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Background We aimed to assess the association between number of pregnancies and long-term progression of cardiac dysfunction, arrhythmias, and event-free survival in women with pathogenic or likely pathogenic variants of gene encoding for Lamin A/C proteins ( LMNA+). Methods and Results We retrospectively included consecutive women with LMNA+ and recorded pregnancy data. We collected echocardiographic data, occurrence of atrial fibrillation, atrioventricular block, sustained ventricular arrhythmias, and implantation of cardiac electronic devices (implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator). We analyzed retrospectively complications during pregnancy and the peripartum period. We included 89 women with LMNA+ (28% probands, age 41±16 years), of which 60 had experienced pregnancy. Follow-up time was 5 [interquartile range, 3-9] years. We analyzed 452 repeated echocardiographic examinations. Number of pregnancies was not associated with increased long-term risk of atrial fibrillation, atrioventricular block, sustained ventricular arrhythmias, or implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator implantation. Women with previous pregnancy and nulliparous women had a similar annual deterioration of left ventricular ejection fraction (-0.5/year versus -0.3/year, P =0.37) and similar increase of left ventricular end-diastolic diameter (0.1/year versus 0.2/year, P =0.09). Number of pregnancies did not decrease survival free from death, left ventricular assist device, or need for cardiac transplantation. Arrhythmias occurred during 9% of pregnancies. No increase in maternal and fetal complications was observed. Conclusions In our cohort of women with LMNA+, pregnancy did not seem associated with long-term adverse disease progression or event-free survival. Likewise, women with LMNA+ generally well-tolerated pregnancy, with a small proportion of patients experiencing arrhythmias.

Moderate hypothermia has been used to improve outcomes in comatose out-of-hospital cardiac arrest survivors during the past two decades, although the effects remain controversial. We have recently shown in an experimental study that myocardial electrophysiological and mechanical relationships were altered during moderate hypothermia. Electromechanical window positivity increased, and electrical dispersion of repolarization decreased, both of which are changes associated with decreased arrhythmogenicity in clinical conditions. Mechanical dispersion, a parameter also linked to arrhythmic risk, remained unaltered. Whether corresponding electrophysiological and mechanical changes occur in humans during moderate hypothermia, has not been previously explored. Twenty patients with normal left ventricular function were included. Measurements were obtained at 36 and 32°C prior to ascending aortic repair while on partial cardiopulmonary bypass and at 36°C after repair. Registrations were performed in the presence of both spontaneous and comparable paced heart rate during standardized loading conditions. The following electrical and mechanical parameters were explored: (1) Electromechanical window, measured as time difference between mechanical and electrical systole, (2) dispersion of repolarization from ECG T-wave, and (3) mechanical dispersion, measured as segmental variation in time to peak echocardiographic strain. At moderate hypothermia, mechanical systolic prolongation (425 ± 43-588 ± 67 ms, p < 0.001) exceeded electrical systolic prolongation (397 ± 49-497 ± 79 ms, p < 0.001), whereby, electromechanical window positivity increased (29 ± 30-86 ± 50 ms, p < 0.001). Dispersion of repolarization and mechanical dispersion remained unchanged. Corresponding electrophysiological and mechanical relationships were present at comparable paced heart rates. After rewarming, the increased electromechanical window was reversed in the presence of both spontaneous and paced heart rates. Moderate hypothermia increased electromechanical window positivity, while dispersion of repolarization and mechanical dispersion remained unchanged. This impact of hypothermia may be clinically relevant for selected groups of patients after cardiac arrest., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objectives: Targeted temperature management (32-36°C) is used for neuroprotection in cardiac arrest survivors. The isolated effects of hypothermia on myocardial function, as used in clinical practice, remain unclear. Based on experimental results, we hypothesized that hypothermia would reversibly impair diastolic function with less tolerance to increased heart rate in patients with uninsulted hearts., Design: Prospective clinical study, from June 2015 to May 2018., Setting: Cardiothoracic surgery operation room, Oslo University Hospital., Patients: Twenty patients with left ventricular ejection fraction greater than 55%, undergoing ascending aorta graft-replacement connected to cardiopulmonary bypass were included., Interventions: Left ventricular function was assessed during reduced cardiopulmonary bypass support at 36°C, 32°C prior to graft-replacement, and at 36°C postsurgery. Electrocardiogram, hemodynamic, and echocardiographic recordings were made at spontaneous heart rate and 90 beats per minute at comparable loading conditions., Measurements and Main Results: Hypothermia decreased spontaneous heart rate, and R-R interval was prolonged (862 ± 170 to 1,156 ± 254 ms, p < 0.001). Although systolic and diastolic fractions of R-R interval were preserved (0.43 ± 0.07 and 0.57 ± 0.07), isovolumic relaxation time increased and diastolic filling time was shortened. Filling pattern changed from early to late filling. Systolic function was preserved with unchanged myocardial strain and stroke volume index, but cardiac index was reduced with maintained mixed venous oxygen saturation. At increased heart rate, systolic fraction exceeded diastolic fraction (0.53 ± 0.05 and 0.47 ± 0.05) with diastolic impairment. Strain and stroke volume index were reduced, the latter to 65% of stroke volume index at spontaneous heart rate. Cardiac index decreased, but mixed venous oxygen saturation was maintained. After rewarming, myocardial function was restored., Conclusions: In patients with normal left ventricular function, hypothermia impaired diastolic function. At increased heart rate, systolic function was subsequently reduced due to impeded filling. Changes in left ventricular function were rapidly reversed after rewarming., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: This study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT)., Background: LBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT., Methods: In 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EF preserved ), 36% to 49% (EF mid ), and ≤35% (EF low ). Sixty-four patients underwent CRT and were re-examined after 6 months., Results: Septal work was successively reduced from controls, through EF preserved , EF mid , and EF low (all p < 0.005), and showed a strong correlation to left ventricular ejection fraction (LVEF; r = 0.84; p < 0.005). In contrast, LV lateral wall work was numerically increased in EF preserved and EF mid versus controls, and did not significantly correlate with LVEF in these groups. In EF low, however, LV lateral wall work was substantially reduced (p < 0.005). There was a moderate overall correlation between LV lateral wall work and LVEF (r = 0.58; p < 0.005). In CRT recipients, LVEF was normalized (≥50%) in 54% of patients with preserved LV lateral wall work, but only in 13% of patients with reduced LV lateral wall work (p < 0.005)., Conclusions: In early stages, LBBB-induced heart failure is associated with impaired septal function but preserved lateral wall function. The advent of LV lateral wall dysfunction may be an optimal time-point for CRT., Competing Interests: Funding Support and Author Disclosures Drs Sletten and Aalen were supported by grants from the Norwegian Health Association. Dr Larsen was a recipient of a clinical research fellowships form the South-Eastern Norway Regional Health Authority. Prof Voigt holds a personal research mandate of the Flemish Research Council. Prof Voigt and Dr Duchenne were further supported by a grant of the University of Leuven. Dr Smiseth is co-inventor, but since May 24, 2017 has had no financial relations to the patent “Method for myocardial segment work analysis,” which was used to calculate the myocardial work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose, (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Adults operated for tetralogy of Fallot (TOF) have high risk of ventricular arrhythmias (VA). QRS duration >180 ms is an established risk factor for VA. We aimed to investigate heart function, prevalence of arrhythmias and sex differences in patients with TOF at long-term follow-up., Methods: We included TOF-operated patients≥18 years from our centre's registry. We reviewed medical records and the most recent echocardiographic exam. VA was recorded on ECGs, 24-hour Holter registrations and from implantable cardioverter defibrillator., Results: We included 148 patients (age 37±10 years). Left ventricular global longitudinal strain (LV GLS, -15.8±3.1% vs -18.8±3.2%, p=0.001) and right ventricular (RV) GLS (-15.8±3.9% vs -19.1±4.1%, p=0.001) were lower in men at all ages compared with women. Higher RV D1 (4.3±0.5 cm vs 4.6±0.6 cm, p=0.01), lower ejection fraction (55%±8% vs 50%±9%, p=0.02), lower RV GLS (-18.1±4.0 ms vs -16.1±4.8 ms, p=0.04) and N-terminal pro-brain natriuretic peptide (NT-proBNP) over reference range (n=27 (23%) vs n=8 (77%), p<0.001) were associated with higher incidence of VA. QRS duration was longer in men (151±30 ms vs 128±25 ms, p<0.001). No patients had QRS duration >180 ms. QRS duration did not differ in those with and without VA (143±32 ms vs 137±28 ms, p=0.06)., Conclusions: Our results confirmed reduced RV function in adults operated for TOF. Male patients had impaired LV and RV function expressed by lower LV and RV GLS values at all ages. Reduced cardiac function and elevated NT-proBNP were associated with higher incidence of VA and may be important in risk assessment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Transpulmonary passage of air emboli can lead to fatal brain- and myocardial infarctions. We studied whether pigs with open chest and pericardium had a greater transpulmonary passage of venous air emboli than pigs with closed thorax., Methods: We allocated pigs with verified closed foramen ovale to venous air infusion with either open chest with sternotomy and opening of the pleura and pericardium (n = 8) or closed thorax (n = 16). All pigs received a five-hour intravenous infusion of ambient air, starting at 4-6 mL/kg/h and increased by 2 mL/kg/h each hour. We assessed transpulmonary air passage by transesophageal M-mode echocardiography and present the results as median with inter-quartile range (IQR)., Results: Transpulmonary air passage occurred in all pigs with open chest and pericardium and in nine pigs with closed thorax (56%). Compared to pigs with closed thorax, pigs with open chest and pericardium had a shorter to air passage (10 minutes (5-16) vs. 120 minutes (44-212), P < .0001), a smaller volume of infused air at the time of transpulmonary passage (12 mL (10-23) vs.170 mL (107-494), P < .0001), shorter time to death (122 minutes (48-185) vs 263 minutes (248-300, P = .0005) and a smaller volume of infused air at the time of death (264 mL (53-466) vs 727 mL (564-968), P = .001). In pigs with open chest and, infused air and time to death correlated strongly (r = 0.95, P = .001)., Conclusion: Open chest and pericardium facilitated the transpulmonary passage of intravenously infused air in pigs., (© 2021 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background and Aim of the Study: Patients with asymptomatic, severe aortic stenosis are presumed to have a benign prognosis. In this retrospective cohort study, we examined the natural history of contemporary patients advised against aortic valve replacement due to a perceived lack of symptoms., Materials and Methods: We reviewed the medical records of every patient given the ICD-10-code for aortic stenosis (I35.0) at Oslo University Hospital, Rikshospitalet, between Dec 1st, 2002 and Dec 31st, 2016. Patients who were evaluated by the heart team due to severe aortic stenosis were categorized by treatment strategy. We recorded baseline data, adverse events and survival for the patients characterized as asymptomatic and for 100 age and gender matched patients scheduled for aortic valve replacement., Results: Of 2341 patients who were evaluated for aortic valve replacement due to severe aortic stenosis, 114 patients received conservative treatment due to a lack of symptoms. Asymptomatic patients had higher mortality than patients who had aortic valve replacement, log-rank p<0.001 (mean follow-up time: 4.0 (SD: 2.5) years). Survival at 1, 2 and 3 years for the asymptomatic patients was 88%, 75% and 63%, compared with 92%, 83% and 78% in the matched patients scheduled for aortic valve replacement. 28 (25%) of the asymptomatic patients had aortic valve replacement during follow-up. Age, previous history of coronary artery disease and N-terminal pro B-type natriuretic peptide (NT-proBNP) were predictors of mortality and coronary artery disease and NT-proBNP were predictors of 3-year morbidity in asymptomatic patients., Conclusions: In this retrospective study, asymptomatic patients with severe aortic stenosis who were advised against surgery had significantly higher mortality than patients who had aortic valve replacement., Competing Interests: The authors have declared that no competing interests exist.

