Cerebrovascular events in takotsubo syndrome: short and long-term outcome. Results from a multicenter-prospective registry

Abstract Background Several studies have shown that Takotsubo syndrome (TTS) secondary to neurological disorders is associated with higher rate of in-hospital complications. Imaging brain studies found that atrophy or damage of some regions and their altered connectivity with other brain regions are typical features of TTS patients. Aim of the study To evaluate rates of in hospital and long-term follow up events in TTS patients with history or acute cerebrovascular events (CVE). Methods 395 consecutive patients were enrolled in a multicenter prospective registry. History, clinical data, echocardiographic parameters and in-hospital and long-term follow up events of all patients were evaluated. Results Prevalence of CVE among TTS patients was 9.4% (N=37). Compared to the control group, these patients were older (80±7 vs 71±12 years, p=0.01) and predominantly men (24% vs 9%, p=0.01). No differences in terms of cardiovascular risk factors and left ventricular ejection fraction at admission and discharge were found between the two groups. The prevalence of physical stressors was higher in the CVE group (67% vs 44% p=0.01). The incidence of in-hospital adverse events was higher in the CVE group (70% vs 29%), mainly driven by higher rates of cardiogenic shock (19 vs 8%, p=0.01) and in-hospital death (19 vs 4%, p=0.01). At long-term follow-up, patients in the CVE group had higher mortality rates (38% vs 20%, p=0.01). Patients presenting with acute CVE, 10 out of 37 patients (27%), when compared with chronic CVE had higher in-hospital mortality rates (40% vs 11%, p=0.01). Conclusion TTS patients with history or CVE had higher rates of in-hospital events and death at long-term follow-up. Acute CVEs in the setting of TTS are associated with a worse prognosis. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Ospedali Riuniti di Foggia. Università di Foggi

Current knowledge and future challenges in takotsubo syndrome: Part 2-treatment and prognosis

Takotsubo syndrome (TTS) represents a form of acute heart failure featured by reversible left ventricular systolic dysfunction. The management during the acute phase is mainly performed with supportive pharmacological (diuretics, ACE-inhibitors/angiotensin-receptor blockers (ARBs), anticoagulants, antiarrhythmics, non-catecholamine inotropics (levosimendan), and non-pharmacological (mechanical circulatory and respiratory support) therapy, due to the wide clinical presentation and course of the disease. However, there is a gap in evidence and there are no randomized and adequately powered studies on clinical effectiveness of therapeutic approaches. Some evidence supports the use ACE-inhibitors/ARBs at long-term. A tailored approach based on cardiovascular and noncardiovascular risk factors is strongly suggested for long-term management. The urgent need for evidence-based treatment approaches is also reflected by the prognosis following TTS. The acute phase of the disease can be accompanied by various cardiovascular complications. In addition, long term outcome of TTS patients is also related to non-cardiovascular comorbidities. Physical triggers such as hypoxia and acute neurological disorders in TTS are associated with a poor outcome

On the role of skin biopsy in the diagnosis of calcific uremic arteriolopathy. A case-based discussion

Calciphylaxis is a rare disease characterized by ectopic calcification of skin arterioles resulting in ischemia, thrombosis and necrosis. Since end stage renal disease patients are those mainly affected, the term calcific uremic arteriolopathy (CUA) is also suggested. Early clinical manifestations are subtle, while overt necrotic ulcers may quickly spread and become infected so as to result in ominous outcome. Diagnosis might not be easy due to the number of other ischemic and non-ischemic skin lesions observed in uraemia. Skin biopsy, has been proposed as the diagnostic test and is often considered, but not systematically performed due to the hypothetical risk of further spreading of the lesions. Such ambiguity could be responsible for misdiagnosis or underdiagnosis. We review here five consecutive cases recorded in our Unit, all submitted to skin biopsy but with inconsistent results which generated some clinical frustration. Thus, we decided to carefully re-evaluate all of them together with pathologists and dermatologists. However, even after this ex-post discussion, we could not reach a complete agreement on the final diagnosis. In the meanwhile, papers were published in the literature that started to shed some light on the role of skin biopsy in the diagnosis of CUA

Neutrophil/lymphocyte ratio predicts in-hospital complications in Takotsubo syndrome. Results from a prospective multi-center registry

