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Background Data on the prognostic value of left ventricular (LV) morphological and functional parameters including LV rotation in patients with dilated cardiomyopathy (DCM) using cardiovascular magnetic resonance (CMR) are currently scarce. In this study, we assessed the prognostic value of global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and LV torsion using CMR feature tracking (FT). Methods CMR was performed in 350 DCM patients and 70 healthy subjects across 5 different European CMR Centers. Myocardial strain parameters were retrospectively assessed from conventional balanced steady-state free precession cine images applying FT. A combined primary endpoint (cardiac death, heart transplantation, aborted sudden cardiac death) was defined for the assessment of clinical outcome. Results GLS, GCS, GRS and LV torsion were significantly lower in DCM patients than in healthy subjects (all p Conclusion LV strain assessed with CMR FT has a high prognostic value in patients with DCM, surpassing routine and dedicated functional parameters. Thus, CMR strain imaging may contribute to the improvement of risk stratification in DCM.

ObjectivesSince the safety of coronary CT angiography (CTA) is of great importance, especially with regard to widening indications and increasing morbidity, the aim of this study was to assess influencing factors.MethodsPatients undergoing coronary CTA in a third-generation dual-source CT in a radiological centre were included in a clinical registry. Up to 20 mg metoprolol was administered intravenously to attain a heart rate ≤65/min. Glyceryl trinitrate (GTN) was administered in doses of 0.8 mg and 0.4 mg. Blood pressure was measured before the administration and after the CTA.ResultsOut of 5500 consecutive patients (3194 men, 62.3 (54.9–70.0) years), adverse events occurred in 68 patients (1.2%) with mild anaphylactoid reactions (0.4%), vasovagal symptoms (0.3%) and extravasation (0.3%) being most frequent. Anti-allergic drugs were given in 17 patients, atropine in 3 patients and volume in 1 patient. Drug administration resulted in a significant mean arterial pressure decline (96.0 (88.3–106.0) vs 108.7 (99.7–117.3) mmHg; p20 mmHg or >40 mmHg were older (66.5 (58.6–73.3) vs 60.5 (53.6–68.3) years; 70.2 (63.3–76.5) vs 62.1 (54.7–69.6) years), more often male (65.1% vs 54.4%; 68.9% vs 57.3%) and had higher Agatston score equivalents (83.0 (2.0–432.0) vs 15.0 (0.0–172.0); 163.0 (16.3–830.8) vs 25.0 (0.0–220.0); all p20 mmHg or >40 mmHg from 34.5% to 27.4% and from 6.1% to 3.5% (both pConclusionsCoronary CTA with intravenous beta-blocker administration is a safe procedure in an outpatient setting as adverse events are rare and mostly mild. Reduced GTN doses can further improve safety by lowering the rate of significant blood pressure drops, which occurred especially in elderly men with increased plaque burden.Trial registration numberNCT03815123.

Mit der Computertomographie (CT) konnen Thromben im linken Vorhofohr (LAA) dargestellt werden. Es wurde untersucht, ob sich die diagnostische Genauigkeit durch die Dual-Energy-Technik im Vergleich zur transosophagealen Echokardiographie (TEE) verbessert. Weiterhin wurde der Einfluss von Protokollparametern auf die Strahlendosis quantifiziert. Die TEE-Patienten wurden den verschiedenen CT-Protokollen zugeordnet. Alle CTs wurden auf das Vorhandensein von LAA-Thromben und Dual-Energy-CT-Scans sowie zusatzlich quantitativ auf die Jodkonzentration analysiert. Die TEE wurde qualitativ auf das Vorhandensein von Thromben untersucht. Von Insgesamt 32 eingeschlossenen Patienten hatten 6 einen mittels TTE diagnostizierten Thrombus. Die qualitative CT-Beurteilung ergab eine Sensitivitat von 83 % und eine Spezifitat von 88 % fur die LAA-Thrombus-Detektion. Bei 26 Patienten wurde eine Dual-Energy-CT durchgefuhrt. Die mittlere Jodkonzentration betrug 8,6 mg/cm3 und war bei Patienten mit LAA-Thromben signifikant niedriger als bei Patienten ohne LAA-Thromben. Ferner ergab sich ein inkrementeller Wert fur die Erkennung von LAA-Thromben (AUC: 0,950 vs. 0,867 bei kombinierter vs. nur qualitativer Beurteilung; p = 0,04). Die mediane Strahlendosis betrug 1,83 mSv. Unabhangig voneinander war die Dosis bei Beschrankung des Scanabschnitts auf den LAA und beim prospektiven Gating niedriger, wahrend Arrhythmie und Dual-Energy-Technik die Strahlendosis nicht beeinflussten. Die CT bietet eine gute diagnostische Genauigkeit fur den Nachweis von LAA-Thromben, die durch Joddichtemessung mittels Dual-Energy-CT noch weiter verbessert werden kann. Mit einem optimierten Protokoll kann eine angemessen niedrige Strahlendosis erreicht werden.

Cardiac tumors are increasingly more often diagnosed with currently available imaging techniques. Although still rare entities, they have an important clinical significance because of possible complications such as heart failure, valve dysfunction, and peripheral embolization.1, 2 Cardiac myxomas were long considered to be the most often encountered benign cardiac tumors.3 However, a recent series analysis from the Mayo Clinic challenged these data, as they identified papillary fibroelastomas (PFE) to be the most frequent benign cardiac tumor.4 Due to their high embolic risk, PFE should be considered in the presence of cryptogenic stroke.5 Transthoracic echocardiography (TTE) is the first‐line diagnostic tool employed for the diagnosis of PFE and cardiac tumors in general. It provides information on the localization, dimension, and mobility of the tumor as well as its effect on the surrounding cardiac structures.6 However, transthoracic echocardiography can miss small PFE and the image acquisition is highly dependent on operator experience and patient's echogenic window. Transesophageal echocardiography (TEE) usually provides better image quality and can more precisely delineate the characteristic of PFE. Still, TEE is sometimes less accurate in the evaluation of right heart structures and provides limited information on tissue composition. Cardiac MRI (CMR) and cardiac CT (CCT) usually complement the evaluation of cardiac tumors, including PFE.7 They have a higher field of view and can provide information regarding the tumor composition. In this regard, CMR was shown to be an excellent tool for tissue characterization in patients with cardiac tumors.8 CCT, on the other hand, can simultaneously evaluate the coronary status of the patient prior to cardiac surgery in low‐ and intermediate‐risk patients. The surgical excision of the PFE provides a curative treatment and the histological examination of the excised tissue is used to establish the definite diagnosis. A small rate of recurrence has been described in patients with PFE who underwent surgical removal of the tumor.4 Herein, we present here the case of a 63‐year‐old patient who was diagnosed with a PFE with a rare localization.

