The prognostic significance of single-lead ST-segment resolution in ST-segment elevation myocardial infarction patients treated with primary PCI - A substudy of the randomized TOTAL trial.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with high morbidity and mortality worldwide. Simple electrocardiogram (ECG) tools, including ST-segment resolution (STR) have been developed to identify high-risk STEMI patients after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: We evaluated the prognostic impact of STR in the ECG lead with maximal baseline ST-segment elevation (STE) 30-60 minutes after primary PCI in 7,654 STEMI patients included in the TOTAL trial. Incomplete or no STR was defined as < 70% STR and complete STR as ≥ 70% STR. The primary outcome was the composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock, or new or worsening New York Heart Association (NYHA) class IV heart failure at 1-year follow-up. RESULTS: Of 7,654 patients, 42.9% had incomplete or no STR and 57.1% had complete STR. The primary outcome occurred in 341 patients (10.4%) in the incomplete or no STR group and in 234 patients (5.4%) in the complete STR group. In Cox regression analysis, adjusted hazard ratio for STR < 70% to predict the primary outcome was 1.56 (95% confidence interval 1.32-1.89; P < .001) (model adjusted for all baseline comorbidities, clinical status during hospitalization, angiographic findings, and procedural techniques). CONCLUSION: In a large international study of STEMI patients, STR < 70% 30-60 minutes post primary PCI in the ECG lead with the greatest STE at admission was associated with an increased rate of the composite of cardiovascular death, recurrent MI, cardiogenic shock, or new or worsening NYHA class IV heart failure at 1-year follow-up. Clinicians should pay attention to this simple ECG finding.

High-dose adenosine versus saline-induced cardioplegic arrest in coronary artery bypass grafting: A randomized double-blind clinical feasibility trial.

BACKGROUND AND OBJECTIVE: In this clinical trial, we evaluated if a short-acting nucleoside, adenosine, as a high-dose bolus injection with blood cardioplegia induces faster arrest and provides better myocardial performance in patients after bypass surgery for coronary artery disease. METHODS: Forty-three patients scheduled for elective or urgent coronary artery bypass grafting were prospectively recruited in two-arm 1:1 randomized parallel groups to either receive 20 mg of adenosine (in 21 patients) or saline (in 22 patients) into the aortic root during the first potassium-enriched blood cardioplegia infusion. The main outcomes of the study were ventricular myocardial performance measured with cardiac index, right ventricular stroke work index, and left ventricular stroke work index at predefined time points and time to asystole after a single bolus injection of adenosine. Conventional myocardial biomarkers were compared between the two groups at predefined time points as secondary endpoints. Electrocardiographic data and other ad hoc clinical outcomes were compared between the groups. RESULTS: Compared with saline, adenosine reduced the time to asystole (68 (95% confidence interval (95% CI) = 37-100) versus 150 (95% CI = 100-210) seconds, p = 0.005). With myocardial performance, the results were inconclusive, since right ventricular stroke work index recovered better in the adenosine group (p = 0.008), but there were no significant overall differences in cardiac index and left ventricular stroke work index between the groups. Only the post-cardiopulmonary bypass cardiac index was better in the adenosine group (2.3 (95% CI = 2.2-2.5) versus 2.1 (95% CI = 1.9-2.2) L/min/m2, p = 0.016). There were no significant differences between the groups in cardiac biomarker values. CONCLUSIONS: A high dose adenosine bolus at the beginning of the first cardioplegia infusion resulted in significantly faster asystole in coronary artery bypass grafting patients but enhanced only partially the ventricular performance.EudraCT number: 2014-001382-26. https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001382-26/FI.

The prognostic significance of the electrical QRS axis on long-term mortality in acute coronary syndrome patients - The TACOS study.