Background: Several hematological indices including subtypes of leukocytes populations have been associated with cardiovascular outcome. Takotsubo syndrome (TTS) is a form of acute heart failure syndrome featured by several in-hospital complications (IHCs). Hypothesis: Hematological indices at admission may predict IHCs in TTS patients. Methods: One hundred and sixty consecutive patients with TTS were enrolled in a multicenter prospective registry. Clinical data, admission hemogram, and IHCs were recorded. Results: Incidence of IHCs was 37%, including pulmonary edema 9%, cardiogenic shock 9%, need of invasive ventilation 10%, death 8%, stroke 2.5%, and left ventricular thrombi 6%. Patients with IHCs were older, more frequently male, with physical stressor-induced TTS, lower left ventricular ejection fraction at admission. Neutrophil/lymphocyte ratio (NLr) (12 ± 12 vs 7 ± 8, P =.002) and white blood cells/mean platelet volume ratio (1.2 ± 0.5 vs 1.0 ± 0.5, P =.03) at admission were significantly higher in patients with IHCs. NLr values were predictor of IHCs (Odds ratios [OR] 1.07, 95% CI 1.03-1.11, P <.01). When stratified according to NLr into tertiles, the rate of IHCs was from first to third tertile was, respectively, 22%, 31%, and 58%. NLr values in the higher tertile were independent predictors of IHCs even at multivariate analysis (OR 3.7, 95% CI 1.5-9.4, P <.01). NLr values higher than 5 were able to predict IHCs with a sensitivity of 82% and specificity of 58%; negative predictive power was 84% (area under the ROC curve 0.73). Conclusions: NLr is an independent predictor of IHCs in patients admitted with TTS. Admission hemogram may represent a potential tool for prediction of IHCs in TTS

Stepwise approach for diagnosis and management of Takotsubo syndrome with cardiac imaging tools

Takotsubo syndrome is featured by transient left ventricle dysfunction in the absence of significant coronary artery disease, mainly triggered by emotional or physical stress. Its clinical presentation is similar to acute coronary syndrome; therefore, cardiac imaging tools have a crucial role. Coronary angiography is mandatory for exclusion of pathological stenosis. On the other side, transthoracic echocardiography is the first non-invasive imaging modality for an early evaluation of left ventricle systolic and diastolic function. Left ventricle morphologic patterns could be identified according to the localization of wall motion abnormalities. Moreover, an early identification of potential mechanical and electrical complications such as left ventricle outflow tract obstruction, mitral regurgitation, thrombus formation, right ventricular involvement, cardiac rupture, and cardiac rhythm disorders could provide additional information for clinical management and therapy. Because of the dynamic evolution of the syndrome, comprehensive serial echocardiographic examinations should be systematically performed. Advanced techniques, including speckle-tracking echocardiography, cardiac magnetic resonance, and nuclear imaging can provide mechanistic and pathophysiologic insights into this syndrome. This review focuses on these aspects and provide a stepwise approach of all cardiac imaging tools for the diagnosis and the management of Takotsubo syndrome

Predictors of right ventricular function improvement with sacubitril/valsartan in a real-life population of patients with chronic heart failure

Background: Observational studies have demonstrated that treatment with sacubitril/valsartan may improve left ventricular (LV) systolic and diastolic function in subjects with reduced LV ejection fraction (LVEF) in real-world studies. Subjects with heart failure and reduced EF (HFrEF), however, are also characterized by an impaired right ventricular (RV) function. We therefore aimed to evaluate whether also RV function may improve after S/V therapy and possible predictors of RV improvement could be identified at echocardiography and tissue Doppler imaging. Methods: Fifty consecutive patients (67 ± 8 years, LVEF 28 ± 6%, male 86%) with chronic HFrEF and NYHA class II-III were followed up for 6 months after therapy with S/V. LV&RV function was assessed at baseline and after 6 months of therapy. Results: After 6-month therapy with S/V a significant improvement was shown in the following echocardiography parameters assessing RV function: PAsP (31 ± 11 vs. 35 ± 10 mmHg, p < 0.001), TAPSE (19 ± 3 vs. 18 ± 3 mm, p < 0.001), RV FAC (38 ± 7 vs. 34 ± 6 mm, p < 0.001), RV S’ (12 ± 2 vs. 10 ± 2 cm/s, p < 0.001), RV-FW-LS (−20 ± 5 vs. −18 ± 5%, p < 0.001), RV-4Ch-LS (−16 ± 5 vs. −14 ± 5%, p < 0.001). At multivariable analysis improvement in RV-FW-LS was associated to baseline levels of RV S’ (r 0.75, p < 0.01) and RAV (r –0.32, p < 0.05). Conclusions: In a real-world scenario, 6-month therapy with S/V was associated with an improved RV function in HFrEF. RV function improvement may be predicted by assessing baseline RV S’ and right atrial volume values