Large animal ischemic cardiomyopathy models are widely used for preclinical testing of promising novel therapeutic approaches. Pressure volume (PV) loop analysis and cardiac magnetic resonance imaging (CMRI) allow functional and morphological phenotyping. In this study we performed a comparative analysis of both methods highlighting the strength of each and their synergistic potential. Myocardial infarction (MI) was created in German farm pigs (German Landrace) by 2 h LCX occlusion (n = 11) and subsequent reperfusion. Cardiac function was assessed by PV-loops and CMRI 56 and 112 days post-MI. Two hours occlusion of the LCX led to mid-size left ventricular (LV) MI represented by high-sensitive troponin T (hsTnT) 3 days post-MI, correlating well with cardiac CMRI late enhancement. CMRI determined end-diastolic and end-systolic volumes significantly increased post-MI, while ejection fraction was reduced in infarcted animals compared to the sham group (n = 6). PV-loop derived preload-insensitive parameters of systolic and diastolic function were diminished post-MI compared to sham animals while preload-dependent parameters only deteriorated in advanced HF. PV-loop analysis significantly correlates with CMRI analysis of cardiac function in pig post-MI ischemic cardiomyopathy. PV-Loop analysis accurately quantifies LV volumetry and function in post-MI HF, and thus eccentric LV morphology. PV-loop analysis correlates well to cardiac MRI. Preload-insensitive parameters show high sensitivity to quantify HF while preload-sensitive parameters are not able to quantify early-stages of LV HF.

The diagnostic performance of adenosine stress cardiovascular magnetic resonance (CMR) for the detection of significant stenosis in infarct-related arteries is widely unknown. Two different types of perfusion defects can be observed: (a) larger than or (b) equal size as scar.We hypothesized that: (a) defectscar predicts significant coronary stenosis, and (b) defect=scar predicts an unobstructed infarct-related artery, and (c) angina symptoms might be of additional value in stratification.Patients with previous myocardial infarction referred for work-up of myocardial ischemia undergoing adenosine stress CMR were included if they had coronary angiography within 4 weeks of CMR.Two hundred patients with a mean age of 66±11 years, ischemic scars (subendocardial/transmural), and a mean left ventricular ejection fraction of 53% were included. In patients with defectscar, the positive predictive value was excellent (88%) and typical angina was reported only in the stenosis group (P=0.002). However, patients with defect=scar (with 50% showing subendocardial scar) had a prevalence of 37% for stenosis, yielding a low negative predictive value of 63%. In this group, symptoms of typical angina were independent of stenosis (P=1.0).A perfusion defect larger than scar is highly predictive for significant stenosis in infarct-related arteries. However, more than a third of the patients with perfusion defect of equal size as scar also showed significant coronary stenosis. As half of these patients showed still viable (subendocardial) scars, there is a high-risk of reinfarction. The addition of angina symptoms seems to increase diagnostic accuracy only in patients with perfusion defects larger than scar.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Siemens Healthineers Introduction Coronary CT angiography (CCTA) plays an increasing role in the detection and risk stratification of patients with coronary artery disease (CAD). The Coronary Artery Disease – Reporting and Data System (CAD-RADS) allows for standardized classification of CCTA results and, thus, may improve patient management. Purpose Aim of this study was to assess the impact of CCTA in combination with CAD-RADS on patient management and to identify the impact of cardiovascular risk factors (CVRF) on CAD severity. Methods CCTA was performed on a third-generation dual-source CT scanner in patients, who were referred to a radiology centre by their attending physicians. In a total of 4801 patients, CVRF were derived from medical reports and anamnesis. Results The study population consisted of 4770 patients (62.0 (54.0-69.0) years, 2841 males) with CAD (CAD-RADS 1-5), while 31 patients showed no CAD and were excluded from further analyses. Age, male gender and the number of CVRF were associated with more severe CAD stages (all p Conclusions CCTA in combination with the CAD-RADS allowed for effective risk stratification of CAD patients. The majority of the patients showed non-obstructive CAD and, thus, could be treated conservatively without the need for further CAD assessment. CVRF out of arterial hypertension and family history had an impact on CAD severity reflected in higher CAD-RADs gradings. Of note, a relevant fraction of patients with CAD did not have any CVRF and, thus, may not be covered by risk stratification models. CAD-RADS n Age (years) Males (%) 1 1453 56.0 (50.0-62.0) 623 (42.9 %) 2 1587 62.0 (55.0-69.0) 918 (57.8 %) 3 1067 66.0 (59.0-71.0) 749 (70.2 %) 4A 397 66.0 (59.0-72.0) 317 (79.8 %) 4B 162 67.0 (61.0-74.0) 139 (85.8 %) 5 104 66.0 (58.5.0-77.0) 95 (91.3 %)

The transcriptome needs to be tightly regulated by mechanisms that include transcription factors, enhancers, and repressors as well as non‐coding RNAs. Besides this dynamic regulation, a large part of phenotypic variability of eukaryotes is expressed through changes in gene transcription caused by genetic variation. In this study, we evaluate genome‐wide structural genomic variants (SVs) and their association with gene expression in the human heart. We detected 3,898 individual SVs affecting all classes of gene transcripts (e.g., mRNA, miRNA, lncRNA) and regulatory genomic regions (e.g., enhancer or TFBS). In a cohort of patients (n = 50) with dilated cardiomyopathy (DCM), 80,635 non‐protein‐coding elements of the genome are deleted or duplicated by SVs, containing 3,758 long non‐coding RNAs and 1,756 protein‐coding transcripts. 65.3% of the SV‐eQTLs do not harbor a significant SNV‐eQTL, and for the regions with both classes of association, we find similar effect sizes. In case of deleted protein‐coding exons, we find downregulation of the associated transcripts, duplication events, however, do not show significant changes over all events. In summary, we are first to describe the genomic variability associated with SVs in heart failure due to DCM and dissect their impact on the transcriptome. Overall, SVs explain up to 7.5% of the variation of cardiac gene expression, underlining the importance to study human myocardial gene expression in the context of the individual genome. This has immediate implications for studies on basic mechanisms of cardiac maladaptation, biomarkers, and (gene) therapeutic studies alike.

Aim To define practical limitations of diagnostic image quality for recently introduced turbo high-pitch scan mode (THP) in third-generation dual-source computed tomography (CT). Materials and Methods Two hundred and twenty-nine consecutive patients undergoing CT coronary angiography were included in this retrospective single-centre analysis. A contrast-enhanced volume dataset was acquired in THP. Image quality of coronary segments was classified as diagnostic or non-diagnostic by three blinded readers. Segments were stated as non-diagnostic if at least one of three readers could neither exclude nor confirm significant stenoses. Multivariable logistic regression was used to assess relationships between number of non-diagnostic segments and common influencing factors. Results Median effective radiation dose was 0.6 (interquartile range [IQR], 0.4–0.8) mSv overall and 0.3 (IQR, 0.3–0.4) mSv in the 70 kV subgroup of this middle aged, predominantly pre-obese cohort (age: 61 [IQR, 52–67] years; body mass index [BMI]: 26 [IQR, 23–29] kg/m2) with a low–moderate median Agatston score (AS) 0 (IQR, 0–70). Diagnostic image quality was found in 98.1% of 3,678 coronary segments. AS was independently associated with diagnostic image quality (B=0.34; p=0.02), whereas heart rate, BMI, and presence of arrhythmia were not. The portion of diagnostic coronary segments decreased slightly in obese patients with heart rates >65 beats/min and dropped significantly in patients with an AS >600 (p=0.003). Conclusion THP enables CT coronary angiography with minimal radiation exposure and is most appropriate in non-obese patients with stable sinus rhythm ≤65 beats/min and a calcium score ≤600.