Postcardiac arrest patients treated with hypothermia, frequently require vasopressors and inotropic medication. The aim of this experimental study was to investigate the effect of epinephrine on left ventricular (LV) function during hypothermia. In an open-chest porcine model, seven animals were equipped with LV micromanometer and epicardial ultrasound transducers to provide LV pressure, Tau , and wall thickness and thickening velocities in systole (S') and early diastole (e'). Arterial, central venous, and pulmonal artery pressures were recorded. Cardiac output (CO) was measured by transit-time flow probe on the ascending aorta. Hypothermia was induced using a cooling catheter through the femoral vein. Pacemaker leads were attached to the right atrium for pacing. LV volumes were obtained by two-dimensional echocardiography. Measurements were made at normothermia (38°C) and hypothermia (33°C), without and with epinephrine infusion (0.03 μg/kg/min), at spontaneous and paced heart rates (HRs) 120 and 140 beats/min. Hypothermia reduced LV stroke volume (SV). Epinephrine during hypothermia increased the SV with reduced end-systolic volumes. LV dP/dt max and wall-thickening velocity increased. During normothermia, epinephrine increased CO mainly due to accelerated HR, but during hypothermia, the increased CO resulted from augmented SV and, to a lesser degree, elevated HR. The incomplete relaxation and shortened diastolic filling time and the following reduction in SV seen in hypothermic animals, was repealed by epinephrine. The CO remained elevated also due to a shortened systolic duration, which gave time for complete relaxation during higher HRs. Epinephrine infusion improved systolic and diastolic function during hypothermia, and thereby reversed the effects induced by hypothermia considerably. Epinephrine augmented CO at hypothermia through increases in both SV and HR, in contrast to a mainly HR-dependent effect during normothermia. Systolic duration was shortened, which gave sufficient diastolic duration for complete relaxation. This allowed diastolic filling and maintained CO at elevated HRs.

Objective: Patients with tetralogy of Fallot (TOF) have high survival rates 30 years after surgical repair. Many patients experience pregnancy; however, the effects of pregnancy on the long-term cardiovascular outcome are not well known. We investigated the association of pregnancy and cardiac function with occurrence of ventricular arrhythmia (VA) in women with TOF., Methods: We recruited 80 women with repaired TOF from the national database. Holter monitoring or implanted devices detected VA, defined as non-sustained or sustained ventricular tachycardia or aborted cardiac arrest. All patients underwent echocardiography. Blood tests included NT-proBNP (N-terminal pro-brain natriuretic peptide)., Results: 55 (69%) women had experienced pregnancy. Mean age was lower in nulliparous compared with those with children (30±9 vs 40±9, p<0.01).VA had occurred in 17 (21%) women. Prevalence of VA was higher in women who had experienced pregnancy (n=16, 94%) compared with nulliparous (n=1, 6%) (p=0.02), also when adjusted for age (OR 12.9 (95% CI 1.5 to 113.2), p=0.02).Right ventricular mechanical dispersion was more pronounced in patients with VA (50±8 ms vs 39±14 ms, p=0.01, age-adjusted OR 2.1 (95% CI 1.3 to 7.5), p=0.01). NT-proBNP was also a marker of VA (211 ng/L (127 to 836) vs 139 ng/L (30 to 465), p=0.007). NT-proBNP >321 ng/L (normal values <170 ng/L) detected women with VA (p=0.019), also independent of age (OR 7.2 (95% CI 1.7 to 30.1), p=0.007)., Conclusion: Pregnancy was associated with higher prevalence of VA among women with TOF. Right ventricular mechanical dispersion and NT-proBNP were age-independent markers of VA. These may have importance for pregnancy counselling and risk stratification., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Targeted hypothermia, as used after cardiac arrest, increases electrical and mechanical systolic duration. Differences in duration of electrical and mechanical systole are correlated to ventricular arrhythmias. The electromechanical window (EMW) becomes negative when the electrical systole outlasts the mechanical systole. Prolonged electrical systole corresponds to prolonged QT interval, and is associated with increased dispersion of repolarization and mechanical dispersion. These three factors predispose for arrhythmias. The electromechanical relations during targeted hypothermia are unknown. We wanted to explore the electromechanical relations during hypothermia at 33 °C. We hypothesized that targeted hypothermia would increase electrical and mechanical systolic duration without more profound EMW negativity, nor an increase in dispersion of repolarization and mechanical dispersion., Methods: In a porcine model (n = 14), we registered electrocardiogram (ECG) and echocardiographic recordings during 38 °C and 33 °C, at spontaneous and atrial paced heart rate 100 beats/min. EMW was calculated by subtracting electrical systole; QT interval, from the corresponding mechanical systole; QRS onset to aortic valve closure. Dispersion of repolarization was measured as time from peak to end of the ECG T wave. Mechanical dispersion was calculated by strain echocardiography as standard deviation of time to peak strain., Results: Electrical systole increased during hypothermia at spontaneous heart rate (p < 0.001) and heart rate 100 beats/min (p = 0.005). Mechanical systolic duration was prolonged and outlasted electrical systole independently of heart rate (p < 0.001). EMW changed from negative to positive value (- 20 ± 19 to 27 ± 34 ms, p = 0.001). The positivity was even more pronounced at heart rate 100 beats/min (- 25 ± 26 to 41 ± 18 ms, p < 0.001). Dispersion of repolarization decreased (p = 0.027 and p = 0.003), while mechanical dispersion did not differ (p = 0.078 and p = 0.297)., Conclusion: Targeted hypothermia increased electrical and mechanical systolic duration, the electromechanical window became positive, dispersion of repolarization was slightly reduced and mechanical dispersion was unchanged. These alterations may have clinical importance. Further clinical studies are required to clarify whether corresponding electromechanical alterations are accommodating in humans.

