Altered Regional Myocardial Mechanics in Transplanted Hearts: Influence of Time and Transplantation.

Background Global longitudinal strain is reduced in heart transplant recipients, but little is known about regional contractility of the transplanted heart. Moreover, it is unclear if factors such as time after transplant and ischemic time have an influence on regional contractility. To test for regional changes in myocardial deformation, we assessed regional myocardial deformation using three-dimensional speckle tracking echocardiography in heart transplant recipients and controls. Methods Global and regional longitudinal, circumferential, and radial strain was assessed in 51 heart transplant recipients and a control group of healthy individuals (n = 26). Moreover, we correlated regional contractility with clinical characteristics and compared subgroups of heart transplant recipients with normal (n = 32) and reduced left ventricular ejection fraction (n = 32). Results Global longitudinal and circumferential strain was significantly reduced in all heart transplant recipients, as well as in the transplant group with normal ejection fraction compared with the control group (p < 0.001). Global radial strain (GRS) was elevated in both transplant groups, but was significantly higher in transplant recipients with normal ejection fraction compared with the control group (p < 0.01). Both transplant groups revealed lower longitudinal and circumferential strain values in the mid- and apical regions (p < 0.001), whereas longitudinal and circumferential strain was higher in the basal region (p < 0.01). In both groups, transplanted hearts showed increased radial strain in the basal (p < 0.05, p < 0.01) and midregions (p = 0.22; p < 0.01) and did not differ in the apical regions. Cold ischemic time (150 ± 12.6 minutes) was independently associated with reduction in circumferential strain. Time since transplantation ranging from 18 days to 21 years had no effect on myocardial deformation parameters. Conclusion Left ventricular mechanics in transplanted hearts display significantly different systolic deformation patterns than native hearts. Strain capability forms a regional gradient from the base toward the apex. The presence of a time-independent deformation pattern and the correlation with cold ischemic time suggest damage induced by the transplantation itself. These findings might be important for understanding pseudo-abnormal echocardiograms in heart transplant patients.

In-hospital resource utilization in surgical and transcatheter aortic valve replacement.

BACKGROUND: Little is known about preoperative predictors of resource utilization in the treatment of high-risk patients with severe symptomatic aortic valve stenosis. We report results from the prospective, medical-economic "TAVI Calculation of Costs Trial". METHODS: In-hospital resource utilization was evaluated in 110 elderly patients (age ≥ 75 years) treated either with transfemoral (TF) or transapical (TA) transcatheter aortic valve implantation (TAVI, N = 83), or surgical aortic valve replacement (AVR, N = 27). Overall, 22 patient-specific baseline parameters were tested for within-group prediction of resource use. RESULTS: Baseline characteristics differed between groups and reflected the non-randomized, real-world allocation of treatment options. Overall procedural times were shortest for TAVI, intensive care unit (ICU) length of stay (LoS) was lowest for AVR. Length of total hospitalization since procedure (THsP) was lowest for TF-TAVI; 13.4 ± 11.4 days as compared to 15.7 ± 10.5 and 21.2 ± 15.4 days for AVR and TA-TAVI, respectively. For TAVI and AVR, EuroScore I remained the main predictor for prolonged THsP (p <0.01). Within the TAVI group, multivariate regression analyses showed that TA-TAVI was associated with a substantial increase in THsP (55 to 61 %, p <0.01). Additionally, preoperative aortic valve area (AVA) was identified as an independent predictor of prolonged THsP in TAVI patients, irrespective of risk scores (p <0.05). CONCLUSIONS: Our results demonstrate significant heterogeneity in patients baseline characteristics dependent on treatment and corresponding differences in resource utilization. Prolonged ThsP is not only predicted by risk scores but also by baseline AVA, which might be useful in stratifying TAVI patients. TRIAL REGISTRATION: German Clinical Trial Register Nr. DRKS00000797.

Normal reference values of left ventricular strain using three-dimensional speckle tracking echocardiography: results from a multicentre study.

