In the context of the coronavirus disease 2019 pandemic, myocardial injury is a relatively frequent finding. Progression to cardiogenic shock has been rarely described, especially in healthy young ...patients. The underlying mechanisms are to date controversial. A previously healthy 18‐year‐old female teenager affected by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) developed fulminant cardiogenic shock requiring a prompt extracorporeal membrane oxygenation support. Cardiac involvement was predominant compared with the pulmonary one. Myocardial biopsies were performed; and in order to clarify the pathophysiology of the acute heart failure, optical and transmission electron microscopy study was realized. Two additional immunohistology techniques were developed in order to (i) detect a SARS‐CoV‐2 recombinant fusion nucleoprotein by using a specific antibody and (ii) study fractalkine expression induced by activated endothelium because this molecule is well known to be elevated in patients with severe cytokine release syndrome. SARS‐CoV‐2 genome was not detected in the myocardium. Even if the clinical presentation, laboratory markers, and cardiac imaging techniques strongly suggested fulminant myocarditis, histology and immunohistology were not fully consistent with this diagnosis according to the Dallas criteria. Although rare suspected coronavirus particles were found by transmission electron microscopy in the cardiac endothelium, neither significant immunoreactivity for the viral nucleocapsid protein nor image suggestive of endotheliitis was detected. Intense endothelial immunoreactivity pattern for fractalkine expression was observed. From a clinical point of view, the left ventricular systolic function gradually improved, and the patient survived after a long stay in the intensive care unit. Our observations suggest that a massive cytokine storm induced by SARS‐CoV‐2 infection was the main cause of the cardiogenic shock, making a direct viral injury pathway very unlikely.
This study sought to evaluate the prognostic value of mean pressure gradient (MPG) increase and peak systolic pulmonary artery pressure (SPAP) measured during exercise stress echocardiography in ...asymptomatic patients with aortic stenosis (AS).
Exercise testing is recommended in asymptomatic AS patients, but the additional value of exercise-stress echocardiography, especially the prognostic value of MPG increase and peak SPAP, is still debated.
We enrolled all consecutive patients with pure, isolated, asymptomatic AS and preserved ejection fraction ≥50% and normal SPAP (<50 mm Hg) who underwent symptom-limited exercise echocardiography at our institution. Occurrence of AS-related events (symptoms or congestive heart failure) or occurrence of aortic valve replacement was recorded.
We enrolled 148 patients (66 ± 15 years of age; 74% males; MPG: 47 ± 13 mm Hg; SPAP: 34 ± 6 mm Hg). No complications were observed. Thirty-six patients (24%) had an abnormal exercise test result (occurrence of symptoms, fall in blood pressure, and/or ST-segment depression) and were referred for surgery. Among the 112 patients with a normal exercise test result, 38 patients (34%) had abnormal exercise echocardiography scores (MPG increase >20 mm Hg and/or SPAP at peak exercise >60 mm Hg). These 112 patients were managed conservatively. During a mean follow-up of 14 ± 8 months, an AS-related event occurred in 30 patients, and 25 patients underwent surgery. Neither MPG increase >20 mm Hg nor peak SPAP >60 mm Hg was predictive of occurrence of AS-related events or aortic valve replacement (all p > 0.20). In contrast, baseline AS severity was an important prognostic factor (all p < 0.01).
In this observational study including 148 patients with asymptomatic AS, we confirmed and extended the importance of exercise testing for unveiling functional limitation. More importantly, neither the increase in MPG nor in SPAP at peak exercise was predictive of outcome. Our results do not support the use of these parameters in risk-stratification and clinical management of asymptomatic AS patients.
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Myocardial fibrosis has been proposed as an outcome predictor in asymptomatic patients with severe aortic stenosis (AS) that may lead to consider prophylactic surgery. It can be detected using MRI ...but its widespread use is limited and development of substitute biomarkers is highly desirable. We analysed the determinants and prognostic value of galectin-3, one promising biomarker linked to myocardial fibrosis.
Patients with at least mild degenerative AS enrolled between 2006 and 2013 in two ongoing studies, COFRASA/GENERAC (COhorte Française de Rétrécissement Aortique du Sujet Agé/GENEtique du Rétrécissement Aortique), aiming at assessing the determinants of AS occurrence and progression, constituted our population.
We prospectively enrolled 583 patients. The mean galectin-3 value was 14.3±5.6 ng/mL. There was no association between galectin-3 and functional status (p=0.55) or AS severity (p=0.58). Independent determinants of galectin-3 were age (p=0.0008), female gender (p=0.04), hypertension (p=0.002), diabetes (p=0.02), reduced left ventricular ejection fraction (p=0.01), diastolic dysfunction (E/e', p=0.02) and creatinine clearance (p<0.0001). Among 330 asymptomatic patients at baseline, galectin-3 was neither predictive of outcome in univariate analysis (p=0.73), nor after adjustment for age, gender, rhythm, creatinine clearance and AS severity (p=0.66).
