Aims
Despite increasing research efforts, the prognostic consequences of takotsubo cardiomyopathy (TTC) remain largely unknown. The aim of this study was therefore to compare the long‐term mortality ...rate of TTC patients with high‐risk patients presenting with ST‐segment elevation myocardial infarction (STEMI).
Methods and results
A total of 286 patients with TTC were matched for age and gender with 286 STEMI patients. Outcome was obtained with a standardized telephone follow‐up. The primary analysis determined long‐term mortality. A secondary analysis was performed evaluating 28‐day and 1‐year mortality. Follow‐up was available for 96% of patients after a mean of 3.8 ± 2.5 years. In TTC patients, long‐term mortality was significantly higher compared with the matched STEMI cohort 24.7% vs. 15.1%, hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.07–2.33; P = 0.02. There was no significant difference in the rates of 28‐day (5.5% vs. 5.7%, HR 0.96, 95% CI 0.47–1.94; P = 0.91) and 1‐year mortality (12.5% vs. 9%, HR 1.42, 95% CI 0.85–2.38; P = 0.18). In multivariable regression analysis, male sex, a high Killip class on admission, and diabetes mellitus were identified as independent predictors of mortality in TTC patients. A risk score consisting of these factors showed a higher mortality with an increasing number of risk factors.
Conclusion
Mortality rates in TTC patients are higher than previously expected and long‐term mortality exceeded that of patients with STEMI. A simple risk score may provide an approach to identify high‐risk patients and predict clinical prognosis.
Importantly, there was a clear divergence of mortality curves <=2 months after initial presentation, which implies that arrhythmias are of higher prognostic mortality in the convalescent phase of ...TTC. ...our data illustrate the significance of arrhythmic events as a determinant of outcome and a useful approach to risk stratification in TTC. ...life-threatening arrhythmias are a common finding in patients with TTC and have a major prognostic effect.
The aims of the study were to assess the prognostic significance of cardiac magnetic resonance myocardial feature tracking (CMR-FT) in a large multicenter study and to evaluate the most potent CMR-FT ...predictor of hard clinical events following myocardial infarction (MI).
CMR-FT is a new method that allows accurate assessment of global and regional circumferential, radial, and longitudinal myocardial strain. The prognostic value of CMR-FT in patients with reperfused MI is unknown.
The study included 1,235 MI patients (n = 795 with ST-segment elevation MI and 440 with non–ST-elevation MI) at 15 centers. All patients were reperfused by primary percutaneous coronary intervention. Central core laboratory–masked analyses were performed to determine left ventricular (LV) circumferential, radial, and longitudinal strain. The primary clinical endpoint of the study was the occurrence of major adverse cardiac events within 12 months after infarction.
Patients with cardiovascular events had significantly impaired CMR-FT strain values (p < 0.001 for all). Global longitudinal strain was identified as the strongest CMR-FT parameter of future cardiovascular events and emerged as an independent predictor of poor prognosis following MI even after adjustment for established prognostic markers. Global longitudinal strain provided an incremental prognostic value for all-cause mortality above LV ejection fraction (c-index increase from 0.65 to 0.73; p = 0.04) and infarct size (c-index increase from 0.60 to 0.78; p = 0.002).
CMR-FT is a superior measure of LV function and performance early after reperfused MI with incremental prognostic value for mortality over and above LV ejection fraction and infarct size. (Abciximab i.v. Versus i.c. in ST-segment elevation Myocardial Infarction AIDA STEMI; NCT00712101; Thrombus Aspiration in ThrOmbus Containing culpRIT Lesions in Non-ST-Elevation Myocardial Infarction TATORT-NSTEMI; NCT01612312)
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Remote ischaemic conditioning (RIC) and postconditioning (PostC) are both potent activators of innate protection against ischaemia-reperfusion injury and have demonstrated cardioprotection in ...experimental and clinical ST-elevation myocardial infarction (STEMI) trials. However, their combined effects have not been studied in detail. The aim of this study was to evaluate if the co-application of intrahospital RIC and PostC has a more powerful effect on myocardial salvage compared with either PostC alone or control.
This prospective, controlled, single-centre study randomized 696 STEMI patients to one of the following three groups: (i) combined intrahospital RIC + PostC in addition to primary percutaneous coronary intervention (PCI); (ii) PostC in addition to PCI; and (iii) conventional PCI (control). The primary endpoint myocardial salvage index was assessed by cardiac magnetic resonance (CMR) imaging within 3 days after infarction. Secondary endpoints included infarct size and microvascular obstruction (MVO) assessed by CMR. The combined clinical endpoint consisted of death, reinfarction, and new congestive heart failure within 6 months. The primary endpoint myocardial salvage index was significantly greater in the combined RIC + PostC group when compared with the control group (49 interquartile range 30-72 vs. 40 interquartile range 16-68, P = 0.02). Postconditioning alone failed to improve myocardial salvage when compared with conventional PCI (P = 0.39). The secondary endpoints, including infarct size and MVO, showed no significant differences between groups. Clinical follow-up at 6 months revealed no differences in the combined clinical endpoint between groups (P = 0.44).
