Transcatheter aortic valve replacement ­ 10 years experience at Gottsegen György National Cardiovascular Center in Hungary / Tíz év tapasztalatai a transzkatéteres aortamubillentyu-implantációval a Gottsegen György Országos Kardiovaszkuláris Intézetben.

Összefoglaló. Bevezetés: A transzkatéteres aortamubillentyu-beültetés (TAVI) az idos, súlyos aortastenosisban szenvedo, multimorbid, magas mutéti kockázattal rendelkezo betegek esetében javasolt a szívsebészeti aortamubillentyu-beültetés alternatívájaként. Célkituzés: Jelen munkánkban az intézetünkben elindult TAVI-program elso 10 éve alatt elvégzett 463, TAVI-n átesett beteg rövid és hosszú távú eredményeit tekintjük át és értékeljük. Külön vizsgáljuk az elso 200 beteg és az utánuk következo 263 beteg eredményeit. Módszer: 2008. november 11. és 2018. december 31. között 463 betegnél végeztünk TAVI-t. Betegeink átlagéletkora 79,6 év, átlagos logisztikus EuroSCORE-értékük 19,0%, átlagos STS-score-értékük pedig 5,2% volt. A beavatkozás elott az esetek 72%-ában NYHA III-as vagy IV-es funkcionális stádiumban voltak. A beavatkozások 92,8%-át transfemoralis behatolásból végeztük. Az aortabillentyun mért átlagos gradiens 50 Hgmm, a billentyuarea 0,55 cm2 volt. Az esetek mintegy 2%-ában az aortabillentyu-bioprotézis restenosisa miatt "valve-in-valve" beavatkozást végeztünk. Eredmények: A TAVI után a 30 napos halálozás 5,2%, az 1 éves pedig 16,4% volt. A TAVI-t követoen kialakult szövodményeket a VARC-2 kritériumrendszere alapján értékeltük. A beavatkozás után 2,2%-ban fordult elo major stroke. A leggyakoribb szövodmény, a posztoperatív pacemakerimplantáció (19,9%) aránya szignifikánsan csökkent a késobb TAVI-n átesett 263 beteg esetében (26,5% vs. 14,8% [p = 0,002]). A vérzéses szövodmények aránya a percutan beavatkozások bevezetésével szignifikánsan emelkedett ugyan (10% vs. 20,2% [p = 0,016]), de ez nem járt a mortalitás emelkedésével. Következtetés: Az eredmények alapján elmondhatjuk, hogy a TAVI intézetünkben is biztonságos alternatívát jelent a magas mutéti rizikóval rendelkezo, súlyos, tünetes aortastenosisban szenvedo betegek esetében. Orv Hetil. 2022; 163(6): 229-235. INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is an alternative treatment to surgical aortic valve replacement for elderly, high surgical risk patients. OBJECTIVE: The aim of this study was to evaluate the short- and long-term outcomes of those 463 patients who underwent TAVI during the first 10 years in our TAVI program. We compare the first 200 patients' results with the further 263 patients' results. METHOD: Between 11th November 2008 and 31st December 2018, 463 patients underwent TAVI. The average age of the patients was 79.6 years, the average logistic EuroSCORE was 19.0%, the average STS score was 5.2%. 72% of the patients were in NYHA III or IV stage before TAVI. 92% of TAVIs were performed from femoral arteries. Average mean gradient was 50.0 mmHg and aortic valve area was 0.55 cm2, respectively. In 2% of the cases, "valve-in-valve" intervention was performed because of the restenosis of former aortic valve prosthesis. RESULTS: 30-day mortality was 5.2% and the 1-year mortality was 16.4% after TAVI. Post-TAVI complications were evaluated according to the VARC-2 definitions. Major stroke occurred in 2.2% after TAVI. The most common complication was pacemaker implantation (19.9%), but their incidence was significantly reduced between the 2 groups (26.5% vs. 14.8% [p = 0.002]). The incidence of vascular access site complications was significantly higher between the 2 groups (10% vs. 20.2% [p = 0.016]), but it did not affect the mortality. CONCLUSION: Based on our results, TAVI is a safe alternative treatment for patients with severe, symptomatic aortic stenosis in our institute as well. Orv Hetil. 2022; 163(6): 229-235.

The prognostic value of immediate post-TAVI hemodynamic evaluation is superior to aortography and transoesophageal echocardiography in predicting patient survival.