Background The aim of this study was to assess the potential for radiation dose reduction using knowledge-based iterative model reconstruction (K-IMR) algorithms in combination with ultra-low dose body mass index (BMI)-adapted protocols in coronary CT angiography (coronary CTA). Methods Forty patients undergoing clinically indicated coronary CTA were randomly assigned to two groups with BMI-adapted (I: 2 , II: 2 , III: 2 , IV: ≥30.0 kg/m 2 ) low dose (LD, I: 100kV p /75 mAs, II: 100kV p /100 mAs, III: 100kV p /150 mAs, IV: 120kV p /150 mAs, n = 20) or ultra-low dose (ULD, I: 100kV p /50 mAs, II: 100kV p /75 mAs, III: 100kV p /100 mAs, IV: 120kV p /100 mAs, n = 20) protocols. Prospectively-triggered coronary CTA was performed using a 256-MDCT with the lowest reasonable scan length. Images were generated with filtered back projection (FBP), a noise-reducing hybrid iterative algorithm (iD, levels 2/5) and K-IMR using cardiac routine (CR) and cardiac sharp settings, levels 1–3. Results Groups were comparable regarding anthropometric parameters, heart rate, and scan length. The use of ULD protocols resulted in a significant reduction of radiation exposure (0.7 (0.6–0.9) mSv vs. 1.1 (0.9–1.7) mSv; p Conclusions The combination of K-IMR with BMI-adapted ULD protocols results in significant radiation dose savings while simultaneously improving image quality compared to LD protocols with FBP or hybrid iterative algorithms. Therefore, K-IMR allows for coronary CTA examinations with high diagnostic value and very low radiation exposure in clinical routine.

Background The diagnosis of cardiac involvement in rheumatic disorders is challenging due to its varying clinical presentation. Since clinical consequences range from immediate treatment changes to adverse long-term outcome, individual risk stratification is of great clinical interest. Primary aim was to evaluate the prevalence of cardiac involvement in patients with different rheumatic disorders using late gadolinium enhancement–cardiac magnetic resonance imaging (LGE-CMR). In addition, we sought to investigate if different rheumatic disorders would demonstrate different LGE patterns. Methods Two-hundred-ninety-seven patients with rheumatic disorders were included and underwent LGE-CMR for work-up of cardiac involvement, which was defined by the presence of LGE in the myocardium. Patients were divided into five subgroups: 1) ANCA-associated vasculitis, 2) non-ANCA-associated vasculitis, 3) connective tissue disorders, 4) arthritis, and 5) sarcoidosis. Results Mean ejection fraction in the overall population was 65%, with a mean age of 55yrs. Prevalence of cardiac involvement in the five subgroups were as follows: 54% in the ANCA-associated vasculitis group, 22% in the non-ANCA-associated vasculitis group, 14% in the group with connective tissue disorders, 21% in the arthritis group, and 24% in sarcoid patients. Each of the five subgroups demonstrated a distinct pattern of LGE. Conclusion There is a wide range in the prevalence of cardiac involvement in different rheumatic disorders (54%–14%). Different groups of rheumatic disorders demonstrate different patterns of LGE. Condensed abstract Primary aim of the study was to evaluate the presence of cardiac involvement in patients with different rheumatic disorders using LGE-CMR. In addition, we sought to investigate if different rheumatic disorders would reveal different LGE patterns. In our 297 patients, the highest prevalence of cardiac involvement was found in patients with ANCA-associated vasculitis (54%), whereas the lowest prevalence was demonstrated in patients with connective tissue disorders (14%). Furthermore, different groups of rheumatic disorders demonstrate distinct patterns of LGE.

Background The differentiated assessment of functional parameters besides morphological changes is essential for the evaluation of prognosis in systemic immunoglobulin light chain (AL) amyloidosis. Methods Seventy-four subjects with AL amyloidosis and presence of late gadolinium enhancement (LGE) pattern typical for cardiac amyloidosis were analyzed. Long axis strain (LAS) and myocardial contraction fraction (MCF), as well as morphological and functional markers, were measured. The primary endpoint was death, while death and heart transplantation served as a composite secondary endpoint. Results After a median follow-up of 41 months, 29 out of 74 patients died and 10 received a heart transplant. Left ventricular (LV) functional parameters were reduced in patients, who met the composite endpoint (LV ejection fraction 51% vs. 61%, LAS − 6.9% vs − 10%, GLS − 12% vs − 15% and MCF 42% vs. 69%; p

Fractional flow reserve based on coronary CT angiography (CT-FFR) is gaining importance for non-invasive hemodynamic assessment of coronary artery disease (CAD). We evaluated the on-site CT-FFR with a machine learning algorithm (CT-FFRML) for the detection of hemodynamically significant coronary artery stenosis in comparison to the invasive reference standard of instantaneous wave free ratio (iFR®). This study evaluated patients with CAD who had a clinically indicated coronary computed tomography angiography (cCTA) and underwent invasive coronary angiography (ICA) with iFR®-measurements. Standard cCTA studies were acquired with third-generation dual-source computed tomography and analyzed with on-site prototype CT-FFRML software. We enrolled 40 patients (73% males, mean age 67 ± 12 years) who had iFR®-measurement and CT-FFRML calculation. The mean calculation time of CT-FFRML values was 11 ± 2 min. The CT-FFRML algorithm showed, on per-patient and per-lesion level, respectively, a sensitivity of 92% (95% CI 64–99%) and 87% (95% CI 59–98%), a specificity of 96% (95% CI 81–99%) and 95% (95% CI 84–99%), a positive predictive value of 92% (95% CI 64–99%), and 87% (95% CI 59–98%), and a negative predictive value of 96% (95% CI 81–99%) and 95% (95% CI 84–99%). The area under the receiver operating characteristic curve for CT-FFRML on per-lesion level was 0.97 (95% CI 0.91–1.00). Per lesion, the Pearson’s correlation between the CT-FFRML and iFR® showed a strong correlation of r = 0.82 (p

This article describes the role of cardiovascular magnetic resonance (CMR) and cardiac computed tomography (CCT) in the diagnostic work-up of patients with suspected acute coronary syndrome (ACS). Recent studies on the principles, diagnostic targets, clinical utility, accuracy, prognostic relevance and implications for clinical decision-making are discussed and current state-of-the-art and novel approaches are presented. The authors recognize that in ACS, time is of the essence and therefore put a special emphasis on the feasibility of tomographic cardiac imaging in realistic clinical settings.

