Acetylsalicylic acid use and development of cardiac allograft vasculopathy: A national prospective study using highly automated 3-D optical coherence tomography analysis.

BACKGROUND: There is conflicting evidence on the role of acetylsalicylic acid (ASA) use in the development of cardiac allograft vasculopathy (CAV). METHODS: A nationwide prospective two-center study investigated changes in the coronary artery vasculature by highly automated 3-D optical coherence tomography (OCT) analysis at 1 month and 12 months after heart transplant (HTx). The influence of ASA use on coronary artery microvascular changes was analyzed in the overall study cohort and after propensity score matching for selected clinical CAV risk factors. RESULTS: In total, 175 patients (mean age 52 ± 12 years, 79% male) were recruited. During the 1-year follow-up, both intimal and media thickness progressed, with ASA having no effect on its progression. However, detailed OCT analysis revealed that ASA use was associated with a lower increase in lipid plaque (LP) burden (p = .013), while it did not affect the other observed pathologies. Propensity score matching of 120 patients (60 patient pairs) showed similar results, with ASA use associated with lower progression of LPs (p = .002), while having no impact on layered fibrotic plaque (p = .224), calcification (p = .231), macrophage infiltration (p = .197), or the absolute coronary artery risk score (p = .277). According to Kaplan-Meier analysis, ASA use was not associated with a significant difference in survival (p = .699) CONCLUSION: This study showed a benefit of early ASA use after HTx on LP progression. However, ASA use did not have any impact on the progression of other OCT-observed pathologies or long-term survival.

Sex-related differences in patients presenting with heart failure-related cardiogenic shock.

BACKGROUND: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of all CS cases. Nevertheless, there is a lack of evidence on sex-related differences in HF-CS, especially regarding use of treatment and mortality risk in women vs. men. This study aimed to investigate potential differences in clinical presentation, use of treatments, and mortality between women and men with HF-CS. METHODS: In this international observational study, patients with HF-CS (without acute myocardial infarction) from 16 tertiary-care centers in five countries were enrolled between 2010 and 2021. Logistic and Cox regression models were used to assess differences in clinical presentation, use of treatments, and 30-day mortality in women vs. men with HF-CS. RESULTS: N = 1030 patients with HF-CS were analyzed, of whom 290 (28.2%) were women. Compared to men, women were more likely to be older, less likely to have a known history of heart failure or cardiovascular risk factors, and lower rates of highly depressed left ventricular ejection fraction and renal dysfunction. Nevertheless, CS severity as well as use of treatments were comparable, and female sex was not independently associated with 30-day mortality (53.0% vs. 50.8%; adjusted HR 0.94, 95% CI 0.75-1.19). CONCLUSIONS: In this large HF-CS registry, sex disparities in risk factors and clinical presentation were observed. Despite these differences, the use of treatments was comparable, and both sexes exhibited similarly high mortality rates. Further research is necessary to evaluate if sex-tailored treatment, accounting for the differences in cardiovascular risk factors and clinical presentation, might improve outcomes in HF-CS.

Clinical presentation, shock severity and mortality in patients with de novo versus acute-on-chronic heart failure-related cardiogenic shock.

AIMS: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of CS cases. Whether patients with de novo HF and those with acute-on-chronic HF in CS differ in clinical characteristics and outcome remains unclear. The aim of this study was to evaluate differences in clinical presentation and mortality between patients with de novo and acute-on-chronic HF-CS. METHODS AND RESULTS: In this international observational study, patients with HF-CS from 16 tertiary care centres in five countries were enrolled between 2010 and 2021. To investigate differences in clinical presentation and 30-day mortality, adjusted logistic/Cox regression models were fitted. Patients (n = 1030) with HF-CS were analysed, of whom 486 (47.2%) presented with de novo HF-CS and 544 (52.8%) with acute-on-chronic HF-CS. Traditional markers of CS severity (e.g. blood pressure, heart rate and lactate) as well as use of treatments were comparable between groups. However, patients with acute-on-chronic HF-CS were more likely to have a higher CS severity and also a higher mortality risk, after adjusting for relevant confounders (de novo HF 45.5%, acute-on-chronic HF 55.9%, adjusted hazard ratio 1.38, 95% confidence interval 1.10-1.72, p = 0.005). CONCLUSION: In this large HF-CS cohort, acute-on-chronic HF-CS was associated with more severe CS and higher mortality risk compared to de novo HF-CS, although traditional markers of CS severity and use of treatments were comparable. These findings highlight the vast heterogeneity of patients with HF-CS, emphasize that HF chronicity is a relevant disease modifier in CS, and indicate that future clinical trials should account for this.

Association between left ventricular ejection fraction, mortality and use of mechanical circulatory support in patients with non-ischaemic cardiogenic shock.

