Sex-and age-related variations in myocardial tissue composition of the healthy heart: A native T1 mapping cohort study.

AIMS: Cardiovascular diseases manifest differently in males and females, potentially influenced by inherent sex- and age-related differences in myocardial tissue composition. Such inherent differences are not well-established in the literature. With this study using cardiac magnetic resonance (CMR) native T1 mapping, we aim to determine the effect of sex and age on myocardial tissue composition in healthy individuals. METHODS AND RESULTS: CMR native T1 mapping was performed in 276 healthy individuals (55% male, age 8---84 years) on a 1.5 Tesla scanner using a MOLLI 5(3)3 acquisition scheme. Additionally, 30 healthy participants (47% male, age 24-68 years) underwent a 1-year follow-up CMR to assess the longitudinal changes of native T1. Mean native T1 values were 1000±22 ms in males and 1022±23 ms in females (mean difference [MD]=22 ms, 95% CI [17, 27]). Female sex was associated with higher native T1 in multivariable linear regression adjusting for age, heart rate, left ventricular mass index, and blood T1 (ß=10 ms, 95% CI [3.4, 15.8]). There was no significant interaction between sex and age (p=0.27). Further, age was not associated with native T1 (ß=0.1 ms, 95% CI [-0.02, 0.2]), and native T1 did not change during a 1-year period (MD -4 ms, 95% CI [-11, 3]). CONCLUSION: Female sex was associated with higher native T1; however, there was no association between age and native T1. Additionally, there was no evidence of an interaction between sex and age. Our findings indicate intrinsic sex-based disparities in myocardial tissue composition.

Myocardial fibrosis associates with lupus anticoagulant in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that carries increased risk of cardiovascular disease; however, the underlying pathophysiological mechanisms remain poorly understood. We aimed to investigate the prevalence and degree of myocardial fibrosis in SLE patients and associated disease characteristics. Forty-nine SLE patients (89% female, mean age 52 ± 13 years, median disease duration 19 (11-25) years) and 79 sex-and age-matched healthy controls were included. CMR with T1 mapping was performed on SLE patients and healthy controls. Fifty-one SLE patients received gadolinium contrast for the evaluation of late gadolinium enhancement (LGE) and extra cellular volume (ECV). Multiple linear regression analyses were performed to investigate the association between markers of myocardial fibrosis on CMR (LGE, T1, ECV) and SLE-related variables [clinical disease activity, lupus nephritis, chronic kidney disease, anti-cardiolipin and/or anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant (LAC)] with adjustment for traditional risk factors. T1 values were elevated in SLE patients compared to healthy controls (1031 ± 36 ms vs. 1019 ± 25 ms, p = 0.01). LGE was present in 20% of SLE patients who received gadolinium contrast. On multivariable analysis, LAC was associated with LGE in SLE patients (ß = 3.87, p = 0.02). Neither T1 nor ECV associated with SLE disease characteristics; however, there was a trend towards an association between LAC and T1 (ß = 16.9, p = 0.08). SLE patients displayed signs of myocardial fibrosis on CMR that were associated with the presence of LAC. These findings support the pathophysiological understanding of LAC as a mediator of microvascular and subsequent myocardial dysfunction.

The COVID-19 in athletes (COVA) study: a national study on cardio-pulmonary involvement of SARS-CoV-2 infection among elite athletes.

Background: COVID-19 can cause cardiopulmonary involvement. Physical activity and cardiac complications can worsen prognosis, while pulmonary complications can reduce performance. Aims: To determine the prevalence and clinical implications of SARS-CoV-2 cardiopulmonary involvement in elite athletes. Methods: An observational study between 1 July 2020 and 30 June 2021 with the assessment of coronary biomarkers, electrocardiogram, echocardiography, Holter-monitoring, spirometry, and chest X-ray in Danish elite athletes showed that PCR-tested positive for SARS-CoV-2. The cohort consisted of male football players screened weekly (cohort I) and elite athletes on an international level only tested if they had symptoms, were near-contact, or participated in international competitions (cohort II). All athletes were categorized into two groups based on symptoms and duration of COVID-19: Group 1 had no cardiopulmonary symptoms and duration ≤7 days, and; Group 2 had cardiopulmonary symptoms or disease duration >7 days. Results: In total 121 athletes who tested positive for SARS-CoV-2 were investigated. Cardiac involvement was identified in 2/121 (2%) and pulmonary involvement in 15/121 (12%) participants. In group 1, 87 (72%), no athletes presented with signs of cardiac involvement, and 8 (7%) were diagnosed with radiological COVID-19-related findings or obstructive lung function. In group 2, 34 (28%), two had myocarditis (6%), and 8 (24%) were diagnosed with radiological COVID-19-related findings or obstructive lung function. Conclusions: These clinically-driven data show no signs of cardiac involvement among athletes who tested positive for SARS-CoV-2 infection without cardiopulmonary symptoms and duration <7 days. Athletes with cardiopulmonary symptoms or prolonged duration of COVID-19 display, exercise-limiting cardiopulmonary involvement.

