Multiple Phenotypes of Chronic Coronary Syndromes Identified by ABCDE Stress Echocardiography.

BACKGROUND: Regional wall motion abnormality is considered a sensitive and specific marker of ischemia during stress echocardiography (SE). However, ischemia is a multifaceted entity associated with either coronary artery disease (CAD) or angina with normal coronary arteries, a distinction difficult to make using a single sign. The aim of this study was to evaluate the diagnostic potential of the five-step ABCDE SE protocol for CAD detection. METHODS: From the 2016-2022 Stress Echo 2030 study data bank, 3,229 patients were selected (mean age, 66 ± 12 years; 2,089 men [65%]) with known CAD (n = 1,792) or angina with normal coronary arteries (n = 1,437). All patients were studied using both the ABCDE SE protocol and coronary angiography, within 3 months. In step A, regional wall motion abnormality is assessed; in step B, B-lines and diastolic function; in step C, left ventricular contractile reserve; in step D, coronary flow velocity reserve in the left anterior descending coronary artery; and in step E, heart rate reserve. RESULTS: SE response ranged from a score of 0 (all steps normal) to a score of 5 (all steps abnormal). For CAD, rates of abnormal results were 347 for step A (19.4%), 547 (30.5%) for step B, 720 (40.2%) for step C, 615 (34.3%) for step D, and 633 (35.3%) for step E. For angina with normal coronary arteries, rates of abnormal results were 81 (5.6%) for step A, 429 (29.9%) for step B, 432 (30.1%) for step C, 354 (24.6%) for step D, and 445 (31.0%) for step E. The dominant "solitary phenotype" was step B in 109 patients (9.1%). CONCLUSIONS: Stress-induced ischemia presents with a wide range of diagnostic phenotypes, highlighting its complex nature. Using a comprehensive approach such as the advanced ABCDE score, which combines multiple markers, proves to be more valuable than relying on a single marker in isolation.

Obstructive Hypertrophic Cardiomyopathy and Takotsubo Syndrome: How to Deal With Left Ventricular Ballooning?

Currently, there are 2 proposed causes of acute left ventricular ballooning. The first is the most cited hypothesis that ballooning is caused by direct catecholamine toxicity on cardiomyocytes or by microvascular ischemia. We refer to this pathogenesis as Takotsubo syndrome. More recently, a second cause has emerged: that in some patients with underlying hypertrophic cardiomyopathy, left ventricular ballooning is caused by the sudden onset of latent left ventricular outflow tract obstruction. When it becomes severe and unrelenting, severe afterload mismatch and acute supply-demand ischemia appear and result in ballooning. In the context of 2 causes, presentations might overlap and cause confusion. Knowing the pathophysiology of each mechanism and how to determine a correct diagnosis might guide treatment.

Rest and Stress Left Atrial Dysfunction in Patients with Atrial Fibrillation.

BACKGROUND: Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. AIM: This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. METHODS: In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. RESULTS: LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). CONCLUSIONS: In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.

Diagnostic pathways to wild-type transthyretin amyloid cardiomyopathy: a multicentre network study.

AIM: Epidemiology of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) remains poorly defined. A better characterization of pathways leading to ATTRwt-CA diagnosis is of key importance, and potentially informative of disease course and prognosis. The aim of this study was to describe the characteristics of contemporary pathways leading to ATTRwt-CA diagnosis, and their potential association with survival. METHODS AND RESULTS: This was a retrospective study of patients diagnosed with ATTRwt-CA at 17 Italian referral centres for CA. Patients were categorized into different 'pathways' according to the medical reason that triggered the diagnosis of ATTRwt-CA (hypertrophic cardiomyopathy [HCM] pathway, heart failure [HF] pathway, incidental imaging or incidental clinical pathway). Prognosis was investigated with all-cause mortality as endpoint. Overall, 1281 ATTRwt-CA patients were included in the study. The diagnostic pathway leading to ATTRwt-CA diagnosis was HCM in 7% of patients, HF in 51%, incidental imaging in 23%, incidental clinical in 19%. Patients in the HF pathway, as compared to the others, were older and had a greater prevalence of New York Heart Association (NYHA) class III-IV and chronic kidney disease. Survival was significantly worse in the HF versus other pathways, but similar among the three others. In multivariate model, older age at diagnosis, NYHA class III-IV and some comorbidities but not the HF pathway were independently associated with worse survival. CONCLUSIONS: Half of contemporary ATTRwt-CA diagnoses occur in a HF setting. These patients had worse clinical profile and outcome than those diagnosed either due to suspected HCM or incidentally, although prognosis remained primarily related to age, NYHA functional class and comorbidities rather than the diagnostic pathway itself.

