenosis with left ventricular hypertrophy, stress transesophageal echocardiography is unable to distinguish between the drop in coronary flow reserve caused by a vascular or a myocardial component, and therefore, not suitable for the selection of patients with significant coronary artery disease, even in cases of left anterior descending coronary artery disease.

Normal reference values of left ventricular strain using three-dimensional speckle tracking echocardiography: results from a multicentre study

AIMS Three-dimensional (3D) speckle tracking echocardiography (3DSTE) has been shown to be an accurate and reliable clinical tool for the evaluation of global and regional left ventricular (LV) function through strain analysis, but the absence of normal values has precluded its widespread use in clinical practice. The aim of this prospective multicentre study was to establish normal reference values of LV strain parameters using 3DSTE in a large healthy population. METHODS AND RESULTS A total of 303 healthy subjects (156 males [51%], between 18 and 82 years of age, ejection fraction [EF] 61 ± 3%), stratified to provide approximately equal proportions of healthy subjects of 18-30, 31-40, 41-50, 51-60, and >60 years of age, underwent 3DSTE. Data were analysed for LV volumes, EF, mass, and global and regional circumferential, longitudinal, radial, and area strain. Significant but small differences between men and women were found for longitudinal and area strains, as well as between different age groups for all LV strain parameters. However, large differences in normal values were observed between different segments, walls, and levels of the LV for radial and longitudinal strains, whereas circumferential and area strains demonstrated generally consistent normal ranges across the LV. CONCLUSIONS Normal ranges of global and regional LV strain using 3DSTE have been established for clinical use. Differences in the magnitude of LV strain are present between men and women as well as different age groups. Moreover, there are differences between different segments, walls, and levels as part of the functional non-uniformity of the normal LV that necessitates the use of segment-specific normal ranges for radial and longitudinal strains. Circumferential and area strains demonstrate the most consistent normal ranges overall.

Three‐Dimensional Speckle Tracking Echocardiography–Derived Left Atrial Strain Parameters Are Reduced in Patients with Atrial Fibrillation (Results from the MAGYAR‐Path Study)

Objective: Three‐dimensional (3D) speckle tracking echocardiography (3DSTE) is a novel imaging modality for assessing cardiac function. We aimed to analyze left atrial (LA) function using 3DSTE in patients with atrial fibrillation (AF). Methods: 3DSTE was performed in 20 patients prior to their pulmonary vein isolation for AF. Every patient underwent a complete two‐dimensional echocardiographic study at the same time. 3DSTE‐derived circumferential (CS), longitudinal (LS), radial (RS), 3D (3DS), and area strain (AS) values were measured in the basal (b), mid (m), and superior (s) regions of the LA. 3DSTE‐defined maximal (LAmax) and minimal LA volumes (LAmin) and LA total emptying fraction were calculated automatically. Eleven randomly selected age‐ and gender‐matched healthy volunteers served as controls. Results: Patients with AF had significantly larger LAmax and LAmin and reduced LS, RS and CS.3DS and AS were significantly lower throughout the LA in cases with AF (3DS−b, −m, −s [AF patients vs. controls]: −18 ± 8% vs. −29 ± 8%, P = 0.001; −14 ± 6% vs. −22 ± 7%, P = 0.002; −10 ± 7% vs. −20 ± 9%, P = 0.002; AS−b, −m, −s [AF patients vs. controls]: 35 ± 15% vs. 52 ± 13%, P = 0.004; 50 ± 21% vs. 72 ± 19%, P = 0.009; 31 ± 21% vs. 65 ± 27%, P < 0.0001, respectively). Conclusions: 3DSTE‐derived “uni‐dimensional” LS, RS, CS, as well as novel strain parameters (3DS, AS) are significantly reduced in patients with AF compared to matched controls. 3DS and AS might be new strain parameters providing further insights into the alterations of LA function in patients developing AF.