BACKGROUND: Currently, use of mechanical circulatory support (MCS) in non-ischaemic cardiogenic shock (CS) is predominantly guided by shock-specific markers, and not by markers of cardiac function. We hypothesise that left ventricular ejection fraction (LVEF) can identify patients with a higher likelihood to benefit from MCS and thus help to optimise their expected benefit. METHODS: Patients with non-ischaemic CS and available data on LVEF from 16 tertiary-care centres in five countries were analysed. Cox regression models were fitted to evaluate the association between LVEF and mortality, as well as the interaction between LVEF, MCS use and mortality. RESULTS: N = 807 patients were analysed: mean age 63 [interquartile range (IQR) 51.5-72.0] years, 601 (74.5%) male, lactate 4.9 (IQR 2.6-8.5) mmol/l, LVEF 20 (IQR 15-30) %. Lower LVEF was more frequent amongst patients with more severe CS, and MCS was more likely used in patients with lower LVEF. There was no association between LVEF and 30-day mortality risk in the overall study cohort. However, there was a significant interaction between MCS use and LVEF, indicating a lower 30-day mortality risk with MCS use in patients with LVEF ≤ 20% (hazard ratio 0.72, 95% confidence interval 0.51-1.02 for LVEF ≤ 20% vs. hazard ratio 1.31, 95% confidence interval 0.85-2.01 for LVEF > 20%, interaction-p = 0.017). CONCLUSION: This retrospective study may indicate a lower mortality risk with MCS use only in patients with severely reduced LVEF. This may propose the inclusion of LVEF as an adjunctive parameter for MCS decision-making in non-ischaemic CS, aiming to optimise the benefit-risk ratio.

Use of mechanical circulatory support in patients with non-ischaemic cardiogenic shock.

AIMS: Despite its high incidence and mortality risk, there is no evidence-based treatment for non-ischaemic cardiogenic shock (CS). The aim of this study was to evaluate the use of mechanical circulatory support (MCS) for non-ischaemic CS treatment. METHODS AND RESULTS: In this multicentre, international, retrospective study, data from 890 patients with non-ischaemic CS, defined as CS due to severe de-novo or acute-on-chronic heart failure with no need for urgent revascularization, treated with or without active MCS, were collected. The association between active MCS use and the primary endpoint of 30-day mortality was assessed in a 1:1 propensity-matched cohort. MCS was used in 386 (43%) patients. Patients treated with MCS presented with more severe CS (37% vs. 23% deteriorating CS, 30% vs. 25% in extremis CS) and had a lower left ventricular ejection fraction at baseline (21% vs. 25%). After matching, 267 patients treated with MCS were compared with 267 patients treated without MCS. In the matched cohort, MCS use was associated with a lower 30-day mortality (hazard ratio 0.76, 95% confidence interval 0.59-0.97). This finding was consistent through all tested subgroups except when CS severity was considered, indicating risk reduction especially in patients with deteriorating CS. However, complications occurred more frequently in patients with MCS; e.g. severe bleeding (16.5% vs. 6.4%) and access-site related ischaemia (6.7% vs. 0%). CONCLUSION: In patients with non-ischaemic CS, MCS use was associated with lower 30-day mortality as compared to medical therapy only, but also with more complications. Randomized trials are needed to validate these findings.

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.

Validation of a semi-automatic software for optical coherence tomography - analysis in heart transplanted patients.

Optical Coherence Tomography (OCT) is an intravascular imaging modality enabling detailed evaluation of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). However, its clinical application remains hampered by time-consuming manual quantitative analysis. We aimed to validate a semi-automated quantitative OCT analysis software (Iowa Coronary Wall Analyzer, ICWA-OCT) to improve OCT-analysis in HTx patients. 23 patients underwent OCT evaluation of all three major coronary arteries at 3 months (3M) and 12 months (12M) after HTx. We analyzed OCT recordings using the semiautomatic software and compared results with measurements from a validated manual software. For semi-automated analysis, 31,228 frames from 114 vessels were available. The validation was based on a subset of 4287 matched frames. We applied mixed model statistics to accommodate the multilevel data structure with method as a fixed effect. Lumen (minimum, mean, maximum) and media (mean, maximum) metrics showed no significant differences. Mean and maximum intima area were underestimated by the semi-automated method (ß-methodmean = - 0.289 mm2, p < 0.01; ß-methodmax = - 0.695 mm2, p < 0.01). Bland-Altman analyses showed increasing semi-automatic underestimation of intima measurements with increasing intimal extent. Comparing 3M to 12M progression between methods, mean intimal area showed minor underestimation (ß-methodmean = - 1.03 mm2, p = 0.04). Lumen and media metrics showed excellent agreement between the manual and semi-automated method. Intima metrics and progressions from 3M to 12M were slightly underestimated by the semi-automated OCT software with unknown clinical relevance. The semi-automated software has the future potential to provide robust and time-saving evaluation of CAV progression.

Cardiovascular disease and COVID-19, a deadly combination: A review about direct and indirect impact of a pandemic.

Coronavirus disease 2019 (COVID-19) is known to present with respiratory symptoms, which can lead to severe pneumonia and respiratory failure. However, it can have multisystem complications such as cardiovascular manifestations. The cardiovascular manifestations reported comprise myocarditis, cardiogenic shock, arrhythmias, pulmonary embolism, deep vein embolism, acute heart failure, and myocardial infarction. There is also an indirect impact of the pandemic on the management of cardiovascular care that has been shown clearly in multiple publications. In this review, we summarize the deadly relation of COVID-19 with cardiovascular events and the wider impact on several cardiovascular care areas by the pandemic situation.