Pulmonary Congestion During Exercise Stress Echocardiography in Ischemic and Heart Failure Patients.

BACKGROUND: Lung ultrasound detects pulmonary congestion as B-lines at rest, and more frequently, during exercise stress echocardiography (ESE). METHODS: We performed ESE plus lung ultrasound (4-site simplified scan) in 4392 subjects referred for semi-supine bike ESE in 24 certified centers in 9 countries. B-line score ranged from 0 (normal) to 40 (severely abnormal). Five different populations were evaluated: control subjects (n=103); chronic coronary syndromes (n=3701); heart failure with reduced ejection fraction (n=395); heart failure with preserved ejection fraction (n=70); ischemic mitral regurgitation ≥ moderate at rest (n=123). In a subset of 2478 patients, follow-up information was available. RESULTS: During ESE, B-lines increased in all study groups except controls. Age, hypertension, abnormal ejection fraction, peak wall motion score index, and abnormal heart rate reserve were associated with B-lines in multivariable regression analysis. Stress B lines (hazard ratio, 2.179 [95% CI, 1.015-4.680]; P=0.046) and ejection fraction <50% (hazard ratio, 2.942 [95% CI, 1.268-6.822]; P=0.012) were independent predictors of all-cause death (n=29 after a median follow-up of 29 months). CONCLUSIONS: B-lines identify the pulmonary congestion phenotype at rest, and more frequently, during ESE in ischemic and heart failure patients. Stress B-lines may help to refine risk stratification in these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03049995.

Left atrial volume changes during exercise stress echocardiography in heart failure and hypertrophic cardiomyopathy.

OBJECTIVE: We aimed to assess feasibility and functional correlates of left atrial volume index (LAVI) changes during exercise stress echocardiography (ESE). METHODS: ESE on a bike or treadmill was performed in 363 patients with heart failure with preserved ejection fraction (HFpEF, n = 173), reduced ejection fraction (HFrEF, n = 59), or hypertrophic cardiomyopathy (HCM, n = 131). The LAVI stress-rest increase ≥6.8 ml/m2 was defined as dilation. RESULTS: LAVI measurements were feasible in 100%. LAVI did not change in HFrEF being at rest 32 (25-45) vs at stress 36 (24-54) ml/m2, P = NS and in HCM at rest 35 (26-48) vs at stress 38 (28-48) ml/m2, P = NS, whereas it decreased in HFpEF from 30 (24-40) to 29 (21-37) ml/m2 at stress, P = 0.007. LA dilation occurred in 107 (30%) patients (27% with treadmill vs 33% with bike ESE, P = NS): 26 with HFpEF (15%), 26 with HFrEF (44%), and 55 with HCM (42%) with P < 0.001 for HFrEF and HCM vs HFpEF. A multivariate analysis revealed as the predictors for LAVI dilation E/e' > 14 at rest with odds ratio (OR) 4.4, LVEF <50% with OR 2.9, and LAVI at rest <35 ml/m2 with OR 2.7. CONCLUSION: The LAVI assessment during ESE was highly feasible and dilation equally frequent with a treadmill or bike. LA dilation was three-fold more frequent in HCM and HFrEF and could be predicted by increased resting E/e' and impaired EF as well as smaller baseline LAVI.

Stress Echo 2030: The Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021-2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Feasibility and functional correlates of left atrial volume changes during stress echocardiography in chronic coronary syndromes.

