Signal transduction pathways initiated by catecholamines in takotsubo syndrome: focus on nitrosative stress and energetic impairment

ESC CardioMed ◽  
2018 ◽  
pp. 1283-1286
Author(s):  
John D. Horowitz ◽  
Thanh Ha Nguyen ◽  
Sven Y. Surikow ◽  
Gao Jing Ong ◽  
Cher-Rin Chong ◽  
...  

Takotsubo syndrome reflects an ‘aberrant’ response to acute catecholamine stimulation, largely but not entirely as a manifestation of increased sensitivity to β‎2-adrenoceptor stimulation and signal transduction via Gi proteins, especially in ageing female hearts. It is now apparent that prolonged impairment of quality of life and slow recovery of echocardiographic parameters such as global longitudinal strain after episodes of takotsubo syndrome reflect ongoing myocardial inflammation and associated oedema, together with impairment of cardiac energetics on phosphorus magnetic resonance spectroscopy.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shaun Khanna ◽  
Aditya Bhat ◽  
Henry H Chen ◽  
Kennith Gu ◽  
Gary Gan ◽  
...  

Introduction: Myocarditis is an inflammatory disease process with growing clinical relevance in the current COVID-19 pandemic. Acute-phase myocarditis is known to result in subclinical changes in left ventricular (LV) function despite normal LV ejection fraction (LVEF), as assessed by myocardial deformation indices. The presence of right ventricular (RV) and left atrial (LA) subclinical dysfunction however has not been well described in current literature. Hypothesis: Myocarditis patients have subclinical impairment of LV, RV and LA function as assessed by global longitudinal strain (GLS) on speckle tracking echocardiography. Methods: Consecutive patients with clinical diagnosis of myocarditis admitted to our institution during 2013-2018 were assessed (n=76). Patients who did not meet appropriate diagnostic criteria (n=14), had impaired LVEF or prior cardiac disease (n=8) or poor transthoracic echocardiogram images (n=14) were excluded from analysis. Clinical and echocardiographic parameters were compared to age- , gender- and risk factor- matched controls. GLS was performed by two independent observers using vendor independent software (TomTec Arena, Germany v4.6). Results: The final cohort consisted 40 patients with myocarditis (age 44.3±16.7, 60% male) and 40 matched controls (44.5±16.6, 60% male). No significant differences in baseline clinical characteristics were observed between groups. No differences in LVEF, indexed LV mass, RV fractional area change, indexed LA volume or TR pressure gradient (p>0.05 for all) were demonstrated between the two groups. Patients with myocarditis had a lower mean LV strain (GLS%: -16.4±2.9 vs -19.7±2.7, p=0.0001), a lower mean RV Free Wall Strain (FWS) (GLS%: -22.1±4.1 vs -26.2±6.9, p=0.03) and a lower mean LA reservoir strain (GLS%: 27.5±4.6 vs. 33.7±6.3, p<0.0001) when compared to controls. Conclusions: Our results demonstrate the presence of significant subclinical global myocardial dysfunction despite normal traditional echocardiographic indices, in patients with acute-phase myocarditis. Routine assessment of GLS may identify such patients for early targeted cardiac therapy.


2020 ◽  
Vol 9 (12) ◽  
pp. 3882
Author(s):  
Thomas Stiermaier ◽  
Kira Busch ◽  
Torben Lange ◽  
Toni Pätz ◽  
Moritz Meusel ◽  
...  