Left ventricular size and function in patients with systemic lupus erythematosus associate with lupus anticoagulant: An echocardiographic follow-up study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with increased risk of cardiac dysfunction. The pathophysiological mechanisms are poorly understood, and prognostic markers are warranted. PURPOSE: We aimed to identify SLE-characteristics associated with measures of cardiac size and function during a five-year follow-up. METHODS: We included 108 patients with SLE: 90% females, mean age 46 ± 13 years, median disease duration 14 (range 7-21) years. We performed blood sampling for potential biomarkers as well as a standard echocardiography at baseline and at a 5-year follow-up. To investigate associations with baseline and prospective 5-year changes in echocardiographic parameters, we performed multivariate regression analyses of SLE-related baseline variables (clinical disease activity, lupus nephritis, chronic kidney disease, anti-cardiolipin and/or anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant (LAC)) and adjusted for traditional risk factors. RESULTS: During follow-up, diastolic function regressed in two out of five echocardiographic measures (E/A ratio 1.4 ± 0.5 vs. 1.3 ± 0.5, p = 0.002; tricuspid regurgitation peak velocity 2.0 ± 0.6 vs. 2.2 ± 0.4 mmHg, p < 0.001). Left ventricular (LV) end-diastolic volume index increased (43.7 ± 13.9 vs. 52.5 ± 15.7 mL/m2, p < 0.001). Left and right ventricular systolic function remained stationary. LAC was associated with inferior diastolic function: lower E/A ratio (p = 0.04) and higher E/e' ratio at baseline (p = 0.04) and increased left ventricular atrial volume index during follow-up (p = 0.01). LAC was further associated with LV dilatation during follow-up (p = 0.01). CONCLUSION: Presence of LAC was associated with measures of diastolic function as well as progressive LV dilatation during the 5-year follow-up. Thus, LAC might be a predictor of cardiac dysfunction in SLE patients. LAC is known to have implications for the microvascular circulation, but the clinical significance of the present findings is yet to be elucidated.

Myositis-specific autoantibodies and QTc changes by ECG in idiopathic inflammatory myopathies.

OBJECTIVES: The aim of this study was to investigate cardiac involvement detected by ECG in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate possible associations between the autoantibody profile and ECG changes in these patients. METHODS: In a Scandinavian cross-sectional study, patients were included from two Danish centres and one Swedish centre. Resting 12-lead ECG was investigated in 261 patients with IIM compared with 102 patients with systemic sclerosis (SSc) and 48 healthy controls (HCs). ECG changes were correlated to clinical manifestations and myositis-specific and myositis-associated autoantibodies (MSAs and MAAs, respectively). RESULTS: Patients with IIM had a longer mean corrected QT (QTc) duration and more frequently presented with prolonged QTc (≥450 ms; P = 0.038) compared with HCs. A longer QTc duration was recorded in SSc compared with IIM [433 ms (s.d. 23) vs 426 (24); P = 0.011], yet there was no significant difference in the fraction with prolonged QTc (SSc: 22%, IIM: 16%; P = 0.19). In multivariable regression analyses, anti-Mi2 (P = 0.01, P = 0.035) and anti-Pl-7 (P = 0.045, P = 0.014) were associated with QTc duration and prolonged QTc in IIM. Elevated CRP was associated with prolonged QTc (P = 0.041). CONCLUSION: The presence of QTc abnormalities was as common in patients with IIM as in patients with SSc, including prolonged QTc seen in almost one-fifth of the patients. Anti-Mi2, anti-Pl-7 and elevated CRP may serve as biomarkers for cardiac disease in IIM, but needs to be confirmed in a larger prospective study.

[Paradox embolism in a patient with pulmonary embolism and unknown patent foramen ovale].

This case report describes a 64-year-old male patient, who presented with sudden onset dyspnoea. A chest CT-angiography revealed the presence of central bilateral pulmonary embolisms (PE), and he was admitted for anticoagulative treatment. Shortly after admission, he developed discomfort and pulselessness in the right leg, and a limb CT-angiography revealed a femoral artery thrombus. PE in conjunction with acute limb ischaemia raised suspicion of a paradoxical mechanism of systemic embolism, which was confirmed by echocardiography with thrombus straddling a patent foramen ovale.