Galectin-3 binding protein (Gal-3BP) is a secreted protein associated with inflammation and carotid atherosclerosis. We hypothesized that high Gal-3BP levels may indicate unfavorable plaque morphology and outcome in coronary artery disease (CAD).Gal-3BP plasma levels were measured by ELISA in 233 patients (63 ± 10 years, 50.2% male) undergoing computed coronary angiography tomography (CCTA).In 149 patients, CCTA confirmed CAD (stenosis grade20%). Mean Gal-3BP plasma levels were 5.9 ± 2.7 μg/mL and did not differ between patients with or without CAD. Over a follow-up time of up to 4.4 years (median 2.5 years), there were 17 cases of revascularization, five cases of myocardial infarction, and five deaths (four non-cardiac, one fatal myocardial infarction). Kaplan-Meier analysis revealed that high Gal-3BP levels were significantly associated with long-term mortality (p 0.001). Cox proportional hazards regression analysis showed that this association was independent of cardiovascular risk factors (HR 1.238, 95%-CI 1.012-1.514, p = 0.038). After adjustment for troponin T and C-reactive protein (hs-CRP) levels, significance was lost (p = 0.123). Further analysis revealed that Gal-3BP levels were significantly related to body mass index and hs-CRP levels indicating an association with metabolic and inflammatory distress. There was no correlation between Gal-3BP and calcium score, plaque volume, or vascular remodeling.While high Gal-3BP plasma levels are associated with long-term mortality, we could not confirm it as a marker of cardiac mortality or unstable plaque morphology.

Introduction: Echocardiography is the first-line imaging modality used to characterize heart compromise in systemic infiltrative diseases and to evaluate response to therapy. Cardiac amyloidosis results in progressive heart failure due to restriction of ventricular filling. However, in early stages, typical findings may not be evident, even when symptoms and signs of heart failure with preserved ejection fraction are already present. Identification of early compromise is now made possible with the advent of new echocardiography techniques as two-dimensional strain imaging.Areas covered: Diagnostic and prognostic parameters that can be assessed by echocardiography are discussed, including M-mode, two-dimensional and Doppler echocardiography, as well as by new tools as tissue Doppler imaging and strain imaging.Expert opinion: Systemic amyloidosis is a rare disorder resulting from the production of misfolded proteins, primarily light-chain (AL) immunoglobulins and transthyretin (ATTR). The prognosis ...

This study sought to evaluate myocardial perfusion reserve index (MPRI) and diastolic strain rate, both assessed by cardiac magnetic resonance (CMR) as a noninvasive tool for the detection of microvasculopathy.Long-term survival of cardiac allograft recipients is limited primarily by cancer and cardiac allograft vasculopathy (CAV). Besides epicardial CAV, diagnosed by coronary angiography, stenotic microvasculopathy was found to be an additional independent risk factor for survival after heart transplantation.Sixty-three consecutive heart transplant recipients who underwent CMR, coronary angiography, and myocardial biopsy were enrolled. Stenotic vasculopathy in microvessels was considered in myocardial biopsies by immunohistochemistry and CAV was graded during coronary angiography according to International Society of Heart and Lung Transplantation criteria. In addition, by CMR microvasculopathy was assessed by myocardial perfusion reserve during pharmacologic hyperemia with adenosine and strain-encoded magnetic resonance using a modified spatial modulation of magnetization tagging pulse sequence in all patients.Decreasing MPRI and diastolic strain rates were observed in patients with decreasing microvessel luminal radius to wall thickness ratio and decreasing capillary density (r = 0.45 and r = 0.61 for MPRI and r = 0.50 and r = 0.38 for diastolic strain rate, respectively; p0.005 for all). Using multivariable analysis, both MPRI and diastolic strain rate were robust predictors of stenotic microvasculopathy, independent of age, organ age, and CAV by International Society of Heart and Lung Transplantation criteria (hazard ratio: 0.07, p = 0.006 for MPRI; hazard ratio: 0.91, p = 0.002 for diastolic strain rate). Patients without stenotic microvasculopathy in the presence of no or mild CAV (n = 36) exhibited significantly higher median survival free of events, compared with patients with stenotic microvasculopathy in the presence of no or mild CAV (n = 18; p = 0.04 by log rank).CMR represents a valuable noninvasive diagnostic tool, which may be used for the early detection of transplant microvasculopathy before the manifestation of CAV during surveillance coronary angiographic procedures.

BACKGROUND Biomarkers are well established for diagnosis of myocardial infarction [cardiac troponins, high-sensitivity cardiac troponins (hs-cTn)], exclusion of acute and chronic heart failure [B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP)] and venous thromboembolism (d-dimers). Several studies have demonstrated acute increases in cardiac biomarkers and altered cardiac function after strenuous sports that can pretend a cardiovascular emergency and interfere with state-of-the-art clinical assessment. METHODS We performed a systematic review and metaanalysis of biomarker and cardiovascular imaging changes after endurance exercise. We searched for observational studies published in the English language from 1997 to 2014 that assessed these biomarkers or cardiac function and morphology directly after endurance exercise. Of 1787 identified abstracts, 45 studies were included. RESULTS Across all studies cardiac troponin T (cTnT) exceeded the cutoff value (0.01 ng/mL) in 51% (95% CI, 37%–64%) of participants. The measured pooled changes from baseline for high-sensitivity cTnT (hs-cTnT) were +26 ng/L (95% CI, 5.2–46.0), for cTnI +40 ng/L (95% CI, 21.4; 58.0), for BNP +10 ng/L (95% CI, 4.3; 16.6), for NT-proBNP +67 ng/L (95% CI, 49.9; 84.7), and for d-dimer +262 ng/mL (95% CI, 165.9; 358.7). Right ventricular end diastolic diameter increased and right ventricular ejection fraction as well as the ratio of the early to late transmitral flow velocities decreased after exercise, while no significant changes were observed in left ventricular ejection fraction. CONCLUSIONS Current cardiovascular biomarkers (cTnT, hs-cTnT, BNP, NT-proBNP, and d-dimer) that are used in clinical diagnosis of pulmonary embolism, acute coronary syndrome, and heart failure are prone to alterations due to strenuous exercise. Hence, it is necessary to take previous physical exercise into account when a cardiac emergency is suspected.

To determine the risk-stratification ability of plaque volume and composition assessment with cardiac computed tomographic (CT) angiography and high-sensitivity troponin T (hsTnT) in patients at intermediate risk for coronary artery disease (CAD).The study complied with the Declaration of Helsinki and was approved by the local ethics committee. All patients gave written informed consent. Five hundred twenty-one consecutive patients (mean age ± standard deviation, 62 years ± 10; 256 men and 265 women) were included in this prospective, observational, longitudinal, single-center study. Quantitative cardiac CT angiography analysis was performed in all patients (for 7690 coronary segments), whereas biomarkers (hsTnT and high-sensitivity C-reactive protein) were available in 408 patients (78%). To evaluate the incremental value of cardiac CT angiography and hsTnT for the prediction of cardiovascular events, multivariate Cox regression and integrated discrimination improvement analysis were applied.In 521 patients, 13 hard cardiac events occurred during a mean follow-up period of 2.3 years ± 1.1 (median, 2.4 years; range, 0.5-4.5 years), while 23 patients underwent late coronary revascularization. The Duke clinical score was 51% ± 30, indicating intermediate risk. The presence of no plaques or purely calcified versus noncalcified plaques, plaque volume according to tertiles, and increased hsTnT (≥14 pg/mL) was independently associated with hard cardiac events (hazard ratio [HR] = 26.08, 95% confidence interval [CI]: 2.78, 244.99; HR = 12.14, 95% CI: 1.87, 78.74; and HR = 10.31, 95% CI: 2.72, 39.0, respectively; P.01 for all). Patients with increased hsTnT and plaque burden (n = 53) showed the highest incidence for hard cardiac events (annual rate, 12.7%), followed by those with either increased hsTnT or plaque burden (n = 145; annual rate = 0.44%, P.03), while those with lower hsTnT and plaque burden exhibited excellent outcomes and no hard event during the follow-up duration (n = 210; annual rate = 0%, P.001).Use of hsTnT as a marker of myocardial microinjury and cardiac CT angiography as a marker of the total atherosclerotic burden improves the prediction of cardiac outcome in patients with presumably stable CAD and may aid in personalized risk stratification in patients at intermediate risk.

