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.

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.

Iron Deficiency in Patients with Advanced Heart Failure.

Background and Objectives: Iron deficiency (ID) is a common comorbidity in patients with heart failure. It is associated with reduced physical performance, frequent hospitalisations for heart failure decompensation, and high cardiovascular and overall mortality. The aim was to determine the prevalence of ID in patients with advanced heart failure on the waiting list for heart transplantation. Methods and Materials: We included 52 patients placed on the waiting list for heart transplantation in 2021 at our centre. The cohort included seven patients with LVAD (left ventricle assist device) as a bridge to transplantation implanted before the time of results collection. In addition to standard tests, the parameters of iron metabolism were monitored. ID was defined as a ferritin value <100 µg/L, or 100−299 µg/L if transferrin saturation (T-sat) is <20%. Results: ID was present in 79% of all subjects, but only in 35% of these patients anaemia was expressed. In the group without LVAD, ID was present in 82%, a median (lower−upper quartile) of ferritin level was 95.4 (62.2−152.1) µg/mL and mean T-sat was 0.18 ± 0.09. In LVAD group, ID was present in 57%, ferritin level was 268 (106−368) µg/mL and mean T-sat was 0.14 ± 0.04. Haemoglobin concentration was the same in patients with or without ID (133 ± 16) vs. (133 ± 23). ID was not associated with anaemia defined with regard to patient's gender. In 40.5% of cases, iron deficiency was accompanied by chronic renal insufficiency, compared to 12.5% of the patients without ID. In the patients with LVAD, ID was present in four out of seven patients, but the group was too small for reliable statistical testing due to low statistical power. Conclusions: ID was present in the majority of patients with advanced heart failure and was not always accompanied by anaemia and renal insufficiency. Research on optimal markers for the diagnosis of iron deficiency, especially for specific groups of patients with heart failure, is still ongoing.

Heart rate and early progression of cardiac allograft vasculopathy: A prospective study using highly automated 3-D optical coherence tomography analysis.

INTRODUCTION: Heart rate slowing agents are frequently prescribed to manage heart transplant (HTx) patients with the assumption that higher heart rate is a risk factor in cardiovascular disease. PATIENTS AND METHODS: This prospective two-center study investigated early progression of cardiac allograft vasculopathy (CAV) in 116 HTx patients. Examinations by coronary optical coherence tomography and 24-hour ambulatory ECG monitoring were performed both at baseline (1 month after HTx) and during follow-up (12 months after HTx). RESULTS: During the first post-HTx year, we observed a significant reduction in the mean coronary luminal area from 9.0 ± 2.5 to 8.0 ± 2.4 mm2 (P < .001), and progression in mean intimal thickness (IT) from 106.5 ± 40.4 to 130.1 ± 53.0 µm (P < .001). No significant relationship was observed between baseline and follow-up mean heart rates and IT progression (R = .02, P = .83; R = -.13, P = .18). We found a mild inverse association between beta-blocker dosage at 12 months and IT progression (R = -.20, P = .035). CONCLUSION: Our study did not confirm a direct association between mean heart rate and progression of CAV. The role of beta blockers warrants further investigation, with our results indicating that they may play a protective role in early CAV development.

[Heart transplantation and follow-up treatment with AL-amyloidosis in 5 patients]. / Transplantace srdce a následující lécba AL-amyloidózy u 5 pacientu.

