Arterial hypertension in patients with takotsubo syndrome: prevalence, long-term outcome, and secondary preventive strategies: a report from the Takotsubo Italian Network register.

AIMS: The aim of this study was to investigate the long-term outcome of takotsubo syndrome (TTS) patients with and without hypertension (HT) and to evaluate the effectiveness of treatment with beta-blockers (BBs) and/or renin-angiotensin-aldosterone system inhibitors (RAASi). METHODS AND RESULTS: The study population includes a register-based, multicentre cohort of consecutive patients with TTS, divided into two groups according to the history of HT. Further stratification was performed for BB/RAASi prescription at discharge. The primary outcome was the composite of all-cause death and TTS recurrence at the longest available follow-up. The propensity score weighting technique was used to account for potential confounding. In the overall population (903 patients, mean age 70 ± 11 years), HT was reported in 66% of cases. At a median 2-year follow-up, there was no difference in the risk of the primary composite outcome between patients with and without HT. The adjusted Cox regression analysis showed a significantly lower risk for the primary outcome [adjusted hazard ratio (aHR): 0.69; 95% confidence interval (CI): 0.49-0.99] in patients who received BB vs. those who did not. Renin-angiotensin-aldosterone system inhibitors treatment was not associated with the primary study outcome. The lower risk for the primary outcome with BB treatment was confirmed in patients with HT (aHR: 0.37; 95% CI: 0.24-0.56) but not in patients without (aHR: 1.83; 95% CI: 0.92-3.64; Pinteraction < 0.001). CONCLUSION: In this TTS study, HT did not affect the long-term risk of adverse events but increased the probability of benefit from BB treatment after discharge. Owing to the favourable outcome impact of BB prescription in TTS patients with HT, a tailored pharmacological therapy should be considered in this cohort.

Although not associated with clinical outcomes, hypertension (HT) seems to modify the long-term effectiveness of pharmacological treatment in patients with takotsubo syndrome (TTS). Beta-blockers improved the overall survival of TTS patients with HT and should be considered as first-line therapy in this patient population. The effectiveness of renin­angiotensin­aldosterone system inhibitors on long-term outcome was not significant regardless of the history of HT.

Beta-blockers are associated with better long-term survival in patients with Takotsubo syndrome.

OBJECTIVE: The advantage of beta-blockers has been postulated in patients with Takotsubo syndrome (TTS) given the pathophysiological role of catecholamines. We hypothesised that beta-blocker treatment after discharge may improve the long-term clinical outcome in this patient population. METHODS: This was an observational, multicentre study including consecutive patients with TTS diagnosis prospectively enrolled in the Takotsubo Italian Network (TIN) register from January 2007 to December 2018. TTS was diagnosed according to the TIN, Heart Failure Association and InterTAK Diagnostic Criteria. The primary study outcome was the occurrence of all-cause death at the longest available follow-up; secondary outcomes were TTS recurrence, cardiac and non-cardiac death. RESULTS: The study population included 825 patients (median age: 72.0 (63.0-78.0) years; 91.9 % female): 488 (59.2%) were discharged on beta-blockers and 337 (40.8%) without beta-blockers. The median follow-up was 24.0 months. The adjusted Cox regression analysis showed a significantly lower risk for all-cause death (adjusted HR: 0.563; 95% CI: 0.356 to 0.889) and non-cardiac death (adjusted HR: 0.525; 95% CI: 0.309 to 0.893) in patients receiving versus those not receiving beta-blockers, but no significant differences in terms of TTS recurrence (adjusted HR: 0.607; 95% CI: 0.311 to 1.187) and cardiac death (adjusted HR: 0.699; 95% CI: 0.284 to 1.722). The positive survival effect of beta-blockers was higher in patients with hypertension than in those without (pinteraction=0.014), and in patients who developed cardiogenic shock during the acute phase than in those who did not (pinteraction=0.047). CONCLUSIONS: In this real-world register population, beta-blockers were associated with a significantly higher long-term survival, particularly in patients with hypertension and in those who developed cardiogenic shock during the acute phase.

"Pac-Man Heart" and Mitral Valve Prolapse: An Unreported Liaison.