Combined intrahospital RIC + PostC in conjunction with PCI in STEMI significantly improves myocardial salvage in comparison with control and PostC.
NCT02158468.
Takotsubo syndrome (TS) is an acute non-ischemic cardiomyopathy characterized by transient regional systolic dysfunction of the left and/or right ventricle with still unknown etiology. The aim of the ...current study was to conduct for the first time a genome-wide association study (GWAS) in a cohort of TS patients to identify potential genetic risk variants.
This single-center study was conducted at the University Heart Center Lübeck from 2008 to 2016. DNA isolation was done according to standard protocols. Imputation of genotypes were performed at the Michigan Imputation Server (https://imputationserver.sph.umich.edu) using the 1000G Phase 3 v5 reference panel.
The study population consisted of 96 TS patients (91 females, 5 males) with a mean age of 71.9±10.4years and 475 healthy controls (268 males, 207 females). The results of GWAS analysis showed several promising candidate loci (68 loci after applying threshold of p<5∗10−4 and MAF>5%). Of these 68 loci, 18 loci contained top single nucleotide polymorphisms (SNPs) that were supported by SNPs in high Linkage Disequilibrium (r2>0.8) with p<10−3. Two out of the 18 loci contained SNP with hits in the GWAS catalog (traits: blood pressure, thyroid stimulating hormone).
This first GWAS analysis in a larger cohort of patients with TS showed promising preliminary results. Further intensive research efforts of international collaborators are now necessary to enable deep-phenotyping of TS patients to ultimately assess a potential genetic cause of TS.
Background Current literature only reports variable information from single-center studies on the recurrence rate, the complications, and the outcome of patients with Takotsubo syndrome ( TTS) ...experiencing recurrent TTS . Therefore, a detailed description of clinical characteristics, predictors, and the prognostic impact of patients with TTS and recurrences in a multicenter registry is needed. Methods and Results We analyzed 749 patients with TTS from 9 European centers being part of the international, multicenter GEIST (German Italian Stress Cardiomyopathy) Registry. Patients were divided into the recurrence group and the nonrecurrence group. The recurrence rate at a median follow-up of 830 days (interquartile range, 118-1701 days) was 4%. Most recurrences were documented in the first 5 years after the index TTS episode. Up to 2 TTS recurrences were documented in 2 of 30 patients (6%). A variable ballooning pattern (n=6, 0.8%) with, in particular, involvement of the right ventricular occurred in 3 cases (0.4%) at the recurrence event. Except for the higher presence of arterial hypertension (86.7% versus 68.3%; P=0.03) in the recurrence group, no other baseline characteristics were different between groups. Observation of TTS complications during follow-up, including stroke, thromboembolic events, in-hospital death, and cardiogenic shock, revealed no significant differences between groups ( P>0.05), except the higher presence of pulmonary edema in the recurrence group versus the nonrecurrence group (13.3% versus 4.9%; P=0.04). Conclusions The incidence of TTS recurrence is estimated to be 4% in this multicenter TTS registry. A variable TTS pattern at recurrence is common in up to 20% of recurrence cases.
Takotsubo syndrome (TTS) is a unique nonischemic cardiac disease characterized by acute myocardial dysfunction of the left and/or right ventricle. Patients are predominantly postmenopausal women and ...usually present with symptoms indistinguishable from acute coronary syndrome. Although the exact pathomechanisms of TTS remain elusive, increasing evidence suggests that sympathetic overdrive and catecholamine excess might play a central role. Despite the complete recovery of ventricular dysfunction within several days to weeks, patients with TTS exhibit considerable short‐ and long‐term mortality rates and ventricular arrhythmias have been identified as key contributor to morbidity and mortality. This article summarizes the prevalence, underlying mechanisms, therapeutic strategies, and prognostic implications of ventricular arrhythmias in TTS. Furthermore, the need for implantable cardioverter‐defibrillators is discussed in view of the transient character of the disease.
