Takotsubo Syndrome: Clinical Manifestations, Etiology and Pathogenesis.

The purpose of the review is the analysis of clinical and experimental data on the etiology and pathogenesis of takotsubo syndrome (TS). TS is characterized by contractile dysfunction, which usually affects the apical region of the heart without obstruction of coronary artery, moderate increase in myocardial necrosis markers, prolonged QTc interval (in 50% of patients), sometimes elevation of ST segment (in 19% of patients), increase N-Terminal Pro-B-Type Natriuretic Peptide level, microvascular dysfunction, sometimes spasm of the epicardial coronary arteries (in 10% of patients), myocardial edema, and life-threatening ventricular arrhythmias (in 11% of patients). Stress cardiomyopathy is a rare disease, it is observed in 0.6 - 2.5% of patients with acute coronary syndrome. The occurrence of takotsubo syndrome is 9 times higher in women, who are aged 60-70 years old, than in men. The hospital mortality among patients with TS corresponds to 3.5% - 12%. Physical or emotional stress do not precede disease in all patients with TS. Most of patients with TS have neurological or mental illnesses. The level of catecholamines is increased in patients with TS, therefore, the occurrence of TS is associated with excessive activation of the adrenergic system. The negative inotropic effect of catecholamines is associated with the activation of ß2 adrenergic receptors. An important role of the adrenergic system in the pathogenesis of TS is confirmed by studies which were performed using 125I-metaiodobenzylguanidine (125I -MIBG). TS causes edema and inflammation of the myocardium. The inflammatory response in TS is systemic. TS causes impaired coronary microcirculation and reduces coronary reserve. There is a reason to believe that an increase in blood viscosity may play an important role in the pathogenesis of microcirculatory dysfunction in patients with TS. Epicardial coronary artery spasm is not obligatory for the occurrence of TS. Cortisol, endothelin-1 and microRNAs are challengers for the role of TS triggers. A decrease in estrogen levels is a factor contributing to the onset of TS. The central nervous system appears to play an important role in the pathogenesis of TS.

Radionuclide Assessment of Cardiac Function and Dyssynchrony in Children with Idiopathic Ventricular Tachycardia.

BACKGROUND: The aim of the study was to evaluate the impact of idiopathic ventricular tachycardia and premature ventricular beats on cardiac function and dyssynchrony and to elucidate relationships between data of scintigraphic and intracardiac electrophysiology studies (EPSs). METHODS: The study comprised 64 patients with idiopathic ventricular arrhythmias (VAs; median age of 14 years ranging from 8 to 18 years). The control group comprised 20 patients (median age of 12 ranging from 7 to 16 years) without cardiac arrhythmias. EPS and radiofrequency ablation (RFA) procedure for VA were performed in 21 children according to indications. The functional state of both ventricles was assessed by gated blood pool single photon emission computer tomography (GBP-SPECT) before and after RFA in all patients. RESULTS: Patients with VA had local areas of asynchronous myocardial contraction (AMC). Compared with the control group, VA patients had significantly higher values of end-diastolic volume, end-systolic volume, and lower contractility indices. Negative association was found between total numbers of AMC areas and cardiac contractility indices. Ectopic foci localization, determined based on EPS data, was associated with AMC areas topography based on GBP-SPECT. RFA procedure significantly improved cardiac contractility indices; AMC areas completely disappeared or decreased compared with the preoperative conditions. CONCLUSION: In VA patients, AMC areas were localized mostly in the right ventricle. Comparison of the results of GBP-SPECT and EPS studies showed a relationship between AMC localizations and ectopic foci topography. The fact that AMC areas disappeared after RFA supports the hypothesis stating that the presence of AMC areas is a scintigraphic symptom of ectopic focus.

Assessment of radiological techniques application possibility for non-invasive diagnostics of latent inflammatory processes in myocardium in patients with atrial fibrillation.