An enlarged left atrial volume index (LAVI) at rest mirrors increased LA pressure and/or impairment of LA function. A cardiovascular stress may acutely modify left atrial volume (LAV) within minutes. Aim of this study was to assess the feasibility and functional correlates of LAV-stress echocardiography (SE) Out of 514 subjects referred to 10 quality-controlled labs, LAV-SE was completed in 490 (359 male, age 67 ± 12 years) with suspected or known chronic coronary syndromes (n = 462) or asymptomatic controls (n = 28). The utilized stress was exercise in 177, vasodilator in 167, dobutamine in 146. LAV was measured with the biplane disk summation method. SE was performed with the ABCDE protocol. The intra-observer and inter-observer LAV variability were 5% and 8%, respectively. ∆-LAVI changes (stress-rest) were negatively correlated with resting LAVI (r = - 0.271, p < 0.001) and heart rate reserve (r = -.239, p < 0.001). LAV-dilators were defined as those with stress-rest increase ≥ 6.8 ml/m2, a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAVI. LAV dilation occurred in 56 patients (11%), more frequently with exercise (16%) and dipyridamole (13%) compared to dobutamine (4%, p < 0.01). At multivariable logistic regression analysis, B-lines ≥ 2 (OR: 2.586, 95% CI = 1.1293-5.169, p = 0.007) and abnormal contractile reserve (OR: 2.207, 95% CI = 1.111-4.386, p = 0.024) were associated with LAV dilation. In conclusion, LAV-SE is feasible with high success rate and low variability in patients with chronic coronary syndromes. LAV dilation is more likely with reduced left ventricular contractile reserve and pulmonary congestion.

[A practical approach to the diagnosis of cardiomyopathy: a roadmap from the phenotype]. / Un approccio pratico alla diagnosi di cardiomiopatia: una roadmap a partire dal fenotipo.

Cardiomyopathies are a heterogeneous group of cardiac diseases for which diagnosis and treatment are not always simple. The diagnosis of cardiomyopathy, in particular the etiology, comes from an integration between symptoms and results collected by several instrumental exams. The brain storming for the diagnosis includes also the identification of the "red flags", i.e. the pathognomonic features for each etiology that can drive the choice of appropriate diagnostic tests and therapy. In this review, we provide a step by step approach in order to help cardiologists, not specifically dedicated to cardiomyopathies, to draw the diagnosis, therapy and follow-up. This approach will be accompanied by the consultation of other specialists to discuss together the results of the exams performed and to deepen extracardiac signs and symptoms.

Preparation and application of an innovative thrombocyte/leukocyte-enriched plasma to promote tissue repair in chelonians.

Platelet concentrates are widely used in mammalian regenerative medicine to improve tissue healing. Chelonians (Testudines) would benefit from the application of thrombocyte preparations to regenerate damaged tissues, since traumatic injuries are leading causes of morbidity and mortality for both wild-living and domesticated animals. The aim of this study was to establish a protocol that optimized the recovery of the thrombocytes from blood samples and to show the efficacy of thrombocyte-enriched plasma in chelonians. Peripheral blood samples were obtained from Testudo spp. (n = 12) and Trachemys scripta elegans (n = 10). Blood cells were fractionated by sodium diatrizoate-sodium polysucrose density gradient using a two-step centrifugation protocol. Thrombocytes and leukocytes were isolated and resuspended to obtain thrombocyte-leucocyte rich plasma (TLRP). The mean recovery of leukocytes and thrombocytes was 48.9% (±4.0 SEM, n = 22) of the whole blood cell content. No statistically significant difference was observed between blood samples collected from different turtle species. The ability of TLRP to form a gel was evaluated by adding variable concentrations of calcium gluconate at room temperature and at 37°C. A reliable and consistent clotting of the TLRP was obtained in glass tubes and dishes by adding 5-20% v/v of a 100 mg/ml solution of calcium gluconate. Furthermore, in order to test the clinical efficacy of TLRP, a preliminary evaluation was performed on four turtles (Testudo spp.) with traumatic injuries. In all the four animals, a successful clinical outcome was observed. The results demonstrated that a thrombocyte-enriched plasma, comparable to mammalian platelet rich plasma, can be prepared from chelonian blood samples. Furthermore, although the low number of cases presented does not allow definitive conclusions from a clinical point of view, their outcome suggests that TLRP application could be further investigated to improve the healing process of both soft and hard tissue injuries in chelonians.