A 50-year-old man accessed the echo laboratory for dyspnea. His medical history was unremarkable. Transthoracic two-dimensional echocardiogram showed a posterior leaflet of the mitral valve prolapse associated with eccentric regurgitant jet. An excavation of the medium interventricular septum, in the absence of left-right interventricular shunt, was detected as an incidental finding and considered as partial ventricular septum defect. Owing to the absence of acute myocardial infarction and thrombolysis in patient's medical history, this finding has been considered "pac-man heart" of the congenital origin. Of note, the association of this deformity with mitral valve prolapse is reported for the first time.

Long-term outcome in patients with Takotsubo syndrome presenting with severely reduced left ventricular ejection fraction.

AIM: To evaluate the long-term outcome of patients with Takotsubo syndrome (TTS) and severely reduced left ventricular ejection fraction (LVEF ≤ 35%) at presentation. METHODS AND RESULTS: The study population included 326 patients (mean age 69.5 ± 10.7 years, 28 male) with TTS enrolled in the Takotsubo Italian Network, divided into two groups according to LVEF (≤ 35%, n = 131; > 35%, n = 195), as assessed by transthoracic echocardiography at hospital admission. In-hospital events were recorded in both groups. At long-term follow-up (median 26.5 months, interquartile range 18-33), composite major adverse cardiac events (MACE: cardiac death, acute myocardial infarction, heart failure, and TTS recurrence) and rehospitalization were investigated. Compared to patients with LVEF > 35%, patients with LVEF ≤ 35% were older (71.2 ± 10.8 vs. 68.4 ± 10.6 years; P = 0.026) and experienced more frequently cardiogenic shock (16% vs. 4.6%; P < 0.001), acute heart failure (28.2% vs. 12.8%; P = 0.001), and intra-aortic balloon pump support (11.5% vs. 2.6%; P = 0.001) in the acute phase. At long-term follow-up, higher rates of composite MACE (25.2% vs. 10.8%; P = 0.001) and rehospitalization for cardiac causes (26% vs. 13.3%; P = 0.004) were observed in these patients. LVEF ≤ 35% at admission [hazard ratio (HR) 2.184, 95% confidence interval (CI) 1.231-3.872; P = 0.008] and age (HR 1.041, 95% CI 1.011-1.073; P = 0.006) were independent predictors of MACE. Patients with LVEF ≤ 35% also had a significant lower freedom from composite MACE during long-term follow-up (χ2 = 11.551, P = 0.001). CONCLUSION: Left ventricular ejection fraction ≤ 35% at presentation is a key parameter to identify TTS patients at higher risk not only in the acute phase but also at long-term follow-up.

Global longitudinal strain predicts outcome after MitraClip implantation for secondary mitral regurgitation.

AIM: The aim of this study was to assess preoperative determinants, prevalence, and prognostic impact of left ventricular (LV) reverse remodeling (LVRR) in patients with secondary mitral regurgitation (SMR), undergoing MitraClip implantation (MCi). METHODS: From March 2012 to January 2015, a total of 41 consecutive patients with moderate-to-severe SMR treated successfully with MCi were enrolled. All patients underwent clinical and echocardiographic follow-up after MCi. Global longitudinal strain (GLS) was obtained using two dimensional speckle tracking analysis. A reduction in LV end-systolic volume more than 10% compared with baseline was considered as a marker of LVRR. Patients were divided into two groups according to the presence or absence of LVRR. Cardiac events were defined as the occurrence of cardiac death, rehospitalization for worsening heart failure, and mitral valve surgery. RESULTS: On univariable analysis, EuroSCORE II and GLS were associated with LVRR. On multivariable logistic regression analysis, GLS was the only independent correlate of LVRR (P = 0.004). A receiver operating characteristic curve identified a cutoff value for GLS of -9.25% (P < 0.001) associated with LVRR, with a sensitivity and specificity of 81 and 74%, respectively. New York Heart Failure Association class more than 2 after MCi, absence of LVRR after MCi, and preoperative GLS more than -9.25% were significantly correlated with adverse cardiac events at long-term follow-up. On multivariable logistic regression analysis, GLS was the only independent predictor of composite adverse cardiac events at 2-year follow-up. CONCLUSION: A worse preoperative GLS predicts no LVRR and is associated with adverse long-term outcome after successful MCi for SMR.

Clinical profile and in-hospital outcome of Caucasian patients with takotsubo syndrome and right ventricular involvement.