Background Since the differentiation between physiological and pathological trabeculation is challenging, we assessed its distribution in a reference population of selected healthy volunteers. Methods We studied 117 subjects (58 males) stratified into age tertiles and by gender. Cardiovascular magnetic resonance images were acquired using a standard SSFP-sequence. Left and right ventricular (LV/RV) end-diastolic (EDV), end-systolic (ESV) and trabeculated volumes indexed to the body surface area as well as ejection fraction (EF) were quantified in short-axis views. The maximum non-compacted-to-compacted (NC/C) ratio was measured in long-axis views. Results The trabeculated volumes were significantly larger in men than in women and decreased with age. The correlation between both was moderate (r=0.46; p 2.3 in 46.2% and >2.5 in 37.6% of the subjects, which is regarded as abnormal in current literature. The fraction of subjects with a maximum NC/C ratio >2.3 and the mean maximum NC/C ratio differed significantly between gender but not between age groups. An increasing NC/C ratio was associated with a significant decrease in EF (r=−0.21; p Conclusion A considerable amount of healthy volunteers fulfils the current diagnostic criteria of LV noncompaction with female subjects showing a higher fraction of false-positive results than males. LV trabeculated volume is more pronounced in young subjects and declines with age. The use of age- and gender-specific reference values as provided in this study may facilitate the delineation of physiological and pathological findings.

Purpose To investigate whether myocardial deformation imaging, assessed by feature tracking cardiac magnetic resonance (FTI-CMR), would allow objective quantification of myocardial strain and estimation of functional recovery in patients with first time ST-elevation myocardial infarction (STEMI). Methods Cardiac magnetic resonance (CMR) imaging was performed in 74 consecutive patients 2–4days after successfully reperfused STEMI, using a 1.5T CMR scanner (Philips Achieva). Peak systolic circumferential and longitudinal strains were measured using the FTI applied to SSFP cine sequences and were compared to infarct size, determined by late gadolinium enhancement (LGE). Follow-up CMR at 6months was performed in order to assess residual ejection fraction, which deemed as the reference standard for the estimation of functional recovery. Results During the follow-up period 53 of 74 (72%) patients exhibited preserved residual ejection fraction ≥50%. A cut-off value of −19.3% for global circumferential strain identified patients with preserved ejection fraction ≥50% at follow-up with sensitivity of 76% and specificity of 85% (AUC=0.86, 95% CI=0.75–0.93, p Conclusions Estimation of circumferential strain by FTI provides objective assessment of infarct size without the need for contrast agent administration and estimation of functional recovery with non-inferior accuracy compared to that provided by LGE.

T1 mapping by cardiac magnetic resonance imaging (CMR) is able to determine the extracellular volume fraction. Wild-type transthyretin amyloidosis (WT-ATTR) is characterized by extracellular amyloid deposition in the heart. Recent reports indicated a reduction of left ventricular (LV) myocardial mass in WT-ATTR after consumption of epigallocatechin-3-gallate, the main catechin in green tea. It remained unclear, whether reduction of LV myocardial mass reflects decrease of amyloid load or progressive atrophy of cardiomyocytes. This study included 7 male patients with CMR repetitively performed before and 12 months after daily consumption of green tea extract (600 mg epigallocatechin-3-gallate). Short axis slices as well as 2-, 3-, and 4-chamber views were acquired using SSFP sequences. T1 mapping was created out of 11 mid-ventricular short axis views with increasing inversion times using a single breath-hold modified look-locker inversion recovery sequence before and 15 min after Gadolinium contrast administration. After 12 months, a significant decrease of LV myocardial mass [198 (160; 212) vs. 180 (142; 204) g; p

Myocardial deformation measurement is superior to left ventricular ejection fraction in identifying early changes in myocardial contractility and prediction of cardiovascular outcome. The lack of standardization hinders its clinical implementation. The aim of the study is to investigate a novel standardized deformation imaging approach based on the feature tracking algorithm for the assessment of global longitudinal (GLS) and global circumferential strain (GCS) in echocardiography and cardiac magnetic resonance imaging (CMR).70 subjects undergoing CMR were consecutively investigated with echocardiography within a median time of 30 min. GLS and GCS were analyzed with a post-processing software incorporating the same standardized algorithm for both modalities. Global strain was defined as the relative shortening of the whole endocardial contour length and calculated according to the strain formula.Mean GLS values were -16.2 ± 5.3 and -17.3 ± 5.3 % for echocardiography and CMR, respectively. GLS did not differ significantly between the two imaging modalities, which showed strong correlation (r = 0.86), a small bias (-1.1 %) and narrow 95 % limits of agreement (LOA ± 5.4 %). Mean GCS values were -17.9 ± 6.3 and -24.4 ± 7.8 % for echocardiography and CMR, respectively. GCS was significantly underestimated by echocardiography (p0.001). A weaker correlation (r = 0.73), a higher bias (-6.5 %) and wider LOA (± 10.5 %) were observed for GCS. GLS showed a strong correlation (r = 0.92) when image quality was good, while correlation dropped to r = 0.82 with poor acoustic windows in echocardiography. GCS assessment revealed only a strong correlation (r = 0.87) when echocardiographic image quality was good. No significant differences for GLS between two different echocardiographic vendors could be detected.Quantitative assessment of GLS using a standardized software algorithm allows the direct comparison of values acquired irrespective of the imaging modality. GLS may, therefore, serve as a reliable parameter for the assessment of global left ventricular function in clinical routine besides standard evaluation of the ejection fraction.

Background Myocardial T1 and extracellular volume (ECV) derived from cardiovascular MRIs are more and more widely accepted as important markers for diagnosis, risk prediction and monitoring of cardiac disease. Yet data regarding long-term stability of myocardial T1 mapping are lacking. The aim of this study was to investigate the long-term stability of native and postcontrast T1 mapping values in healthy volunteers. Methods 18 strictly selected healthy volunteers (52±10 years, 12 men) were studied on a Philips Achieva 1.5 Tesla scanner. T1 relaxation times were measured before and 15 min after a bolus contrast injection of gadolinium diethylenetriamine penta-acetic acid (DTPA) (0.2 mmol/kg) using a single-breath-hold modified Look-Locker inversion recovery 3(3)3(3)5 sequence. ECV was calculated using native and postcontrast T1 times of myocardium and blood correcting for blood haematocrit. Exams were repeated 3.6±0.5 years later under the same conditions and using the same scan protocols. Results Cardiac biomarkers (high-sensitivity troponin T and N terminal pro-brain natriuretic peptide) remained unchanged, as well as left ventricular mass, and global and longitudinal function. No significant change occurred regarding native T1 times (1017±24 ms vs 1015±21 ms; P=0.6), postcontrast T1 times (426±38 ms vs 413±20 ms; P=0.13) or ECV (22%±2% vs 23%±2%; P=0.3). Native T1 time and ECV appeared to be better reproducible than postcontrast T1, resulting in lower coefficients of variation (ECV: 3.5%, native T1: 1.3%, postcontrast T1: 6.4%) and smaller limits of agreement (ECV: 2%/−2%, native T1: 39 ms/−35 ms, postcontrast T1: 85 ms/−59 ms). Conclusions During long-term follow-up, native T1 and ECV values are very robust markers, whereas postcontrast T1 results appear less stable.