F-18 FDG PET/CT detects muscle involvement in Erdheim-Chester disease.

A case of Erdheim-Chester disorder, a rare non-Langerhans' cell histiocytosis, was referred for restaging by F-18 FDG PET/CT more than 10 years after initial diagnosis. The patient presented diabetes insipidus, hypergondotropic hypogonadism, and osteosclerotic lesions. Previous bone scintigraphy documented pathognomonic long bones' involvement. Chronic steroid and hormone replacement therapy was administered, and the patient was asymptomatic. F-18 FDG PET/CT was useful for disease restaging at cardiac and soft tissues level.

Abnormalities of left ventricular function in asymptomatic patients with systemic sclerosis using Doppler measures of myocardial strain.

OBJECTIVE: To verify whether myocardial impairment can be detected by tissue Doppler imaging (TDI) in patients with asymptomatic systemic sclerosis (SSc), 35 patients with SSc with normal left ventricular (LV) ejection fraction and 35 control subjects were studied. METHODS: Myocardial longitudinal peak systolic velocity, strain, and strain rate (SR) were measured by TDI at a regional level, and for each parameter the average value was calculated using an LV 12-segment model. In addition, the mitral annulus diastolic velocities and the E/Ea ratio were obtained. Myocardial calibrated integrated backscatter (cIB) was used as an index of fibrosis. RESULTS: Compared with controls, patients with SSc showed lower peak strain (-19.5% +/- 2.3% vs -26.1% +/- 2.4%, P < .001), peak SR (-1.34 +/- 0.14 s(-1) vs -1.59 +/- 0.14 s(-1), P < .001), septal cIB (-19.5 +/- 3.1 dB vs -23.8 +/- 1.6 dB, P < .001), and posterior wall cIB (-23.4 +/- 2.9 dB vs -28.6 +/- 2.5 dB, P = .001), and higher E/Ea (11.7 +/- 2.5 vs 9.8 +/- 1.1, P < .001), whereas peak systolic velocities did not differ. Strain, SR, and E/Ea correlated better with cIB than systolic velocities. CONCLUSION: TDI-derived strain, SR, and E/Ea can detect impairment of LV myocardial function in asymptomatic patients with SSc with normal LV ejection fraction better than TDI systolic velocities.

Usefulness of changes in left ventricular wall thickness to predict full or partial pressure reperfusion in ST-elevation acute myocardial infarction.

Experimental studies have shown that if an acute transmural myocardial infarction is reperfused at full pressure there is an immediate and persisting increase in end-diastolic wall thickness (EDWT) due to massive intramural edema, with the amount of edema inversely related to the residual stenosis in the infarct-related artery. This study investigated if these findings are paralleled in the clinical setting and whether the resultant myocardial substrate differs after percutaneous coronary intervention (PCI) versus thrombolysis (the latter having a higher incidence of residual flow limiting stenosis in the culprit vessel). Eighty-eight consecutive patients with ST-elevation myocardial infarction were enrolled. Twenty-seven patients underwent primary PCI, 23 had rescue PCI, and 38 had thrombolysis. Standard M-mode and 2-dimensional echocardiographies were performed within 12 hours. Regional EDWT was measured in 904 infarct-related segments after the different reperfusion strategies and compared with 504 remote noninfarcted segments. EDWT of infarct-related segments after primary PCI was significantly increased compared with normal segments. At follow-up, after 6 months, EDWT of these segments was significantly decreased, indicating transmural infarction. EDWT of infarct-related segments after thrombolysis did not differ from that of normal segments. After rescue PCI, EDWT of infarct-related segments was significantly decreased compared with that of normal segments. In conclusion, full-pressure restoration of epicardial blood flow after transmural myocardial infarction causes an immediate increase in EDWT, easily detected by echocardiography. In contrast, pressure-limiting reperfusion (typical for thrombolysis) resultsin normal EDWT. This confirms experimental data that PCI and thrombolysis can differ in their resultant myocardial substrate.