Cardiac arrest in anti-mitochondrial antibody associated inflammatory myopathy.

Insight into predictors of cardiac involvement in inflammatory myopathies is sparse. A negative prognostic role of anti-mitochondrial antibodies (AMA) has been noticed and is supported by the current case. We describe a male patient who at the age 40 suffered a cardiac arrest and over the following months experienced progressive heart failure, arrhythmias and proximal muscle weakness. Clinical, genetic and serologic testing and repeated imaging- and histopathological investigations resulted in a diagnosis of AMA-associated, necrotizing, inflammatory myositis with cardiac involvement. Besides a cardiac resynchronization therapy defibrillator, heart failure and antiarrhythmic drugs the patient received successive immunosuppressants, which improved skeletal muscle strength but not cardiac disease progression. At age 45 he died from end-stage heart failure. Clinicians must be aware of AMA-associated myositis as a cause of unclarified heart disease, even in patients with initially sparse extra-cardiac manifestations. Further knowledge of treatment strategies is highly needed for this disease entity.

Management of Myocarditis in Myositis: Diagnosis and Treatment.

PURPOSE OF REVIEW: To provide a summary of the current knowledge on myocarditis in idiopathic inflammatory myopathies (IIMs). RECENT FINDINGS: There is increasing epidemiological knowledge about heart involvement generally and myocarditis specifically in IIMs. Cardiac magnetic resonance (CMR) plays an important role in this regard. Myocarditis occupies an important place in the spectrum of pathologies that involve the myocardium in patients with IIMs. Nevertheless, its full impact still remains to be elucidated. A larger cooperation between rheumatologists and cardiologists in the clinical, as well as in the research field, is necessary to expand our knowledge in the area.

Association between left ventricular diastolic function and right ventricular function and morphology in asymptomatic aortic stenosis.

BACKGROUND: Aortic stenosis (AS) is a progressive disease in which left ventricular (LV) diastolic dysfunction is common. However, the association between diastolic dysfunction and right ventricular (RV) loading conditions and function has not been investigated in asymptomatic AS patients. METHODS AND FINDINGS: A total of 41 patients underwent right heart catheterization and simultaneous echocardiography at rest and during maximal supine exercise, stratified according to resting diastolic function. Cardiac chamber size and morphology was assessed using cardiac magnetic resonance imaging (cMRI). RV stroke work index, pulmonary artery (PA) compliance, PA elastance, PA pulsatility index, and right atrial pressure (RAP) were calculated at rest and maximal exercise. Ten patients (24%) had normal LV filling pattern, 20 patients (49%) had grade 1, and 11 patients (27%) had grade 2 diastolic dysfunction. Compared to patients with normal diastolic filling pattern, patients with diastolic dysfunction had lower RV end-diastolic volume (66 ± 11 ml/m2 vs. 79 ± 15 ml/m2, p = 0.02) and end-systolic volume (25 ± 7 ml/m2 vs. 32 ± 9 ml/m2, p = 0.04). An increase in mean RAP to ≥15 mmHg following exercise was not seen in patients with normal LV filling, compared to 4 patients (20%) with mild and 7 patients (63%) with moderate diastolic dysfunction (p = 0.003). PA pressure and PA elastance was increased in grade 2 diastolic dysfunction and correlated with RV volume and maximal oxygen consumption (r = -0.71, p < 0.001). CONCLUSIONS: Moderate diastolic dysfunction is associated with increased RV afterload (elastance), which is compensated at rest, but is associated with increased RAP and inversely related to maximal oxygen consumption during maximal exercise.

End-systolic wall stress in aortic stenosis: comparing symptomatic and asymptomatic patients.