INTRODUCTION: There are several potential causes of QRS-axis deviation in the ECG, but there is limited data on the prognostic significance of QRS-axis deviation in ACS patients. SUBJECTS AND METHODS: We evaluated the long-term prognostic significance of acute phase frontal plane QRS-axis deviation and its shift during hospital stay in ACS patients. A total of 1026 patients who met the inclusion criteria were divided into three categories: normal (n = 823), left (n = 166) and right/extreme axis (n = 37). RESULTS: The median survival time was 9.0 years (95% CI 7.9-10.0) in the normal, 3.6 years (95% CI 2.4-4.7) in the left and 1.3 years (95% CI 0.2-2.4) in the right/extreme axis category. Both short and long-term all-cause mortality was lowest in the normal axis category and highest in the right/extreme axis category. Compared to normal axis, both admission phase QRS-axis deviation groups were independently associated with a higher risk of all-cause mortality. When including left ventricular hypertrophy in the ECG, only the right/extreme axis retained its statistical significance (aHR 1.76; 95% CI 1.16-2.66, p = 0.007). Axis shift to another axis category had no effect on mortality. CONCLUSION: In ACS patients, acute phase QRS-axis deviation was associated with higher risk of all-cause mortality. Among the axis deviation groups, right/extreme QRS-axis deviation was the strongest predictor of mortality in the multivariable analysis. Further studies are required to investigate to what extent this association is caused by pre-existing or by ACS-induced axis deviations. QRS-axis shift during hospital stay had no effect on all-cause mortality.

Evaluation of the QRS score for diagnosing coronary artery disease in women: A Finnish cardiovascular study.

BACKGROUND: Exercise electrocardiography is a widely used diagnostic modality for diagnosing coronary artery disease. This method has been used for both sexes; however, its diagnostic accuracy in women is limited. METHODS: The study analyzed 332 women participating in the Finnish Cardiovascular Study. Among 332 women, 125 with angiographically proven coronary artery disease (mean age 62.1 ± 9.5 years), 91 with a low likelihood of coronary artery disease (mean age 47.3 ± 13.5 years), and 116 without angiographically proven coronary artery disease (mean age 56.3 ± 9.9 years) were analyzed. The Q, R, S, and ST-segment changes and QRS score were determined by subtracting the Q, R, S, and ST-segment amplitudes immediately after the maximal exercise changes from their rest values (Δ). Receiver operating characteristic curve analysis was performed to evaluate the overall diagnostic performance of the parameters for predicting coronary artery disease. RESULTS: The areas under the receiver operating characteristic curve between coronary artery disease and low likelihood of coronary artery disease groups for the QRS score and ΔSTV5, ΔQaVF, and ΔRaVF were 0.75, 0.73, 0.71, and 0.71, respectively. These areas were lower (0.62, 0.57, 0.60, and 0.60, respectively) between the groups with and without angiographically proven coronary artery disease. QRS score demonstrated the highest sensitivity at 80% specificity (61.5%) and the highest specificity at 80% sensitivity (57.6%). CONCLUSIONS: This study suggests that the QRS and ST-segment depression have a moderate diagnostic ability to predict coronary artery disease in women. Q and R waves in lead aVF showed good diagnostic ability.

The Effect of Atrial Fibrillation on the Long-Term Mortality of Patients with Acute Coronary Syndrome: The TACOS Study.

INTRODUCTION: Atrial fibrillation (AF) is a frequent finding in acute coronary syndrome (ACS), but there is conflicting scientific evidence regarding its long-term impact on patient outcome. The aim of this study was to survey and compare the ≥10-year mortality of ACS patients with sinus rhythm (SR) and AF. METHODS: Patients were divided into 2 groups based on rhythm in their 12-lead ECGs: (1) SR (n = 788) at hospital admission and discharge (including sinus bradycardia, physiological sinus arrhythmia, and sinus tachycardia) and (2) AF/atrial flutter (n = 245) at both hospital admission and discharge, or SR and AF combination. Patients who failed to match the inclusion criteria were excluded from the final analysis. The main outcome surveyed was long-term all-cause mortality between AF and SR groups during the whole follow-up time. RESULTS: Consecutive ACS patients (n = 1,188, median age 73 years, male/female 58/42%) were included and followed up for ≥10 years. AF patients were older (median age 77 vs. 71 years, p < 0.001) and more often female than SR patients. AF patients more often presented with non-ST-elevation myocardial infarction (69.8 vs. 50.4%, p < 0.001), had a higher rate of diabetes (31.0 vs. 22.8%, p = 0.009), and were more often using warfarin (32.2 vs. 5.1%, p < 0.001) or diuretic medication (55.1 vs. 25.8%, p < 0.001) on admission than patients with SR. The use of warfarin at discharge was also more frequent in the AF group (55.5 vs. 14.8%, p < 0.001). The rates of all-cause and cardiovascular mortality were higher in the AF group (80.9 vs. 50.3%, p < 0.001, and 73.8 vs. 69.6%, p = 0.285, respectively). In multivariable analysis, AF was independently associated with higher mortality when compared to SR (adjusted HR 1.662; 95% CI: 1.387-1.992, p < 0.001). CONCLUSION: AF/atrial flutter at admission and/or discharge independently predicted poorer long-term outcome in ACS patients, with 66% higher mortality within the ≥10-year follow-up time when compared to patients with SR.