BACKGROUND: Although post-TAVI PAR is commonly seen, its exact evaluation, grading and the true impact on patients' survival are still debated. This single center study aimed to evaluate the effect of post transcatheter aortic valve implantation (TAVI) paravalvular aortic regurgitation (PAR) on patients' survival. The outcome was evaluated by the three most commonly used techniques just after TAVI in the interventional arena. METHODS: 201 high risk patients with severe symptomatic aortic stenosis underwent TAVI with the self-expandable system. The severity of post-TAVI PAR was prospectively evaluated by aortography and transesophageal echocardiography (TEE) using a four-class scheme and hemodynamic evaluation by calculation of the regurgitation index (RI). Median follow up time was 763 days. RESULTS: Post-TAVI PAR results of the three different modalities were concordant with each other (all p < 0.001). Patients with grade 0-I PAR by aortography had better long term outcomes compared to those who had grade II-III PAR (unadjusted HR 1.77 [95% CI, 1.04-3.01], p = 0.03). Although in multivariate analysis neither aortography nor TEE were shown to be significant predictors of survival, hemodynamic assessment using the exact RI result was a significant predictor of survival and its effect was found to be linear (adjusted HR 0.72 [95% CI, 0.52-0.98] for 10% point increase in RI, p = 0.03595). CONCLUSIONS: Among the three modalities that are frequently used to evaluate the outcome, post-TAVI RI showed the highest added predictive value for survival.

Titin isoform expression in aortic stenosis.

Titin is a giant sarcomeric protein that plays a major role in determining passive myocardial stiffness. The shorter N2B isoform results in a higher passive myocardial stiffness than the longer N2BA isoform. We hypothesised that the expression of the short N2B isoform would be increased in patients with aortic stenosis compared with healthy controls in response to pressure overload, in order to act as a modulator for the increased demand placed on the left ventricle during the early stages of the hypertrophic response. Myocardial biopsies were obtained from the left ventricle of 19 patients undergoing aortic valve replacement for aortic stenosis who had no significant co-existing coronary artery disease. Left ventricular biopsies were also obtained from 13 donor hearts for comparison. SDS-agarose gels revealed small N2B and large N2BA cardiac titin isoforms, with a mean N2BA/N2B ratio that was significantly decreased in the 19 aortic stenotic patients compared with the 13 controls (0.66+/-0.04 in the normal donor hearts compared with 0.48+/-0.03 in patients with aortic stenosis; P=0.02). However, total titin remained unchanged (0.28+/-0.02 compared with 0.24+/-0.02 respectively; P=0.29). In conclusion, the expression of less N2BA and more N2B titin in response to pressure overload may result in the generation of higher passive tension upon stretch to a given sarcomere length and this might affect cardiac performance.

[Transient left ventricular apical akinesis with systolic dysfunction after physical exercise: a form of tako-tsubo syndrome]. / Fizikai terhelés indukálta reverzíbilis csúcsi akinézis szisztolés diszfunkcióval: a tako-tsubo-szindróma egyik formája.

A 43-year-old woman with mild hypertension and type-2 diabetes mellitus was presented to the coronary care unit because of ongoing chest pain and associated dyspnea after physical exercise. On arrival, her ECG disclosed ST-segment elevations in the precordial leads. The emergent cardiac catheterization failed to demonstrate coronary artery disease. The prompt performed transthoracic echocardiogram demonstrated systolic dysfunction with apical ballooning. Akinetic segments were irrespective of coronary artery anatomy. Laboratory tests revealed only slightly elevated cardiac enzymes: we observed a significant discrepancy between the extent of akinesis and the minimal increase in cardiac necroenzymes. The patient was medically managed and discharged in stable condition, with follow-up at 4 weeks demonstrating nearly total recovery of cardiac function and total resolution of wall motion disorder. Her clinical presentation is consistent with that of tako-tsubo cardiomyopathy, a syndrome that is characterized by transient apical regional wall motion abnormalities in the absence of epicardial coronary artery disease. Main precipitating factor is thought to be the cathecolamin excess due to emotional or physical stress, subarachnoid hemorrhage, phaeochromocytoma or cocaine use. The authors report the first physical exercise induced tako-tsubo syndrome in the Hungarian medical literature.

Drugs, gene transfer, signaling factors: a bench to bedside approach to myocardial stem cell therapy.

In the past few years, the dogma that the heart is a terminally differentiated organ has been challenged. Evidence from preclinical investigations emerged that there are cells, even in the heart itself, that may be able to restore impaired cardiac function after myocardial infarction. Although the exact mechanisms by which the infarcted heart can be repaired by stem cells are not yet fully defined, there is a new optimism among cardiologists that this treatment will prove successful in addressing the cause of heart failure after myocardial infarction-myocyte loss. Despite the promising preliminary data of human myocardial stem cell trials, scientists have also focused on the possibility of enhancing the underlying mechanisms of stem cell repair to gain healthier myocardial tissue. Attempts to induce neo-angiogenesis by transfecting stem cells with signaling factors (such as VEGF), to raise the number of endothelial progenitor cells with medical treatments (such as statins), to transfect stem cells with heat shock protein 70 (as a cardioprotective agent against ischemia) and to enhance the healing process after myocardial infarction with the use of various forms of stimulating factors (G-CSF, SCF, GM-CSF) have been made with notable results. In this article, we summarize the evidence from preclinical and clinical myocardial stem cell studies that have addressed the possibility of enhancing the regenerative capacity of cells used after myocardial infarction.

Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs.

BACKGROUND: Ischaemic preconditioning results in a reduction in ischaemic-reperfusion injury to the heart. This beneficial effect is seen both with direct local preconditioning of the myocardium and with remote preconditioning of easily accessible distant non-vital limb tissue. Ischaemic postconditioning with a comparable sequence of brief periods of local ischaemia, when applied immediately after the ischaemic insult, confers benefits similar to preconditioning. OBJECTIVE: To test the hypothesis that limb ischaemia induces remote postconditioning and hence reduces experimental myocardial infarct size in a validated swine model of acute myocardial infarction. METHODS: Acute myocardial infarction was induced in 24 pigs with 90 min balloon inflations of the left anterior descending coronary artery. Remote ischaemic postconditioning was induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after the balloon deflation. Infarct size was assessed by measuring 72 h creatinine kinase release, MRI scan and immunohistochemical analysis. RESULTS: Area under the curve of creatinine kinase release was significantly reduced in the postconditioning group compared with the control group with a 26% reduction in the infarct size (p<0.05). This was confirmed by MRI scanning and immunohistochemical analysis that revealed a 22% (p<0.05) and a 47.52% (p<0.01) relative reduction in the infarct size, respectively. CONCLUSION: Remote ischaemic postconditioning is a simple technique to reduce infarct size without the hazards and logistics of multiple coronary artery balloon inflations. This type of conditioning promises clear clinical potential.

[Experiences with the first, Hungarian autologous bone marrow cell transplantation in acute myocardial infarction]. / Akut szívizom-infarctusban végzett elso magyar autológ csontveloi o'ssejt transzplantációk során szerzett tapasztalataink.

Intracoronary transfer of autologous bone marrow cells promotes recovery of left ventricular systolic function in patients with acute myocardial infarction. Although the exact mechanisms of stem cell therapy are still intensely debated, the concept of stem cell therapy has already been introduced into the clinical practice--at least as an adjunctive therapy in clinical trials. In this article the authors report their experiences about the first Hungarian phase I. trial in bone marrow stem cell transplantation after acute myocardial infarction. So far, four patients with acute ST elevation myocardial infarction were eligible and recruited into the trial. All patients received purified, autologous bone marrow stem cells into the re-opened infarct related artery via a second catheterisation. The primary end point of the study is ejection fraction, which is measured by cardiac MRI at the beginning and 6 months after recruitment. So far, cell transfer did not increase the risk of adverse clinical events or proarrhythmic effects.

[Stem cell therapy in cardiovascular diseases]. / Ossejtek alkalmazása a cardiovascularis betegségek kezelésében.

Myocardial infarction is the leading cause of congestive heart failure in the industrialized world. Current treatments fail to address the underlying scarring and cell loss, which are the causes of ischaemic heart failure. Recent interest has focused on stem cells, which are undifferentiated and pluripotent cells that can proliferate, potentially self-renew, and differentiate into cardiomyocytes and endothelial cells. Myocardial regeneration is the most widely studied and debated example of stem cell plasticity. Early reports from animal and clinical investigations disagree on the extent of myocardial renewal in adults, but evidence indicates that cardiomyocytes were generated in what was previously considered a postmitotic organ. So far, candidates for cardiac stem cell therapy have been limited to patients with acute myocardial infarction and chronic ischaemic heart failure. Currently, bone marrow stem cells seem to be the most attractive cell type for these patients. The cells may be delivered by means of direct surgical injection, intracoronary infusion, retrograde venous infusion, and transendocardial infusion. Stem cells may directly increase cardiac contractility or passively limit infarct expansion and remodeling. Early phase I clinical studies indicate that stem cell transplantation is feasible and may have beneficial effects on ventricular remodeling after myocardial infarction. Future randomized clinical trials will establish the magnitude of benefit and the effect on mortality after stem cell therapy.

[The role of caveolin-1 gene in carcinogenesis]. / A caveolin-1 gén szerepe a carcinogenesisben.

Caveolin-1 is responsible for the development of caveolae, which are vesicular invaginations of the plasma membrane, and plays a key role in membrane traffic and signal transduction. The role of caveolin-1 in carcinogenesis has been a subject to numerous investigations, however, the expression pattern and the function of caveolin-1 are rather controversial both in gastrointestinal and extraintestinal cancers. The vast majority of results based on cancer cell line experiments indicate that caveolin-1 might act as a tumor suppressor gene. In tumor tissues, however, caveolin-1 seem to fulfill a tumor promoting role, since the expression of caveolin-1 is increased when compared to normal tissue counterparts. In this review, the authors summarize the results of caveolin-1 expression in gastrointestinal and extraintestinal cancer emphasizing possible future therapeutic implications.