Aims: In aortic stenosis (AS), there is poor association between symptoms and conventional markers of AS severity or left ventricular (LV) systolic function. This may reflect that symptoms arise from LV diastolic dysfunction or that aortic valve area (AVA) and transvalvular gradient do not reflect afterload. We aimed to study the impact of afterload (end-systolic wall stress [ESWS]) on the presence of symptoms in AS and to test whether symptoms are related to increased ESWS or LV remodelling. Methods and results: In a prospective study, ESWS was estimated by measuring LV wall thickness from MRI and estimated LV end systolic pressure from echocardiographic mean gradient and systolic blood pressure in 78 patients with severe AS scheduled for aortic valve replacement and 91 patients with asymptomatic severe AS. Symptomatic patients had lower indexed AVA (0.40±0.11 vs 0.45±0.09 cm2/m2, p=0.009). They had undergone more extensive remodelling (MRI LV mass index [LVMi]: 85±24 vs 69±17 g/m2, p<0.0001), had higher tricuspid regurgitant gradient (24±8 mm Hg vs 19 ± 7 mm Hg, p=0.0001) and poorer global longitudinal strain (-15.6±3.8 vs -19.9±3.2%, p<0.0001). ESWS was higher among symptomatic patients (96±51 vs 76±25 kdynes/cm2, p=0.003). Multivariate logistic regression identified echocardiographic relative wall thickness, tricuspid gradient, mitral deceleration time, early diastolic strain rate, MRI LVMi, MRI LV end-diastolic volume index and ESWS as independently associated with being symptomatic. Conclusion: ESWS can be estimated from multimodality imaging combining MRI and echocardiography. It is correlated with LV remodelling and neurohormonal activation and is independently associated with symptomatic status in AS.

[Randomised double-blind tests and invasive cardiology].

Virtually all the new medical treatments nowadays are tested in randomised double-blind tests, before they are introduced as routine treatment. However, this is not always the case for the new surgical or catheter-based treatments. Although different in some aspects, it is practically possible for surgical and catheter-based treatments to follow the same scientific principles as medical treatments in order to test their efficacy. In this review, we argue that it is necessary to conduct randomised double-blind tests of these interventions prior to their introduction in clinical practice.

Postoperative atrial fibrillation after aortic valve replacement is a risk factor for long-term atrial fibrillation.

OBJECTIVES: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery. However, knowledge on the rate of long-term atrial fibrillation (LTAF) after POAF remains unclear. We investigated predictors of POAF in patients with aortic stenosis undergoing surgical aortic valve replacement, and assessed the rate of LTAF during follow-up. METHODS: We prospectively included 96 adult patients with severe aortic stenosis undergoing surgical aortic valve replacement. Patients with previous atrial fibrillation (AF) were excluded. Patients underwent echocardiography, cardiac computed tomography and magnetic resonance imaging immediately prior to surgery. Surgical aortic clamp time and postoperative C-reactive protein (CRP) were documented. POAF was defined as AF recorded within 7 days of surgery. Through chart review, patients were followed up for documented episodes of LTAF occurring more than 7 days after surgery. RESULTS: POAF occurred in 51 patients (53%). It was associated with larger preoperative echocardiographic left atrial volume index (44 ± 12 vs 37 ± 8 ml/m2, P = 0.004), longer aortic clamp time [80 (70-102) vs 72 (62-65) min, P = 0.04] and higher CRP on first postoperative day [80 (64-87) vs 65 (44-83) mg/l, P = 0.001]. Multivariable logistic regression revealed that left atrial volume index [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.02-1.13; P = 0.005] and postoperative CRP (OR 1.03, 95% CI 1.01-1.05; P = 0.006) were the only independent predictors of POAF. During 695 days (25th-75th percentile: 498-859 days) of follow-up, LTAF occurred in 11 patients of whom 10 were in the POAF group (hazard ratio 9.4, 95% CI 1.2-74; P = 0.03). CONCLUSIONS: POAF is predicted by left atrial volume index and postoperative CRP. Patients with POAF have a 9-fold increase risk of developing symptomatic LTAF during follow-up. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02316587).

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.

Measurement of left atrial volume by 2D and 3D non-contrast computed tomography compared with cardiac magnetic resonance imaging.

BACKGROUND: Cardiac magnetic resonance imaging (MRI) is considered the gold standard for assessment of left atrial (LA) volume. We assessed the feasibility of evaluating LA volume using 3D non-contrast computed tomography (NCCT). Furthermore, since manual tracing of LA volume is time consuming, we evaluated the accuracy of the LA area using 2D NCCT imaging for LA volume assessment. METHODS: MRI and NCCT imaging were performed in 69 patients before and one year after aortic valve replacement. In 3D MRI and 3D NCCT, each slice was manually traced, excluding the pulmonary veins and atrial appendage, and multiplied by slice spacing, thus generating a measure of LA volume. The LA volume was indexed to body surface area. On 2D NCCT, the largest axial cross-section LA area was traced manually. RESULTS: The mean LA volume was 102 ±â€¯28 ml in MRI compared with 103 ±â€¯28 ml in 3D NCCT. 3D NCCT showed good agreement with MRI measurements (mean difference -0.7 ml/m2; 95% confidence interval (CI) -2.2 to 0.9). By Bland-Altman, 3D NCCT also showed good agreement with MRI (limits of agreement: -18.7-17.4 ml/m2). Furthermore, good correlation was found between 2D NCCT and 3D NCCT LA volume (r = 0.93). CONCLUSION: 2D and 3D measurements of LA volume in non-contrast computed tomography are feasible and accurate.