OBJECTIVE: Aim was to study the performance of single-photon emission computed tomography (SPECT) with 99mTc-pyrophosphate (99mTc-PYP) in diagnostics of chronic latent inflammation in myocardium of patients with atrial fibrillation (AF). METHODS: The research included 70 patients (the average age of 49.3 ± 10.2 years) with persistent form of idiopathic AF. All patients underwent myocardium SPECT with 99mTc-PYP and cardiac magnetic resonance imaging (CMR) before the ablation. During the ablation endomyocardium sampling for histological and immunohistochemical verification of myocarditis was performed. RESULTS: Sensitivity of SPECT with 99mTc-PYP in diagnoses of chronic latent myocarditis in patients with AF in relation to endomyocardial biopsy was 80 %, specificity-83 % and diagnostic accuracy-82 %. Sensitivity, specificity and diagnostic accuracy of myocardium perfusion scintigraphy for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 30, 50 and 50 % correspondingly. Also the close correlation between the size of the perfusion defect and the severity of myocardial fibrosis in patients with AF was revealed. Specificity of the Lake Louise criteria for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 77.6 %, sensitivity-60 % and diagnostic accuracy-74.5 %. For only LGE specificity was 16 %, sensitivity-90 % and diagnostic accuracy-28 %. CONCLUSIONS: The study showed the possibility of successful application of radionuclide methods for diagnoses of chronic latent myocarditis at AF. Taking into account high informative values the results of scintigraphy can be also considered as a promising additional criteria for selecting patients with AF of unexplained etiology for non-invasive endomyocardial biopsy procedure.

Perfusion and metabolic scintigraphy with (123)I-BMIPP in prognosis of cardiac resynchronization therapy in patients with dilated cardiomyopathy.

OBJECTIVE: The objective of the study was to investigate the left ventricular (LV) myocardial perfusion and metabolism in patients with idiopathic dilated cardiomyopathy (DCM) and to identify the scintigraphic predictors of the efficacy of cardiac resynchronization therapy (CRT). METHODS: The study comprised 63 patients with DCM and severe heart failure (NYHA class III-IV). Before CRT, all patients received gamma-scintigraphy with (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) and with (123)I-ß-methyl-iodophenyl pentadecanoic acid ((123)I-BMIPP) for evaluation of myocardial perfusion and metabolism, respectively. Before and after 6 months of CRT, all patients underwent echocardiography study to assess cardiac hemodynamics. RESULTS: After 6 months of CRT, patients were divided into two groups: group 1 comprised responders in whom LV end systolic volume (LVESV) decreased by ≥15 % (n = 39); group 2 comprised non-responders in whom LVESV decreased by <15 % (n = 24). Before CRT, LV pumping function did not significantly differ between groups. Significant differences were found in the following preoperative scintigraphic parameters: myocardial perfusion defect size [7.4 % (5.9; 13.2) % and 11.8 (8.8; 16.2) %, p < 0.05] and metabolic defect size [7.4 (4.4; 14.7) % and 8.8 (8.8; 17.6) %, p < 0.05]. Metabolic scintigraphy showed greater diagnostic efficacy in determining the indications for CRT compared with perfusion scintigraphy [areas under the ROC curves (AUC) of 0.722 and 0.612, respectively]. The best metabolic defect size threshold value of 7.35 % predicted CRT efficacy with the sensitivity and specificity rates of 77.8 and 66.7 %, respectively. CONCLUSION: Data of metabolic scintigraphy may be useful for the integrated prediction of CRT efficacy.

Influence of antihypertensive therapy on cerebral perfusion in patients with metabolic syndrome: relationship with cognitive function and 24-h arterial blood pressure monitoring.

AIMS: To investigate the regional cerebral blood flow, cognitive function, and parameters of 24-h arterial blood pressure monitoring in patients with metabolic syndrome before and after combination antihypertensive therapy. METHODS: The study involved 54 patients with metabolic syndrome (MetS) investigated by brain single-photon emission computed tomography, 24-h blood pressure monitoring (ABPM), and comprehensive neuropsychological testing before and after 24 weeks of combination antihypertensive therapy. RESULTS: Patients with metabolic syndrome had significantly poorer regional cerebral blood flow compared with control group: by 7% (P = 0.003) in right anterior parietal cortex, by 6% (P = 0.028) in left anterior parietal cortex, by 8% (P = 0.007) in right superior frontal lobe, and by 10% (P = 0.00002) and 7% (P = 0.006) in right and left temporal brain regions, correspondingly. The results of neuropsychological testing showed 11% decrease in mentation (P = 0.002), and 19% (P = 0.011) and 20% (P = 0.009) decrease in immediate verbal and visual memory in patients with MetS as compared with control group. Relationships between the indices of ABPM, cerebral perfusion, and cognitive function were found. Data showed an improvement of regional cerebral blood flow, ABPM parameters, and indicators of cognitive functions after 6 months of antihypertensive therapy in patients with MetS. CONCLUSION: The study showed the presence of diffuse disturbances in cerebral perfusion is associated with cognitive disorders in patients with metabolic syndrome. Combination antihypertensive treatment exerts beneficial effects on the 24-h blood pressure profile, increases cerebral blood flow, and improves cognitive function in patients with MetS.