To analyze clinical predictors of mortality in wild-type transthyretin amyloidosis (wt-ATTR). In total, 191 patients (73.8 ± 0.5 years; 176 males, 15 females) with histologically proven wt-ATTR amyloidosis and genetic exclusion of a transthyretin gene variant were included. Comprehensive clinical characteristics, ECG, biomarkers, and echocardiography were analyzed retrospectively. Strain analyses were performed offline using TomTec Imaging Systems, Germany. Univariable and multivariable analyses predicting all-cause mortality were carried out. Patients presented with significant heart failure (NYHA 2.5 ± 0.8; NT-proBNP 3644 (4981) pg/ml; LV ejection fraction 45.8 ± 15.0%). LogNT-proBNP correlated with indicators of disease severity. Similar results were obtained for basal and midventricular, but not apical longitudinal strain. During median follow-up of 26.2 ± 1.7 months 46 (25.5%) patients died (40 males, 23%; six females, 40%). In female patients 1-/2-year survival was lower [92.9/67.7%; median survival 30.6 (21.1–40.1) months] when compared to male patients [96.5%/86.6%; median survival 63.9 (45.8–82.0) months]. Parameters associated with survival were NT-proBNP, NYHA class, heart rate, midventricular longitudinal strain, mitral annular plane systolic excursion (MAPSE), Karnofsky Index, systolic blood pressure, estimated glomerular filtration rate. Multivariable analysis revealed MAPSE and NT-proBNP as independent predictors of mortality in the whole cohort and midventricular strain in the subgroup of patients in sinus rhythm. No sex-specific bias was observed between male and female patients with wt-ATTR regarding age at onset and morphological characteristics. Multivariable analysis revealed MAPSE and NT-proBNP as independent predictors of survival in the whole cohort, whereas midventricular longitudinal strain was the only independent predictor in patients in sinus rhythm.

Longitudinal shortening (LS) allows additive information in the diagnosis and prognosis of cardiomyopathies. This review provides an overview of different LS assessment techniques using CMR and their supplemental value in various cardiomyopathies. Assessment of LS using CMR-derived mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE) as well as feature tracking imaging (FTI) has been proven useful in the diagnosis of dilated cardiomyopathies (DCM), hypertrophic cardiomyopathies (HCM), ischemic heart disease, pulmonary artery hypertension, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy, and valvular and congenital heart disease. Furthermore, measurement of LS using FTI and MAPSE was identified as a robust predictor of cardiac outcome. LS assessment with long axis strain (LAS) outperformed the diagnostic accuracy of MAPSE and TAPSE and provided relevant information on discriminative performance in DCM. Due to the simple determination and the great clinical relevance of LS, we recommend its routine assessment in cardiomyopathies.

Background To compare the prognostic value of cardiac valve plane displacement (CVPD) on various locations in cardiac light chain (AL) amyloidosis. Methods Consecutive patients with biopsy-proven cardiac involvement in AL amyloidosis who had undergone cardiovascular magnetic resonance (CMR) between 2005 and 2014 in our institution, were retrospectively identified and data analyzed. The primary combined endpoint was all-cause mortality or heart transplantation. Systolic CVPD were obtained from standard cine bSSFP in 2-, 3- and 4-chamber views at anterior aortic plane systolic excursion (AAPSE); anterior, anterolateral, inferolateral, inferior, inferoseptal mitral (MAPSE); and lateral tricuspid (TAPSE) annular segments. Results We identified 68 patients (58 ± 10 years; 59% male). Median follow-up period was 1.2 years (IQR, 0.3-4.1). Significant differences in CVPD between patients who reached a primary endpoint (n = 44) and transplant-free survivors were found only for AAPSE (6.1 mm (IQR, 4.6-9.4) vs. 8.8 mm (IQR, 6.9-10.4); p = 0.02) and MAPSEanterolateral (7.3 mm (IQR, 5.4-11.7) vs. 10.5 mm (IQR, 8.1-13.4); p = 0.03). AAPSE (χ2 = 15.6; p = 0.0002) provided the best predictive value for transplant-free survival compared to all other valvular plane locations. A high-risk cutoff (AAPSE ≤ 7.6 mm) was calculated by ROC analysis to predict all-cause death or heart transplantation within 6 months from index examination (AUC = 0.80; CI: 0.68 to 0.89; p

Purpose To assess the utility of established functional markers versus two additional functional markers derived from standard cardiovascular magnetic resonance (MR) images for their incremental diagnostic and prognostic information in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods Approval was obtained from the local ethics committee. MR images from 453 patients with NIDCM and 150 healthy control subjects were included between 2005 and 2013 and were analyzed retrospectively. Myocardial contraction fraction (MCF) was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume, and long-axis strain (LAS) was calculated from the distances between the epicardial border of the LV apex and the midpoint of a line connecting the origins of the mitral valve leaflets at end systole and end diastole. Receiver operating characteristic curve, Kaplan-Meier method, Cox regression, and classification and regression tree (CART) analyses were performed for diagnostic and prognostic performances. Results LAS (area under the receiver operating characteristic curve [AUC] = 0.93, P.001) and MCF (AUC = 0.92, P.001) can be used to discriminate patients with NIDCM from age- and sex-matched control subjects. A total of 97 patients reached the combined end point during a median follow-up of 4.8 years. In multivariate Cox regression analysis, only LV ejection fraction (EF) and LAS independently indicated the combined end point (hazard ratio = 2.8 and 1.9, respectively; P.001 for both). In a risk stratification approach with classification and regression tree analysis, combined LV EF and LAS cutoff values were used to stratify patients into three risk groups (log-rank test, P.001). Conclusion Cardiovascular MR-derived MCF and LAS serve as reliable diagnostic and prognostic markers in patients with NIDCM. LAS, as a marker for longitudinal contractile function, is an independent parameter for outcome and offers incremental information beyond LV EF and the presence of myocardial fibrosis.

