Role of genetics in the development of cardiac allograft vasculopathy.

BACKGROUND: The association between genetic polymorphisms and early cardiac allograft vasculopathy (CAV) development is relatively unexplored. Identification of genes involved in the CAV process may offer new insights into pathophysiology and lead to a wider range of therapeutic options. METHODS: This prospective study of 109 patients investigated 44 single nucleotide polymorphisms (SNPs) within the susceptibility loci potentially related to coronary artery disease, carotid artery intima-media thickness (cIMT), and in nitric oxide synthase gene. Genotyping was done by the Fluidigm SNP Type assays and Fluidigm 48.48 Dynamic Array IFC. The intima thickness progression (IT) was evaluated by coronary optical coherence tomography performed 1 month and 12 months after heart transplantation (HTx). RESULTS: During the first post-HTx year, the mean intima thickness (IT) increased by 24.0 ± 34.2 µm (p < 0.001) and lumen area decreased by ‒0.9 ± 1.8 mm2 (p < 0.001). The rs1570360 (A/G) SNP of the vascular endothelial growth factor A (VEGFA) gene showed the strongest association with intima thickness progression, even in the presence of the traditional CAV risk factors. SNPs previously related to carotid artery intima-media thickness rs11785239 (PRAG1), rs6584389 (PAX2), rs13225723 (LINC02577) and rs17477177 (CCDC71L), were among the five most significantly associated with IT progression but lost their significance once traditional CAV risk factors had been added. CONCLUSION: Results of this study suggest that genetic variability may play an important role in CAV development. The vascular endothelial growth factor A gene SNP rs1570360 showed the strongest association with intima thickness (IT) progression measured by OCT, even in the presence of the traditional CAV risk factors (Tab. 3, Fig. 3, Ref. 36). Text in PDF www.elis.sk Keywords: cardiac allograft vasculopathy, optical coherence tomography, vascular endothelial growth factor A, intimal thickening, genetic polymorphism.

Characteristics, management, and outcomes of patients with left-sided infective endocarditis complicated by heart failure: a substudy of the ESC-EORP EURO-ENDO (European infective endocarditis) registry.

AIMS: To evaluate the current management and survival of patients with left-sided infective endocarditis (IE) complicated by congestive heart failure (CHF) in the ESC-EORP European Endocarditis (EURO-ENDO) registry. METHODS AND RESULTS: Among the 3116 patients enrolled in this prospective registry, 2449 (mean age: 60 years, 69% male) with left-sided (native or prosthetic) IE were included in this study. Patients with CHF (n = 698, 28.5%) were older, with more comorbidity and more severe valvular damage (mitro-aortic involvement, vegetations >10 mm and severe regurgitation/new prosthesis dehiscence) than those without CHF (all p ≤ 0.019). Patients with CHF experienced higher 30-day and 1-year mortality than those without (20.5% vs. 9.0% and 36.1% vs. 19.3%, respectively) and CHF remained strongly associated with 30-day (odds ratio[OR] 2.37, 95% confidence interval [CI] [1.73-3.24; p < 0.001) and 1-year mortality (hazard ratio [HR] 1.69, 95% CI 1.39-2.05; p < 0.001) after adjustment for established outcome predictors, including early surgery, or after propensity matching for age, sex, and comorbidity (n = 618 [88.5%] for each group, both p < 0.001). Early surgery, performed on 49% of these patients with IE complicated by CHF, remained associated with a substantial reduction in 30-day mortality following multivariable analysis, after adjustment for age, sex, Charlson comorbidity index, cerebrovascular accident, Staphylococcus aureus IE, streptococcal IE, uncontrolled infection, vegetation size >10 mm, severe valvular regurgitation and/or new prosthetic dehiscence, perivalvular complication, and prosthetic IE (OR 0.22, 95% CI 0.12-0.38; p < 0.001) and in 1-year mortality (HR 0.29, 95% CI 0.20-0.41; p < 0.001). CONCLUSION: Congestive heart failure is common in left-sided IE and is associated with older age, greater comorbidity, more advanced lesions, and markedly higher 30-day and 1-year mortality. Early surgery is strongly associated with lower mortality but is performed on only approximately half of patients with CHF, mainly because of a surgical risk considered prohibitive.

Surgery and outcome of infective endocarditis in octogenarians: prospective data from the ESC EORP EURO-ENDO registry.