Background: The combination of jaundice and acute abdominal pain is a common clinical problem associated with a broad array of aetiologies., Case Presentation: A 36-year-old male with Down's syndrome and Eisenmenger's syndrome presented with abdominal pain, jaundice and acute liver failure. Initial transabdominal ultrasound and subsequent magnetic resonance cholangiopancreatography (MRCP) revealed gallbladder stones, but no common bile duct stones. During the course of the patient's hospital admission, his liver chemistries were consistently elevated. Thus, endoscopic retrograde cholangiography (ERC) with sphincterotomy was performed, despite the anaesthesiological risk associated with his chronic heart failure. However, the ERC and sphincterotomy did not relieve the patient's symptoms and had no apparent effect on his abnormal liver chemistries. By the end of his hospital stay, the patient recovered spontaneously and was discharged with no final conclusion having been reached. An unexpected turn of events led us to conclude upon a diagnosis a few weeks later., Interpretation: This case illustrates the challenges of a multidisciplinary approach in a complex patient, and an overlooked detail that became a lesson to learn from.

Objectives. Infective endocarditis has potential for severe complications and high mortality. The number of patients with prosthetic valves has risen, and an increase in incidence of infective endocarditis has been suggested. We aimed to examine the epidemiology, etiology, treatment and outcome of patients admitted to Division of Cardiovascular and Pulmonary Diseases at Oslo University Hospital, and explore changes in incidence over the last four years. Design. We conducted a retrospective study including all patients admitted to a tertiary hospital in Oslo, Norway, and diagnosed with infective endocarditis according to ICD-10 between 2014 and 2017. Results. Two hundred and ninety-one patients ≥18 years were included (61.3 ± 13.8 years, 75.6% men). 36.4% had previous valve surgery and this proportion decreased during the period. The aortic valve was most commonly affected (51.9%). Streptococci were the most frequent microorganisms (35.1%), while staphylococci accounted for 26.8%. 81.8% were treated surgically, at a median of 6.5 (0-120) days after admission. Hemodynamic changes or instability was the primary surgical indication (51.5%). One-year mortality was 20.6%. Surgery within a week after admission resulted in poorer 1-year prognosis than surgery after one week. Also, surgically treated patients who died were significantly older than those who survived. Conclusions. In this cohort, streptococci were the most common causative microorganism. Approximately, one-third of the patients had prosthetic valves. Mortality remains high, underscoring the need for continuous medical awareness. A high number of streptococcus infections in this cohort suggest dental origin.

Objectives: The purpose of this study was to investigate how LBBB and CRT modify RV free wall function by direct ventricular interaction., Background: Right ventricular (RV) function influences prognosis in patients with left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). There is, however, limited insight into how LBBB and CRT affect RV function., Methods: In 24 patients with LBBB with nonischemic cardiomyopathy, RV and left ventricular (LV) strain by speckle-tracking echocardiography was measured before and after CRT. Underlying mechanisms were studied in 16 anesthetized dogs with ultrasonic dimension crystals and micromanometers., Results: Patients with LBBB demonstrated distinct early systolic shortening in the RV free wall, which coincided with the typical abnormal early systolic septal shortening. In animals, this RV free wall contraction pattern resulted in reduced myocardial work as a large portion of the shortening occurred against low pressure during early systole, coinciding with abnormal leftward septal motion. RV systolic function was maintained by vigorous contraction in the late-activated LV lateral wall, which pushed the septum toward the RV. CRT reduced abnormal septal motion and increased RV free wall work because there was less inefficient shortening against low pressure., Conclusions: LBBB reduces workload on the RV free wall because of abnormal septal motion and delayed activation of the LV lateral wall. Restoring septal and LV function by CRT increases workload in RV free wall and may explain why patients with RV failure respond poorly to CRT. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: We aimed to assess structural progression in arrhythmogenic cardiomyopathy (AC) patients and mutation-positive family members and its impact on arrhythmic outcome in a longitudinal cohort study., Methods and Results: Structural progression was defined as the development of new Task Force imaging criteria from inclusion to follow-up and progression rates as annual changes in imaging parameters. We included 144 AC patients and family members (48% female, 47% probands, 40 ± 16 years old). At genetic diagnosis and inclusion, 58% of family members had penetrant AC disease. During 7.0 [inter-quartile range (IQR) 4.5-9.4] years of follow-up, 47% of family members without AC at inclusion developed AC criteria, resulting in a yearly new AC penetrance of 8%. Probands and family members had a similar progression rate of right ventricular outflow tract diameter (0.5 mm/year vs. 0.6 mm/year, P = 0.28) by mixed model analysis of 598 echocardiographic examinations. Right ventricular fractional area change progression rate was even higher in family members (-0.6%/year vs. -0.8%/year, P < 0.01). Among 86 patients without overt structural disease or arrhythmic history at inclusion, a first severe ventricular arrhythmic event occurred in 8 (9%), of which 7 (88%) had concomitant structural progression. Structural progression was associated with higher incidence of severe ventricular arrhythmic events adjusted for age, sex, and proband status (HR 21.24, 95% CI 2.47-182.81, P < 0.01)., Conclusion: More than half of family members had AC criteria at genetic diagnosis and yearly AC penetrance was 8%. Structural progression was similar in probands and family members and was associated with higher incidence of severe ventricular arrhythmic events., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

We investigated whether tachycardia in left bundle branch block (LBBB) decreases left ventricular (LV) diastolic distensibility and increases diastolic pressures due to incomplete relaxation, and if cardiac resynchronization therapy (CRT) modifies this response. Thirteen canines were studied at baseline heart rate (120 beats/min) and atrial paced tachycardia (180 beats/min) before and after induction of LBBB and during CRT. LV and left atrial pressures (LAP) were measured by micromanometers and dimensions by sonomicrometry. The time constant τ of exponential pressure decay and degree of incomplete relaxation at mitral valve opening (MVO) and end diastole (ED) based on extrapolation of the exponential decay were assessed. Changes in LV diastolic distensibility were investigated using the LV transmural pressure-volume (PV) relation. LBBB caused prolongation of τ ( P < 0.03) and increased the degree of incomplete relaxation during tachycardia at MVO ( P < 0.001) and ED ( P = 0.08) compared with normal electrical activation. This was associated with decreased diastolic distensibility seen as upward shift of the PV relation at MVO by 18.4 ± 7.0 versus 12.0 ± 5.0 mmHg, at ED by 9.8 ± 2.3 versus 4.7 ± 2.3 mmHg, and increased mean LAP to 11.4 ± 2.7 versus 8.5 ± 2.6 mmHg, all P < 0.006. CRT shifted the LV diastolic PV relation downwards during tachycardia, reducing LAP and LV diastolic pressures ( P < 0.03). Tachycardia in LBBB reduced LV diastolic distensibility and increased LV diastolic pressures due to incomplete relaxation, whereas CRT normalized these effects. Clinical studies are needed to determine whether a similar mechanism contributes to dyspnea and exercise intolerance in LBBB and if effects of CRT are heart rate dependent. NEW & NOTEWORTHY Compared with normal electrical conduction, tachycardia in left bundle branch block resulted in incomplete relaxation during filling, particularly of the late activated left ventricular lateral wall. This further resulted in reduced left ventricular diastolic distensibility and elevated diastolic pressures and thus amplified the benefits of cardiac resynchronization therapy in this setting.

We have recently demonstrated that accelerometer-based pump thrombosis and thromboembolic events detection is feasible in vitro. This article focuses on detection of these conditions in vivo. In an open-chest porcine model (n = 7), an accelerometer was attached to the pump casing of an implanted HeartWare HVAD. Pump vibration was analyzed by Fast Fourier Transform of the accelerometer signals, and the spectrogram third harmonic amplitude quantified and compared with pump power. Interventions included injection of thrombi into the left atrium (sized 0.3-0.4 ml, total n = 35) and control interventions; pump speed change, graft obstruction, and saline bolus injections (total n = 47). Graft flow to cardiac output ratio was used to estimate the expected number of thrombi passing through the pump. Sensitivity/specificity was assessed by receiver operating characteristic curve. Graft flow to cardiac output ratio averaged 66%. Twenty-six of 35 (74%) thrombi caused notable accelerometer signal change. Accelerometer third harmonic amplitude was significantly increased in thromboembolic interventions compared with control interventions, 64.5 (interquartile range [IQR]: 18.8-107.1) and 5.45 (IQR: 4.2-6.6), respectively (p < 0.01). The corresponding difference in pump power was 3 W (IQR: 2.9-3.3) and 2.8 W (IQR: 2.4-2.9), respectively (p < 0.01). Sensitivity/specificity of the accelerometer and pump power to detect thromboembolic events was 0.74/1.00 (area under the curve [AUC]: 0.956) and 0.40/1.00 (AUC: 0.759), respectively. Persistent high third harmonic amplitude was evident at end of all experiments, and pump thrombosis was confirmed by visual inspection. The findings demonstrate that accelerometer-based detection of thromboembolic events and pump thrombosis is feasible in vivo and that the method is superior to detection based on pump power.