AIMS: Three-dimensional (3D) speckle tracking echocardiography (3DSTE) has been shown to be an accurate and reliable clinical tool for the evaluation of global and regional left ventricular (LV) function through strain analysis, but the absence of normal values has precluded its widespread use in clinical practice. The aim of this prospective multicentre study was to establish normal reference values of LV strain parameters using 3DSTE in a large healthy population. METHODS AND RESULTS: A total of 303 healthy subjects (156 males [51%], between 18 and 82 years of age, ejection fraction [EF] 61 ± 3%), stratified to provide approximately equal proportions of healthy subjects of 18-30, 31-40, 41-50, 51-60, and >60 years of age, underwent 3DSTE. Data were analysed for LV volumes, EF, mass, and global and regional circumferential, longitudinal, radial, and area strain. Significant but small differences between men and women were found for longitudinal and area strains, as well as between different age groups for all LV strain parameters. However, large differences in normal values were observed between different segments, walls, and levels of the LV for radial and longitudinal strains, whereas circumferential and area strains demonstrated generally consistent normal ranges across the LV. CONCLUSIONS: Normal ranges of global and regional LV strain using 3DSTE have been established for clinical use. Differences in the magnitude of LV strain are present between men and women as well as different age groups. Moreover, there are differences between different segments, walls, and levels as part of the functional non-uniformity of the normal LV that necessitates the use of segment-specific normal ranges for radial and longitudinal strains. Circumferential and area strains demonstrate the most consistent normal ranges overall.

Analysis of the additional costs of clinical complications in patients undergoing transcatheter aortic valve replacement in the German Health Care System.

BACKGROUND: This study aims at analyzing complication-induced additional costs of patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: In a prospective observational study, a total of 163 consecutive patients received either transfemoral (TF-, n=97) or transapical (TA-) TAVR (n=66) between February 2009 and December 2012. Clinical endpoints were categorized according to VARC-2 definitions and in-hospital costs were determined from the hospital perspective. Finally, the additional costs of complications were estimated using multiple linear regression models. RESULTS: TF-TAVR patients experienced significantly more minor access site bleeding, major non-access site bleeding, minor vascular complications, stage 2 acute kidney injury (AKI) and permanent pacemaker implantation. Total in-hospital costs did not differ between groups and were on average €40,348 (SD 15,851) per patient. The average incremental cost component of a single complication was €3438 (p<0.01) and the estimated cost of a TF-TAVR without complications was €34,351. The complications associated with the highest additional costs were life-threatening non-access site bleeding (€47,494; p<0.05), stage 3 AKI (€20,468; p<0.01), implantation of a second valve (€16,767; p<0.01) and other severe cardiac dysrhythmia (€10,611 p<0.05). Overall, the presence of complication-related in-hospital mortality increased costs. CONCLUSIONS: Bleeding complications, severe kidney failure, and implantation of a second valve were the most important cost drivers in our TAVR patients. Strategies and advances in device design aimed at reducing these complications have the potential to generate significant in-hospital cost reductions for the German Health Care System.

Prevalence of potential retrograde embolization pathways in the proximal descending aorta in stroke patients and controls.

BACKGROUND: Retrograde diastolic blood flow in the proximal descending aorta (DAo) connecting complex plaques (≥4 mm thick) with brain-supplying supra-aortic arteries may constitute a source of stroke. Yet, data only from high-risk populations (cryptogenic stroke patients with aortic atheroma≥3 mm) regarding the prevalence of this potential stroke mechanism are available. We aimed to quantify the frequency of this mechanism in unselected patients with cryptogenic stroke after routine diagnostics and controls without a history of stroke. METHODS: 88 patients (67 stroke patients, 21 cardiac controls) were prospectively included. 3D T1-weighted bright blood MRI of the aorta was applied for the detection of complex DAo atheroma. ECG-triggered and navigator-gated 4D flow MRI allowed measuring time-resolved 3D blood flow in vivo. Potential retrograde embolization pathways were defined as the co-occurrence of complex plaques and retrograde blood flow in the DAo reaching the outlet of (a) the left subclavian artery, (b) the left common carotid artery, or/and (c) the brachiocephalic trunk. The frequency of these pathways was analyzed by importing 2D plaque images into 3D blood flow visualization software. RESULTS: Complex DAo plaques were more frequent in stroke patients (44 in 31/67 patients (46.3%) vs. 5 in 4/21 controls (19.1%); p=0.039), especially in older patients (29/46 (63.04%) patients≥60 years of age with 41 plaques vs. 2/21 (9.14%) patients<60 years of age with 3 plaques; p<0.001). Contrary to our assumption, retrograde diastolic blood flow at the DAo occurred in every patient irrespective of the existence of plaques with a similar extent in both groups (26±14 vs. 32±18 mm; p=0.114). Therefore, only the higher prevalence of complex DAo plaques in stroke patients resulted in a three times higher frequency of potential retrograde embolization pathways compared to controls (22/67 (32.8%) vs. 2/21 (9.5%) controls; p=0.048). CONCLUSIONS: This study revealed that retrograde flow in the descending aorta is a common phenomenon not only in stroke patients. The existence of potential retrograde embolization pathways depends mainly on the occurrence of complex plaques in the area 0 to ∼30 mm behind the outlet of the left subclavian artery, which is exposed to flow reversal. In conclusion, we have shown that the frequency of potential retrograde embolization pathways was significantly higher in stroke patients suggesting that this mechanism may play a role in retrograde brain embolism.