The prognosis for patients with cardiac impairment due to AL-amyloid deposition and severe cardiac insufficiency is poor, with a survival median in the order of months. The classical treatment of AL-amyloidosis in combination with cardiac insufficiency is very poorly tolerated and the treatment of such patients is associated with considerably higher mortality than among other patients with AL-amyloidosis. If, however, patients with an isolated or another dominating cardiac impairment, without severe damage to other organs and tissues, have a heart transplant performed, their cardiovascular condition will significantly improve as a result, along with their ability to tolerate any kind of treatment for AL-amyloidosis including that using high-dose chemotherapy with a transplant of autologous hematopoietic stem cells. The achievement of complete remission of AL-amyloidosis is a precondition for long-term survival, since when not achieved, amyloid deposition also arises in the transplanted heart. At the Centre for Cardiovascular and Transplantation Surgery, Brno, the first heart transplant due to its impairment by AL-amyloidosis was performed in 2010. By the year 2017 the number of patients with AL-amyloidosis, who had first undergone a heart transplant with subsequent treatment for AL-amyloidosis, increased to 5. The median age at which a heart transplant was performed is 60 (48-65) years. Four patients were men, one was a woman. The median monitoring equals 65 (88-15) months. Complete remission of AL-amyloidosis was achieved in all the patients. There were 5 lines of treatment needed for the first patient to attain it, of that twice high-dose melphalan with autologous stem cell transplantation, for the second patient a second-line treatment, high-dose melphalan and bortezomib-based therapy. No specific therapy was needed for the third patient, as immunosuppressive therapy following the heart transplant containing prednison led to complete remission of AL-amyloidosis. In the fourth case, sustainable complete remission was reached by high-dose melphalan and in the fifth case by one line of bortezomib-based therapy. The aforementioned data illustrate that a heart transplant is the first step which makes the patients with a severe heart failure, not tolerating any efficient therapy of AL-amyloidosis, capable of undergoing intense treatment of AL-amyloidosis. Sometimes one high-dose chemotherapy is sufficient, while at other times multiple treatment lines are needed to reach complete remission of AL-amyloidosis.Key words: AL-amyloidosis - autologous hematopoietic stem cells transplantation - bortezomib - cardiomyopathy - lenalidomide - thalidomide - heart transplantation.

[Heart transplantation and infection]. / Transplantace srdce a infekce.

Heart transplantation (HTx) is a method of treatment for patients with end-stage heart failure with severe symptoms despite complex therapy. Post-transplant difficulties include acute rejection and infectious complications, which are the most common reason of morbidity and mortality in the first year after heart transplant. It requires the patient to remain on immunosuppressive medication to avoid the possibility of graft rejection. Therefore the range of infection is much larger. The diagnosis and treatment of viral, bacterial and fungal infections is often difficult.Key words: heart transplantation - immunosuppression - infection.

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.

Viral genome changes and the impact of viral genome persistence in myocardium of patients with inflammatory cardiomyopathy.

INTRODUCTION: Viral infections are considered the most frequent cause of myocarditis and dilated cardiomyopathy (DCM). MATERIAL AND METHODS: We investigated the changes in viral presence and the impact of viral genome persistence in the myocardium on echocardiographic parameters, functional status and some laboratory parameters in a 6-month follow-up. Fifty-four patients with recent onset DCM, left ventricular ejection fraction < 40% and biopsy-proven myocarditis (> 14 mononuclear leukocytes/mm2 and/or > 7 T-lymphocytes/mm2) were enrolled. Polymerase chain reaction (PCR) was performed to detect pathogens in the myocardium. Patients were divided according to the administered therapy: standard heart failure medication (46 patients) and immunosuppressive therapy (8 patients). RESULTS: In the standard heart failure medication group viral clearance was observed in 13 patients and viral persistence in 24 patients in the follow-up period. Comparing both groups, there was no statistically significant difference - LVEF improvement of 12.0 ±11.4% vs. 18.3 ±12.6%, decrease in NYHA class of 0.7 ±0.7 vs. 1.0 ±0.7, decline in NT-proBNP of 1335 ±1933 ng/l vs. 1942 ±3242 ng/l and decrease in infiltrating leukocytes of 11.1 ±15.8 vs. 6.7 ±23.0 cells/mm2 and T-lymphocytes of 5.8 ±15.1 vs. 1.8 ±10.9 cells/mm2 (all p = NS). A decrease in PCR positive patients from 37 to 29 was observed. The number of PVB19 positive PCR findings decreased from 5 to 4 in patients with immunosuppressive therapy. CONCLUSIONS: A decrease in the number of positive PCR findings in control endomyocardial biopsy was observed. Viral genome persistence was not associated with worse outcome in short-term follow-up.

Early detection of cardiac allograft vasculopathy using highly automated 3-dimensional optical coherence tomography analysis.