Objectives: This study sought to investigate how regional left ventricular (LV) function modifies septal motion in left bundle branch block (LBBB)., Background: In LBBB, the interventricular septum often has marked pre-ejection shortening, followed by immediate relengthening (rebound stretch). This motion, often referred to as septal flash, is associated with positive response to cardiac resynchronization therapy (CRT)., Methods: In 10 anesthetized dogs, we induced LBBB by radiofrequency ablation and occluded the circumflex (CX) (n = 10) and left anterior descending (LAD) (n = 6) coronary arteries, respectively. Myocardial dimensions were measured by sonomicrometry and myocardial work by pressure-segment length analysis. In 40 heart failure patients with LBBB, including 20 with post-infarct scar and 20 with nonischemic cardiomyopathy, myocardial strain was measured by speckle-tracking echocardiography and myocardial work by pressure-strain analysis. Scar was assessed by cardiac magnetic resonance imaging with late gadolinium enhancement., Results: During LBBB, each animal showed typical septal flash with pre-ejection shortening and rebound stretch, followed by reduced septal systolic shortening (p < 0.01). CX occlusion caused LV lateral wall dysfunction and abolished septal flash due to loss of rebound stretch (p < 0.0001). Furthermore, CX occlusion restored septal systolic shortening to a similar level as before induction of LBBB and substantially improved septal work (p < 0.001). LAD occlusion, however, accentuated septal flash by increasing rebound stretch (p < 0.05). Consistent with the experimental findings, septal flash was absent in patients with LV lateral wall scar due to lack of rebound stretch (p < 0.001), and septal systolic shortening and septal work far exceeded values in nonischemic cardiomyopathy (p < 0.0001). Septal flash was present in most patients with anteroseptal scar., Conclusions: LV lateral wall dysfunction and scar abolished septal flash and markedly improved septal function in LBBB. Therefore, function and scar in the LV lateral wall should be taken into account when septal motion is used to evaluate dyssynchrony., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Right ventricular (RV) myocardial dysfunction is a common feature in septic shock. It can worsen outcome, but the etiology is poorly understood. Pulmonary artery hypertension (PAH) plays a part in the pathogenesis of the right heart dysfunction in sepsis but its importance is unknown. In pigs, PAH in sepsis is substantial and the translational value of porcine sepsis models therefore questioned. We hypothesized that porcine sepsis causes a myocardial inflammatory response which leads to myocardial dysfunction independent of PAH., Materials and Methods: Sepsis was induced by Escherichia coli-infusion in 10 pigs resulting in PAH and increased right ventricular pressure (RVP). The same degree of RVP was achieved by external pulmonary artery banding (PAB) in a consecutive series of 6 animals., Results: Sepsis, but not PAB, led to increase in endothelial damage marker PAI-1 and cytokines TNF and IL-6 (all p<0.05) in plasma. In myocardium, TNF and IL-6 were significantly elevated in sepsis, TNF in both ventricles and IL-6 mostly in RV, while IL-1β, IL-18 and C5a were significantly higher in RV compared to LV after PAB (all p<0.05). Myocardial mRNA levels of IL-1β, IL-6, IL-18, IP-10, E-selectin and PAI-1 were significantly elevated in RV and LV during sepsis compared to PAB, while Caspase-1 was decreased in septic compared to PAB animals (all p<0.05). Cathepsin L activity was increased in RV by PAB, while sepsis inhibited this response. Escherichia coli-induced sepsis caused myocardial inflammation independent of PAH., Conclusion: Prominent PAH should therefore not exclude porcine sepsis models to further our understanding of human sepsis., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study sought to investigate the hypothesis that patients with left bundle branch block (LBBB) are hypersensitive to elevated afterload., Background: Epidemiological data suggest that LBBB can provoke heart failure in patients with hypertension., Methods: In 11 asymptomatic patients with isolated LBBB and 11 age-matched control subjects, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured by echocardiography. Systolic arterial pressure was increased by combining pneumatic extremity constrictors and handgrip exercise. To obtain more insight into mechanisms of afterload response, 8 anesthetized dogs with left ventricular (LV) micromanometer and dimension crystals were studied during acutely induced LBBB and aortic constriction. Regional myocardial work was assessed by LV pressure-dimension analysis., Results: Consistent with normal afterload dependency, elevation of systolic arterial pressure by 38 ± 12 mm Hg moderately reduced LVEF from 60 ± 4% to 54 ± 6% (p < 0.01) in control subjects. In LBBB patients, however, a similar blood pressure increase caused substantially larger reduction in LVEF (p < 0.01), from 56 ± 6% to 42 ± 7% (p < 0.01). There were similar findings for GLS. In the dog model, aortic constriction abolished septal shortening (p < 0.02), and septal work decreased to negative values (p < 0.01). Therefore, during elevated systolic pressure, the septum made no contribution to global LV work, as indicated by net negative work, and instead absorbed energy from work done by the LV lateral wall., Conclusions: Moderate elevation of arterial pressure caused marked reductions in LVEF and GLS in patients with LBBB. This reflects a cardiodepressive effect of elevated afterload in the dyssynchronous ventricle and was attributed to loss of septal function., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Approximately one half of all patients with heart failure have normal ejection fraction in the left ventricle, and heart failure is attributed to stiffness of the cardiac muscle. The most common cause is hypertension with ventricular hypertrophy., Material and Method: Literature searches were conducted in PubMed. After we made our selection, a total of 15 articles on heart failure with normal ejection fraction were included. In addition, we included nine articles from our own literature archive., Results: The diagnosis of heart failure with normal ejection fraction presupposes clinical findings consistent with heart failure and objective signs of diastolic dysfunction. The main objective sign is increased left ventricular filling pressure estimated by echocardiography. Ventricular hypertrophy and increased natriuretic peptides support the diagnosis., Interpretation: Underlying conditions and symptoms are treated, and in general the same drugs are used as for heart failure with reduced ejection fraction.

Aims: There are conflicting data and no consensus on how to measure acute response to cardiac resynchronization therapy (CRT). This study investigates, which contractility indices are best markers of acute CRT response., Methods and Results: In eight anaesthetized dogs with left bundle branch block, we measured left ventricular (LV) pressure by micromanometer and end-diastolic volume (EDV) and end-systolic volume (ESV) by sonomicrometry. Systolic function was measured as LV ejection fraction (EF), peak rate of LV pressure rise (LV dP/dtmax) and as a gold standard of contractility, LV end-systolic elastance (Ees), and volume axis intercept (V0) calculated from end-systolic pressure-volume relations (ESPVR). Responses to CRT were compared with inotropic stimulation by dobutamine. Both CRT and dobutamine caused reduction in ESV (P < 0.01) and increase in LV dP/dtmax (P < 0.05). Both interventions shifted the ESPVR upwards indicating increased contractility, but CRT which reduced V0 (P < 0.01), caused no change in Ees. Dobutamine markedly increased Ees, which is the typical response to inotropic stimulation. Preload (EDV) was decreased (P < 0.01) by CRT, and there was no change in EF. When adjusting for the reduction in preload, CRT increased EF (P = 0.02) and caused a more marked increase in LV dP/dtmax (P < 0.01)., Conclusion: Increased contractility by CRT could not be identified by Ees, which is a widely used reference method for contractility. Furthermore, reduction in preload by CRT attenuated improvement in contractility indices such as EF and LV dP/dtmax. These results suggest that changes in LV volume may be more sensitive markers of acute CRT response than conventional contractility indices.