Fibrinolysis for patients with intermediate-risk pulmonary embolism.

BACKGROUND: The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial. METHODS: In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization. RESULTS: Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42). CONCLUSIONS: In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).

Diagnosis of viral myocarditis by cardiac magnetic resonance and viral genome detection in peripheral blood.

In patients with acute myocarditis, viral genome can be detected in plasma and peripheral leukocytes. Its relationship with active myocardial inflammation, however, is not well understood. Myocardial edema as a feature of inflammation and myocardial necrosis or fibrosis can be frequently observed in patients with acute myocarditis by cardiovascular magnetic resonance (CMR). We assessed the association of viral genome presence in peripheral blood samples with myocardial edema and irreversible injury. We examined consecutive patients with clinically suspected myocarditis after an episode of viral illness. State-of-the-art methods were used for detecting myocardial edema and irreversible injury using CMR and viral genome applying reverse transcribed, nested polymerase chain reaction in peripheral blood samples. The specificity of viral amplification products was confirmed by automatic DNA sequencing. Of a total of 55 patients (53.5 ± 15.6 years), 21 were positive for viral genome in peripheral leukocytes. Interestingly, 18 (86%) of these patients also showed global myocardial edema, as compared to only 7/34 (21%) without PCR evidence for viral genome. The overall agreement between CMR criteria for edema and viral PCR was 84%. In contrast, there was no significant relationship of viral genome presence with myocardial necrosis or scars. In patients with clinically suspected myocarditis, myocardial edema but not irreversible myocardial injury is associated with the presence of viral genome in peripheral blood.

Evidence of myocardial edema in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Nonischemic dilated cardiomyopathy (DCM) is associated with high mortality and morbidity. Cardiovascular magnetic resonance allows for the noninvasive assessment of function, morphology, and myocardial edema. Activation of inflammatory pathways may play an important role in the etiology of chronic DCM and may also be involved in the disease progression. HYPOTHESIS: The purpose of our study was to assess the incidence of myocardial edema as a marker for myocardial inflammation in patients with nonischemic DCM. METHODS: We examined 31 consecutive patients ( mean age, 57 ± 12 years) with idiopathic DCM. Results were compared with 39 controls matched for gender and age (mean age, 53 ± 13 years). Parameters of left ventricular function and volumes, and electrocardiogram-triggered, T2-weighted, fast spin echo triple inversion recovery sequences were applied in all patients and controls. Variables between patients and controls were compared using t tests for quantitative and χ2 tests for categorical variables. RESULTS: Ejection fraction (EF) was 40.3 ± 7.8% in patients and 62.6 ± 5.0% in controls (P < 0.0001). In T2-weighted images, patients with DCM had a significantly higher normalized global signal intensity ratio compared to controls (2.2 ± 0.6 and 1.8 ± 0.3, respectively, P = 0.0006), consistent with global myocardial edema. There was a significant but moderate negative correlation between signal intensity ratio in T2-weighted images and EF (-0.39, P < 0.001). CONCLUSIONS: Evidence shows that myocardial edema is associated with idiopathic nonischemic DCM. Further studies are needed to assess the clinical and prognostic impact of these findings.

Acute pulmonary embolism and a patent foramen ovale: analysis of atrial right-to-left shunting by biphasic transcardiopulmonary thermodilution curves.

A 69-year-old woman with an acute pulmonary embolism developed an intracardiac right-to-left shunt, which was diagnosed early on and quantified via biphasic transcardiopulmonary thermodilution curves. With transesophageal echocardiography, a patent foramen ovale and an impressive atrial right-to-left shunt were visualized.

Diagnosis of early myocarditis after respiratory or gastrointestinal tract viral infection: insights from cardiovascular magnetic resonance.