AIM: To determine the prevalence, clinical characteristics, in-hospital course and determinants of major adverse events in a cohort of Caucasian patients with Takotsubo syndrome (TTS) and right ventricular involvement (RVi), regardless of left ventricular variant forms. METHODS AND RESULTS: The study population consisted of 424 patients (mean age 69.1±11.5years; female 92.2%) with a diagnosis of TTS divided into two groups according to the presence or absence of RVi. RVi patients (n=57; 13.4%) showed a higher prevalence of comorbidities, especially respiratory diseases (p=0.011), and a higher Charlson comorbidity index (CCI; p=0.006) than non-RVi patients. In-hospital major adverse events (acute heart failure, cardiogenic shock and death) occurred more frequently in RVi patients (p<0.001). Heart rate and CCI, along with the echocardiographic parameters of wall motion score index, E/e' ratio, tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) were associated with adverse in-hospital outcome. At multivariate analysis, CCI (HR: 1.871; 95% CI: 1.202-2.912; p=0.006), sPAP (HR: 1.059; 95% CI: 1.016-1.104; p=0.007) and TAPSE (HR: 0.728; 95% CI: 0.619-0.855; p<0.001) were independent correlates of the composite outcome in patients with RVi. CONCLUSION: Patients with RVi are characterized by distinct clinical profile and should undergo closely clinical and echocardiographic monitoring. The presence of echocardiographic signs of right ventricular failure along with substantial comorbidities burden identify a cohort at higher risk of in-hospital major adverse cardiovascular events.

Echocardiographic correlates of acute heart failure, cardiogenic shock, and in-hospital mortality in tako-tsubo cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine clinical and echocardiographic correlates of acute heart failure, cardiogenic shock and in-hospital mortality in a large cohort of tako-tsubo cardiomyopathy (TTC) patients. BACKGROUND: Despite good long-term prognosis, life-threatening complications due to hemodynamic instability can occur early in TTC patients. METHODS: The study population consisted of 227 patients (66.2 ± 12.2 years of age; females, 90.3%) enrolled in the Tako-tsubo Italian Network, undergoing transthoracic two-dimensional echocardiography on admission and at short-term follow-up (4.3 [4 to 6] weeks). Patients were divided into two groups according to the presence or absence of major adverse events, a composite of acute heart failure, cardiogenic shock, and in-hospital mortality. RESULTS: Major adverse events occurred in 59 patients (25.9%). The variables for elderly patients ≥ 75 years of age (42.4% vs. 23.8%; p = 0.011): left ventricular (LV) ejection fraction (35.1 ± 5.9% vs. 38.4 ± 4.6%, p < 0.001), wall motion score index (1.9 ± 0.2 vs. 1.7 ± 0.2, p < 0.001), E/e' ratio (13.5 ± 4.3 vs. 9.9 ± 3.3 [where E/e' is ratio of mitral E peak velocity and averaged e' velocity], p < 0.001), LV outflow tract obstruction (23.7 vs. 8.9%, p = 0.006), pulmonary artery systolic pressure (47.4 ± 12.3 mm Hg vs. 38.0 ± 9.2 mm Hg; p < 0.001), right ventricular involvement (28.8 vs. 9.5%; p < 0.001), and reversible moderate-to-severe mitral regurgitation (49.1 vs. 11.9%; p < 0.001), were significantly different between groups and were associated with adverse events. At multivariate analysis, LV ejection fraction (HR: 0.92; 95% CI: 0.89 to 0.95; p < 0.001), E/e' ratio (HR: 1.13; 95% CI: 1.02 to 1.24; p = 0.011), reversible moderate to severe mitral regurgitation (HR: 3.25; 95% CI: 1.16 to 9.10; p = 0.025), and age ≥ 75 years (HR: 2.81; 95% CI: 1.05 to 7.52; p = 0.039) were independent correlates of major adverse events. CONCLUSIONS: Echocardiographic parameters provide additional information compared to other variables routinely used in clinical practice to identify patients at higher risk of hemodynamic deterioration and poor in-hospital outcome, allowing prompt institution of appropriate pharmacological treatment and adequate mechanical support.

Tako-tsubo cardiomyopathy and coronary artery disease: a possible association.