Poor long-term outcome in acute coronary syndrome in a real-life setting: Ten-year outcome of the TACOS study.

BACKGROUND: Long-term outcome of the three categories of acute coronary syndrome (ACS) in real-life patient cohorts is not well known. The objective of this study was to survey the 10-year outcome of an ACS patient cohort admitted to a university hospital and to explore factors affecting the outcome. METHODS: A total of 1188 consecutive patients (median age 73 years) with ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) or unstable angina pectoris (UA) in 2002-2003 were included and followed up for ≥ 10 years. RESULTS: Mortality for STEMI, NSTEMI and UA patients during the follow-up period was 52.5%, 69.9% and 41.0% (p < 0.001), respectively. In multivariable Cox regression analysis, only age and creatinine level at admission were independently associated with patient outcome in all the three ACS categories when analyzed separately. CONCLUSIONS: All the three ACS categories proved to have high mortality rates during long-term followup in a real-life patient cohort. NSTEMI patients had worse outcome than STEMI and UA patients during the whole follow-up period. Our study results indicate clear differences in the prognostic significance of various demographic and therapeutic parameters within the three ACS categories.

Long-term outcome of pre-specified ECG patterns in acute coronary syndrome.

BACKGROUND: Long-term outcome of real-life acute coronary syndrome (ACS) patients with selected ECG patterns is not well known. PURPOSE: To survey the 10-year outcome of pre-specified ECG patterns in ACS patients admitted to a university hospital. METHODS: A total of 1184 consecutive acute coronary syndrome patients in 2002-2003 were included and followed up for 10 years. The patients were classified into nine pre-specified ECG categories: 1) ST elevation; 2) pathological Q waves without ST elevation; 3) left bundle branch block (LBBB); 4) right bundle branch block (RBBB) 5) left ventricular hypertrophy (LVH) without ST elevation except in leads aVR and/or V1; 6) global ischemia ECG (ST depression ≥0.5 mm in 6 leads, maximally in leads V4-5 with inverted T waves and ST elevation ≥0.5 mm in lead aVR); 7) other ST depression and/or T wave inversion; 8) other findings and 9) normal ECG. RESULTS: Any abnormality in the ECG, especially Q waves, LBBB, LVH and global ischemia, had negative effect on outcome. In age- and gender adjusted Cox regression analysis, pathological Q waves (HR 2.28, 95%CI 1.20-4.32, p = .012), LBBB (HR 3.25, 95%CI 1.65-6.40, p = .001), LVH (HR 2.53, 95%CI 1.29-4.97, p = .007), global ischemia (HR 2.22, 95%CI 1.14-4.31, p = .019) and the combined group of other findings (HR 3.01, 95%CI 1.56-6.09, p = .001) were independently associated with worse outcome. CONCLUSIONS: During long-term follow-up of ACS patients, LBBB, ECG-LVH, global ischemia, and Q waves were associated with worse outcome than a normal ECG, RBBB, ST elevation or ST depression with or without associated T-wave inversion. LBBB was associated with the highest mortality rates.

The de Winter ECG pattern: Distribution and morphology of ST depression.

