João Ferreira-Martins

Background: Patent foramen ovale (PFO) has been identified as a conduit for paradoxical embolism causing stroke or transient ischemic attack (TIA). Long‐term data of PFO closure beyond 10 years are rare. Aims: We aimed to report the very long‐term outcomes of PFO closure and compare the efficacy of different post?procedural antithrombotic treatment (AT). Methods: Very long‐term outcomes of a previously reported cohort of patients undergoing PFO closure between May 2004 and January 2013 were reviewed. Outcomes, including recurrent stroke or TIA, bleeding, venous thromboembolism (VTE), newly diagnosed atrial fibrillation (AF), and all‐cause death, were adjudicated. The cohort was further stratified into short‐ and long‐term post‐procedural AT groups. Propensity‐score matching was performed to adjust for differences in baseline characteristics across subgroups. Results: Three hundred and one patients were included in the analysis. Median follow‐up duration was 15.0 [95% confidence interval 14.7−15.3] years. Stroke and TIA occurred in 3.4% (0.27 per 100 patient‐year) and 6.2% (0.46 per 100 patient‐year), respectively. Bleeding and VTE were noted in 3.8% and 6.5%. 9.6% of patients (0.71 per 100 patient‐year) developed AF. Thirty patients (0.70 per 100 patient‐year) died. Patients receiving long‐term AT (a single antiplatelet in > 85% of the population) experienced more bleeding and major bleeding events (log‐rank p = 0.03 and 0.02, respectively), and had a tendency toward more frequent bleeding after propensity score matching ( p = 0.09). Other outcome events were similar between subgroups. Conclusion: Benefits from PFO closure persist over the long term. A limited post‐closure AT regimen is equally effective in preventing recurrent embolic events and is associated with potentially less bleeding.

Background: Transcaval transcatheter aortic valve implantation (TAVI) is well described for patients with severe peripheral arterial disease. Conventionally, secondary arterial access via the femoral artery is used to allow bail‐out stenting of the aortotomy site in case of complications. Transradial access may reduce the risk of complications related to the secondary access itself but prevents effective bail‐out. We use the transradial approach for secondary access, accepting this risk. Aim: We aim to report the feasibility and acute outcomes following transcaval TAVI with transradial secondary access. Methods: All patients with transcaval TAVI performed from November 2016 to March 2024 at our center were identified. Patients with secondary access via the radial artery were included. The primary outcome was postprocedural mortality to hospital discharge. Secondary outcomes were the incidence of major vascular complications, bleeding, and stroke up to 72 h after the procedure. Results: A total of 20 patients were included. Procedural success was achieved in all the patients. Ten (50%) patients received cerebral protection via the right radial artery in addition to left radial secondary access. All 20 patients had successful closure of the aortotomy with a 10/8 or 8/6 mm Amplatzer ductal occluder (Abbott, USA). No patient had major complications of the aortocaval shunt either during or after the procedure. No patient needed a bailout aortic intervention. There was one death (5%) secondary to peri‐procedural stroke. Patients were usually discharged on the first postprocedural day. Conclusions: Transcaval TAVI with transradial secondary access appeared to be safe. Bailout stenting is not possible but is rarely needed. Overall, procedural vascular risks are reduced.

The radial artery is the preferred access site for cardiac catheterization because of patient comfort, early ambulation, and improved survival in acute coronary syndromes, when compared to the femoral artery route. However, it is associated with a high radial artery occlusion (RAO) rate, and patent haemostasis which can reduce this is extremely hard to implement in a busy clinical practice. Smaller sized sheaths are associated with less RAO but are uncommonly used as they could limit procedural prowess and complexity. Alternatively, the distal radial artery (dRA) approach appears to be safer with observed RAO rates of well under 1 percent without compromising benefits offered by the radial artery access. Default dRA can be accessed by palpation alone in most cases with some practice, and this can be improved further with ultrasound guidance. There is a subset of patients, especially in the elderly, where dRA access can be particularly challenging. To mitigate this, we propose a two-step cannulation strategy and illustrate this with a few cases with difficult dRA and radial artery anatomies.

Objective: We tested whether ablation methodology and study design can explain the varying outcomes in terms of atrial fibrillation (AF)‐free survival at 1 year.Background: There have been numerous paroxysmal AF ablation trials, which are heterogeneous in their use of different ablation techniques and study design. A useful approach to understanding how these factors influence outcome is to dismantle the trials into individual arms and reconstitute them as a large meta‐regression.Methods: Data were collected from 66 studies (6941 patients). With freedom from AF as the dependent variable, we performed meta‐regression using the individual study arm as the unit.Results: Success rates did not change regardless of the technique used to produce pulmonary vein isolation (PVI). Neither was adjunctive lesion sets associated with any improvement in outcome. Studies that included more males and fewer hypertensive patients were found more likely to report better outcomes. The electrocardiography method selected to assess outcome also plays an important role. Outcomes were worse in studies that used regular telemonitoring (by 23%; P < 0.001) or in patients who had implantable loop recorders (by 21%; P = 0.006), rather than those with the less thorough periodic Holter monitoring.Conclusions: Outcomes of AF ablation studies involving PVI are not affected by the technologies used to produce PVI. Neither do adjunctive lesion sets change the outcome. Achieving high success rates in these studies appears to be dependent more on patient mix and on the thoroughness of AF detection protocols. These should be carefully considered when quoting the success rates of AF ablation procedures that are derived from such studies.