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.

Cardiac remodelling and haemodynamic characteristics in primary mitral valve regurgitation.

Objective: To assess the association between cardiac morphology and function assessed with cardiac MRI (CMRI) and haemodynamics at rest and during exercise in patients with primary mitral regurgitation (MR). Methods: In an observational study, subjects with significant primary MR (N = 46) with effective regurgitant orifice ≥ 0.30 cm2 and left ventricular (LV) ejection fraction > 60% were examined with right heart catheterisation during rest and exercise and CMRI at rest. End-diastolic pressure volume relationship (EDPVR) was assessed using a single beat method using pulmonary capillary wedge pressure (PCWP) and end-diastolic volume. Patients were divided according to normal PCWP at rest (> 12 mm Hg) and with exercise (> 28 mm Hg). Results: Resting regurgitant volume correlated positively with resting PCWP, (r = 0.42, p = 0.002). However, with exercise no association between PCWP and regurgitant volume was seen (r = 0.09, p = 0.55). At rest left atrial (LA) maximal, minimal and volume index at atrial contraction correlated positively with PCWP (r = 0.60; r = 0.55; r = 0.58, all p < 0.001); in contrast none of these correlated with exercise PCWP (all p > 0.2). EDPVR in patients with high PCWP at rest was shifted towards higher volumes for the same pressures. The opposite was seen for patients with high PCWP during exercise where estimated volumes were smaller for the same pressure than patients with normal exercise PCWP. Conclusion: In patients with significant MR the degree of regurgitation and LA dilatation is associated with resting PCWP. However, with exercise this association disappears. Estimation of EDPVR suggests lower LV compliance in patients where PCWP is increased with exercise. Clinical trial registration: URL: https://clinicaltrials.gov/ct2/show/NCT02961647?term=HEMI&rank=1. ID: NCT02961647.

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.

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.

Beneficial effects of elevating cardiac preload on left-ventricular diastolic function and volume during heat stress: implications toward tolerance during a hemorrhagic insult.

Volume loading normalizes tolerance to a simulated hemorrhagic challenge in heat-stressed individuals, relative to when these individuals are thermoneutral. The mechanism(s) by which this occurs is unknown. This project tested two unique hypotheses; that is, the elevation of central blood volume via volume loading while heat stressed would 1) increase indices of left ventricular diastolic function, and 2) preserve left ventricular end-diastolic volume (LVEDV) during a subsequent simulated hemorrhagic challenge induced by lower-body negative pressure (LBNP). Indices of left ventricular diastolic function were evaluated in nine subjects during the following conditions: thermoneutral, heat stress, and heat stress after acute volume loading sufficient to return ventricular filling pressures toward thermoneutral levels. LVEDV was also measured in these subjects during the aforementioned conditions prior to and during a simulated hemorrhagic challenge. Heat stress did not change indices of diastolic function. Subsequent volume infusion elevated indices of diastolic function, specifically early diastolic mitral annular tissue velocity (E') and early diastolic propagation velocity (E) relative to both thermoneutral and heat stress conditions (P < 0.05 for both). Heat stress reduced LVEDV (P < 0.05), while volume infusion returned LVEDV to thermoneutral levels. The reduction in LVEDV to LBNP was similar between thermoneutral and heat stress conditions, whereas the reduction after volume infusion was attenuated relative to both conditions (P < 0.05). Absolute LVEDV during LBNP after volume loading was appreciably greater relative to the same level of LBNP during heat stress alone. Thus, rapid volume infusion during heat stress increased indices of left ventricular diastolic function and attenuated the reduction in LVEDV during LBNP, both of which may serve as mechanisms by which volume loading improves tolerance to a combined hyperthermic and hemorrhagic challenge.

[Commotio cordis]. / Commotio cordis.

Blunt, non-penetrating trauma of the chest (commotio cordis) can cause sudden death in individuals without known cardiac disease. Sudden death in commotio cordis is due to ventricular fibrillation. The timing of the blow must be during the electric vulnerable period of the ECG cyclus, 10-40 milliseconds before the peak of the T-wave. The risk of arrhythmia increases progressively, until a velocity of 64 km/h, and at higher velocities the risk of ventricular fibrillation begins to diminish. The location of the impact must be directly over the cardiac silhouette.