Atrial switch operation in patients with transposition of the great arteries (TGA) leads to leftward shift and changes the geometry of the interventricular septum. By including the implications of regional work and septal curvature, this study investigates if changes in septal function and geometry contribute to reduced function of the systemic right ventricle (RV) in adult TGA patients. Regional myocardial work estimation has been possible by applying a recently developed method for noninvasive work calculation based on echocardiography. In 14 TGA patients (32 ± 6 yr, means ± SD) and 14 healthy controls, systemic ventricular systolic strains were measured by speckle tracking echocardiography and regional work was calculated by pressure-strain analysis. In TGA patients, septal longitudinal strain was reduced to -14 ± 2 vs. -20 ± 2% in controls ( P < 0.01) and septal work was reduced from 2,046 ± 318 to 1,146 ± 260 mmHg·% ( P < 0.01). Septal circumferential strain measured in a subgroup of patients was reduced to -11 ± 3 vs. -27 ± 3% in controls ( P < 0.01), and a reduction of septal work (540 ± 273 vs. 2,663 ± 459 mmHg·%) was seen ( P < 0.01). These reductions were in part attributed to elevated afterload due to increased radius of curvature of the leftward shifted septum. To conclude, in this mechanistic study we demonstrate that septal dysfunction contributes to failure of the systemic RV after atrial switch in TGA patients. This is potentially a long-term response to increased afterload due to a flatter septum and suggests that medical therapy that counteracts septal flattening may improve function of the systemic RV. NEW & NOTEWORTHY We have demonstrated that transposition of the great arteries patients with systemic right ventricles (RVs) have reduced function of the interventricular septum (IVS). Since the IVS is constructed to eject into the systemic circulation, it may seem unexpected that it does not maintain function when being part of the systemic RV. By applying the principles of regional work, wall tension, and geometry, we have identified unfavorable working conditions for the IVS when the RV adapts to systemic pressures.

Objective: Patients with univentricular hearts (UVH) have high mortality despite modern treatment, and better methods to identify patients at highest risk are needed. We wanted to improve risk stratification in patients with UVH by focusing on the prognostic significance of single right versus single left ventricular morphology (SRV vs SLV)., Methods: All 395 patients with UVH operated at our centre were prospectively included from 1972 to 2016 (195 SRV, 166 SLV, 34 mixed or indeterminate ventricular morphology). Diagnoses, UVH morphology, types of all operations and time and causes of death or heart transplantation (HTX) were recorded. The primary endpoint was death or HTX., Results: Among the 111 non-Fontan patients, 88 died (SRV 62 vs SLV 20; p<0.0001), 32 due to heart failure (SRV 23 vs SLV 5; p=0.0012). Twenty-five  years of cumulative SRV versus SLV survival among the 284 Fontan patients (41 deaths/HTX) was 66.9% vs 87.9% (p=0.0027), partly explained by more deaths/HTX due to heart failure among patients with SRV (p=0.0006). Survival in patients with SRV with and without hypoplastic left heart syndrome (HLHS) was similar. SRV versus SLV was a strong predictor of death/HTX in multivariable proportional hazards analyses (RR 3.3, 95% CI 1.6 to 6.6)., Conclusion: SRV versus SLV is a strong short-term and long-term predictor of survival among patients with UVH, mainly explained by higher rates of death/HTX due to heart failure in the SRV group. Our findings apply to patients with SRV both with and without HLHS., Competing Interests: Competing interests: None declared.

Therapeutic hypothermia is an established treatment in patients resuscitated from cardiac arrest. It is usually well-tolerated circulatory, but hypothermia negatively effects myocardial contraction and relaxation velocities and increases diastolic filling restrictions. A significant proportion of resuscitated patients are treated with long-acting beta-receptor blocking agents' prearrest, but the combined effects of hypothermia and beta-blockade on left ventricle (LV) function are not previously investigated. We hypothesized that beta 1 -adrenergic receptor blockade (esmolol infusion) exacerbates the negative effects of hypothermia on active myocardial motions, affecting both systolic and diastolic LV function. A pig (n = 10) study was performed to evaluate the myocardial effects of esmolol during hypothermia (33°C) and during normothermia, at spontaneous and pacing-increased heart rates (HRs). LV function was assessed by a LV pressure transducer, an epicardial ultrasonic transducer (wall thickness, wall thickening/thinning velocity) and an aortic ultrasonic flow-probe (stroke volume, cardiac output). The data were compared using a paired two-tailed Students t-test, and also analyzed using a linear mixed model to handle dependencies introduced by repeated measurements within each subject. The significance level was p ≤ 0.05. The effects of hypothermia and beta blockade were distinct and additive. Hypothermia reduced myocardial motion velocities and increased diastolic filling restrictions, but end-systolic wall thickness increased, and stroke volume and dP/dt max (pumping function) were maintained. In contrast, esmolol predominantly affected systolic pumping function, by a negative inotropic effect. In combination, hypothermia and esmolol reduced myocardial velocities in systole and diastole by ∼40%, compared with normothermia without esmolol, inducing in combination both systolic and diastolic LV function impairment. The cardiac dysfunction deteriorated at increased HRs during hypothermia. Beta 1 -adrenergic receptor blockade (esmolol) exacerbates the negative effects of hypothermia on active myocardial contraction and relaxation. The combination of hypothermia with beta-blockade induces both systolic and diastolic LV function impairment.

Objectives: Myocardial dysfunction may occur during weaning from cardiopulmonary bypass (CPB). Epicardial accelerometers have been shown to be useful in continuous monitoring of myocardial ischaemia during beating-heart surgery. We aimed to investigate whether an accelerometer can detect myocardial dysfunction during weaning from CPB., Methods: In 23 patients undergoing isolated aortic valve replacement (AVR), a three-axis accelerometer was attached to the left ventricle and 3D velocity was calculated from the signals. Peak early systolic velocity (Vsys) and velocity at aortic valve closure (Vavc) were measured. Measurements were undertaken during normothermia with 50% bypass flow and atrial pacing (90 beats/min) before aortic cross-clamping and after cross-clamp removal. Myocardial dysfunction was defined as Vsys < Vavc, and patients were classified as having normal function or dysfunction. Left ventricular (LV) stroke work via pulmonary artery catheter and systolic velocity by echocardiography were compared between groups and used as reference methods., Results: The accelerometer identified a substantial proportion of patients with myocardial dysfunction during weaning from CPB, 56% of patients compared with 11% before aortic cross-clamping. Patients classified with normal myocardial function during weaning significantly improved their LV stroke work and systolic velocity by echocardiography in response to AVR, whereas those classified with dysfunction did not. Accelerometer classification of normal function predicted an increase in echocardiographic systolic velocity [r = 0.63, regression coefficient 1.98, 95% CI (0.57, 3.40) (P < 0.01)]., Conclusions: The accelerometer detected myocardial dysfunction during weaning from CPB in accordance with measures obtained by echocardiography and pulmonary artery catheter., Clinical Trials Identifier: NCT01926067. https://clinicaltrials.gov/., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Extracorporeal cardiopulmonary resuscitation (E-CPR) is increasingly used as a rescue method in the management of cardiac arrest and provides the opportunity to rapidly induce therapeutic hypothermia. The survival after a cardiac arrest is related to post-arrest cardiac function, and the application of therapeutic hypothermia post-arrest is hypothesized to improve cardiac outcome. The present animal study compares normothermic and hypothermic E-CPR considering resuscitation success, post-arrest left ventricular function and magnitude of myocardial injury., Methods: After a 15-min untreated ventricular fibrillation, the pigs (n = 20) were randomized to either normothermic (38 °C) or hypothermic (32-33 °C) E-CPR. Defibrillation terminated ventricular fibrillation after 5 min of E-CPR, and extracorporeal support continued for 2 h, followed by warming, weaning and a stabilization period. Magnetic resonance imaging and left ventricle pressure measurements were used to assess left ventricular function pre-arrest and 5 h post-arrest. Myocardial injury was estimated by serum concentrations of cardiac TroponinT and Aspartate transaminase (ASAT)., Results: E-CPR resuscitated all animals and the hypothermic strategy induced therapeutic hypothermia within minutes without impairment of the resuscitation success rate. All animals suffered a severe global systolic left ventricular dysfunction post-arrest with 50-70% reductions in stroke volume, ejection fraction, wall thickening, strain and mitral annular plane systolic excursion. Serum concentrations of cardiac TroponinT and ASAT increased considerably post-arrest. No significant differences were found between the two groups., Conclusions: Two-hour therapeutic hypothermia during E-CPR offers an equal resuscitation success rate, but does not preserve the post-arrest cardiac function nor reduce the magnitude of myocardial injury, compared to normothermic E-CPR. Trial registration FOTS 4611/13 registered 25 October 2012.

Background: Veno-arterial extracorporeal membrane oxygenation (ECMO-CPR) is a life-saving rescue for selected patients when standard cardiopulmonary resuscitation fails. The use is increasing although the treatment modality is not fully established. Resuscitated patients typically develop a detrimental early post-arrest cardiac dysfunction that also deserves main emphasis. The present study investigates an ECMO-CPR strategy in pigs and assesses early post-arrest left ventricular function in detail. We hypothesised that a significant dysfunction could be demonstrated with this model using magnetic resonance imaging (MRI), not previously used early post-arrest., Methods: In eight anaesthetised pigs, a 15-min ventricular fibrillation was resuscitated by an ECMO-CPR strategy of 150-min veno-arterial ECMO aiming at high blood flow rate and pharmacologically sustained aortic blood pressure and pulse pressure of 50 and 15 mmHg, respectively. Pre-arrest cardiac MRI and haemodynamic measurements of left ventricular function were compared to measurements performed 300-min post-arrest., Results: All animals were successfully resuscitated, weaned from the ECMO circuit, and haemodynamically stabilised post-arrest. Cardiac output was maintained by an increased heart rate post-arrest, but left ventricular ejection fraction and stroke volume were decreased by approximately 50 %. Systolic circumferential strain and mitral annular plane systolic excursion as well as the left ventricular wall thickening were reduced by approximately 50-70 % post-arrest. The diastolic function variables measured were unchanged., Conclusions: The present animal study demonstrates a successful ECMO-CPR strategy resuscitating long-lasting cardiac arrest with adequate post-arrest haemodynamic stability. The associated severe systolic left ventricular dysfunction could be charted in detail by MRI, a valuable tool for future cardiac outcome assessments in resuscitation research., Trial Registration: Institutional protocol number: FOTS 4611/13 .