Deswapping bovine odorant binding protein.

The X-ray structure of bovine Odorant Binding Protein (bOBP) revealed its association as a domain swapped dimer. bOBP, devoid of any cysteines, contrasts with other mammalian OBPs, which are monomeric and possess at least one disulfide bridge. We have produced a mutant of bOBP in which a glycine residue was inserted after position 121. This mutation yielded a monomeric bOBP-121Gly+ in which domain swapping has been reverted. Here, we have subsequently introduced two mutations, Trp64Cys and His155Cys, in view to stabilize the putative monomer with a disulfide bridge. We have determined the crystal structure of this triple mutant at 1.65 A resolution. The mutant protein is monomeric, stabilized by a disulfide bridge between Trp64Cys and His155Cys, with a backbone superimposable to that of native bOBP, with the exception of the hinge and of the 10 residues at the C-terminus. bOBP triple mutant binds 1-amino-anthracene, 1-octen-3-ol (bOBP co-purified ligand) and other ligands with microM Kd values comparable to those of the swapped dimer.

Changes in systolic left ventricular function in isolated mitral regurgitation. A strain rate imaging study.

AIMS: The aim of the present study is to understand the changes in left ventricular (LV) regional systolic deformation based on strain rate (SR) imaging in patients with isolated mitral regurgitation (MR). Progressive LV dilatation and irreversible myocardial damage as a result of chronic isolated MR are important causes of morbidity and mortality in patients following valve surgery. To date, there is no specific diagnostic method to detect subclinical changes in systolic function before irreversible dysfunction occurs. METHODS AND RESULTS: Seventy-seven individuals were studied: 54 asymptomatic patients (age 56 +/- 12) with isolated non-ischaemic MR divided into three groups: mild, moderate, and severe and 23 healthy subjects. All underwent a standard echo examination and a tissue Doppler study. A mathematical study was carried out to predict how SR should alter with increasing dimensions and due to irreversible myocardial damage. Radial as well as longitudinal peak systolic SR was significantly decreased in patients with severe MR compared to the other groups (LV posterior wall: P = 0.0006, septum: P = 0.0004, LV lateral wall: P = 0.0003). From both modelling and in our patients, deformation correlated inversely with LV end-diastolic diameter and end-systolic diameter (ESD). Deformation measurements (corrected for increased geometry) enabled the identification of patients classically referred to as at risk of irreversible myocardial damage (ESD > or = 4.5 cm). CONCLUSION: In patients with a wide range of MR, deformation remains unchanged due to a balance of increased dimensions and increased stroke volume. Only when contractility is expected to change, deformation will significantly decrease. SR imaging indices, corrected for geometry, might potentially be useful in detecting subclinical deterioration in LV function in asymptomatic patients with severe MR.

Improved detection of left ventricular thrombi and spontaneous echocontrast by tissue harmonic imaging in patients with myocardial infarction.

BACKGROUND: Tissue harmonic imaging (THI) reduces near-field and side-lobe artifacts. This could improve recognition of cardiac masses, including thrombi and spontaneous echocontrast (SEC), a known thromboembolic risk factor. OBJECTIVES: We tested the hypothesis that THI improves detection of left ventricular (LV) thrombi and SEC compared with transthoracic fundamental imaging in patients with recent myocardial infarction. METHODS: In all, 118 consecutive patients with recent myocardial infarction were studied at predischarge. The echocardiographic examination was performed in both fundamental imaging and THI modality and evaluated by 3 skilled and 3 nonexperienced observers for recognition of LV thrombosis and SEC. RESULTS: THI increased LV thrombi diagnosis by 25% by skilled observers and by 50% by nonexperienced readers, reducing the number of false-positive diagnoses by 67%. Also, compared with fundamental imaging, THI improved recognition of LV SEC by both experienced and nonexperienced observers by 56% and 62%, respectively. CONCLUSIONS: The improved recognition of LV thrombosis and SEC by THI in patients with myocardial infarction is clinically relevant allowing appropriate treatment and prognostic stratification. Therefore, routine use of THI should be recommended when studying such patients in clinical practice.