Cardiac magnetic resonance (CMR)-derived left ventricular (LV) global longitudinal strain (GLS) provides incremental prognostic information on various cardiovascular diseases but has not yet been investigated comprehensively in patients with Takotsubo syndrome (TS). This study evaluated the prognostic value of feature tracking (FT) GLS, tissue tracking (TT) GLS, and fast manual long axis strain (LAS) in 147 patients with TS, who underwent CMR at a median of 2 days after admission. Long-term mortality was assessed 3 years after the acute event. In contrast to LV ejection fraction and tissue characteristics, impaired FT-GLS, TT-GLS and fast manual LAS were associated with adverse outcome. The best cutoff points for the prediction of long-term mortality were similar with all three approaches: FT-GLS −11.28%, TT-GLS −11.45%, and fast manual LAS −10.86%. Long-term mortality rates were significantly higher in patients with FT-GLS > −11.28% (25.0% versus 9.8%; p = 0.029), TT-GLS > −11.45% (20.0% versus 5.4%; p = 0.016), and LAS > −10.86% (23.3% versus 6.6%; p = 0.014). However, in multivariable analysis, diabetes mellitus (p = 0.001), atrial fibrillation (p = 0.001), malignancy (p = 0.006), and physical triggers (p = 0.006) outperformed measures of myocardial strain and emerged as the strongest, independent predictors of long-term mortality in TS. In conclusion, CMR-based longitudinal strain provides valuable prognostic information in patients with TS, regardless of the utilized technique of assessment. Long-term mortality, however, is mainly determined by comorbidities.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
P Geenty ◽  
S Sivapathan ◽  
T Deshmukh ◽  
P Brown ◽  
A Boyd ◽  
...  

Abstract Background AL-amyloidosis has a rapid clinical progression, with cardiac involvement associated with a particularly poor prognosis. Cardiac amyloidosis is diagnosed by either invasive biopsy or conventional echocardiographic parameters such as increased wall thickness, in the absence of other causes. More recently, novel parameters including 2D longitudinal strain have demonstrated diagnostic utility in a range of infiltrative cardiomyopathies including cardiac amyloidosis. Aim/Method: We sought to evaluate traditional and novel echocardiographic parameters in their ability to predict adverse outcomes in a cohort of AL-amyloid patients. 80 patients who had transthoracic echocardiograms at a single centre were included. Comprehensive echocardiographic assessment was performed, including left ventricular ejection fraction (LVEF), LV Global Longitudinal Strain (GLS), LV mass (indexed to BSA). The primary endpoint was a composite of of major adverse cardiac events (MACE) and all-cause mortality, that was assessed by interrogation of the medical records on a specified censor date. Results At a mean follow-up (time from echo to censor date) of 5.4 ± 2.6years, 38/80 (47.5%) of patients experienced the primary endpoint of MACE or death, of which 25/80 (31%) were deaths. LVEF (59 ± 5.6%vs56 ± 6.4%, p = 0.04), GLS (17.4 ± 3.9%vs14.8 ± 4.9%, p = 0.01) basal longitudinal strain (12.3 ± 3.2%vs9.6 ± 3.9%, p = 0.002), indexed LV mass (107 ± 36g/m2vs130 ± 34g/m2, p = 0.06) and E/E’ (13.7 ± 4.9vs20.6 ± 9.6, p &lt; 0.001) were all significantly different between patients who experienced the primary endpoint and those that didn’t. The strongest predictors of outcome were E/E’ (AUC 0.74), LV mass (AUC 0.73) and the ratio GLS:LV mass (AUC 0.73). An E/E’ of 15 had a sensitivity of 71% and specificity of 69%, while an indexed LV mass of 108 had a sensitivity and specificity of 74% and 67% respectively. GLS to LV mass as a cutoff of 0.16 had a sensitivity and specificity of 70% and 69% respectively. Conclusion In a cohort of 80 patients with AL-amyloid cardiomyopathy, almost half (47.5%) reached the primary composite endpoint. Diastolic dysfunction as expressed as E/E’, and LV mass were the most powerful predictors of outcome, while global longitudinal strain and LV basal strain were also reduced, and showed superiority over LV ejection fraction in predicting prognosis.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Gegenava ◽  
N Leeuwen ◽  
S Wijngaarden ◽  
J Vries-Bouwstra ◽  
D Cassani ◽  
...  