Background—: Little is known about the function of inositol 1,4,5-trisphosphate receptors (IP3Rs) in the adult heart experimentally. Moreover, whether these Ca ²⁺ release channels are present and play a critical role in human cardiomyocytes remains to be defined. IP3Rs may be activated after Gαq-protein–coupled receptor stimulation, affecting Ca ²⁺ cycling, enhancing myocyte performance, and potentially favoring an increase in the incidence of arrhythmias. Methods and Results—: IP3R function was determined in human left ventricular myocytes, and this analysis was integrated with assays in mouse myocytes to identify the mechanisms by which IP3Rs influence the electric and mechanical properties of the myocardium. We report that IP3Rs are expressed and operative in human left ventricular myocytes. After Gαq-protein–coupled receptor activation, Ca ²⁺ mobilized from the sarcoplasmic reticulum via IP3Rs contributes to the decrease in resting membrane potential, prolongation of the action potential, and occurrence of early afterdepolarizations. Ca ²⁺ transient amplitude and cell shortening are enhanced, and extrasystolic and dysregulated Ca ²⁺ elevations and contractions become apparent. These alterations in the electromechanical behavior of human cardiomyocytes are coupled with increased isometric twitch of the myocardium and arrhythmic events, suggesting that Gαq-protein–coupled receptor activation provides inotropic reserve, which is hampered by electric instability and contractile abnormalities. Additionally, our findings support the notion that increases in Ca ²⁺ load by IP3Rs promote Ca ²⁺ extrusion by forward-mode Na ⁺ /Ca ²⁺ exchange, an important mechanism of arrhythmic events. Conclusions—: The Gαq-protein/coupled receptor/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias.

Background—: Two opposite views of cardiac growth are currently held; one views the heart as a static organ characterized by a large number of cardiomyocytes that are present at birth and live as long as the organism, and the other views the heart a highly plastic organ in which the myocyte compartment is restored several times during the course of life. Methods and Results—: The average age of cardiomyocytes, vascular endothelial cells (ECs), and fibroblasts and their turnover rates were measured by retrospective ¹⁴ C birth dating of cells in 19 normal hearts 2 to 78 years of age and in 17 explanted failing hearts 22 to 70 years of age. We report that the human heart is characterized by a significant turnover of ventricular myocytes, ECs, and fibroblasts, physiologically and pathologically. Myocyte, EC, and fibroblast renewal is very high shortly after birth, decreases during postnatal maturation, remains relatively constant in the adult organ, and increases dramatically with age. From 20 to 78 years of age, the adult human heart entirely replaces its myocyte, EC, and fibroblast compartment ≈8, ≈6, and ≈8 times, respectively. Myocyte, EC, and fibroblast regeneration is further enhanced with chronic heart failure. Conclusions—: The human heart is a highly dynamic organ that retains a remarkable degree of plasticity throughout life and in the presence of chronic heart failure. However, the ability to regenerate cardiomyocytes, vascular ECs, and fibroblasts cannot prevent the manifestations of myocardial aging or oppose the negative effects of ischemic and idiopathic dilated cardiomyopathy.

RETRACTION This article has been retracted: Circ Res. 2018;123:e00. DOI: 10.1161/RES.0000000000000253. Rationale: According to the immortal DNA strand hypothesis, dividing stem cells selectively segregate chromosomes carrying the old template DNA, opposing accumulation of mutations resulting from nonrepaired replication errors and attenuating telomere shortening. Objective: Based on the premise of the immortal DNA strand hypothesis, we propose that stem cells retaining the old DNA would represent the most powerful cells for myocardial regeneration. Methods and Results: Division of human cardiac stem cells (hCSCs) by nonrandom and random segregation of chromatids was documented by clonal assay of bromodeoxyuridine-tagged hCSCs. Additionally, their growth properties were determined by a series of in vitro and in vivo studies. We report that a small class of hCSCs retain during replication the mother DNA and generate 2 daughter cells, which carry the old and new DNA, respectively. hCSCs with immortal DNA form a pool of nonsenescent cells with longer telomeres and higher proliferative capacity. The self-renewal and long-term repopulating ability of these cells was shown in serial-transplantation assays in the infarcted heart; these cells created a chimeric organ, composed of spared rat and regenerated human cardiomyocytes and coronary vessels, leading to a remarkable restoration of cardiac structure and function. The documentation that hCSCs divide by asymmetrical and symmetrical chromatid segregation supports the view that the human heart is a self-renewing organ regulated by a compartment of resident hCSCs. Conclusions: The impressive recovery in ventricular hemodynamics and anatomy mediated by clonal hCSCs carrying the “mother” DNA underscores the clinical relevance of this stem cell class for the management of heart failure in humans.

RETRACTION: This article has been retracted: Circ Res . 2018;123:e00. DOI: 10.1161/RES.0000000000000252.