Cerebral blood flow and cognitive function in patients with metabolic syndrome: effect of antihypertensive therapy.

The aim of the study was to estimate regional cerebral blood flow (rCBF) and cognitive function in patients with metabolic syndrome (MetS) before and after antihypertensive combination therapy. The study included 24 patients with MetS (average age 52.4±1.6 years). All patients underwent brain single-photon emission computed tomography with technetium-99m hexamethylpropyleneamine oxime and comprehensive neuropsychological testing before and after 6-month antihypertensive combination therapy. All patients with MetS showed lower rCBF values in all regions of the brain compared with the control group. Their parameters of attention, immediate visual memory, and mentation were lower by 25%, 22%, and 13% compared with the control group, respectively. Six-month antihypertensive combination therapy increased cerebral perfusion and improved attention, mentation, and visual memory in MetS patients.

The usefulness of gated blood pool scintigraphy for right ventricular function evaluation in pulmonary embolism patients.

OBJECTIVE: According to the international registry ICOPER, right ventricular (RV) dysfunction is the most significant predictor of mortality in patients with pulmonary embolism (PE). AIM: To identify the most informative indicators of gated blood pool single photon emission computer tomography (GBP-SPECT) for evaluation of RV function in patients with PE. METHODS: A total of 52 patients were included in the study. The main group (n = 37) comprised patients with PE, and the comparison group (n = 15) patients suffering from coronary heart disease (NYHA class I-II). All patients received GBP-SPECT, and assessment of plasma levels of endothelin-1, stable nitric oxide (NO) metabolites, and 6-keto-PG F1α. RESULTS: In patients with PE, RV end-systolic volume, stroke volume, ejection fraction, peak ejection rate, peak filling rate, and mean filling rate were significantly lower in comparison with patients without PE. In patients with PE, the levels of endothelin-1, 6-keto-PG F1α, and stable NO metabolites were increased in comparison with patients without PE. CONCLUSIONS: GBP-SPECT facilitates verification of RV dysfunction in patients without massive PE or severe pulmonary hypertension. Dissociation between the volume of PE and degree of RV dysfunction may be caused by an unbalance between humoral vasoactive factors.

The possible role of nuclear imaging in assessment of the cardiac resynchronization therapy effectiveness in patients with moderate heart failure.

BACKGROUND: The aim of the study was to elucidate the role of nuclear medicine imaging in the selection of candidates for cardiac resynchronization therapy (CRT) and in the evaluation of CRT effectiveness METHODS: We studied 28 patients (19 male and 9 female) with dilated cardiomyopathy (DCM) and heart failure (HF). Before implantation of CRT device, all patients underwent SPECT with (99m)Tc-MIBI at rest to evaluate the myocardial perfusion, (123)I-BMIPP to evaluate the myocardial metabolism, and gated cardiac blood-pool SPECT (GBPS) to assess the myocardial contractile function. Following CRT, all patients were examined with 99mTc-MIBI SPECT and GBPS 12 ± 3 months after the intervention. RESULTS: All patients after CRT were divided into three groups. The first group included 10 patients with LVEF increased by more than 10 % (hyperresponders), the 2nd group included 11 patients with an increase in EF of more than 5 % but less than 10 % (responders) and third group consisted of 7 males whose LVEF remained unchanged or worsened compared with pre-operative values (nonresponders). Prior to CRT, no statistically significant differences were found between groups in hemodynamic parameters (EF, EDV, ESV, SV), intra- and interventricular dyssynchrony, as well as in the midsize of perfusion defects. Following long-term CRT, we found increase in LVEF and decrease in average size of perfusion defects in groups of hyperresponders and responders (p < 0.05). Results of SPECT with (123)I-BMIPP, performed prior to CRT, showed that nonresponders had more pronounced disturbance of myocardial metabolism compared with the group of hyperresponders (20 vs. 14.7 %, p < 0.05). CONCLUSION: The radionuclide methods can be used as possible indicators in the evaluation effectiveness and selection of candidates on the CRT.

Ablation and pacing: improving brain perfusion and cognitive function in patients with atrial fibrillation and uncontrolled ventricular rates.

