Prognostic impact of late gadolinium enhancement at the right ventricular insertion points in non-ischaemic dilated cardiomyopathy.

AIMS: To evaluate the baseline characteristics and the prognostic implications associated with late gadolinium enhancement limited to the right ventricular insertion points (IP-LGE) or present at both the right ventricular insertion points and the left ventricle (IP&LV-LGE) in non-ischaemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: This is a retrospective observational multicentre cohort study including 1165 consecutive patients with DCM evaluated by cardiac magnetic resonance. The primary endpoint included appropriate defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, or sudden death. The secondary outcome encompassed heart failure hospitalizations, heart transplant, left ventricular assist device implantation, and end-stage heart failure death. IP-LGE was found in 72 patients (6%), who had clinical characteristics closer to LGE- than to LGE+ patients. During follow-up (median 36 months), none of the IP-LGE patients experienced the primary endpoint. The cumulative incidence of the primary endpoint was similar between IP-LGE and LGE- patients (P = 1), while IP-LGE had significantly lower cumulative incidence when compared with LGE+ patients (P < 0.001). When compared with IP-LGE patients, the cumulative incidence of the secondary endpoint was similar in LGE- cases (P = 0.86) but tended to be higher in LGE+ patients (P = 0.06). Both clinical characteristics and outcomes were similar between IP&LV-LGE patients and the rest of LGE+ cases. CONCLUSIONS: In a large cohort of DCM patients, IP-LGE was associated with similar outcome when compared with LGE- patients and with significant lower risk of ventricular arrhythmias and sudden death when compared with LGE+ cases. Patients with IP&LV-LGE had clinical characteristics and outcomes similar to the rest of LGE+ cases.

Oxidative Stress in Structural Valve Deterioration: A Longitudinal Clinical Study.

The cause of structural valve deterioration (SVD) is unclear. Therefore, we investigated oxidative stress markers in sera from patients with bioprosthetic heart valves (BHVs) and their association with SVD. Blood samples were taken from SVD (Phase A) and BHV patients during the first 24 (Phase B1) and >48 months (Phase B2) after BHV implantation to assess total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrotyrosine (NT). The results show that MDA levels increased significantly 1 month after surgery in all groups but were higher at 6 months only in incipient SVD patients. NT levels increased gradually for the first 24 months after implantation in the BHV group. Patients with transcatheter aortic valve implantation (TAVI) showed even higher levels of stress markers. After >48 months, MDA and NT continued to increase in BHV patients with a further elevation after 60-72 months; however, these levels were significantly lower in the incipient and established SVD groups. In conclusion, oxidative stress may play a significant role in SVD, increasing early after BHV implantation, especially in TAVI cases, and also after 48 months' follow-up, but decreasing when SVD develops. Oxidative stress potentially represents a target of therapeutic intervention and a biomarker of BHV dysfunction.

The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration.

Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-αGal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-αGal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack αGal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in αGal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability.

Increased Prevalence of Moderate to Severe Mitral and Aortic Valve Dysfunction in Systemic Sclerosis: A Case-control Study.

OBJECTIVE: To investigate the prevalence, severity, and associated clinical factors of mitral and aortic valvular involvement in patients with systemic sclerosis (SSc). METHODS: Our case-control study included 172 patients with SSc and 172 non-SSc adults without known cardiac disease matched by age, sex, and prevalence of cardiovascular (CV) risk factors. The screening of mitral and aortic valvular involvement was performed by transthoracic Doppler echocardiogram. The prevalence of aortic stenosis (AS) was also compared with that reported in a population-based study performed in our community during the same period. RESULTS: Patients with SSc showed an almost 5-fold increased prevalence of moderate to severe mitroaortic valve dysfunction compared to non-SSc controls (OR 4.60, 95% CI 1.51-13.98; P = 0.003). The most common lesion was mitral regurgitation (MR), which was observed in 5.2% of patients, followed by AS in 3.5%, and aortic regurgitation (AR) in 1.7%. Analyzing the different types of valvular lesion separately, we observed a significantly higher frequency of MR compared to controls (OR 4.69, 95% CI 1.12-22.04; P = 0.032), as well as a higher frequency of AS in the 65-75 (OR 7.51, 95% CI 1.22-46.23, P = 0.01) and 76-85 age groups (OR 3.53, 95% CI 1.03-12.22, P = 0.043) when compared to the general population in our community. CONCLUSION: We found an increased prevalence of moderate to severe MR and AS in SSc compared to age-matched non-SSc controls with similar CV comorbidities. While results from this study do not allow for establishing a direct causal relationship, they strongly support the contribution of SSc-specific factors in the development of these complications.

Twenty-Year Secular Trends in Infective Endocarditis in a Teaching Hospital.

BACKGROUND: The purpose of this study was to analyze the secular trends of infective endocarditis in a teaching hospital between January 1996 and December 2015. METHODS: We report on a single-center retrospective study of patients with left-side valve infective endocarditis. We performed an analysis of secular trends in the main epidemiological and etiological aspects, as well as clinical outcomes, in 5 successive 4-year periods (P1 to P5). RESULTS: In total, 595 episodes of infective endocarditis were included, of which 76% were community-acquired and 31.3% involved prosthetic valves. Among the cases, 70% occurred in men, and the mean age (SD) was 64.1 (14.3) years. A significant increase in older patients (age ≥70 years) between P1 (15.332%) and P5 (51.9%; P < .001) was observed. The rate of infective endocarditis on biological prostheses also increased in the prosthetic group, accounting for 30% in P1 and 67.3% in P5 (P < .001). By contrast, there were significant decreases in vascular and immunological phenomena over the study period, with decreases in the presence of moderate to severe valvular insufficiency (75.9% in P1 to 52.6% in P5; P < .001) and valvular surgery (43% in P1 vs 29.6% in P5; P = .006). Finally, overall mortality was 23.9%, and although it was highest in P1, it subsequently remained stable through P2 to P5 (38% in P1 to 20% in P5; P = .004). CONCLUSIONS: There has been a significant increase in infective endocarditis in older patients. The decrease in moderate to severe valve regurgitation at diagnosis could explain the stable mortality despite the increase in the mean age of patients over time.