Prognostic role of neoplastic markers in Takotsubo syndrome

Takotsubo syndrome (TTS) is an acute heart failure syndrome with significant rates of in and out-of-hospital mayor cardiac adverse events (MACE). To evaluate the possible role of neoplastic biomarkers [CA-15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)] as prognostic marker at short- and long-term follow-up in subjects with TTS. Ninety consecutive subjects with TTS were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9 and CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Forty-three (46%) patients experienced MACE during hospitalization. These patients had increased admission levels of CEA (4.3 ± 6.2 vs. 2.2 ± 1.5 ng/mL, p = 0.03). CEA levels were higher in subjects with in-hospital MACE. At long term follow-up, CEA and CA-19.9 levels were associated with increased risk of death (log rank p < 0.01, HR = 5.3, 95% CI 1.9–14.8, HR = 7.8 95% CI 2.4–25.1, respectively, p < 0.01). At multivariable analysis levels higher than median of CEA, CA-19.9 or both were independent predictors of death at long term (Log-Rank p < 0.01). Having both CEA and CA-19.9 levels above median (> 2 ng/mL, > 8 UI/mL respectively) was associated with an increased risk of mortality of 11.8 (95% CI 2.6–52.5, p = 0.001) at follow up. Increased CEA and CA-19.9 serum levels are associated with higher risk of death at long-term follow up in patients with TTS. CEA serum levels are correlated with in-hospital MACE

Left Atrial Functional Remodeling in Patients with Chronic Heart Failure Treated with Sacubitril/Valsartan

(1) Background: Previous studies showed left ventricular (LV) and left atrial (LA) improvement and reverse remodeling after therapy with Sacubitril/Valsartan (S/V) in patients affected by heart failure with reduced ejection fraction (HFrEF). Therefore, we sought to investigate predictors of LA structural and functional reverse remodeling (LARR) in this setting of patients after therapy with S/V, focusing on left atrial strain parameters, such as peak atrial longitudinal strain (PALS). (2) Methods: Patients with HFrEF underwent clinical and echocardiographic evaluation at baseline and after six months of therapy with S/V. Measures of LA structure (LA volume index, LAVi) and function (LA emptying fraction (LAEF), PALS, LA conduit strain and peak atrial contraction strain (PACS) were also analyzed. Patients were divided in two groups, those with a LARR (relative reduction in LAVi > 15%, LARR+) and those without (LARR−). (3) Results: A total of 47 consecutive patients (66 ± 8 years, 85% male, mean LVEF 28 ± 6%) were enrolled in the study and followed up. A significant increase of LAEF (46 ± 13 vs. 37 ± 11%, p < 0.001) and a significant reduction of LAVi (42 ± 15 vs. 45 ± 15 mL/m2, p = 0.008) were found after 6 months of S/V therapy; 47% of the population showed LA reverse remodeling. LA strain parameters, PALS (19 ± 8 vs. 15 ± 7 %, p < 0.001) and LA conduit (−9.7 ± 5.2% vs. −7.6 ± 4.1%, p = 0.007) significantly improved after 6 months of S/V therapy. At multivariable stepwise regression analysis, changes in LV End Diastolic Volume (LVEDV) and PALS were significantly proportional to changes in LAVi values. (4) Conclusions: Six months of treatment with S/V in patients with HFrEF was associated with an improvement in LA functional reverse remodeling in a real-world scenario. LARR was not significantly correlated to baseline echocardiographic variables, but was proportional to changes in LV volumes and LA strain parameters. Finally, after S/V therapy, a strict connection between LA and LV reverse remodeling and between LA anatomical and functional reverse remodeling seems to be outlined