Background: Systolic left ventricular function during therapeutic hypothermia is found both to improve and to decline. We hypothesized that this discrepancy would depend on the heart rate and the variables used to assess systolic function., Methods: In 16 pigs, cardiac performance was assessed by measurements of invasive pressures and thermodilution cardiac output and with 2D strain echocardiography. Left ventricle (LV) volumes, ejection fraction (EF), transmitral flow, and circumferential and longitudinal systolic strain were measured. Miniaturized ultrasonic transducers were attached to the epicardium of the LV to obtain M-mode images, systolic thickening, and diastolic thinning velocities and to determine LV pressure-wall dimension relationships. Preload recruitable stroke work (PRSW) was calculated. Measurements were performed at 38 and 33°C at spontaneous and paced heart rates, successively increased in steps of 20 up to the toleration limit. Effects of temperature and heart rate were compared in a mixed model analysis., Results: Hypothermia reduced heart rate from 87 ± 10 (SD) to 76 ± 11 beats/min without any changes in LV stroke volume, end-diastolic volume, EF, strain values, or PRSW. Systolic wall thickening velocity (S') and early diastolic wall thinning velocity decreased by approximately 30%, making systolic duration longer through a prolonged and slow contraction and changing the diastolic filling pattern from predominantly early towards late. Pacing reduced diastolic duration much more during hypo- than during normothermia, and combined with slow myocardial relaxation, incomplete relaxation occurred with all pacing rates. Pacing did not affect S' or PRSW at physiological heart rates, but stroke volume, end-diastolic volume, and strain were reduced as a consequence of reduced diastolic filling and much more accentuated during hypothermia. At the ultimate tolerable heart rate during hypothermia, S' decreased, probably as a consequence of myocardial hypoperfusion due to sustained ventricular contraction throughout a very short diastole., Conclusions: Systolic function was maintained at physiological heart rates during therapeutic hypothermia. Reduced tolerance to increases in heart rate was caused by lack of ventricular filling due to diastolic dysfunction and shorter diastolic duration.

Objectives: Cardiac wall motions reflect systolic and diastolic function. We have previously demonstrated the ability of a miniaturized three-axis (3D) accelerometer to monitor left ventricular function in experimental models and in patients. The main aim of this study was to investigate the clinical utility of the method for monitoring the left and right ventricular function during changes in global and regional cardiac function in a postoperative closed-chest situation., Methods: In 13 closed-chest pigs, miniaturized 3D accelerometers were placed on the left ventricle in the apical and basal regions and in the basal region of the right ventricle. An epicardial 3D motion vector was calculated from the acceleration signals in each heart region. Peak systolic velocity along this 3D vector (3D V(sys)) was compared with the positive time derivative of the left and right ventricular pressure and with cardiac index during changes in global LV function (unloading, fluid loading, esmolol, dobutamine) and with ultrasound during regional left ventricular dysfunction (3-min occlusion of the left anterior descending coronary artery)., Results: Significant and typical changes in accelerometer 3D V(sys) were seen in all heart regions during changes in global cardiac function. 3D V(sys) reflected the left and right ventricular contractility via significant correlations with the positive time derivative of the left and right ventricular pressure, r = 0.86 and r = 0.72, and with cardiac index r = 0.82 and r = 0.73 (all P < 0.001), respectively. The miniaturized accelerometers also detected regional dysfunction, but showed reduced ability to localize ischaemia as the 3D V(sys) in all heart regions showed similar reductions during coronary artery occlusion., Conclusions: Miniaturized 3D accelerometers placed on the heart can assess global and regional function in a closed-chest model. The technique may be used for continuous postoperative monitoring after cardiac surgery., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Acute coronary artery occlusion (ACO) occurs in ∼30% of patients with non-ST-segment elevation-acute coronary syndrome (NSTE-ACS). We investigated the ability of a regional non-invasive myocardial work index (MWI) to identify ACO., Methods and Results: Segmental strain analysis was performed before coronary angiography in 126 patients with NSTE-ACS. Left ventricular (LV) pressure was estimated non-invasively using a standard waveform fitted to valvular events and scaled to systolic blood pressure. MWI was calculated as the area of the LV pressure-strain loop. Empirical cut-off values were set to identify segmental systolic dysfunction for MWI (<1700 mmHg %) and strain (more than -14%). The number of dysfunctional segments was used in ROC analysis to identify ACO. The presence of ≥4 adjacent dysfunctional segments assessed by MWI was significantly better than both global strain and ejection fraction at detecting the occurrence of ACO (P < 0.05). Regional MWI had a higher sensitivity (81 vs. 78%) and especially specificity (82 vs. 65%) compared with regional strain. Logistic regression demonstrated that elevated systolic blood pressure significantly decreased the probability of actual ACO in a patient with an area of impaired regional strain., Conclusion: The presence of a region of reduced MWI in patients with NSTE-ACS identified patients with ACO and was superior to all other parameters. The regional MWI was able to account for the influence of systolic blood pressure on regional contraction. We therefore propose that MWI may serve as an important clinical tool for selecting patients in need of prompt invasive treatment., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponins (cTns) measured with sensitive assays provide strong prognostic information in patients with stable coronary artery disease. However, the relationship between these biomarkers and myocardial contractile function, as well as infarct size, in this patient group, remains to be defined. The study population consisted of 160 patients referred to a follow-up echocardiography scheduled 1 year after coronary revascularization. Concentrations of NT-proBNP, high-sensitive cTnT (hs-cTnT) and sensitive cTnI assays were assessed. Left ventricular function was measured as global peak systolic longitudinal strain by speckle tracking echocardiography and infarct size was assessed by late-enhancement MRI. NT-proBNP and sensitive cTnI levels were significantly associated with left ventricular function by peak systolic strain (R-values 0.243 and 0.228, p = 0.002 and 0.004) as well as infarct size (R-values 0.343 and 0.366, p = 0.014 and p = 0.008). In contrast, hs-cTnT did not correlate with left ventricular function (R = 0.095, p = 0.231) and only marginally with infarct size (R = 0.237, p = 0.094). NT-proBNP and sensitive cTnI levels correlate with left ventricular function and infarct size in patients with stable coronary artery disease after revascularization. As opposed to hs-cTnT, NT-proBNP and cTnI seem to be indicators of incipient myocardial dysfunction and the extent of myocardial necrosis.

Background: Sensitive methods for the early detection of myocardial dysfunction are still needed, as ischemia is a leading cause of decreased ventricular function during and after heart surgery. The aim of this study was to test the hypothesis that low-grade ischemia could be detected quantitatively by a miniaturized epicardial ultrasound transducer (Ø = 3 mm), allowing continuous monitoring., Methods: In 10 pigs, transducers were positioned in the left anterior descending and circumflex coronary artery areas. Left ventricular pressure was obtained by a micromanometer. The left internal mammary artery was grafted to the left anterior descending coronary artery, which was occluded proximal to the anastomosis. Left internal mammary artery flow was stepwise reduced by 25%, 50%, and 75% for 18 min each. From the transducers, M-mode traces were obtained, allowing continuous tissue velocity traces and displacement measurements. Regional work was assessed as left ventricular pressure-displacement loop area. Tissue lactate measured from intramyocardial microdialysis was used as reference method to detect ischemia., Results: All steps of coronary flow reduction demonstrated reduced peak systolic velocity (P < .05) and regional work (P < .01).The decreases in peak systolic velocity and regional work were closely related to the degree of ischemia, demonstrated by their correlations with lactate (R = -0.74, P < .01, and R = -0.64, P < .01, respectively). The circumflex coronary artery area was not affected by any of the interventions., Conclusions: The epicardially attached miniaturized ultrasound transducer allowed the precise detection of different levels of coronary flow reduction. The results also showed a quantitative and linear relationship among coronary flow, ischemia, and myocardial function. Thus, the ultrasound transducer has the potential to improve the monitoring of myocardial ischemia and to detect graft failure during and after heart surgery., (Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Deformation imaging by tissue Doppler imaging (TDI) and speckle-tracking echocardiography (STE) are emerging clinical methods. TDI- and STE-derived parameters, such as myocardial strain and strain rate, as well as torsion and twist, provide detailed information about myocardial function and are associated with cardiovascular morbidity and mortality. However, only echocardiographic laboratories with experience in deformation imaging have included these methods in daily clinical practice. In this review, we describe myocardial deformation parameters and relevant echocardiographic methods and address recent developments in the clinical application of deformation imaging.