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.

Cardiac device-related infective endocarditis in the Czech Republic: Prospective data from the ESC EORP EURO-ENDO registry.

AIM: Understanding cardiac electronic device infective endocarditis epidemiology is essential for the management of this serious complication. Only monocentric and limited data have been published regarding patients in the Czech republic so far. The aim of this study was to describe the current profile, microbiology and clinical characteristics of this population. PATIENTS AND METHODS: National data from the prospective ESC-EORP EURO-ENDO registry were collected. 57 consecutive patients with a diagnosis of cardiac device-related infective endocarditis (CDRIE) from 11 Czech centres were included. RESULTS: Staphylococcus spp. was responsible for 43.9% of isolates, whereas Culture negative endocarditis was documented in 26.3% episodes. The most frequent complications under therapy were acute renal failure (17.5%), septic shock and heart failure (both 10.5%). Extraction of device was performed in 75.4% of all patients, and the 1-year mortality was 22.5%. CONCLUSIONS: The high proportion of culture-negative endocarditis is alarming and warrants further investigation. Cardiac device related infective endocarditis is a serious complication with a high 1-year mortality in a highly polymorbid spectrum of patients.

Regional differences in presentation characteristics, use of treatments and outcome of patients with cardiogenic shock: Results from multicenter, international registry.

BACKGROUND: Concurrent evidence about cardiogenic shock (CS) characteristics, treatment and outcome does not represent a global spectrum of patients and is therefore limited. The aim of this study was to investigate these regional differences. METHODS: To investigate regional differences in presentation characteristics, treatments and outcomes of patients treated with all types of cardiogenic shock (CS) in a single calendar year on a multi-national level. Consecutive patients from 19 tertiary care hospitals in 13 countries with CS who were treated between January 1, 2018 and December 31, 2018 were enrolled in this study. RESULTS: In total, 699 cardiogenic shock patients were included in this study. Of these patients, 440 patients (63%) were treated in European hospitals and 259 (37%) were treated in Non-European hospitals. Female patients (P<0.01) and patients with a previous myocardial infarction (P=0.02) were more likely to present at Non-European hospitals; whereas older patients (P=0.01) and patients with cardiogenic shock due to acute heart failure (P<0.01) were more likely to present at European hospitals. Vasopressor use was more likely in Non-European hospitals (P=0.04), whereas use of mechanical circulatory support (MCS) was more likely in European hospitals (P<0.01). Despite adjustment for relevant confounders, 30-day in-hospital mortality risk was comparably high in CS patients treated in European vs. Non-European hospitals (hazard ratio 1.08, 95% CI 0.84-1.39, P=0.56). CONCLUSION: Despite marked heterogeneity in characteristics and treatment of CS patients, including fewer use of MCS but more frequent use of vasopressors in Non-European hospitals, 30-day in-hospital mortality did not differ between regions.

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.

Effects of implanting a long-term left ventricle assist device on post-transplant outcomes.

BACKGROUND: An increasing number of patients are receiving left ventricle assist devices as a bridge to heart transplantation. The aim of this study was to determine the difference between patients who received transplants from a left ventricle assist device and those who underwent heart transplantation without a prior left ventricle assist device implantation. MATERIAL AND METHODS: The study included patients who underwent heart transplantation in our institute between January 2010 and November 2018. The following clinical variables were evaluated: donor characteristics, patient's pre-transplant demographical data, post-transplant data, and patient survival. Cardiac allograft vasculopathy progression was prospectively examined (after 1 month and 12 months after heart transplantation) by coronary optical coherence tomography. We were interested in the difference in 1- and 5-year survival between the left ventricle assist device and non-left ventricle assist device groups. RESULTS: A total of 248 patients were identified; out of them, 48 patients received a left ventricle assist device before heart transplantation, whereas 200 had transplants with no prior left ventricle assist device implantation. There were no significant differences in any donor characteristics. The mean duration of cardiopulmonary bypass time in the non-left ventricle assist device group was 156 versus 175 min in the left ventricle assist device group (p = 0.009), blood loss was 650 versus 1045 mL (p < 0.001), the need to implant an extracorporeal membrane oxygenation was 10% versus 23% (p = 0.02). There was no difference in cardiac allograft vasculopathy progression between the groups 1 year after heart transplantation (p = 0.528). The 1- and 5-year survival, according to Kaplan-Meier, was 80% and 70% in the left ventricle assist device group, compared to 80% and 73%, respectively, in the non-left ventricle assist device group (Log-rank test: p = 0.945). CONCLUSION: Our results indicate that patients undergoing heart transplantation from left ventricle assist devices suffer significantly more from intraoperative and post-operative complications; however, only insignificant cardiac allograft vasculopathy progression and survival differences between the two groups were observed.

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.