In heart failure (HF), a disturbed cardiac norepinephrine (NE) homeostasis is characterized by depleted cardiac NE stores, impairment of the cardiac NE re-uptake by the neuronal norepinephrine transporter (NET) and enhanced cardiac NE net release. Reduced cardiac NE content appears to be caused by enhanced cardiac NE net release from sympathetic neurons in HF, triggered by neurohumoral activation. However, it remains unclear whether reduced NE itself has an impact on cardiac NE re-uptake, independent of neurohumoral activation. Here, we evaluated whether depletion of cardiac NE stores alone can regulate cardiac NE re-uptake. Treatment of Wistar rats with reserpine (5 mg/kg/d) for one (1d) or five days (5d) resulted in markedly reduced cardiac NE content, comparable to NE stores in experimental HF due to pressure overload. In order to assess cardiac NE re-uptake, the specific cardiac [3H]-NE uptake via the NET in a Langendorff preparation was measured. Reserpine treatment led to decreased NE re-uptake at 1d and 5d compared to saline treatment. Expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of the NE synthesis, was elevated in left stellate ganglia after reserpine. Mechanistically, measurement of NET mRNA expression in left stellate ganglia and myocardial NET density revealed a post-transcriptional downregulation of the NET by reserpine. In summary, present data demonstrate that depletion of cardiac NE stores alone is sufficient to impair cardiac NE re-uptake via downregulation of the NET, independent of systemic neurohumoral activation. Knowledge about the regulation of the cardiac NE homeostasis may offer novel therapeutic strategies in HF.

We sought to determine the ability of quantitative myocardial perfusion reserve index (MPRI) by cardiac magnetic resonance (CMR) and high-sensitive troponin T (hsTnT) for the prediction of cardiac allograft vasculopathy (CAV) and cardiac outcomes in heart transplant (HT) recipients. In 108 consecutive HT recipients (organ age 4.1 ± 4.7 years, 25 [23%] with diabetes mellitus) who underwent cardiac catheterization, CAV grade by International Society for Heart & Lung Transplantation (ISHLT) criteria, MPRI, late gadolinium enhancement (LGE) and hsTnT values were obtained. Outcome data including cardiac death and urgent revascularization (“hard cardiac events”) and revascularization procedures were prospectively collected. During a follow-up duration of 4.2 ± 1.4 years, seven patients experienced hard cardiac events and 11 patients underwent elective revascularization procedures. By multivariable analysis, hsTnT and MPRI both independently predicted cardiac events, surpassing the value of LGE and CAV by ISHLT criteria. Furthermore, hsTnT and MPRI provided complementary value. Thus, patients with high hsTnT and low MPRI showed the highest rates of cardiac events (annual event rate = 14.5%), while those with low hsTnT and high MPRI exhibited excellent outcomes (annual event rate = 0%). In conclusion, comprehensive “bio-imaging” using hsTnT, as a marker of myocardial microinjury, and CMR, as a marker of microvascular integrity and myocardial damage by LGE, may aid personalized risk-stratification in HT recipients.

Impairment of the cardiac norepinephrine (NE) reuptake by the neuronal NE transporter contributes to enhanced cardiac NE net release in congestive heart failure. Elevated plasma levels of aldosterone (AL) promote sympathetic overstimulation in failing hearts by unclear mechanisms. Our aim was to evaluate if elevated AL and/or alterations in Na+ intake regulate cardiac NE reuptake. To test the effects of AL and Na+ on cardiac NE reuptake, Wistar rats were fed a normal-salt (NS) diet (0.2% NaCl), a low-salt (LS) diet (0.015% NaCl), or a high-salt (HS) diet (8% NaCl). Another group of animals received AL infusion alone (0.75 μg/h) or AL infusion plus HS diet. Specific cardiac [3H]NE uptake via the NE transporter in a Langendorff preparation and AL plasma levels were measured at different time points between 5 and 42 days of treatment. To compare these findings from healthy animals with a disease model, Dahl salt-sensitive rats were investigated as a model of congestive heart failure with endogenously elevated AL. In summary, neither exogenous nor endogenous elevations of AL alone were sufficient to reduce cardiac NE reuptake. Only the HS diet induced a reduction of NE reuptake by 26%; additional infusion of AL augmented this effect to a further reduction of NE reuptake by 36%. In concordance, Dahl salt-sensitive rats treated with a HS diet displayed elevated AL and a marked reduction of NE reuptake. We conclude that exogenous or endogenous AL elevations alone do not reduce cardiac NE reuptake, but AL serves as an additional factor that negatively regulates cardiac NE reuptake in concert with HS intake.

Transthyretin-related amyloidosis (ATTR) is characterized by a wide heterogeneity of genotypes and predominantly neurological and cardiac phenotypes. This study aims to characterize a cohort of patients with the rare transthyretin (TTR) Val20Ile (p.TTRVal40Ile) variant.This study comprises a single-center cohort of 59 individuals subsequently evaluated for TTRVal20Ile variant due to clinical (n = 13) or predictive (n = 46) reasons. All patients were mainly related to Wagshurst, a small village in the South of Germany. Clinical assessment was performed by neurological evaluation, echocardiography, electrocardiography, cardiac biomarkers, cardiac MRI (n = 13), and (99m)Tc-DPD scintigraphy (n = 16). The rare TTRVal20Ile variant was found in 41 patients; evidence of cardiac amyloidosis was present in 22 patients. Evidence of pulmonary involvement was obtained by (99m)Tc-DPD scintigraphy in eight patients. No further organ involvement was observed in any of the patients carrying TTRVal20Ile variant. Correlation of inter-ventricular septum thickness as well as decrease of left ventricular longitudinal contractility with age was observed. Moreover, thickness of inter-ventricular septum correlated with NT-proBNP plasma levels and decrease in mitral annular plane systolic excursion. Cardiac manifestation started during the early sixth life decade indicated by higher left ventricular septum thickness and NT-proBNP plasma levels as compared to patients in fifth decade of life. All patients of the seventh and eighth life decade (n = 10) presented with cardiac amyloidosis. During median follow-up of 26 (0-108) months, eight patients underwent heart transplantation with 1-year mortality rate of 25%.This large cohort of individuals carrying the TTRVal20Ile mutation reveals a predominantly cardiac phenotype with high penetrance and late onset of symptoms. Cardiac manifestation progressed to end-stage heart failure within a few years, finally requiring heart transplantation with promising long-term survival rates.

Background Routine quantitative assessment of left ventricular (LV) volumes with echocardiography is hindered by time-consuming methods requiring a manual trace of the LV cavity from two apical two-dimensional planes. Thus, the aim of this study was to evaluate faster new semiautomatic echocardiographic methods that could represent a feasible alternative for the assessment of LV volumes and ejection fraction (EF) in clinical practice. Methods Two semiautomatic methods, the automated EF (Auto-EF) for two-dimensional echocardiography and the 4D Auto LVQ tool for three-dimensional echocardiography (3DE), were compared with the biplane modified Simpson's method and cardiac magnetic resonance (CMR) imaging in 47 patients. To evaluate the accuracy of volumetry, additional in vitro measurements using water-filled latex balloons were performed with both modalities. Results Results of balloon volumetry by echocardiography and CMR measurements were in good agreement with real balloon volumes. The mean LV EF was 45 ± 11% by Auto-EF, 45 ± 11% by 3DE, 48 ± 11% by Simpson's method, and 54 ± 12% by CMR. Linear regression and Bland-Altman analyses showed good associations for semiautomatic methods with Simpson's method (Auto-EF, r = 0.85, bias = 3%, limits of agreement [LOA] = 12%; 3DE, r = 0.79, bias = 3%, LOA = 14%), as well as with CMR (Auto-EF, r = 0.74, bias = 9%, LOA = 17%; 3DE, r = 0.73, bias = 9%, LOA = 17%). Intra- and interobserver variability were 6% and 12% with Auto-EF and 8% and 11% with 3DE, respectively. Conclusions Good correlations between semiautomatic echocardiographic parameters for assessment of LV volumes and EF could be observed when compared with Simpson's method or CMR. However, intertechnique agreement analysis of absolute LV volumes revealed considerable differences, with significant underestimation of volumes and EF with respect to CMR.