Abstract Background Cardiac involvement is an important cause of hospitalization and mortality in patients with systemic sclerosis (SSc). Advanced echocardiographic measures such as global longitudinal strain (GLS) have already demonstrated to help identifying cardiac involvement and improve risk-stratification in these patients. However, possible sex differences in echocardiographic parameters including GLS have not been explored so far. Purpose To compare standard and advanced (GLS) echocardiographic parameters between male and female patients with SSc and evaluate their association with cardiovascular outcomes. Methods A total of 408 patients (345 females, 54±14 years old and 63 males 51±13 years old) were included in the study. The study endpoint was all-cause mortality combined with hospitalisations for heart failure, myocardial infarction, coronary interventions, device implantations, arrhythmias, cerebral infarction and peripheral ischemic disease. Results Males and females were comparable in terms of cardiovascular risk-factors and comorbidities but showed differences in terms of disease characteristics: greater modified rodnan skin score and higher creatine phosphokinase was observed in males as compared to females, although high NT-proBNP and deteriorated glomerular filtration rate was more prevalent in females. By standard echocardiography, male SSc patients were characterised by greater left ventricular (LV) volumes, but no difference was observed in LV ejection fraction. By advanced echocardiographic analysis, LV GLS was more preserved in female patients (−21% (IQR: −22% to −20%) as compared to males (−20% (IQR −21% to −19%), p&lt;0.001. After median follow-up of 39 months (IQR: 22–66), the combined endpoint occurred in 84 patients, males were affected significantly more frequently as compared to females (20 (32%) vs. 64 (19%), p=0.017). Kaplan-Meier survival analysis showed that impaired LV GLS (based on median value −20%) was associated with higher cumulative rates of all-cause mortality both in males and females with SSc (females: Chi-Square = 80.307 Log Rank &lt;0.001; males: Chi-Square = 4.493 Log Rank = 0.034) (Fig. 1). In univariate cox regression analyses, LV GLS was also significantly associated with the endpoint both in males and females (in males HR: 1.291, 95% CI: 1.033–1.612, p=0.025, in females HR: 1.386, 95% CI: 1.290–1.491, p&lt;0.001). Conclusions Our study shows that among patients with SSc, LV GLS is more impaired in males as compared to females but in both groups is associated with higher prevalence of death and cardiovascular hospitalization. Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Kawakami ◽  
S Ramkumar ◽  
F Pathan ◽  
L Wright ◽  
T H Marwick

Abstract Background Although LV hypertrophy and dysfunction are associated with atrial fibrillation (AF), AF often occurs in the absence of LV hypertrophy or reduced ejection fraction. The effect of subclinical LV dysfunction on AF has not been fully studied. Purpose We sought the association between subclinical LV dysfunction (measured with global longitudinal strain, GLS) and new-onset AF. Methods This observational study evaluated 531 consecutive patients (median age, 67 years [interquartile range, 56 to 78]; 56% male), without a history of AF who underwent strain echocardiography after cryptogenic stroke. The CHARGE-AF score was used to calculate the 5-year risk of developing AF. Standard echocardiographic parameters were measured, and speckle-tracking was used to measure LA (reservoir strain, pump strain, and conduit strain) and LV strain (GLS). A strain analysis was conducted using a dedicated software package, using R-R gating. The baseline clinical and echocardiographic parameters of the patients who developed AF and those who did not were compared. Results Over 2.5 years of follow-up, 61 patients (11%) had new-onset AF. Patients who developed AF were older, had a higher CHARGE-AF score, larger LA volume, worse LA strain, and worse GLS than those who did not. Areas under the receiver-operating curve for GLS (0.84) was comparable to CHARGE-AF (0.79), LA pump strain (0.83), and LA reservoir strain (0.85). In the nested Cox models, GLS demonstrated an independent and incremental predictive value over the clinical and LA parameters (Figure). Moreover, adding GLS to the combined clinical and LA parameters model resulted in a significantly improved reclassification (net reclassification improvement, 0.32; p=0.016). Importantly, the predictive value of GLS was confirmed in patients with abnormal LA volumes (LA volume index≥34ml/m2) but not in patients with normal LA volumes. Figure 1 Conclusion GLS is associated with new-onset AF, especially in patients with abnormal LA volumes. This effect is independent of and incremental to the clinical and LA parameters.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Negareh Mousavi ◽  
Timothy Tan ◽  
Mohammad Ali ◽  
Elkan F. Halpern ◽  
Lin Wang ◽  
...  