BACKGROUND: The reported positive predictive value (PPV) for the "de Winter ECG pattern" to predict an acute left anterior descending artery (LAD) lesion is inconsistent. Besides, the morphology of upsloping or nonupsloping ST depression (STD) may have different significance of severity and prognostication. METHODS: We searched the MEDLINE database using "de Winter" or "junctional ST-depression with tall symmetrical T-waves" or "tall T wave" or "STEMI equivalent" as the item up to March 2020. We compared the ECG differences between the different culprit arteries and various morphological STD. RESULTS: A total of 70 patients with analyzable ECGs were included. In 60 patients (LAD group), the LAD was the culprit artery, while in 10 patients (non-LAD group), there were other etiologies. Maximal STD in V2 or V3 had a PPV of 89% of all patients and 98% of patients without ST elevation in V2 to detect an acute LAD lesion. The presence of q/Q-wave or poor R-wave progression in the precordial leads was significantly more often found in patients with upsloping STD than in patients with nonupsloping STD in the LAD group (84% vs. 27%, p < .01). In 18 patients, the ECG showed a change from upsloping to nonupsloping STD from the leads with maximal STD to the surrounding leads with less STD. CONCLUSIONS: The location of the maximal STD in the precordial leads differs between patients with LAD as the culprit artery and other etiologies of the de Winter ECG pattern. Upsloping STD signifies more severe signs of ischemia than nonupsloping STD.

The prognostic significance of a positive or isoelectric T wave in lead aVR in patients with acute coronary syndrome and ischemic ECG changes in the presenting ECG - Long-term follow-up data of the TACOS study.

BACKGROUND: A positive T wave in lead aVR (aVRT+) is an independent prognostic predictor of cardiovascular mortality in the general population as well as in cardiovascular disease. SUBJECTS AND METHODS: We evaluated the prognostic impact of aVRT+ in an ECG recorded as close to hospital discharge as possible in acute coronary syndrome patients (n = 527). We divided the patients into three categories based on the findings in the admission ECG: ST elevation, global ischemia and other ST/T changes. RESULTS: In the whole study population, and in all the three ECG subgroups, the 10-year all-cause mortality rate was higher in the aVRT+ group than in the aVRT- group. In Cox regression analysis, the age and gender adjusted hazard ratio (HR) for aVRT+ to predict all-cause mortality in the whole study population was 1.43 (95% confidence interval [CI] 1.12-1.83; p = 0.004). To predict cardiovascular mortality, the age and gender adjusted HR for aVRT+ was 1.54 (95% CI 1.14-2.07; p = 0.005) in the whole study population and 2.07 (95% CI 1.07-4.03; p = 0.032) in the category with other ST/T changes. CONCLUSION: In ACS patients with or without ST elevation, but with ischemic ST/T changes in their presenting ECG, a positive or isoelectric T wave in lead aVR in an ECG recorded in the subacute in-hospital stage is associated with all-cause and cardiovascular mortality during long-term follow-up. Clinicians should pay attention to this simple ECG finding at hospital discharge.

Electrocardiographic findings of acute total occlusion associated with a sub-occlusion involving the left anterior descending and the right coronary artery.

BACKGROUND: The ECG characteristics of simultaneous acute occlusion/sub-occlusion of two coronary arteries involving the left anterior descending (LAD) and right (RCA) coronary artery have been rarely described in the literature. METHODS: We present two patient cases, where one of the arteries was totally occluded and the other one had a sub-occlusion with severely limited flow to demonstrate the ECG characteristics of this severe presentation of acute coronary syndrome. RESULTS: Two ECG patterns suggested simultaneous occlusions of the RCA and LAD. One pattern was ST-segment elevation (STE) in lead III higher than in lead II with concomitant STE in leads V3-V4. The other pattern was STE in lead III higher than in lead II with the concomitant Dressler - de Winter ECG pattern in leads V2-V4. CONCLUSIONS: We present two ECG presentations of simultaneous RCA and LAD occlusion/sub-occlusion. We consider these ECG features as high-risk markers in acute ST-elevation myocardial infarction.

Differential diagnostic dilemma between pulmonary embolism and acute coronary syndrome.

Acute pulmonary embolism (PE) is a frequent life-threatening condition in emergency departments. Careful diagnosis is important, and different diagnostic tests such as electrocardiogram (ECG), biochemical markers, echocardiogram, and computed tomography are required. Although ECG is a cheap and rapid diagnostic test for pulmonary embolism, it has some limitations in the differential diagnosis of acute coronary syndrome and acute PE. Herein, we report ECG results of a patient diagnosed with acute PE mimicking acute coronary syndrome.

R-Peak Time: An Electrocardiographic Parameter with Multiple Clinical Applications.