PURPOSE: High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE. METHODS: Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age. RESULTS: As compared to < 80 yo patients, ≥ 80 yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p < 0.001), of surgery performed (37.0% vs. 75.5%, p < 0.001), and a higher in-hospital (25.9% vs. 15.8%, p < 0.001) and 1-year mortality (41.3% vs. 22.2%, p < 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive (HR 2.98 [2.43-3.66]). By propensity analysis, 304 ≥ 80 yo were matched to 608 < 80 yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p < 0.0001) in ≥ 80 yo. Overall mortality remained higher in ≥ 80 yo (in-hospital: HR 1.50[1.06-2.13], p = 0.0210; 1-yr: HR 1.58[1.21-2.05], p = 0.0006), but was not different from that of < 80 yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176). CONCLUSION: Although mortality rates are consistently higher in ≥ 80 yo patients than in < 80 yo patients in the general population, mortality of surgery in ≥ 80 yo is similar to < 80 yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80 yo patients.

Donor specific anti-HLA antibodies and cardiac allograft vasculopathy: A prospective study using highly automated 3-D optical coherence tomography analysis.

INTRODUCTION: Recent studies suggested potential positive correlations between HLA-specific antibodies and development of cardiac allograft vasculopathy (CAV). METHODS: This prospective two-center study investigated early progression of CAV by coronary optical coherence tomography in 1 month and 12 months after heart transplantation (HTx) in 104 patients. Detection and characterization of donor specific (DSA) and MHC class-I polypeptide-related sequence A (MICA) antibodies were performed before, 1, 6 and 12 months after transplantation. RESULTS: During the first post-HTx year, we observed a significant reduction in the mean coronary luminal area (P < .001), and progression in mean intimal thickness (IT) (P < .001). DSA and anti-MICA occurred in 17% of all patients, but no significant relationship was observed between presence of DSA/anti-MICA and IT progression within 12 months after HTx. In contrast, we observed significant association between presence of DSA (p=0.031), de-novo DSA (p=0.031), HLA Class II DSA (p=0.017) and media thickness (MT) progression. CONCLUSION: Results of our study did not identify a direct association between presence of DSA/anti-MICA and intimal thickness progression in an early period after HTx. However, we found significant relationships between DSA and media thickness progression that may identify a newly recognized immune-pathological aspect of CAV.

Challenges and possibilities of developing cardiac surgery in a peripheral hospital of low- and middle-income countries.

OBJECTIVE: Over a million cardiac surgeries are performed every year around the globe. However, approximately 93% of world population living in low- and middle-income countries have no access to cardiac surgery. The incidence of rheumatic and congenital heart disease is high in Nepal, while only 2,500-3,000 cardiac surgeries are performed annually. The aim of our study is to analyze challenges and opportunities of establishing a cardiac surgery program in a peripheral hospital of Nepal. METHODS: We analyzed our effort to establish a cardiac surgery program in a peripheral hospital in Nepal. RESULTS: Out of 2,659 consulted and diagnosed patients, we performed 85 open-heart surgeries in 4 years. Mean age of patients was 38.35 ± 14.13 years. The majority of patients were male (62.4% of patients) with 65.9% suffering from rheumatic heart disease. Average intensive care unit stay and hospital stay were 2.32 ± 1.1 and 8.29 ± 2.75 days, respectively. No in-hospital mortality was observed. CONCLUSION: We conclude that developing cardiac surgical care in a peripheral hospital of a developing country is feasible with support from government, foreign colleagues, local teams, and non-governmental organizations. The availability of a regular cardiac surgery service in the periphery of the country makes such services more accessible for the patients and helps in reducing the long waiting lists and unmanageable workload in the established cardiac centers in the capital city.

The ESC-EORP EURO-ENDO (European Infective Endocarditis) registry.

AIMS: The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) European Endocarditis (EURO-ENDO) registry aims to study the care and outcomes of patients diagnosed with infective endocarditis (IE) and compare findings with recommendations from the 2015 ESC Clinical Practice Guidelines for the management of IE and data from the 2001 Euro Heart Survey. METHODS AND RESULTS: Patients (n = 3116) aged over 18 years with a diagnosis of IE based on the ESC 2015 IE diagnostic criteria were prospectively identified between 1 January 2016 and 31 March 2018. Individual patient data were collected across 156 centres and 40 countries. The primary endpoint is all-cause mortality in hospital and at 1 year. Secondary endpoints are 1-year morbidity (all-cause hospitalization, any cardiac surgery, and IE relapse), the clinical, epidemiological, microbiological, and therapeutic characteristics of patients, the number and timing of non-invasive imaging techniques, and adherence to recommendations as stated in the 2015 ESC Clinical Practice Guidelines for the management of IE. CONCLUSION: EURO-ENDO is an international registry of care and outcomes of patients hospitalized with IE which will provide insights into the contemporary profile and management of patients with this challenging disease.