BACKGROUND: The diagnosis of myocarditis continues to be a challenging task in clinical practice. The purpose of our study was to investigate cardiovascular magnetic resonance imaging in the diagnostic workup of ambulatory patients with the suspicion of early myocarditis after respiratory or gastrointestinal tract viral infection. The need for accurate diagnosis of early myocarditis arises from the low diagnostic accuracy of routine clinical tests. METHODS: We examined 67 consecutive patients with symptoms of weakness, palpitations, and fatigue after respiratory or gastrointestinal tract infection. We compared these patients to 31 controls. ECG-triggered, T2-weighted, fast-spin-echo triple inversion recovery sequences and delayed enhancement imaging were obtained in all patients, as well as functional parameters of left ventricular function and dimensions. In addition, in 25 patients and 10 controls, ECG-triggered, T1-weighted, multi-slice spin-echo images were obtained in axial orientation. RESULTS: We found a significant difference between patients with suspected myocarditis and controls in T2-global myocardial signal intensity. In addition, the ratio of global myocardial signal intensity/muscle signal intensity was 2.3 ± 0.4 in patients and 1.8 ± 0.3 in controls, which was highly significant (p < 0.001). In 23 patients, a pathological late enhancement pattern was seen, but only in one of the controls. There was no significant difference in T1-signal parameters. CONCLUSION: Cardiovascular magnetic resonance technique is able to detect early myocardial involvement after respiratory or gastrointestinal tract infection.

Three-dimensional echocardiography for quantitative analysis of left-ventricular aneurysm.

BACKGROUND: Quantitative analysis of left-ventricular (LV) aneurysms after myocardial infarction is prognostically relevant and assists in planning surgery. Three-dimensional (3D) echocardiography facilitates clear visualization of cardiac anatomy and accurate assessment of functional parameters. The aim of the present study was to determine the ability of 3D echocardiography to quantify LV aneurysms. METHODS: Ten patients with a known LV-aneurysm after myocardial infarction underwent 3D echocardiography and cardiac magnetic resonance (CMR) imaging at 1.5 Tesla within 3 days. For 3D echocardiography, a multiplanar transesophageal examination was performed with full LV coverage and the 3D dataset was analyzed offline. The LV-aneurysm was defined by a wall thickness <5 mm. The following quantitative parameters were determined: left ventricular end-diastolic and end-systolic volumes, LV myocardial mass (LV-mass) and mass of the LV-aneurysm. LV ejection fraction and percentage of aneurysm mass (%-aneurysm) were calculated. RESULTS: LV volumes and ejection fraction showed a strong correlation between 3D echocardiography and CMR (r = 0.94-0.97; P < 0.01). Importantly, the mass and percentage of mass of the LV-aneurysm demonstrated a high correlation as well (r = 0.94 and r = 0.86, respectively; P < 0.01). For all parameters, the calculated bias between both methods was found to be minimal (0.8-7.6%). CONCLUSIONS: Three-dimensional echocardiography proved to be a reliable tool for quantitative analysis of LV volumes, ejection fraction and aneurysm size in patients with prior myocardial infarction. In addition, 3D visualization of the complex cardiac anatomy in patients with LV-aneurysm may assist surgical procedure planning.

Magnetic resonance tissue phase mapping of myocardial motion: new insight in age and gender.

BACKGROUND: An exact understanding of normal age- and gender-matched regional myocardial performance is an essential prerequisite for the diagnosis of heart disease. Magnetic resonance phase-contrast imaging (tissue phase mapping) enabling the analysis of segmental, 3-directional myocardial velocities with high temporal resolution (13.8 ms) was used to assess left ventricular motion. METHODS AND RESULTS: Radial, long-axis, and rotational myocardial velocities were acquired in 58 healthy volunteers (3 age groups, 29 women) in left ventricular basal, midventricular, and apical short-axis locations. For increased age, reduced (P<0.003) and prolonged long-axis and radial velocities (P<0.05) during diastole and reduced long-axis velocities (P<0.001) and apical rotation (P<0.005) during systole were found for both genders. Women demonstrated a reduced systolic twist (P=0.009), apical rotation (P=0.01), and systolic radial velocities (P<0.02) compared with men. Segmental analysis of long-axis motion with aging revealed differences in regional reduction of systolic (lateral 52% versus 30%) and diastolic (lateral 57% versus 41%) velocities in women compared with men. In basal segments, young women demonstrated higher long-axis velocities (+11% during diastole) than men, whereas this difference was reversed in older subjects (same segments, -20%). In addition, increased age resulted in a prolonged time to peak diastolic apical rotation (P<0.04) in women compared with men. CONCLUSIONS: Age and gender strongly influence regional myocardial motion. Tissue phase mapping provides a comprehensive quantitative analysis of all myocardial velocities with high temporal and spatial resolution. The knowledge of the detected age- and gender-related differences in myocardial motion is fundamental for further investigations of cardiac disease. Clinical Trial Registration- http://www.zks.uni-freiburg.de/uklreg/php/suchergebnis_all.php. Identifier: UKF001739.