BACKGROUND: In the medical literature, several cases of Tako-tsubo cardiomyopathy (TTC) with coronary artery disease (CAD) have been reported, and in clinical practice, several typical TTC cases show relevant stenoses of the coronary arteries spatially unrelated to the dysfunctional myocardium. OBJECTIVE: This study aimed to evaluate the prevalence, clinical characteristics, and outcome of patients with TTC and relevant CAD in a large multicenter database. METHODS: In 26 centers, 450 patients admitted with a diagnosis of TTC underwent coronary angiography within 48 h of hospital admission and were included prospectively in the Tako-tsubo Italian Network Registry. RESULTS: Overall, 43 (9.6%) patients had at least one relevant (≥50%) coronary stenosis not supplying the dysfunctional myocardium, whereas 407 patients (90.4%) had irrelevant stenosis or angiographically normal coronary arteries. TTC patients with relevant CAD were more likely to be older in age, to have diabetes, a familial history of CAD, and acute functional mitral regurgitation compared with those without relevant CAD. At the 6-month follow-up, the incidence of death, TTC recurrence, and rehospitalization rates in patients with and without relevant CAD were similar. On multivariable Cox analysis, an independent predictor of death was the Charlson Comorbidity Index, whereas the presence of CAD did not influence the mid-term outcome significantly. CONCLUSION: The presence of CAD is a rather common finding in a large proportion of patients with TTC. Thus, when the stenotic artery does not supply the dysfunctional myocardium or when the extent of dysfunctional myocardium is wider than the territory of distribution supplied by a single stenotic coronary artery, the presence of angiographically relevant CAD should not be considered an exclusion criterion for TTC.

Surgical treatment of impending paradoxical embolization associated with pulmonary embolism in a patient with heterozygosis of factor V Leiden.

We report an unusual case of impending paradoxical embolization in a 69-year-old woman heterozygote carrier of factor V Leiden mutation. The patient presented to the emergency room with the clinical scenario of massive pulmonary embolism. Serial echocardiographic examinations revealed a large thrombus in the right atrium floating via a patent foramen ovale into the left atrium. Anticoagulation therapy was started. After 72 h, due to the unresolved thrombus, the patient underwent surgical treatment consisting of complete excision of the thrombus, closure of the foramen ovale, and pulmonary embolectomy. No in-hospital complications were noted. At 1-year follow-up, the patient is doing well on long-term anticoagulation treatment free of thromboembolic events.

Differences in clinical features and in-hospital outcomes of older adults with tako-tsubo cardiomyopathy.

OBJECTIVES: To describe the clinical characteristics and in-hospital outcomes of older adults with tako-tsubo cardiomyopathy (TTC). DESIGN: Partially retrospective, partially prospective observational study. SETTING: Eleven Italian referral cardiac centers included in the Tako-tsubo Italian Network. PARTICIPANTS: One hundred ninety consecutive individuals with TTC (92.1% female, mean age 66) were divided into three groups according to age (<65, n = 78; 65-74, n = 61; ≥75, n = 51). MEASUREMENTS: Clinical findings and in-hospital outcomes were evaluated in each group. RESULTS: Participants aged 65 and older had a greater prevalence of hypertension (P = .001) and a lower glomerular filtration rate (P < .001), and those aged 65 to 74 had a greater prevalence of psychiatric disorders (P = .01), ST-segment elevation on admission (P = .01) and a cerebrovascular disease (P = .003) than those younger than 65. Despite similar left ventricular ejection fraction (LVEF) on admission (P = .26), the oldest group had a lower LVEF at discharge (P = .03). Inotropic agents were used more frequently in older adults (P = .03). In-hospital composite adverse events (all-cause death, acute heart failure, life-threatening arrhythmias, stroke, and cardiogenic shock; P = .03) and overall complications (P = .004) were more common in participants aged 75 and older. Overall in-hospital mortality was low (2.8%) but was more prevalent in participants aged 75 and older (6.3%). On multivariate analysis, age of 75 and older (hazard ratio (HR) = 2.45, 95% confidence interval (CI) = 1.28-5.82, P = .04) and LVEF on admission (HR = 0.874, 95% CI = 0.81-0.95, P < .001) were the only independent predictors of in-hospital adverse events. CONCLUSION: The clinical profile of participants aged 75 and older with TTC was different from that of those younger than 75 with TTC, and they had a higher in-hospital complication rate.

Echocardiographic assessment of regional left ventricular wall motion abnormalities in patients with tako-tsubo cardiomyopathy: comparison with anterior myocardial infarction.