A Complex Heart Team's Approach to a Patient With Giant Cell Myocarditis.

Giant cell myocarditis is known as a rare and frequently fatal type of myocarditis that is usually characterized by progressive congestive heart failure and frequent ventricular arrhythmias. We report a rare case of giant cell myocarditis in a 64-year-old previously healthy woman. The case was complicated by the rapid development of progressive acute heart failure, which required the comprehensive care of our heart team. Using a broad spectrum of therapeutic approaches, the patient successfully underwent heart transplantation.

The role of timely measurement of galectin-3, NT-proBNP, cystatin C and hsTnT in predicting prognosis and heart function after heart transplantation.

BACKGROUND: Changes of biomarkers measured soon after heart transplantation (HTx) can reflect different processes: cardiomyocyte necrosis (troponins, high-sensitivity cardiac TnT and TnI), heart function (natriuretic peptides, BNP and NT-proBNP), fibrosis (galectin-3 and ST2), and global cardiorenal risk (cystatin C). We assessed the prognostic role of hsTnT, NT-proBNP, galectin-3 and cystatin C during the early post-transplant period. METHODS: A total of 121 consecutive post-HTx patients were assessed. The main outcomes were survival, left ventricular ejection fraction (LVEF) and rejection periods. Survival was assessed after intermediate (12 months) and long periods (total follow-up during study, median of survival 763 days, IR 527-1038 days). LVEF was assessed 12 months after HTx. Rejection was evaluated during follow-up. We report biomarker concentrations measured 10 days and 12 months after HTx. RESULTS: Ten days after HTx, cystatin C and hsTnT predicted death both under univariable and multivariable analysis. These two biomarkers along with galectin-3 were increased in patients with decreased LVEF measured 1 year after HTx. NT-proBNP did not show early prognostic power. None of the measured biomarkers predicted rejection, but hsTnT and NT-proBNP were increased significantly 12 months after HTx in patients with at least one rejection. CONCLUSIONS: Cystatin C and hsTnT measured 10 days after HTx can provide prognostic information on survival and galectin-3 measured at the same time may display a relationship to heart function assessed 1 year after HTx. Further study should be carried out in a large cohort of patients.

Bone marrow suppression and associated consequences in patients after heart transplantation: A 6-year retrospective review.

AIMS: To evaluate the incidence of bone marrow suppression and consequences of MMF dose adjustment in patients within the first year after heart transplantation. METHODS: Group I (n=47) was treated with a regimen currently used in patients after heart transplantation (mycophenolatemofetil - MMF, valganciclovir - VGC and trimethoprim/sulfamethoxazole - TMP-SMX). Group II (n=47) received only MMF of potentially myelotoxic medications. The myelotoxic effect and need for dose modification were assessed. The incidence of rejections and infectious episodes associated with MMF adjustment were analyzed during the first 12 months in Group I. RESULTS: There was a significantly greater proportion of patients with leukopenia (leukocyte count < 4 x 10^9/L) at 3 months after orthotopic heart transplantation in Group I compared with Group II (19.1% vs 2.1%; P = 0.02). The difference in lymphopenia (lymphocyte count < 0.8 x 10^9/L) at 3 months follow-up was highly significant (38.3 % vs 6.4 %; P = 0.0002). MMF was modified due to bone marrow suppression or severe infection in 63.8% patients in Group I and in only 8.5% of patients in Group II (P < 0.001). Reducing or stopping MMF was not associated with increased rejections. In Group I, at least 1 episode of higher degree cellular or humoral rejection occurred in 35% of patients with the standard MMF dosage compared with only 26% in patients with modified MMF (P = 0.0534). CONCLUSIONS: Addition of VGC+TMP-SMX to current immunosuppressive medication regimen in patients after heart transplantation is associated with significant lymphocytopenia and leukopenia. Importantly, modification of immunosuppressive prophylaxis (reducing or stopping MMF) leads to normalization of blood count without increased incidence of rejections.