In the 12-lead electrocardiogram (ECG), the time from the onset of the QRS complex (Q or R wave) to the apex or peak of R or to R' (when present), using indirect or semidirect surface unipolar precordial leads, bipolar limb leads or unipolar limb leads, is called ventricular activation time (VAT), R wave peak time (RWPT), R-peak time or intrinsicoid deflection (ID). The R-peak time in a specific ECG lead is the interval from the earliest onset of the QRS complex, preferably determined from multiple simultaneously recorded leads, to the peak (maximum) of the R wave or R' if present. Irrespective of the relative height of the R and R' waves, the R-peak time is measured to the second peak. The parameter corresponds to the time of the electrical activation occurring from the endocardium to the epicardium as reflected by the recording electrode located at a variable distance on the body surface, depending on the lead type: a unipolar precordial lead, a bipolar or unipolar limb lead. In normal conditions, the R-peak time for the thinner-walled right ventricle is measured from lead V1 or V2 and its upper limit of normal is 35 ms. The R-peak time for the left ventricle (LV) is measured from leads V5 to V6 and 45 ms is considered the upper limit of normal. In this manuscript, we review the clinical applications of this parameter.

Significance of ST-segment deviation in patients with acute pulmonary embolism and negative T waves.

BACKGROUND: Common electrocardiogram (ECG) manifestations in acute pulmonary em-bolism (APE) include ST-segment deviation (STDV) along with negative T-waves (NTW). STDV could occur in 3 typical ischemic patterns: (i) the left ventricular (LV) subendocardial ischemic pattern; (ii) the right ventricular (RV) transmural ischemic pattern; and (iii) the LV subendocardial plus RV transmural ischemic pattern. The purpose of this study was to evalu-ate the relationship of STDV and adverse clinical outcomes and to identify the relationship of relatively normal ECG and favorable clinical outcomes. METHODS: Retrospective analysis of electronic charts in APE patients was performed in a tertiary hospital. ECGs on admission were obtained and classified as with or without STDV. Adverse clinical outcomes were defined as need to intensify therapy and 30-day mortality. Relatively normal ECG was defined as without any STDV, abnormal QRS morphology in lead V1 and S1Q3T3. RESULTS: From a total of 210 patients with NTW, 131 had STDV ≥ 0.1 mV, while 79 did not. Patients with STDV had worse evolution: higher incidence of dyspnea, hypotension, cardiogen-ic shock, intensification of therapy, and death compared to patients without STDV (p = 0.001 for each variable). The majority (89%) of the patients with STDV presented with 1 of the 3 typical ischemic ECG patterns. LV subendocardial ischemic pattern (OR = 4.963, p = 0.004), RV transmural ischemic pattern (OR = 3.128, p = 0.021) and LV subendocardial plus RV transmural ischemic pattern (OR = 3.036, p = 0.017) independently predicted the need to intensify therapy. RV transmural ischemic pattern (OR = 4.227, p = 0.031) and LV subendocardial plus RV transmural ischemic pattern (OR = 4.022, p = 0.032) independently predicted 30-day mortality. Compared to the patients with abnormal ECG, the patients with relatively normal ECG had a significant lower incidence of death (0% vs. 16%; p = 0.001) and need to intensify therapy during hospitalization (6% vs. 30%; p = 0.002). CONCLUSIONS: Ischemic ECG patterns are common ECG manifestations of APE and predict worse evolution and 30-day mortality. Additionally, relatively normal ECGs may associate with favorable clinical outcomes.

Agreement between cardiologists and fellows in interpretation of ischemic electrocardiographic changes in acute myocardial infarction.

BACKGROUND: Time from symptom onset may not be the best indicator for choosing reperfusion therapy for patients presenting with acute ST-elevation myocardial infarction (STEMI); consequently ECG-based methods have been developed. METHODS: This study evaluated the inter-observer agreement between experienced cardiologists and junior doctors in identifying the ECG findings of the pre-infarction syndrome (PIS) and evolving myocardial infarction (EMI). The ECGs of 353 STEMI patients were independently analyzed by two cardiologists, one fellow in cardiology, one fellow in internal medicine and a medical student. The last two were given a half-hour introduction of the PIS/EMI-algorithm. RESULTS: The inter-observer reliability between all the investigators was found to be good according to kappa statistics (κ 0.632-0.790) for the whole study population. When divided into different subgroups, the inter-observer agreements were from good to very good between the cardiologists and the fellow in cardiology (κ 0.652 -0.813) and from moderate to good (κ 0.464-0.784) between the fellow in internal medicine, medical student and the others. CONCLUSIONS: The PIS and EMI ECG patterns are reliably identified by experienced cardiologists and can be easily adopted by junior doctors.