In a prospective cohort of patients with a wide range of AS severity, galectin-3 was not associated with AS severity or functional status. Main determinants of galectin-3 were age, hypertension and renal function. Galectin-3 did not provide prognostic information on the occurrence of AS-related events. Our results do not support the use of galectin-3 in the decision-making process of asymptomatic patients with AS.
COFRASA NCT00338676 and GENERAC CT00647088.
It has been suggested that myocardial systolic deformation parameters may be a more sensitive marker of left ventricular (LV) systolic dysfunction than LV ejection fraction (LVEF). However, its ...prognostic value in patients with aortic stenosis (AS) remains debated.
In an ongoing prospective cohort of asymptomatic patients with at least mild, pure, isolated AS, global longitudinal strain (GLS) was measured at baseline using 2D speckle tracking imaging, and AS related events (occur-rence of symptoms, congestive heart failure and sudden death) were prospectively collected.
We prospectively enrolled 176 patients (mean age 72 years, 70% male). Mean aortic valve area was 1.25cm2and mean gradient 28.8mmHg. Overall, 88 patients had mild AS, 50 patients moderate AS and 38 patients severe AS. During a mean follow up period of 2.2 years, 38 events occurred. GLS was not correlated to pic velocity, mean gradient or aortic valve area (AVA) (all p>0.05). In univariate analysis, neither in the whole cohort (p=0.75), nor in the subgroup of moderate/severe AS, GLS was predictive of future AS related events. Results were unchanged after adjustment for AS hemodynamic severity (p=0.66 and p=0.82, respectively).
Our data suggest that longitudinal strain assessed by 2D speckle tracking echocardiography, is not predictive of future symptomatic status in asymptomatic patients with AS and preserved LVEF. Thus, this index should not be recommended in daily practice, in order to select patients who should undergo an early aortic valve replacement.
Usefulness of exercise-stress echocardiography for risk-stratification of asymptomatic patients with aortic stenosis (AS) is still debated (Class IIb recommendation). The exercise-induced increase in ...transvalvular gradient has been proposed as a prognostic factor but data are scarce. We sought to evaluate the additional prognostic value of echocardiographic parameters during exercise-stress echocardiography.
In this observational prospective study, we enrolled all consecutive asymptomatic patients with moderate/severe AS and normal ejection fraction who underwent an exercise-stress echocardiography at our institution. Clinical and echocardiographic data at rest and at peak exercise were collected. The composite primary outcome variable was the occurrence of AS related events (symptoms or heart failure related to the AS or cardiovascular death during follow-up).
Among the 121 patients enrolled, 35 (29%) had an abnormal exercise test (occurrence of symptoms or abnormal blood pressure profile during exercise) and were operated on within the following weeks. Eighty-six patients (mean quartiles; age 67 57-75 years, 68 male, mean gradient 46 35-52mmHg, aortic valve area 0,97 0,82-1,11) had a normal exercise test and 39 (48%) reached the clinical endpoint during follow-up (17.5 10.9-36.4 months). The proposed threshold of 18mmHg mean gradient increase had no prognostic value. In multivariate analysis, rest mean gradient (p<0.001; HR 1.07 1.03-1.11) but not exercise-induced increase mean gradient (p=0.4; HR 0.69 0.29-1.65) were predictive of outcome.
Exercise-induced increase in mean gradient was not predictive of outcome in patients with normal exercise-test. Our results raise question regarding the additional value and therefore the use of exercise-stress echocardiography for risk-stratification of asymptomatic patients with AS.
Identifying subgroups of asymptomatic patients with aortic stenosis (AS) who may benefit from early intervention is a critical challenge due to the risk of sudden death and irreversible myocardial ...dysfunction without preceding symptoms. In this study, we analyzed the determinants and prognostic value of Galectin-3 in a large cohort of patients with AS.
We included patients with at least mild degenerative AS enrolled in 2 ongoing prospective clinical studies, COFRASA and GENERAC, aiming at assessing the determinants of AS occurrence and progression.
Between November 2006 and July 2013, 583 patients were prospectively enrolled. Severe AS was diagnosed in 312 (56%) patients among whom 220 (38%) were symptomatic. Age (p<0.0001) and reduced creatinine clearance (p<0.0001) were positively associated with Galectin-3 level.
No significant association was found between Galectin-3 and echocardio-graphic parameters of AS severity including aortic valve area (p=0.41), mean transvalvular gradient (p=0,27), and AS jet velocity (p=0.52). Galectin-3 did not provide diagnostic evidence of severe AS (area under the curve=0.53). Galectin-3 was not influenced by symptomatic status. Echocardiographic parameters of LV remodeling were not associated with Galectin-3 in multivariate analysis. Event-free survival analysis revealed no prognostic value of Galectin-3.
The main determinants of Galectin-3 level were age and renal function. There was no association between Galectin-3 and symptomatic status and echocardiographic parameters associated with LV remodeling. Galectin-3 didn’t provide prognostic information on the occurrence of AS related events. These results do not support the use of Galectin-3 in the decision making process of patients with AS.
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