764 Prevalence and clinical implications of cardiac involvement in individuals with paucisymptomatic SARS-CoV-2 infection

Aims Myocardial involvement has been reported in SARS-CoV-2 infection, especially in hospitalized patients during the acute phase of the disease. However, the exact prevalence and the clinical implications of cardiac involvement in young individuals with paucisymptomatic SARS-CoV-2 infection are debated. Methods and results We gathered data on 100 young patients with previous paucisymptomatic SARS-CoV-2 infection, not undergoing hospitalization and without previous diagnosis of structural heart disease, who underwent cardiological evaluation in our clinic at IRCCS ICS Maugeri (Pavia, Italy). Results were validated in an external cohort of 28 patients who underwent cardiac magnetic resonance (MRI) at Humanitas Research Hospital (Rozzano, Italy). The study population included 100 patients with previous paucisymptomatic SARS-CoV-2 infection: 60 (60%) males; median age 36 years (IQR: 22–50 years); median time after SARS-CoV-2 infection 181 days (IQR: 76–218 days). At the cardiological evaluation, 31/100 (31%) of patients referred cardiological symptoms, including dyspnoea, palpitations, chest pain or syncope. Overall, 26/100 (26%) patients showed on or more of the following instrumental alterations at first level assessment: 4/100 (4%) increase of TnI; 7/100 (7%) electrocardiographic abnormalities, 12/100 (12%) ventricular arrhythmias, and 11/100 (11%) echocardiographic abnormalities. Of 32 patients who underwent cardiac MRI, myocardial involvement was detected in 6/32 (19%) patients (Figure 1), similarly to what was observed in the validation cohort [54% males; median age 47 years (IQR: 26–55 years); myocardial involvement at MRI 4/28, 14%]. Furthermore, the proportion of patients with myocardial involvement was significantly higher in patients with first-level cardiac alterations (6/18, 28%) as compared with patients without cardiac alterations at first-level examination (0/14, 0%, P = 0.024). When analysing possible predictors for the occurrence of cardiac involvement at the MRI, documentation of ventricular arrhythmias at Holter ECG or exercise test was associated with an 87-fold higher probability of cardiac involvement at the MRI (OR: 87.3; 95% CI: 4.0–1914.3; P < 0.001). Conclusions Around 15–20% of patients with paucisymptomatic SARS-CoV-2 infection exhibit cardiac involvement documented at the cardiac MRI after a mean of 6 months from the onset of the disease. The presence of instrumental alterations detected with first level diagnostic tests, and in particular the documentation of ventricular arrhythmias at the 24 h-Holter ECG or at the exercise stress test, is a powerful predictor of myocardial involvement.

Prognostic value of secondary cardiac alterations in patients with moderate aortic valve stenosis

Purpose Echocardiographic characteristics that predict the progression of moderate aortic valve stenosis (mAS) are lacking. The aim of the present study was to evaluate the prognostic value of left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and pulmonary artery hypertension (PAH) in patients with mAS. Methods A total of 137 patients with asymptomatic mAS (age 72±10 years; females: 51 (37%); Blood Pressure: 143±21 / 78±13 mmHg) were included. Echocardiography was performed at baseline and at follow-up every six or/and twelve months. Patients with concomitant valvular defects, hypertrophic cardiomyopathy or chronic obstructive pulmonary disease were excluded. mAS was defined by current guideline criteria. Left ventricular ejection fraction (LVEF), LVH (LV mass index, males: >115g/m2, females: >95 g/m2), DD (E/e' >14) and PAH (maximum regurgitant velocity of tricuspid valve (TRVmax) >2.8m/s) were assessed. mAS patients were divided into 4 subgroups based on the number of secondary cardiac alterations: (0) no; (1) one; (2) two; (3) three cardiac alterations. The primary endpoint was progression to severe AS with indication for treatment (effective aortic orifice area (EOA) by continuity equation <1 cm2/<0.6 cm2/m2) or the onset of symptoms. Results mAS patients showed (0) no secondary cardiac alterations in 20% (n=28), (1) one in 40% (n=55), (2) two in 26% (n=35) and (3) three in 14% (n=19). Among mAS subgroups, no significant differences were observed for age and comorbidities. Echocardiographic parameters are summarised in Tab.1. In general, mAS patients with ≥ two cardiac alterations showed significantly smaller EOA ((0): 1.32±0.19 vs. 1.29±0.19, p>0.05; (1): 1.26±0.21 vs. 1.18±0.21, p>0.05; (2): 1.29±0.20 vs. 1.01±0.20, p<0.01; (3): 1.31±0.16 vs. 1.06±0.25, p<0.01) and higher mean pressure gradients (PGmean) ((0): 19.8±6.64 vs. 21.8±6.32, p>0.05; (1): 20.0±9.26 vs. 22.3±9.94, p>0.05; (2): 22.7±9.32 vs. 30.5±12.61, p<0.01 (3): 25.0±8.87 vs. 29.4±10.67, p<0.01) between baseline and follow-up (mean follow-up 20±9 months). Further, decrease of EOA/days was significantly higher in these patients ((0) −0.003; (1) −0.006; (2) −0.016; (3) −0.028; p<0.01, Fig. 1). As shown in Kaplan-Meier curve, mAS with ≥ two cardiac alterations showed rapid progression of moderate to severe AS (Fig. 2). Conclusions In 40% of patients with mAS ≥ two secondary cardiac alterations (LV hypertrophy, DD and PAH) were observed. The presence of ≥ two of these secondary cardiac alterations is associated with rapid progression of mAS. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

IGFBP7 and GDF-15, but not P1NP, are associated with cardiac alterations and 10-year outcome in an elderly community-based study

Background Little is known about the clinical value of Insulin-like growth factor-binding protein-7 (IGFBP7), a cellular senescence marker, in an elderly general population with multiple co-morbidities and high prevalence of asymptomatic cardiovascular ventricular dysfunction. Inflammation and fibrosis are hallmarks of cardiac aging and remodelling. Therefore, we assessed the clinical performance of IGFBP7 and two other biomarkers reflecting these pathogenic pathways, the growth differentiation factor-15 (GFD-15) and amino-terminal propeptide of type I procollagen (P1NP), for their association with cardiac phenotypes and outcomes in the PREDICTOR study. Methods 2001 community-dwelling subjects aged 65–84 years who had undergone centrally-read echocardiography, were selected through administrative registries. Atrial fibrillation (AF) and 4 echocardiographic patterns were assessed: E/e’ (> 8), enlarged left atrial area, left ventricular hypertrophy (LVH) and reduced midwall circumference shortening (MFS). All-cause and cardiovascular mortality and hospitalization were recorded over a median follow-up of 10.6 years. Results IGFBP7 and GDF-15, but not P1NP, were independently associated with prevalent AF and echocardiographic variables after adjusting for age and sex. After adjustment for clinical risk factors and cardiac patterns or NT-proBNP and hsTnT, both IGFBP7 and GDF-15 independently predicted all-cause mortality, hazard ratios 2.13[1.08–4.22] and 2.03[1.62–2.56] per unit increase of Ln-transformed markers, respectively. Conclusions In a community-based elderly cohort, IGFBP7 and GDF-15 appear associated to cardiac alterations as well as to 10-year risk of all-cause mortality.