BACKGROUND: Optical coherence tomography (OCT)-based studies of cardiac allograft vasculopathy (CAV) published thus far have focused mainly on frame-based qualitative analysis of the vascular wall. Full capabilities of this inherently 3-dimensional (3D) imaging modality to quantify CAV have not been fully exploited. METHODS: Coronary OCT imaging was performed at 1 month and 12 months after heart transplant (HTx) during routine surveillance cardiac catheterization. Both baseline and follow-up OCT examinations were analyzed using proprietary, highly automated 3D graph-based optimal segmentation software. Automatically identified borders were efficiently adjudicated using our "just-enough-interaction" graph-based segmentation approach that allows to efficiently correct local and regional segmentation errors without slice-by-slice retracing of borders. RESULTS: A total of 50 patients with paired baseline and follow-up OCT studies were included. After registration of baseline and follow-up pullbacks, a total of 356 ± 89 frames were analyzed per patient. During the first post-transplant year, significant reduction in the mean luminal area (p = 0.028) and progression in mean intimal thickness (p = 0.001) were observed. Proximal parts of imaged coronary arteries were affected more than distal parts (p < 0.001). High levels of LDL cholesterol (p = 0.02) and total cholesterol (p = 0.031) in the first month after HTx were the main factors associated with early CAV development. CONCLUSIONS: Our novel, highly automated 3D OCT image analysis method for analyzing intimal and medial thickness in HTx recipients provides fast, accurate, and highly detailed quantitative data on early CAV changes, which are characterized by significant luminal reduction and intimal thickness progression as early as within the first 12 months after HTx.

Improvement of left ventricular systolic function in inflammatory cardiomyopathy: What plays a role?

AIMS: To compare the differences between patients with inflammatory cardiomyopathy (ICM) with and without improvement in left ventricular (LV) systolic function and to identify the relevant predictors of LV improvement. PATIENTS AND METHODS: The study included 63 patients with biopsy-proven ICM and heart failure symptoms of at least NYHA II, symptom duration ≤ 6 months, LV ejection fraction (LVEF) ≤ 40% assessed by echocardiography and presence of >14 mononuclear leukocytes (LCA+ cells)/mm2 in biopsy samples. Patients were evaluated at baseline and after 6 months. RESULTS: In the group with LVEF improvement of ≥ 10% (I+ group, n = 41), LVEF increased from 24 ± 7% to 47 ± 8% (P < 0.001). In 22 patients (group I-), there was no or minimal LVEF increase (< 10%). In the I+ group, there were more LCA+ cells/mm2 at baseline (25.1 ± 16.5 vs. 18.5 ± 4.4 cells/mm2; P = 0.032) and a more significant decrease in LCA+ cells in the follow-up (reduction of 13.6 ± 14.3 cells/mm2 vs. 5.0 ± 7.7 cells/mm2 in the I- group; P = 0.009). The univariate logistic regression showed a possible association of number of LCA+ cells, LV end-diastolic diameter and N-terminal fragment of pro-brain natriuretic peptide (NTproBNP) value with LVEF improvement. In the multivariate analysis, only NTproBNP at diagnosis was confirmed as an independent predictor of LVEF improvement (OR=1.2; 1.003 to 1.394; P = 0.046). CONCLUSION: The LV systolic function improvement was observed in 65% of the patients. In these patients, the number of inflammatory cells at baseline was higher and decreased more but the higher baseline NTproBNP value was the only independent predictor of LVEF improvement.

Usefulness of left ventricle dyssynchrony assessment before cardiac resynchronization implantation.

BACKGROUND: A number of trials have demonstrated the effect of cardiac resynchronization therapy (CRT) on functional improvement and reversed left ventricle remodeling. Meeting contemporary guidelines approximately 30- 40% of patients do not respond to CRT (non-responders). AIM: To quantify the predictive ability of basal QRS width and basal echocardiographic parameters of left ventricle contraction dyssynchrony in our group of CRT patients. To compare effectiveness of these parameters assessment in patients with ischemic (iCMP) and non-ischemic cardiomyopathy (niCMP) and with sinus rhythm (SR) and atrial fibrillation (AF). PATIENTS AND METHODS: 194 patients after successful introduction of CRT device were evaluated. Evaluation of NYHA function class, QRS width and echocardiographic parameters including parameters of left ventricle contraction dyssynchrony (SPWMD: septal-to-posterior wall motion delay, Ts-sep-lat: time interval between maximum of systolic movement of septum and lateral wall using tissue Doppler imaging, IVMD: interventricular mechanical delay) performed before implantation and 3 months after implantation of CRT device. RESULTS: Responder (improved in NYHA class after CRT) rate was 61%. SR patients showed higher benefit compared to AF patients (responder rate 63% vs. 52%, p<0.05). Narrowing of QRS width after CRT was observed only in responders. SPWMD and Ts-sep-lat decreased after CRT in all subgroups. SPWMD dyssynchrony (SPMWD > or = 130 ms) reduction after CRT was more expressed in niCMP population. Ts-sep-lat dyssynchrony (Ts-sep-lat > or = 65 ms) reduction after CRT was more expressed in SR patients. IVMD (IVMD > or = 60 ms) remained unchanged in average, but significant decrease was observed in responders and significant increase in non-responders. QRS width, SPWMD and Ts-sep-lat showed moderate sensitivity but poor specificity to predict CRT benefit. QRS width > or = 150 ms in niCMP patients showed higher sensitivity to predict CRT effect compared to iCMP patients (91%, 65% respectively). IVMD showed poor sensitivity but good specificity to predict CRT benefit. IVMD in SR patients (compared to AF patients) showed higher specificity to predict CRT effect (90%, 63% respectively). CONCLUSION: None of tested left ventricle contraction dyssynchrony parameters showed good sensitivity and specificity to predict CRT benefit. QRS width as a predictor factor was more beneficial in non-ischemic patients and IVMD in sinus rhythm patients.