Odorant binding protein has the biochemical properties of a scavenger for 4-hydroxy-2-nonenal in mammalian nasal mucosa.

Odorant binding proteins (OBP) are soluble lipocalins produced in large amounts in the nasal mucosa of several mammalian species. Although OBPs can bind a large variety of odorous compounds, direct and exclusive involvement of these proteins in olfactory perception has not been clearly demonstrated. This study investigated the binding properties and chemical resistance of OBP to the chemically reactive lipid peroxidation end-product 4-hydroxy-2-nonenal (HNE), in an attempt to establish a functional relationship between this protein and the molecular mechanisms combating free radical cellular damage. Experiments were carried out on recombinant porcine and bovine OBPs and results showed that both forms were able to bind HNE with affinities comparable with those of typical OBP ligands (K(d) = 4.9 and 9.0 microm for porcine and bovine OBP, respectively). Furthermore, OBP functionality, as determined by measuring the binding of the fluorescent ligand 1-aminoanthracene, was partially lost only when incubating HNE levels and exposure time to HNE exceeded physiological values in nasal mucosa. Finally, preliminary experiments in a simplified model resembling nasal epithelium showed that extracellular OBP can preserve the viability of an epithelial cell line derived from bovine turbinates exposed to toxic amounts of the aldehyde. These results suggest that OBP, which is expressed at millimolar levels, might reduce HNE toxicity by removing from the nasal mucus a significant fraction of the aldehyde that is produced as a consequence of direct exposure to the oxygen present in inhaled air.

Tako-Tsubo cardiomyopathy: new insights into the possible underlying pathophysiology.

UNLABELLED: Tako-Tsubo cardiomyopathy is characterised by an atypical distribution of left ventricular (LV) dysynergy with apical ballooning and compensatory basal hyperkinesis. Coronary angiography is normal. Several substrates have been put forward to explain the underlying pathophysiology such as raised catecholamine levels (due to physical or emotional stress), multivessel epicardial coronary spasm or diffuse microvascular spasm. However, the pathophysiology has not yet been fully clarified. We present a series of cases whose findings could explain the mechanism underlying this syndrome. Four consecutives patients, all female, were admitted with the clinical features typical of Tako-Tsubo syndrome. In all, severe widespread transient LV mid-apical a/dyskinesia was associated with a mid-cavity dynamic obstruction which resolved prior to the resolution of the LV wall motion abnormalities. In all cases the dynamic LV obstruction was related to localised mid-ventricular septal thickening. After improvement in wall motion, a low-dose strain/strain rate dobutamine stress-echocardiography (DSE) was performed to determine the underlying ischaemic substrate. This provoked an LV mid-cavity gradient at peak dose in all. Regional deformation changes during DSE showed the affected myocardium to have the typical response diagnostic of regional stunning. CONCLUSION: We postulate that an important unrecognised factor in the development of Tako-Tsubo cardiomyopathy is the presence of abnormal myocardial functional architecture (such as localised mid-ventricular septal thickening), which in the presence of dehydration and/or raised catecholamine levels due to physical or emotional stress, leads the development of a severe transient LV mid-cavity obstruction. This effectively sub-divides the LV into two functionally different chambers with a marked increase in wall stress in the high pressure distal apical chamber. This, in combination with the abnormal high circulating catecholamine levels, induces widespread sub-endocardial ischaemia which is unrelated to a specific coronary artery territory. With rehydration/fall in catecholamine levels the interventricular gradient resolves and distal function recovers. Low dose SR/S DSE confirms that the distal ischaemic substrate is myocardial stunning.