Background: Coronary stenosis after coronary artery bypass grafting (CABG) may lead to myocardial ischaemia and is clinically difficult to diagnose. In a CABG model, we aimed at defining variables that detect hypoperfusion in real-time and correlate with impaired regional ventricular function by monitoring myocardial tissue metabolism., Methods: Off-pump CABG was performed in 10 pigs. Graft blood flow was reduced in 18 min intervals to 75, 50, and 25% of baseline flow with reperfusion between each flow reduction. Myocardial tissue Pco2 (Pt(CO2)), Po2, pH, glucose, lactate, and glycerol from the graft supplied region and a control region were obtained. Regional cardiac function was assessed as radial strain., Results: In comparison with baseline, myocardial pH decreased during 75, 50, and 25% flow reduction (-0.15; -0.22; -0.37, respectively, all P<0.05) whereas Pt(CO2) increased (+4.6 kPa; +7.8 kPa; +12.9 kPa, respectively, all P<0.05). pH and Pt(CO2) returned to baseline upon reperfusion. Lactate and glycerol increased flow-dependently, while glucose decreased. Regional ventricular contractile function declined significantly. All measured variables remained normal in the control region. Pt(CO2) correlated strongly with tissue lactate, pH, and contractile function (R=0.86, R=-0.91, R=-0.70, respectively, all P<0.001). New conductometric Pt(CO2) sensors were in agreement with established fibre-optic probes. Cardiac output was not altered., Conclusions: Myocardial pH and Pt(CO2) monitoring can quantify the degree of regional tissue hypoperfusion in real-time and correlated well with cellular metabolism and contractile function, whereas cardiac output did not. New robust conductometric Pt(CO2) sensors have the potential to serve as a clinical cardiac monitoring tool during surgery and postoperatively., (© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Miniaturized accelerometers attached to the epicardium have been shown to provide useful clinical information. However, attachment of such a sensor has been cumbersome due to requirement of aligning the three sensor axes with the cardiac coordinate axes, limiting clinical utility. We propose a new method to process the three-dimensional (3D) accelerometer signal that does not require such alignment., Methods: In 20 open-chest pigs, miniaturized 3D accelerometers were fixated on the epicardium in apical and basal regions of left ventricle. Accelerations in circumferential, longitudinal and radial directions were measured and a 3D velocity vector was calculated. Systolic velocity along the 3D vector and velocities in circumferential, longitudinal and radial directions were compared with the positive time derivate of left ventricular pressure during changes in global left ventricular function (epinephrine, esmolol and fluid loading) and to strain echocardiography during left anterior descending artery occlusion., Results: Distinct changes in all accelerometer velocities were observed during alterations on global and regional left ventricular function. Accelerometer 3D and circumferential systolic velocities in apical region best reflected left ventricular function during interventions on global function by correlating significantly with the positive time derivate of left ventricular pressure, r = 0.83 and r = 0.86, respectively. The accelerometer 3D velocity also demonstrated equally good capacity as circumferential velocity in discriminating coronary occlusion from interventions on global left ventricular function with sensitivity/specificity of 0.90/0.83 and 0.90/0.86, respectively., Conclusions: Accelerometer 3D systolic velocity showed very good correspondence to changes in global and regional left ventricular function. Our results demonstrate that by the use of the accelerometer 3D motion vector, no alignment of the sensor with the cardiac coordinate axes was required. This increases potential clinical applicability of the accelerometer in cardiac surgery., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: This article presents an update of the results achieved by modern surgery in congenital heart defects (CHDs) over the past 40 years regarding survival and the need for reoperations, especially focusing on the results from the past 2 decades., Methods and Results: From 1971 to 2011, all 7038 patients <16 years of age undergoing surgical treatment for CHD at Rikshospitalet (Oslo, Norway) were enrolled prospectively. CHD diagnosis, date, and type of all operations were recorded, as was all-cause mortality until December 31, 2012. CHDs were classified as simple (3751/7038=53.2%), complex (2918/7038=41.5%), or miscellaneous (369/7037=5.2%). Parallel to a marked, sequential increase in operations for complex defects, median age at first operation decreased from 1.6 years in 1971 to 1979 to 0.19 years in 2000 to 2011. In total, 1033 died before January 1, 2013. Cumulative survival until 16 years of age in complex CHD operated on in 1971 to 1989 versus 1990 to 2011 was 62.4% versus 86.9% (P<0.0001). In the comparison of patients operated on in 2000 to 2004 versus 2005 to 2011, 1-year survival was 90.7% versus 96.5% (P=0.003), and 5-year cumulative survival was 88.8% versus 95.0% (P=0.0003). In simple versus complex defects, 434 (11.6%) versus 985 (33.8%) patients needed at least 1 reoperation before 16 years of age. In complex defects, 5-year cumulative freedom of reoperation among patients operated on in 1990 to 1999 versus 2000 to 2011 was 66% versus 73% (P=0.0001)., Conclusions: Highly significant, sequential improvements in survival and reductions in reoperations after CHD surgery were seen. A future challenge is to find methods to reduce the need for reoperations and further reduce long-term mortality., (© 2014 American Heart Association, Inc.)

Aims: Ischaemic myocardial segments tend to stretch as the intraventricular pressure rises steeply during the isovolemic contraction phase, before they contract during ejection. We hypothesized that the time they remain stretched, called duration of early systolic lengthening (DESL), correlates with final infarct size as defined by contrast enhanced magnetic resonance imaging (CE-MRI). We also assessed whether DESL could identify patients with acute coronary occlusion, and compared it with traditional measures for myocardial function., Methods and Results: In this retrospective study, 150 consecutive patients with Non-ST-elevation acute coronary syndrome (NSTE-ACS) referred for coronary angiography were included. Speckle tracking echocardiography was performed prior to angiography to determine DESL. The final infarct size was quantified at follow-up 9 ± 3 months after initial admission in 61 patients and echocardiography performed in 143 patients. DESL showed good correlation with the final infarct size (r = 0.67, P < 0.001). Thirteen patients had no visible sign of infarct on CE-MRI (minimal myocardial damage), and DESL was significantly shorter in these patients than in patients with signs of infarct (27 ± 19 vs. 84 ± 41 ms, P < 0.001). Compared with left ventricular ejection fraction, wall motion score index, and global longitudinal strain, DESL showed the best accuracy in detecting patients with minimal myocardial damage, with an area under the receiver operating characteristic curve of 0.92 (0.82 to 0.99, P < 0.001). DESL was more prolonged in patients with coronary occlusions, compared with those without occlusions (86 ± 45 vs. 63 ± 31 ms, P < 0.01). DESL was significantly shorter at follow-up, compared with baseline (P = 0.04)., Conclusions: DESL could identify patients with minimal myocardial damage, differentiate between occlusion and non-occlusion, and may be helpful in the risk stratification of patients with NSTE-ACS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Cardiac resynchronization therapy (CRT) has been proposed in heart failure patients with narrow QRS, but the mechanism of a potential beneficial effect is unknown. The present study investigated the hypothesis that left ventricular (LV) pacing increases LV end-diastolic volume (LVEDV) by allowing the LV to start filling before the right ventricle (RV) during narrow QRS in an experimental model. LV and biventricular pacing were studied in six anesthetized dogs before and after the induction of LV failure. Function was evaluated by pressures and dimensions, and dyssynchrony was evaluated by electromyograms and deformation. In the nonfailing heart, LV pacing gave the LV a head start in filling relative to the RV (P < 0.05) and increased LVEDV (P < 0.05). The response was similar during LV failure when RV diastolic pressure was elevated. The pacing-induced increase in LVEDV was attributed to a rightward shift of the septum (P < 0.01) due to an increased left-to-right transseptal pressure gradient (P < 0.05). LV pacing, however, also induced dyssynchrony (P < 0.05) and therefore reduced LV stroke work (P < 0.05) during baseline, and similar results were seen in failing hearts. Biventricular pacing did not change LVEDV, but systolic function was impaired. This effect was less marked than with LV pacing. In conclusion, pacing of the LV lateral wall increased LVEDV by displacing the septum rightward, suggesting a mechanism for a favorable effect of CRT in narrow QRS. The pacing, however, induced dyssynchrony and therefore reduced LV systolic function. These observations suggest that detrimental effects should be considered when applying CRT in patients with narrow QRS., (Copyright © 2014 the American Physiological Society.)