Aim The aim of this study was to determine the value of extracellular volume fraction (ECV) for the non-invasive assessment of diffuse myocardial fibrosis (MF) in different stages of systolic left ventricular (LV) dysfunction in dilated cardiomyopathy (DCM) in comparison with endomyocardial biopsy. Background Non-invasive ECV assessment using cardiovascular magnetic resonance (CMR) T1 mapping reflects diffuse MF in patients with severe DCM, but earlier stages of DCM with mild LV functional impairment have not been investigated yet. Methods Forty-five subjects with mild functional impairment and LV dilation [‘early DCM’, ejection fraction (EF) 45–55%], 29 with LV dysfunction and volume dilatation (‘DCM’, EF

Low anti-phosphorylcholine (PC) IgM plasma levels have been associated with increased incidence of adverse events in coronary artery disease (CAD). The underlying mechanisms are unclear. We hypothesized that atheroprotection mediated by anti-PC IgM antibodies is associated with reduced vascular remodeling and therefore tested whether anti-PC IgM plasma levels independently predict vascular remodeling. In a prospective cross-sectional study, anti-PC IgM plasma levels were measured in 175 consecutive patients with suspected CAD undergoing cardiac computed tomography angiography. Plaque morphology was thoroughly analyzed. Vascular remodeling was defined by a change in the vessel diameter at the plaque site in comparison to the reference segment proximal to the lesion (reference diameter) of ≥10 %. Mean age of the patients was 64.8 ± 10.7 years, 48.6 % were female. In 98 patients CAD was diagnosed, 57 (58.2 %) of which displayed non-obstructive CAD (stenosis

BACKGROUND: Inherited arrhythmias were originally considered isolated electrical defects. There is growing evidence that ion channel dysfunction also contributes to myocardial disorders, but genetic overlap has not been reported for sinus node dysfunction (SND) and noncompaction cardiomyopathy (NCCM). OBJECTIVES: The study sought to investigate a familial electromechanical disorder characterized by SND and NCCM, and to identify the underlying genetic basis. METHODS: The index family and a cohort of unrelated probands with sinus bradycardia were examined by electrocardiography, Holter recording, exercise stress test, echocardiography, and/or cardiac magnetic resonance imaging. Targeted next-generation and direct sequencing were used for candidate gene analysis and mutation scanning. Ion channels were expressed in HEK293 cells and studied using patch-clamp recordings. RESULTS: SND and biventricular NCCM were diagnosed in multiple members of a German family. Segregation analysis suggested autosomal-dominant inheritance of the combined phenotype. When looking for potentially disease-causing gene variants with cosegregation, a novel hyperpolarization-activated cyclic nucleotide channel 4 (HCN4)-G482R mutation and a common cysteine and glycine-rich protein 3 (CSRP3)-W4R variant were identified. HCN4-G482R is located in the highly conserved channel pore domain. Mutant subunits were nonfunctional and exerted dominant-negative effects on wild-type current. CSRP3-W4R has previously been linked to dilated and hypertrophic cardiomyopathy, but was also found in healthy subjects. Moreover, different truncation (695X) and missense (P883R) HCN4 mutations segregated with a similar combined phenotype in an additional, unrelated family and a single unrelated proband respectively, which both lacked CSRP3-W4R. CONCLUSIONS: The symptom complex of SND and NCCM is associated with heritable HCN4 defects. The NCCM phenotype may be aggravated by a common CSRP3 variant in one of the families.

To investigate whether cardiac computed tomography (CCT) can determine left ventricular (LV) radial, circumferential and longitudinal myocardial deformation in comparison to two-dimensional echocardiography in patients with congestive heart failure.Echocardiography allows for accurate assessment of strain with high temporal resolution. A reduced strain is associated with a poor prognosis in cardiomyopathies. However, strain imaging is limited in patients with poor echogenic windows, so that, in selected cases, tomographic imaging techniques may be preferable for the evaluation of myocardial deformation.Consecutive patients (n=27) with congestive heart failure who underwent a clinically indicated ECG-gated contrast-enhanced 64-slice dual-source CCT for the evaluation of the cardiac veins prior to cardiac resynchronization therapy (CRT) were included. All patients underwent additional echocardiography. LV radial, circumferential and longitudinal strain and strain rates were analyzed in identical midventricular short axis, 4-, 2- and 3-chamber views for both modalities using the same prototype software algorithm (feature tracking). Time for analysis was assessed for both modalities.Close correlations were observed for both techniques regarding global strain (r=0.93, r=0.87 and r=0.84 for radial, circumferential and longitudinal strain, respectively, p0.001 for all). Similar trends were observed for regional radial, longitudinal and circumferential strain (r=0.88, r=0.84 and r=0.94, respectively, p0.001 for all). The number of non-diagnostic myocardial segments was significantly higher with echocardiography than with CCT (9.6% versus 1.9%, p0.001). In addition, the required time for complete quantitative strain analysis was significantly shorter for CCT compared to echocardiography (877±119 s per patient versus 1105±258 s per patient, p0.001).Quantitative assessment of LV strain is feasible using CCT. This technique may represent a valuable alternative for the assessment of myocardial deformation in selected patients with poor echogenic windows and general contraindications for magnetic resonance imaging.

Purpose To compare the value of Dobutamine stress echocardiography (DSE) with that provided by Dobutamine Cardiac Magnetic Resonance (DCMR) for the non-invasive risk stratification of patients with suspected or known coronary artery disease (CAD). Methods Patients with suspected or known CAD underwent either DSE or DCMR using the same standardized protocol. Patient matching was then performed retrospectively for age, gender and risk factors. Outcome data including cardiac death and non-fatal myocardial infarction (defined as hard cardiac events) and ‘late' revascularization performed >90days after the diagnostic procedures were collected during at least 6months. Results Follow-up data were available in 1852 patients who completed either DSE (n=884) or DCMR (n=884) during a mean follow-up duration of 4.1±2.4 and 3.9±1.9years, respectively (p=NS). Matched patients exhibited an overall high risk profile (69±9years; 69% male, 70% history of CAD and 26% diabetes mellitus in both groups). Using multivariable analysis, both modalities successfully identified patients with inducible ischemia at higher risk for subsequent hard cardiac events, surpassing the value of conventional risk factors like age, male gender and diabetes (HR=9.2; 95%CI=5.6–14.9 for DCMR versus 2.5; 95%CI=1.7–3.7 for DSE). By testing for interaction the predictive capacity of DCMR was higher than that provided by DSE (p=0.02). Patients with negative DCMR exhibited lower event rates compared to those with negative DSE (annual hard cardiac event rate of 0.8% versus 3.2%, p=0.002). Conclusions DSE & DCMR aid the risk stratification of CAD patients. However, inducible WMA during DCMR are associated with a higher risk for subsequent cardiac events. Patients with negative DCMR on the other hand, exhibited a lower event rate compared to those with negative DSE.