Data on the impact of initial Thrombolysis In Myocardial Infarction (TIMI) flow in the culprit coronary artery on myocardial damage after ST-elevation myocardial infarction (STEMI) are limited. Aim ...of this multicenter study was, therefore, to elucidate the impact of TIMI flow grade before percutaneous coronary intervention (PCI) on infarct size (IS), myocardial salvage index (MSI), and microvascular obstruction (MVO) assessed by cardiac magnetic resonance (CMR) imaging in patients with STEMI. We enrolled 738 patients with STEMI reperfused by primary PCI within 12 hours after symptom onset at 8 centers. Impaired coronary flow was defined as an initial coronary TIMI flow grade ≤1, whereas preserved coronary flow was defined as an initial coronary TIMI flow grade ≥2. CMR was performed in median 3 days (interquartile range 2 to 4 days) after infarction using a standardized infarction protocol. IS, MVO, and MSI were determined in central core laboratory–masked analyses. The primary clinical end point of the study was the time to major adverse cardiac events defined as death, reinfarction, and new onset of heart failure within 12 months after infarction. TIMI flow ≤1 before PCI was present in 507 patients (68.7%) and was significantly associated with larger IS (19% left ventricular LV vs 9% LV; p <0.001), less MSI (0.46 vs 0.65; p <0.001), reduced left ventricular ejection fraction (49% vs 55%; p <0.001), and a higher extent of MVO (0.6% LV vs 0.0% LV; p <0.001). Moreover, TIMI flow before PCI was identified as an independent predictor of IS, MVO, and MSI. However, there were no significant differences in major adverse cardiac event rates between groups (6.1% vs 7.5%; p = 0.48). In conclusion, TIMI flow pre-PCI is reversely associated with myocardial injury and is an independent predictor of myocardial damage assessed by CMR.
This study aims at identifying risk-related patterns of left ventricular contraction dynamics via novel volume transient characterization. A multicenter cohort of AMI survivors (n = 1021) who ...underwent Cardiac Magnetic Resonance (CMR) after infarction was considered for the study. The clinical endpoint was the 12-month rate of major adverse cardiac events (MACE, n = 73), consisting of all-cause death, reinfarction, and new congestive heart failure. Cardiac function was characterized from CMR in 3 potential directions: by (1) volume temporal transients (i.e. contraction dynamics); (2) feature tracking strain analysis (i.e. bulk tissue peak contraction); and (3) 3D shape analysis (i.e. 3D contraction morphology). A fully automated pipeline was developed to extract conventional and novel artificial-intelligence-derived metrics of cardiac contraction, and their relationship with MACE was investigated. Any of the 3 proposed directions demonstrated its additional prognostic value on top of established CMR indexes, myocardial injury markers, basic characteristics, and cardiovascular risk factors (P < 0.001). The combination of these 3 directions of enhancement towards a final CMR risk model improved MACE prediction by 13% compared to clinical baseline (0.774 (0.771-0.777) vs. 0.683 (0.681-0.685) cross-validated AUC, P < 0.001). The study evidences the contribution of the novel contraction characterization, enabled by a fully automated pipeline, to post-infarction assessment.
Abstract
Feasibility of automated volume-derived cardiac functional evaluation has successfully been demonstrated using cardiovascular magnetic resonance (CMR) imaging. Notwithstanding, strain ...assessment has proven incremental value for cardiovascular risk stratification. Since introduction of deformation imaging to clinical practice has been complicated by time-consuming post-processing, we sought to investigate automation respectively. CMR data (n = 1095 patients) from two prospectively recruited acute myocardial infarction (AMI) populations with ST-elevation (STEMI) (AIDA STEMI n = 759) and non-STEMI (TATORT-NSTEMI n = 336) were analysed fully automated and manually on conventional cine sequences. LV function assessment included global longitudinal, circumferential, and radial strains (GLS/GCS/GRS). Agreements were assessed between automated and manual strain assessments. The former were assessed for major adverse cardiac event (MACE) prediction within 12 months following AMI. Manually and automated derived GLS showed the best and excellent agreement with an intraclass correlation coefficient (ICC) of 0.81. Agreement was good for GCS and poor for GRS. Amongst automated analyses, GLS (HR 1.12, 95% CI 1.08–1.16,
p
< 0.001) and GCS (HR 1.07, 95% CI 1.05–1.10,
p
< 0.001) best predicted MACE with similar diagnostic accuracy compared to manual analyses; area under the curve (AUC) for GLS (auto 0.691 vs. manual 0.693,
p
= 0.801) and GCS (auto 0.668 vs. manual 0.686,
p
= 0.425). Amongst automated functional analyses, GLS was the only independent predictor of MACE in multivariate analyses (HR 1.10, 95% CI 1.04–1.15,
p
< 0.001). Considering high agreement of automated GLS and equally high accuracy for risk prediction compared to the reference standard of manual analyses, automation may improve efficiency and aid in clinical routine implementation.
Trial registration: ClinicalTrials.gov, NCT00712101 and NCT01612312.
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