Objectives: Cardiovascular failure is an important feature of severe sepsis and mortality in sepsis. The aim of our study was to explore myocardial dysfunction in severe sepsis., Design: Prospective experimental study., Setting: Operating room at Intervention Centre, Oslo University Hospital., Subjects: Eight Norwegian Landrace pigs., Interventions: The pigs were anesthetized, a medial sternotomy performed and miniature sensors for wall-thickness measurements attached to the epicardium and invasive pressure monitoring established, and an infusion of Escherichia coli started. Hemodynamic response was monitored and myocardial strain assessed by echocardiography., Measurements and Main Results: Left ventricular myocardial function was significantly reduced assessed by longitudinal myocardial strain (-17.2% ± 2.8% to -12.3% ± 3.2%, p = 0.04), despite a reduced afterload as expressed by the left ventricular end-systolic meridional wall stress (35 ± 13 to 18 ± 8 kdyn/cm, p = 0.04). Left ventricular ejection fraction remained unaltered (48% ± 7% to 49% ± 5%, p = 0.4) as did cardiac output (6.3 ± 1.3 to 5.9 ± 3 L/min, p = 0.7). The decline in left ventricular function was further supported by significant reductions in the index of regional work by pressure-wall thickness loop area (121 ± 45 to 73 ± 37 mm × mm Hg, p = 0.005). Left ventricular myocardial wall thickness increased in both end diastole (11.5 ± 2.7 to 13.7 ± 2.4 mm, p = 0.03) and end systole (16.1 ± 2.9 to 18.5 ± 1.8 mm, p = 0.03), implying edema of the left ventricular myocardial wall. Right ventricular myocardial function by strain was reduced (-24.2% ± 4.1% to -16.9% ± 5.7%, p = 0.02). High right ventricular pressures caused septal shift as demonstrated by the end-diastolic transseptal pressure gradient (4.1 ± 3.3 to -2.2 ± 5.8 mm Hg, p = 0.01)., Conclusions: The present study demonstrates myocardial dysfunction in severe sepsis. Strain echocardiography reveals myocardial dysfunction before significant changes in ejection fraction and cardiac output and could prove to be a useful tool in clinical evaluation of septic patients.

Background: Many patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) do not have significant coronary artery disease. The current diagnostic approach of repeated electrocardiography and cardiac biomarker assessment requires observation for >6 to 12 hours. This strategy places a heavy burden on hospital facilities. The objective of this study was to investigate whether myocardial strain assessment by echocardiography could exclude significant coronary artery stenosis in patients presenting with suspected NSTE-ACS., Methods: Sixty-four patients presenting to the emergency department with suspected NSTE-ACS without known coronary artery disease, inconclusive electrocardiographic findings, and normal cardiac biomarkers at arrival were enrolled. Twelve-lead electrocardiography, troponin T assay, and echocardiography were performed at arrival, and all patients underwent coronary angiography. Significant coronary stenosis was defined as >50% luminal narrowing. Global myocardial peak systolic longitudinal strain was measured using speckle-tracking echocardiography. Left ventricular ejection fraction and wall motion score index were calculated., Results: No significant stenosis in any coronary artery was found in 35 patients (55%). Global peak systolic longitudinal strain was superior to conventional echocardiographic parameters in distinguishing patients with and without significant coronary artery stenosis (area under the curve, 0.87). Sensitivity and specificity were calculated as 0.93 and 0.78, respectively, and positive predictive value and negative predictive value as 0.74 and 0.92, respectively. Feasibility of the strain measurements was excellent, with 97% of segments analyzed., Conclusions: Myocardial strain by echocardiography may facilitate the exclusion of significant coronary artery stenosis among patients presenting with suspected NSTE-ACS with inconclusive electrocardiographic findings and normal cardiac biomarkers., (Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Therapeutic hypothermia is used after cardiac arrest. The aim of this study was to investigate the effects of therapeutic hypothermia on left ventricular (LV) function assessed by ultrasonic imaging., Methods: In 10 pigs, LV volumes, ejection fractions, and longitudinal strain were measured using two-dimensional echocardiography. Midwall fractional shortening and end-systolic wall stress were calculated. Wall thickness was continuously measured using an epicardial ultrasonic transducer placed on the LV anterior wall. Wall thickening velocity (S') and pressure-wall thickness loops were used to assess systolic function. Diastolic function was assessed by echocardiographic transmitral flow and mitral annular velocity (e') measurements, calculation of the LV relaxation constant, and determination of LV stiffness and restoring forces using the end-diastolic pressure-wall thickness relation during volume unloading. Early wall thinning velocity (e'wt) and early diastolic wall thinning were calculated. Measurements were done at 38°C and 33°C, at spontaneous heart rate and at atrial pacing at 100 beats/min., Results: End-diastolic volume, stroke volume, midwall fractional shortening, and longitudinal strain remained unchanged during hypothermia, but end-systolic wall stress, S', and pressure-wall thickness loop area decreased. A shift from early to late diastolic LV filling occurred during hypothermia, with concurrent decreases in e', e'wt, and early wall thinning fraction. Relaxation was prolonged, LV stiffness was increased, and restoring force was decreased during hypothermia. Hypothermia induced a decrease in relative diastolic duration at spontaneous heart rate, which was further reduced during pacing. During paced heart rate at 33°C, stroke volume, ejection fraction, and strain were reduced., Conclusions: Hypothermia induced systolic and diastolic dysfunction, with reduced tolerance to increased heart rate. These findings may have implications for patient management during hypothermia., (Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Left ventricular (LV) dyssynchrony reduces myocardial efficiency because work performed by one segment is wasted by stretching other segments. In the present study, we introduce a novel noninvasive clinical method that quantifies wasted energy as the ratio between work consumed during segmental lengthening (wasted work) divided by work during segmental shortening. The wasted work ratio (WWR) principle was studied in 6 anesthetized dogs with left bundle branch block (LBBB) and in 28 patients with cardiomyopathy, including 12 patients with LBBB and 10 patients with cardiac resynchronization therapy. Twenty healthy individuals served as controls. Myocardial strain was measured by speckle tracking echocardiography, and LV pressure (LVP) was measured by micromanometer and a previously validated noninvasive method. Segmental work was calculated by multiplying strain rate and LVP to get instantaneous power, which was integrated to give work as a function of time. A global WWR was also calculated. In dogs, WWR by estimated LVP and strain showed a strong correlation (r = 0.94) and good agreement with WWR by the LV micromanometer and myocardial segment length by sonomicrometry. In patients, noninvasive WWR showed a strong correlation (r = 0.96) and good agreement with WWR using the LV micromanometer. Global WWR was 0.09 ± 0.03 in healthy control subjects, 0.36 ± 0.16 in patients with LBBB, and 0.21 ± 0.09 in cardiomyopathy patients without LBBB. Cardiac resynchronization therapy reduced global WWR from 0.36 ± 0.16 to 0.17 ± 0.07 (P < 0.001). In conclusion, energy loss due to incoordinated contractions can be quantified noninvasively as the LV WWR. This method may be applied to evaluate the mechanical impact of dyssynchrony.

Background: Mitral annular displacement (MAD) is a simple marker of left ventricular (LV) systolic function. The aim of this study was to test the hypothesis that MAD can distinguish patients with non-ST-segment elevation myocardial infarctions (NSTEMIs) from those with significant coronary artery disease without infarctions, identify coronary occlusion, and predict mortality in patients with NSTEMIs. MAD was compared with established indices of LV function., Methods: In this retrospective study, 167 patients with confirmed NSTEMIs were included at two Scandinavian centers. Forty patients with significant coronary artery disease but without myocardial infarctions were included as controls. Doppler tissue imaging was performed at the mitral level of the left ventricle in the three apical planes, and velocities were integrated over time to acquire MAD. LV ejection fraction, global longitudinal strain (GLS), and wall motion score index were assessed according to guidelines., Results: MAD and GLS could accurately distinguish patients with NSTEMIs from controls. During 48.6 ± 12.1 months of follow-up, 22 of 167 died (13%). MAD, LV ejection fraction, and GLS were reduced and wall motion score index was increased among those who died compared with those who survived (P < .001, P < .001, P < .001, and P = .02, respectively). Multivariate Cox proportional-hazards analyses revealed that MAD was an independent predictor of death (hazard ratio, 1.36; 95% confidence interval, 1.07-1.73; P = .01). MAD and GLS were reduced and wall motion score index was increased in patients with coronary artery occlusion compared with those without occlusion (P = .006, P = .001, and P = .02), while LV ejection fraction did not differ (P = .20)., Conclusions: MAD accurately identified patients with NSTEMIs, predicted mortality, and identified coronary occlusion in patients with NSTEMIs., (Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)