BACKGROUND: The aim of our study was to determine if ablation and pacing improved brain perfusion (BP) and cognitive function (CF) in patients with medically refractory rapidly conducted atrial fibrillation (Med Refr RCAF). METHODS AND RESULTS: The study included 17 patients with Med Refr RCAF (average age 55.3 ± 4.5 years). All patients underwent brain single photon emission computed tomography scanning with (99m) Tc-hexamethylpropylene amine oxime and comprehensive neuropsychological testing before and after 3 months following pacemaker implantation. The BP was significantly lower in all regions in patients with Med Refr RCAF compared with the control group. The greatest BP decrease was revealed in the inferior frontal (P = 0.002) and posterior parietal (P = 0.024) brain regions. These patients showed cognitive deficit in 94%. There was a direct correlation between BP and CF parameters. Ablation followed by pacemaker implantation had a positive effect on BP and CF in all patients with Med Refr RCAF. Thus, BP increased in the right inferior frontal (P = 0.01), in the left superior frontal (P = 0.007), and in the left temporal (P = 0.005) cortex. These patients demonstrated improvements in immediate and delayed verbal memory, immediate and delayed visual memory, abstract mentation, attention, psychomotor speed, as well as in learning. CONCLUSIONS: Patients with atrial fibrillation and rapid ventricular rates refractory to medical treatment have marked signs of brain hypoperfusion and impaired CF. Ablation and pacing improve left ventricular systolic function, thereby increasing BP and improving CF.

Brain perfusion and cognitive function changes in hypertensive patients.

The aim of our study was to estimate brain perfusion and cognitive function (CF) in patients with arterial hypertension (AH) before and after hypotensive therapy. The study included 15 patients (mean age, 53.0+/-5.7 years) with previously untreated or ineffectively treated essential hypertension of the second degree. All patients underwent brain single photon emission computed tomography (SPECT) scanning with 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) and comprehensive neuropsychological testing before and after 24 weeks of hypotensive therapy (angiotensin-converting enzyme [ACE] inhibitor or diuretics). The brain perfusion was significantly lower (15-22%) in all regions of AH patients. These patients showed a 25% decrease in attention and psychomotor speed as well as a 14% decrease in mentation. Six months of hypotensive therapy led to an increase in brain perfusion by an average of 7-11% in all brain regions. After treatment these patients demonstrated an average 11-18% improvements in attention and psychomotor speed, as well as an average 10% improvement in abstract mentation. Marked signs of brain hypoperfusion and impaired CF: decrease in attention, slowing psychomotor speed and mentation was found in hypertensive patients even without focal neurological symptomatology. Twenty-four weeks of hypotensive treatment with ACE inhibitors or diuretics had a positive effect on cerebral perfusion and led to CF improvement.

Short-term and long-term cognitive function and cerebral perfusion in off-pump and on-pump coronary artery bypass patients.

OBJECTIVE: The aim of this study was to evaluate cognitive function, as measured by serial neuropsychological testing, and cerebral perfusion, as measured by brain SPECT scanning in patients with coronary artery diseases (CAD) following off-pump and on-pump coronary artery bypass graft surgery. Besides, the relationship between cerebral blood flow, cognitive functions, surgery parameters, and cardiac function in these patients were estimated. Also, brain-protective effects of instenon were studied. METHODS: Brain SPECT and comprehensive neuropsychological testing were performed 1 day before, 10-14 days and 6 months after coronary artery bypass graft surgery (CABG). The study involved 65 patients (62 males and 3 females, mean age 55+/-2) who underwent CABG with cardiopulmonary bypass (CPB) (43 pts) and off-pump coronary revascularization (OPCAB) using the Octopus stabilization system (22 pts). In 21 cases employing CPB, for prevention of the impairments of cerebral perfusion and cognitive deficit instenon was administered. RESULTS: CABG with the use of extracorporeal circulation is complicated by short-term and long-term neurocognitive dysfunction (in 96 and 55% cases, correspondingly). Also, in the early period after CABG, in 68% patients, decrease in regional cerebral blood flow (rCBF) was found, and after 6 months brain perfusion was lower than the baseline in 55% cases. Relationship between postoperative rCBF changes and the dynamics of cognitive function was found in early period and after 6 months following CABG. CONCLUSION: The coronary revascularization on beating heart or preventive administration of instenon in CPB patients helps significantly to diminish the risk of cerebrovascular complication.