Objectives: The aim of this study was to assess whether baseline echocardiographic measures of left ventricular (LV) size and function predict the development of symptomatic heart failure or cardiac death (major adverse cardiac events, MACE) in patients treated with anthracyclines who have a pre-chemotherapy left ventricular ejection fraction (LVEF) in the low normal range (between 50-59%). Background: Anthracycline-induced symptomatic heart failure and impaired LVEF are late and often irreversible manifestations of anthracycline-induced cardiotoxicity. The value of echocardiographic parameters of myocardial size and function before chemotherapy to identify patients at high-risk for development of symptomatic heart failure in patients with low normal LVEF was studied. Methods: Patients with a LVEF between 50 and 59% before anthracyclines were selected. In these patients, LV volumes, LVEF and peak longitudinal strain (GLS) were measured. Individuals were followed for MACE and all-cause mortality over a median of 659 days (range; 3-3704 days). Results: Of 2234 patients undergoing echocardiography for pre-anthracycline assessment, 158 (7%) had a resting ejection fraction of 50-59%. Their average LV end-diastolic volume (LVEDV) was 101±22ml, LVEF was 54 ±3% and global longitudinal strain (GLS) was -17.7±2.6%. Twelve patients experienced a MACE (congestive heart failure) at a median of 173 days (range; 15-530). Age, diabetes, previous coronary artery disease, LVEDV, LVESV and GLS were all-predictive of MACE (P= 0.015, 0.0043 and 0.0065 for LVEDV, LVESV, and GLS respectively). LVEDV and GLS remained predictive of MACE when adjusted for age. Age and GLS were also predictive of overall mortality (p<0.0001 and 0.0105 respectively). Conclusions: In patients treated with anthracyclines with an LVEF of 50-59%, both baseline EDV and GLS predict the occurrence of MACE. These parameters may help target patients who could bene[[Unable to Display Character: &#64257;]]t from closer cardiac surveillance and earlier initiation of cardioprotective medical therapy.


Cardiology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Mitsushige Murata ◽  
Takashi Kawakami ◽  
Masaharu Kataoka ◽  
Hidenori Moriyama ◽  
Takahiro Hiraide ◽  
...  

<b><i>Background:</i></b> Riociguat is a soluble guanylate cyclase stimulator that improves hemodynamics in patients with pulmonary hypertension (PH). Accumulating evidence implicates the additional effect of riociguat on the increase in cardiac output. However, its mechanisms have not been fully understood. This study aimed to investigate whether riociguat could ameliorate right ventricular (RV) contraction as well as hemodynamics. <b><i>Methods:</i></b> We studied 45 patients with pulmonary arterial hypertension (14) or chronic thromboembolic pulmonary hypertension (31) and evaluated hemodynamics, using right-sided heart catheterization, before and after the administration of riociguat. RV function was assessed by echocardiography, including speckle-tracking echocardiography. <b><i>Results:</i></b> Riociguat significantly improved the WHO functional class and reduced the mean pulmonary arterial pressure and vascular resistance. In addition, the cardiac index increased. RV remodeling was ameliorated after riociguat administration as assessed by the echocardiographic parameters, such as RV diameter and RV area index. RV function, including RV fractional area change and RV global longitudinal strain, also significantly improved, and their improvement was even observed in patients with mild PH after pulmonary endarterectomy or balloon pulmonary angioplasty. Furthermore, covariance analysis revealed that RV global longitudinal strain and RV fractional area change improved after riociguat administration, even with the same mean pulmonary arterial pressure, implicating the improvement of RV contractile function by riociguat, regardless of RV loading. <b><i>Conclusions:</i></b> Riociguat not only improved the hemodynamics of patients with PH but also ameliorated the echocardiographic parameters with RV function. RV strain could detect the subtle improvement in mild PH, and riociguat may have a benefit even after intervention, as assessed by speckle-tracking echocardiography.


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