Nicolaj Lyhne Christensen

Left Ventricular Diastolic Function Is Associated With Symptom Status in Severe Aortic Valve Stenosis

Background—In aortic valve stenosis (AS), the occurrence of heart failure symptoms does not always correlate with severity of valve stenosis and left ventricular (LV) function. Therefore, we tested the hypothesis that symptomatic patients with AS have impaired diastolic, longitudinal systolic function, and left atrial dilatation compared with asymptomatic patients. Methods and Results—In a retrospective descriptive study, we compared clinical characteristics and echocardiographic parameters in 99 symptomatic and 139 asymptomatic patients with severe AS and LV ejection fraction ≥50%. Independent predictors of symptomatic state were identified using logistic regression analysis. Symptomatic patients were younger (72±10 versus 76±12 years of age; P=0.002), presented less often with atrial fibrillation (13% versus 24%; P=0.05) and chronic obstructive pulmonary disease (2% versus 19%; P<0.001), and had a lower prevalence of hypertension (73% versus 40%; P<0.001). Despite similar AS severity, symptomatic patients had higher LV mass index (120±39 versus 95±25 g/m2; P<0.0001), increased relative wall thickness (0.61±0.15 versus 0.50±0.11; P<0.0001), shorter mitral deceleration time (199±58 versus 268±62 ms; P<0.0001), and increased left atrial volume index (49±18 versus 42±15 mL/m2; P=0.02). When adjusting for age, history of hypertension, atrial fibrillation, and chronic obstructive pulmonary disease in a multivariable logistic regression analysis, LV mass index, relative wall thickness, left atrial volume index, and deceleration time were still associated with the presence of symptoms. Conclusions—The present study demonstrates that symptomatic status in severe AS is associated with impaired diastolic function, LV hypertrophy, concentric remodeling, and left atrial dilatation when corrected for indices of AS severity. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00294775.

Association Between Left Atrial Dilatation and Invasive Hemodynamics at Rest and During Exercise in Asymptomatic Aortic Stenosis

Background—Transition from an asymptomatic to symptomatic state in severe aortic stenosis is often difficult to assess. Identification of a morphological sign of increased hemodynamic load may be important in asymptomatic aortic stenosis to identify patients at risk. Methods and Results—Thirty-nine patients with asymptomatic severe aortic stenosis (aortic valve area <1 cm2, peak jet velocity >3.5 m/s) underwent exercise testing with simultaneous invasive hemodynamic monitoring and Doppler echocardiography. Cardiac index, pulmonary artery pressure, and pulmonary capillary wedge pressure (PCWP) were recorded. Patients were followed up for the composite end point of death, unplanned hospitalization, or aortic valve replacement. Patients were stratified into 2 groups according to left atrial (LA) volume index ≥35 mL/m2. In 25 patients (64%) LA volume index was ≥35 mL/m2. Aortic valve area was similar between groups (0.81±0.15 versus 0.84±0.18 cm2; P=0.58). PCWP was higher at rest and during exercise in patients with LA volume index ≥35 mL/m2 (P<0.01), despite similar cardiac index. At rest, PCWP was <12 mm Hg in 11 patients (44%) with LA dilatation, whereas PCWP was <25 mm Hg in 1 patient (4%) with exercise. LA volume index and E/e′ predicted exercise PCWP>30 mm Hg with areas under the receiver operating curve of 0.75 and 0.84, respectively. During follow-up, 14 cardiac events were recorded. LA volume was associated with a hazard ratio of 1.90 (95% confidence interval, 0.92–4.15). Conclusions—LA size reflects hemodynamic burden in patients with asymptomatic severe aortic stenosis. Quantitative measurements of LA and diastolic function are associated with left ventricular filling pressures with exercise and could be used to identify asymptomatic patients with increased hemodynamic burden. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02395107.

The Stop-Only-While-Shocking algorithm reduces hands-off time by 17% during cardiopulmonary resuscitation - a simulation study.

Introduction Reducing hands-off time during cardiopulmonary resuscitation (CPR) is believed to increase survival after cardiac arrests because of the sustaining of organ perfusion. The aim of our study was to investigate whether charging the defibrillator before rhythm analyses and shock delivery significantly reduced hands-off time compared with the European Resuscitation Council (ERC) 2010 CPR guideline algorithm in full-scale cardiac arrest scenarios. Methods The study was designed as a full-scale cardiac arrest simulation study including administration of drugs. Participants were randomized into using the Stop-Only-While-Shocking (SOWS) algorithm or the ERC2010 algorithm. In SOWS, chest compressions were only interrupted for a post-charging rhythm analysis and immediate shock delivery. A Resusci Anne HLR-D manikin and a LIFEPACK 20 defibrillator were used. The manikin recorded time and chest compressions. Results Sample size was calculated with an &agr; of 0.05 and 80% power showed that we should test four scenarios with each algorithm. Twenty-nine physicians participated in 11 scenarios. Hands-off time was significantly reduced 17% using the SOWS algorithm compared with ERC2010 [22.1% (SD 2.3) hands-off time vs. 26.6% (SD 4.8); P<0.05]. Conclusion In full-scale cardiac arrest simulations, a minor change consisting of charging the defibrillator before rhythm check reduces hands-off time by 17% compared with ERC2010 guidelines.