Electrocardiogram patterns during hemodynamic instability in patients with acute pulmonary embolism.

BACKGROUND: We have previously described new electrocardiogram (ECG) findings for massive pulmonary embolism, namely ST-segment elevation in lead aVR with ST-segment depression in leads I and V4 -V6 . However, the ECG patterns of patients with acute pulmonary embolism during hemodynamic instability are not fully described. METHODS: We compared the differences between the ECG at baseline and after deterioration during hemodynamic instability in twenty patients with acute pulmonary embolism. RESULTS: Compared with the ECG at baseline, three ischemic ECG patterns were found during clinical deterioration with hemodynamic instability: ST-segment elevation in lead aVR with concomitant ST-segment depression in leads I and V4 -V6 , ST-segment elevation in leads V1 -V3 /V4 , and ST-segment elevation in leads III and/or V1 /V2 with concomitant ST-segment depression in leads V4 /V5 -V6 . Ischemic ECG patterns with concomitant S1Q3 and/or abnormal QRS morphology in lead V1 were more common (90%) during hemodynamic instability than at baseline (5%) (P = 0.001). CONCLUSIONS: Hemodynamic instability in acute pulmonary embolism is reflected by signs of myocardial ischemia combined with the right ventricular strain pattern in the 12-lead ECG.

Correlation between ST-segment elevation and negative T waves in the precordial leads in acute pulmonary embolism: insights into serial electrocardiogram changes.

BACKGROUND: Acute pulmonary embolism (APE) is often misdiagnosed as acute coronary syndrome because of the similarity of the presenting symptoms and of the electrocardiogram (ECG) manifestations. In APE, ST-segment elevation (STE) in leads V1 to V3 /V4 , mimicking anteroseptal myocardial infarction, is not a rare phenomenon. Negative T waves (NTW) in the precordial leads mimicking the "Wellens' syndrome" is an important ECG manifestation of APE. The evolution of these ECG changes-STE and NTW-in APE has not been thoroughly studied. METHODS: We present two patient cases with APE and their evolving serial ECGs to analyze the correlation between STE and NTW. RESULTS: NTW developed later than STE in these two patient cases. CONCLUSIONS: NTW might represent a "postischemic" ECG pattern indicating a previous stage with transmural myocardial ischemia.

Electrocardiographic findings in accessory right precordial leads in adults and seniors with notched S waves in lead V1-a preliminary study.

BACKGROUND: Atypical right bundle branch block (RBBB) may present with an rS pattern and notched S wave in lead V1 . The notched S wave may represent slowed conduction or delayed activation of the right ventricular conduction system or ventricular myocardium. METHODS: We retrospectively analyzed the QRS patterns in accessory right precordial leads (from V3 R to V5 R) in 15 adults/senior individuals with notched S wave in lead V1 . RESULTS: In the right accessory precordial leads, 13 showed triphasic QRS pattern with final R' wave in their QRS complexes. This QRS pattern in association with notched S wave in lead V1 is suggestive of the presence of RBBB (incomplete or complete). CONCLUSIONS: A notched S wave in lead V1 and in the right precordial accessory leads associated with a final R' wave suggests the possibility of concealed RBBB (incomplete or complete).

Correlation between ECG presentation and cardiovascular magnetic resonance imaging in Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is characterized by acute and reversible ventricular dysfunction in the absence of significant coronary artery disease, typically triggered by acute emotional or physical stress. In the acute phase of TTC, the electrocardiogram (ECG) shows ST-segment elevation, which rapidly evolves into negative T waves and QT prolongation. However, different types of ventricular dysfunction may be associated with different patterns of ECG presentation. In this paper, we discuss the correlation between ECG presentation and cardiovascular magnetic resonance imaging in TTC.