Does the resynchronization therapy lead to reduction of symptoms and to improvement of left ventricular functions in patients with chronic heart failure?

AIM: To evaluate the therapeutic effect of resynchronization in patients with chronic heart failure who are symptomatic despite adequate pharmacological medication. SAMPLE AND METHODOLOGY: 118 patients with chronic heart failure, mostly dilated cardiomyopathy and ischaemic heart disease, with depressed systolic function, decreased left ventricular ejection fraction (LVEF) and left bundle branch block wide QRS complex, underwent implantation of the biventricular system between the years 2000-2006. We assessed changes in the NYHA functional class, hemodynamic parameters acquired during right heart catheterization, the maximum oxygen consumption during stress spiroergometric examination, as well as echocardiographic parameters. RESULTS: A statistically significant improvement was found in the NYHA functional class (from 2.8 +/- 0.4 to 2.3 +/- 0.5 after 3 m, p < 0,001 and to 2.5 +/- 0.6 after 12 m, p < 0,01 respectively), as well as an increase in the maximum oxygen consumption during spiroergometric examination (VO2 max from 14.1 +/- 3.1 ml/kg/min to 15.3 +/- 3.1 ml/kg/ min, p < 0,001 and to 15.3 +/- 2.5 ml/kg/min, p = NS respectively). In regard to hemodynamic parameters, there were increases in cardiac output and cardiac index after three months. After 12 months the change was not statistically significant (CO from 3.9 +/- 1 l/min to 4.2 +/- 0.9 l/min, p < 0,05, and to 4.1 +/- 0.9 l/min, p = NS, CI from 2 +/- 0.5 l/kg/min to 2.2 +/- 0.4 l/kg/min, p < 0,05, and to 2.1 +/- 0.4 l/kg/min, p = NS). Mean pulmonary artery pressure, as well as pulmonary capillary wedge pressure was reduced after 3, as well as after 12 months to a statistically significant degree (MPA from 29.1 +/- 11.5 mm Hg to 23.9 +/- 10.3 mm Hg, p< 0,001, and to 24.9 +/- 11.8 mm Hg, p < 0,01 respectively, and PCWP from 19.9 +/- 9.5 mm Hg to 15.2 +/- 9.2 mm Hg, p < 0,01, and to 15.6 +/- 9 mm Hg, p < 0,01 respectively). In regard to echocardiographic parameters, there was an increase in LVEF, a reduction in the end-diastolic diameter of the left ventricle, as well as a statistically significant reduction in severity of mitral regurgitation after 3, as well as 12 months (LVEF from 20.5 +/- 5.3%, to 23 +/- 6.5%, p < 0,001, and to 24.5 +/- 8%, p < 0,001, LVEDD from 69 +/- 9 mm to 68 +/- 9 mm, p < 0.01 and to 65 +/- 12 mm, p< 0.01 respectively, mitral regurgitation from 2.2 +/- 0.8 to 1.9 +/- 0.8, p< 0.001, and to 2 +/- 0.8, p < 0.001. CONCLUSIONS: In patients with chronic heart failure, resynchronization therapy leads to reduced symptoms, reduction in dyspnea and to improvements in cardiac performance due to increase in the systolic function of the left ventricle and hemodynamic changes.