Postoperative Reverse Remodeling and Symptomatic Improvement in Normal-Flow Low-Gradient Aortic Stenosis After Aortic Valve Replacement

Background— Severe aortic stenosis (AS) most often presents with reduced aortic valve area (<1 cm2), normal stroke volume index (≥35 mL/m2), and either high mean gradient (≥40 mm Hg; normal-flow high-gradient AS) or low mean gradient (normal-flow low-gradient [NFLG] AS). The benefit of aortic valve replacement (AVR) among NFLG patients is controversial. We compared the impact of NFLG condition on preoperative left ventricular (LV) remodeling and myocardial fibrosis and postoperative remodeling and symptomatic benefit. Methods and Results— Eighty-seven consecutive patients with reduced aortic valve area and normal stroke volume index undergoing AVR underwent echocardiography, magnetic resonance imaging, a 6-minute walk test, and measurement of natriuretic peptides before and 1 year after AVR. Myocardial fibrosis was assessed from magnetic resonance imaging. Patients were stratified as NFLG or normal-flow high-gradient. In total, 33 patients (38%) had NFLG. Before AVR, they were characterized by similar symptom burden but less severe AS measured by aortic valve area index (0.50±0.09 versus 0.40±0.08 cm2/m2; P<0.0001), lower LV mass index (74±18 versus 90±26 g/m2; P=0.01), but the same degree of myocardial fibrosis. After AVR, NFLG had a smaller reduction in LV mass index (−3±10 versus −±18 g/m2; P<0.0001) and a smaller reduction in natriuretic peptides. Both groups experienced similar symptomatic improvement. Normal-flow high-gradient condition independently predicted change in LV mass index. Conclusions— Patients with NFLG had less severe AS and LV remodeling than patients with normal-flow high-gradient. Furthermore, NFLG patients experienced less reverse remodeling but the same symptomatic benefit. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02316587.

Hemodynamic Characteristics in Significant Symptomatic and Asymptomatic Primary Mitral Valve Regurgitation at Rest and During Exercise

Background— In severe asymptomatic primary mitral valve regurgitation without risk factors, surgery strategy is controversial. We sought to clarify whether being symptomatic corresponds to the hemodynamic burden and reduced exercise capacity. A better understanding of this may contribute to optimize timing of surgery. Methods and Results— Subjects with asymptomatic (New York Heart Association functional class I, n=29) or symptomatic (New York Heart Association functional class II and III, n=28) significant primary mitral valve regurgitation (effective regurgitant orifice, ≥0.30 cm2; left ventricular ejection fraction, >60%) were included. Right heart catheterization during rest and exercise, echocardiography, magnetic resonance imaging, and peak oxygen consumption test was performed. Symptomatic subjects had significantly higher pulmonary capillary wedge pressure at rest (14±4 versus 11±3 mm Hg; P=0.003) and at maximal exercise (30±6 versus 25±7 mm Hg; P=0.02) and higher mean pulmonary artery pressure (PAP) at rest (22±7 versus 18±4 mm Hg; P=0.005) and maximal exercise (46±8 versus 39±7 mm Hg; P=0.005) than asymptomatic subjects. Among asymptomatic subjects with normal resting value, exercise testing revealed a systolic PAP >60 mm Hg in 34%. Also the reverse response with minimal increase in pulmonary capillary wedge pressure and mean PAP during exercise was seen, especially in asymptomatic subjects. Among symptomatic subjects, we found a significant inverse correlation between resting mean PAP and left ventricular ejection fraction (r=−0.52; P=0.02) and right ventricular ejection fraction (r=−0.67; P<0.01). Peak oxygen consumption was equal and normal in both groups and correlated with left ventricular stroke volume but not with pulmonary capillary wedge pressure. Conclusions— Symptoms in patients with severe mitral valve regurgitation relate to congestion (pulmonary capillary wedge pressure and PAP), but not to peak oxygen consumption, which is determined by forward left ventricular stroke volume. Exercise testing reveals a higher mitral valve regurgitation burden in apparently asymptomatic patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02961647.