AIMS: The aim of this study was to assess the echocardiographic distribution of regional wall motion abnormalities (RWMA) in patients with tako-tsubo cardiomyopathy (TTC) compared with anterior ST-elevation myocardial infarction (ant-STEMI). METHODS AND RESULTS: Thirty-seven TTC and 37 ant-STEMI patients underwent standard echocardiographic examination at the time of hospital admission. RWMA and the involvement of the left ventricular territories supplied by each coronary artery according to the American Society of Echocardiography classification were reported. TTC patients showed a lower left ventricular ejection fraction (37.6 ± 5.1 vs. 40.9 ± 3.7%; P = 0.002) and a higher wall motion score index (WMSI; 1.98 ± 0.2 vs. 1.51 ± 0.14; P < 0.001) compared with ant-STEMI patients. No significant differences were observed between groups with regard to detection of RWMA in the territory supplied by the left anterior descending coronary artery (LAD) (37 vs. 37; P = 1). Conversely, in TTC patients, the territories supplied by the LAD/left circumflex coronary artery (LCX) (37 vs. 31; P = 0.011), LAD/right coronary artery (RCA) (34 vs. 13; P < 0.001), RCA (33 vs. 5; P < 0.001), and RCA/LCX (31 vs. 2; P < 0.001) were more frequently involved. A cut-off value of WMSI ≥1.75 (area under the curve 0.956) and for the number of territories with RWMA ≥4 (AUC = 0.928) predicted TTC with a sensitivity of 83 and 84% and a specificity of 100 and 97%, respectively. CONCLUSION: Echocardiography revealed a distinctive pattern of contractility in TTC patients, characterized by symmetrical RWMA extending equally into the territory of distribution of all coronary arteries.

Monday preference in onset of takotsubo cardiomyopathy.

OBJECTIVE: Acute cardiovascular events show definite temporal patterns of occurrence. Takotsubo cardiomyopathy (TTC) has been recently shown to exhibit a seasonal (summer) and circadian (morning) temporal distribution. The aim of this study, based on the database of a multicenter Italian network, was to investigate the possible existence of a weekly pattern of onset of TTC. METHODS: The study included all cases of TTC admitted to the coronary care unit of 8 referral cardiac centers in Italy (five in Southern Italy and three in Northern Italy, respectively), belonging to the Takotsubo Italian Network (January 2002-December 2008). Day of admission was categorized into seven 1-day intervals according by week, and chronobiological analysis was performed by partial Fourier series. RESULTS: The database included 112 patients with TTC (92.9% females). The weekly distribution identified the highest number of cases on Monday and the lowest on Saturday. Chronobiologic analysis yielded a rhythmic pattern with a significant peak on Monday (P = .036). CONCLUSIONS: This study confirms a Monday preference for TTC occurrence on Monday, similar to that reported for acute myocardial infarction. Stress of starting weekly day life activities, could play a triggering role.

Right ventricular involvement and pulmonary hypertension in an elderly woman with tako-tsubo cardiomyopathy.

We describe a case of tako-tsubo cardiomyopathy in an elderly woman with a permanent pacemaker admitted to the ED with chest pain and dyspnea. Coronary angiography revealed normal coronary arteries. Typical left ventricular apical ballooning was demonstrated on contrast ventriculography. Left and right ventricular ballooning with pulmonary artery systolic hypertension was detected by transthoracic echocardiography. Velocity vector imaging and strain analysis showed a typical pattern of regional myocardial apical right ventricular contraction characterized by paradoxical positive longitudinal systolic strain. Biventricular involvement was associated with hemodynamic instability, signs of pulmonary vascular congestion, and bilateral basal pleural effusion. The patient's clinical condition gradually improved, and she was discharged after prolonged hospitalization. Predischarge echocardiography showed substantial recovery of left and right systolic function along with normalization of pulmonary artery systolic pressure. Right ventricular function should be carefully evaluated in patients with tako-tsubo cardiomyopathy, especially in the acute phase.

Transient left ventricular ballooning (tako-tsubo cardiomyopathy) soon after intravenous ergonovine injection following caesarean delivery.

Transient left ventricular ballooning also called tako-tsubo syndrome, is increasingly being recognized as cardiomyopathy mimicking the clinical scenario of an acute myocardial infarction. Generally, it is characterized by apical ballooning appearance of the left ventricle in the presence of normal coronary arteries on the angiogram. Recently, a variant form involving the midventricle with sparing of the apical and basal segments has been described. This syndrome is more prevalent in postmenopausal woman and usually preceded by extreme emotional and/or physical stress. We describe a case never reported before of transient left ventricular ballooning occurring during the early postpartum period after ergonovine injection rapidly evolving from a 'typical apical' ballooning into a 'midventricular' myocardial dysfunction.