Non-invasive imaging in the diagnosis of acute viral myocarditis.

Autopsy series of consecutive cases have demonstrated an incidence of myocarditis at approximately 1-10%; on the contrary, myocarditis is seriously underdiagnosed clinically. In a traditional view, the gold standard has been myocardial biopsy. However, it is generally specific but invasive and less sensitive, mostly because of the focal nature of the disease. Thus, non-invasive approaches to detect myocarditis are necessary. The traditional diagnostic tools are electrocardiography, laboratory values, especially troponin T or I, creatine kinase and echocardiography. For a long period, nuclear technique with indium-111 antimyosin antibody has been used as a diagnostic approach. In the last years, the use of this technique has declined because of radiation exposure and 48-h delay in obtaining imaging after injection to prevent blood pool effect. Thus, a non-invasive diagnostic approach without radiation and online image availability has been awaited. Cardiac magnetic resonance imaging has these promising characteristics. With this technique, it is possible to analyse inflammation, oedema and necrosis in addition to functional parameters such as left ventricular function, regional wall motion and dimensions. Thus, cardiovascular magnetic resonance imaging has emerged as the most important imaging tool in the diagnostic procedure and the review focus on this field. But there are also advances in echocardiography and computer tomography, which are described in detail.

Patent foramen ovale and cryptogenic stroke: a matter of age?

A patent foramen ovale (PFO) enables a right-to-left shunt in about a quarter of the population. The marked association between cryptogenic stroke and PFO supports the hypothesis that paradoxical embolism could be a relevant cause of stroke. Although this association has been described in several studies for patients <55 years of age, only limited data are available on the role of PFO in older patients. Recent studies, however, have also shown a significant association between cryptogenic stroke and PFO in patients >55 years of age. The relationship is especially marked in the presence of atrial septum aneurysm (ASA). This finding is in accordance with previous reports indicating that PFO and concomitant ASA is a high-risk feature. Factors promoting paradoxical embolism, such as deep vein thrombosis (DVT) and elevated right-heart pressure, are more frequently encountered in older than in younger patients. Independent of age, contrast-enhanced transthoracic and transesophageal echocardiography are the methods of choice for the detection and imaging of PFO and atrial septal aneurysm. Transcranial Doppler can be used as a screening method in patients with cryptogenic stroke to detect a right-to-left shunt. Proof of DVT strongly supports the suspicion of paradoxical embolism and should lead to oral anticoagulation. If paradoxical embolism is suspected without proof of DVT, both drug therapy with aspirin or warfarin and percutaneous closure of the PFO are available as therapeutic options. Recent studies have shown that percutaneous closure can be performed safely and with a low rate of recurrence both in older and younger patients. Thus far, however, there is no clear-cut evidence of superiority for either therapeutic strategy.

Cardiac involvement after respiratory tract viral infection--detection by cardiac magnetic resonance.

OBJECTIVE: The purpose of our study was to investigate whether cardiovascular magnetic resonance imaging can detect early myocardial tissue edema as a first step in the development of myocarditis. METHODS: We examined 36 consecutive patients who were presented with symptoms of fatigue, weakness, and/or palpitations after respiratory tract infection but normal left ventricular function and compared these patients with 21 consecutive controls without acute symptoms. Electrocardiogram-triggered, T2-weighted, fast spin echo triple-inversion recovery sequences were performed in all patients. RESULTS: We found a significant difference between patients with suspected myocarditis and controls in global myocardial signal intensity. The ratio of global myocardial signal intensity/muscle signal intensity was 2.4 +/- 0.3 in patients and 1.9 +/- 0.3 in controls, which was highly significant (P < 0.001). CONCLUSIONS: Patients with symptoms of fatigue, weakness, and/or palpitations after respiratory tract infection showed an elevated signal intensity of the myocardium, indicating edematous tissue, which may be the first step in the development of myocarditis.