Exercise Hemodynamics After Aortic Valve Replacement for Severe Aortic Stenosis

Background: Severe aortic stenosis (AS) is often accompanied by diastolic dysfunction. After aortic valve replacement (AVR), the left ventricle often undergoes considerable reverse remodeling. Despite this, diastolic dysfunction may persist after AVR. The aims of this study were to determine the incidence of elevated left ventricular (LV) filling pressure at rest and during exercise among patients with severe AS after AVR and to describe factors related to elevated LV filling pressure, especially its association with LV and left atrial remodeling and myocardial fibrosis. Methods: Thirty‐seven patients undergoing AVR were included. Echocardiography, cardiac computed tomography, and magnetic resonance imaging were performed before AVR. An LV biopsy sample was obtained during AVR and analyzed for collagen fraction. One year after AVR, right heart catheterization with exercise was performed. A mean pulmonary capillary wedge pressure (PCWP) ≥ 28 mm Hg during exercise was considered elevated. Results: Twelve patients (32%) had elevated exercise PCWP 1 year after AVR. Exercise PCWP was highest among patients undergoing concomitant coronary artery bypass graft surgery (30 ± 7 vs 25 ± 6 mm Hg, P = .04) and among patients with preoperative stroke volume index < 35 mL/m2 (28 ± 8 vs 23 ± 4 mm Hg, P < .05). Baseline LV ejection fraction was lower among patients with elevated PCWP (56 ± 8% vs 64 ± 8%, P = .01), and coronary calcium score was significantly higher (median 870 AU [interquartile range, 454–2,491 AU] vs 179 AU [interquartile range, 63–513 AU], P = .02). Conversely, exercise PCWP was not related to the presence of high LV wall mass or to the severity of AS. Among patients undergoing isolated AVR, there was a correlation between LV interstitial volume fraction and PCWP (r = 0.57, P = .01) and mean pulmonary artery pressure (r = 0.51, P = .03) during exercise. Conclusions: Elevated filling pressure during exercise was seen in one third of patients after AVR in this population and was seen primarily among patients with coexisting ischemic heart disease or diffuse myocardial fibrosis but was unrelated to preoperative severity of AS and LV remodeling. Highlights:Exercise hemodymics were evaluated in patients with severe symptomatic AS after AVR.One‐third of the patients had elevated PCWP during exercise one year after AVR.High PCWP was associated with diffuse myocardial fibrosis and ischemic heart disease.

Layer-specific deformation analysis in severe aortic valve stenosis, primary mitral valve regurgitation, and healthy individuals validated against invasive hemodynamic measurements of heart function

Speckle tracking echocardiography is considered valuable in assessing left ventricular (LV) function. The method has been refined to assess deformation in different myocardial layers, but the effect of volume vs pressure overload on this pattern is unknown. The aim was to test whether layer‐specific myocardial strain (LSS) obtained by speckle tracking echocardiography exhibits different patterns in conditions with different loading conditions.

Relation of Left Atrial Size, Cardiac Morphology, and Clinical Outcome in Asymptomatic Aortic Stenosis

Left atrial (LA) dilation in asymptomatic severe aortic stenosis (AS) may be an indicator of advanced disease. We aimed to investigate the association between LA volume index and left ventricular (LV) morphology assessed with cardiac magnetic resonance imaging (cMRI), and to assess the association with cardiac events. Ninety-two asymptomatic patients with aortic valve area <1 cm2, aortic peak jet velocity >3.5 m/s, and ejection fraction ≥50% were prospectively enrolled and divided according to echocardiographic-derived LA volume index  <35 ml/m2. Patients underwent echocardiography, cMRI, exercise testing, and were followed for the composite end point of death, readmission, or aortic valve replacement. Aortic valve area index was similar (0.45 ± 0.08 cm2/m2 vs 0.45 ± 0.09 cm2/m2, p = 0.85) in patients with a dilated and normal LA. On cMRI patients with dilated LA were characterized by higher LV mass index (73 ± 17 g/m2 vs 66 ± 16 g/m2, p = 0.03), increased right ventricle (70 ± 14 ml/m2 vs 63 ± 12 ml/m2, p = 0.01) and LV end-diastolic volume index (84 ± 18 ml/m2 vs 77 ± 16 ml/m2, p = 0.05), and higher brain natriuretic peptide. Late enhancement pattern was similar. During follow-up 20 events were recorded in patients with LA dilation compared with 8 in patients with normal LA (adjusted hazard ratio 2.77, 95% confidence interval 1.19 to 6.46, p = 0.02); also B-type natriuretic peptide  >125 pg/ml was associated with adverse outcome (adjusted hazard ratio 3.63, 95% confidence interval interval 1.28 to 10.32, p = 0.02). LA dilation is associated with LV remodeling and provides prognostic information in severe asymptomatic AS.

Sudden cardiac death in asymptomatic aortic stenosis: is the valve to blame?

An active 68-year-old man with asymptomatic severe aortic stenosis and normal functional capacity on a conventional bicycle exercise test underwent a haemodynamic stress test with simultaneous invasive haemodynamic monitoring and echocardiography during supine bicycle testing as part of a research project. With exercise, the patient developed pulmonary venous hypertension and mild regional wall motion abnormalities on echocardiography. The patient terminated the test due to exhaustion. In the recovery period, he developed sustained ventricular tachycardia and became unconscious. No symptoms were present during exercise or prior to cardiac arrest. The following coronary angiogram revealed significant 2-vessel disease, and the patient subsequently underwent successful aortic valve replacement and coronary-artery bypass graft surgery.

IMPORTANCE OF AORTIC VALVE REPLACEMENT ON STROKE VOLUME INDEX IN LOW FLOW SEVERE AORTIC VALVE STENOSIS

A subgroup of patients with severe aortic stenosis (AS), have reduced stroke volume index (SVi) despite preserved ejection fraction. It is uncertain if SVi improves after aortic valve replacement (AVR). The purpose of this study was to evaluate the importance of AVR on SVi in patients with severe AS