Effects of preoperative magnetic resonance image on survival rates and surgical planning in breast cancer conservative surgery: randomized controlled trial (BREAST-MRI trial).

BACKGROUND: Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. Controversy remains about its impact on the preoperative staging of breast cancer surgery. This study evaluated survival and surgical outcomes of preoperative MRI in conservative breast cancer surgery. METHODS: A phase III, randomized, open-label, single-center trial including female breast cancer participants, stage 0-III disease, and eligible for breast-conserving surgery. We compared the role of including MRI in preoperative evaluation versus radiologic exam routine with mammography and ultrasound in breast cancer conservative candidates. The primary outcome was local relapse-free survival (LRFS), and secondary outcomes were overall survival (OS), mastectomy rate, and reoperation rate. RESULTS: 524 were randomized to preoperative MRI group (n = 257) or control group (n = 267). The survival analysis showed a 5.9-years LRFS of 99.2% in MRI group versus 98.9% in control group (HR = 0.72; 95% CI 0.12-4.28; p = 0.7) and an OS of 95.3% in the MRI group versus 96.3% in the control group (HR = 1.37 95% CI 0.59-3.19; p = 0.8). Surgical management changed in 21 ipsilateral breasts in the MRI group; 21 (8.3%) had mastectomies versus one in the control group. No difference was found in reoperation rates, 22 (8.7%) in the MRI group versus 23 (8.7%) in the control group (RR = 1.002; 95% CI 0.57-1.75; p = 0.85). CONCLUSION: Preoperative MRI increased the mastectomy rates by 8%. The use of preoperative MRI did not influence local relapse-free survival, overall survival, or reoperation rates.

Malignant Primary and Metastatic Cardiac Tumors: A Single-Center 27-Year Case Review.

BACKGROUND: Malignant primary cardiac tumors are exceedingly rare, and despite surgical exeresis or chemotherapy, their prognosis remains poor. Cardiac invasion by metastatic tumors, while more common, also entails an unsatisfactory outcome. This study aimed to review patients diagnosed with malignant primary and secondary cardiac tumors in a tertiary center between 1995 and 2022. METHODS: Clinical data, echocardiographic, computed tomography, and magnetic resonance assessments of tumor location and morphology, histology, treatment, and survival were retrospectively analyzed. RESULTS: Sixty malignant cardiac tumors were diagnosed: 17 primary (A) and 43 metastatic (B) tumors. A: the most common types were angiosarcoma (41%), undifferentiated sarcoma (23%), and fibrosarcoma (18%). Patients with primary tumors were younger than patients with metastatic tumors (41 ± 13 years vs. 57 ± 18 years, p = 0.001), with no significant gender difference. The most frequent presentations were heart failure (59%) and arrhythmia (23%). The most prevalent tumor location was the right heart chambers (71%), mostly in the right atrium (35%). 47% were submitted to tumor resection, and 29% received chemotherapy. The mortality rate was 82% with a median survival of 6.0 (interquartile range: 1.0-11.8) months after diagnosis (minimum of 12 days and maximum of 19 years). One patient with fibrosarcoma underwent heart transplantation and was still alive and well after 19 years. B: regarding metastatic cardiac invasion, the most common primary tumor sites were lung carcinomas (38%), thymomas (17%), and lymphomas (14%). Presentation with pericardial effusion was common (33%). The mortality rate was 72%, with a median survival of 3.6 (1.0-13.4) months (minimum of 7 days, maximum of 5 years). CONCLUSION: Diagnosis of metastatic cardiac tumors was more common than that of malignant primary tumors, both with a dismal prognosis. When radical exeresis is not possible, heart transplantation can be an option with a favorable outcome in carefully selected patients with sarcomas.

Urgent versus Non-Urgent Transcatheter Aortic Valve Implantation Outcomes.

INTRODUCTION: There are limited data about the outcomes of nonelective transcatheter aortic valve implantation (TAVI). Some studies suggest that these patients (pts) have worst results. Our purpose was to compare outcomes in pts submitted to urgent versus elective TAVI. METHODS: Retrospective analysis of 298 consecutive pts submitted to TAVI between 2018 and 2021 in a single tertiary center. Baseline characteristics and outcomes were collected and compared between elective and nonelective TAVI. RESULTS: Pts submitted to urgent TAVI (79 pts) had worse baseline characteristics, with higher EuroScore risk (9.26 vs. 5.17%, p < 0.0001), STS score (7.09 vs. 4.4%, p < 0.0001), and NT pro-natriuretic peptide B (10,168 vs. 3,241 pg/mL, p = 0.001), lower left ventricle ejection fraction (45 vs. 52%, p = 0.003), more diabetes (46.8 vs. 32.4%, p = 0.0.22), peripheral artery disease (21.5 vs. 6.8%, p < 0.0001), and poor vascular accesses (18.4 vs. 7.4%, p = 0.007). Urgent TAVI was associated with higher mortality (25.3 vs. 15.1%, p = 0.043), 30-day cardiovascular mortality (17.5 vs. 4%, p = 0.001), life-threatening bleeding (11.5 vs. 4.1%, p = 0.018), vascular complications (11.5 vs. 4.6%, p = 0.031), and longer hospital stay (28 vs. 12 days, p < 0.0001), but not with intensive care unit or post-TAVI hospital stay (5 vs. 4 days, p = 0.197 and 11 vs. 10 days, p = 0.572). When adjusted to differences in baseline characteristics, urgent TAVI was only associated with longer hospital stay (p < 0.0001). CONCLUSION: Pts submitted to urgent TAVI have worse short-term outcomes, but this seems to be attributable to the worse baseline characteristics instead of the urgent nature of the procedure.

Non-VKA Oral Anticoagulants in Adult Congenital Heart Disease: a Single-Center Study.

PURPOSE: Non-VKA oral anticoagulants (NOACs) prescription is increasing in adults with congenital heart disease (ACHD). However, data on efficacy and safety in ACHD is unclear, particularly in severe CHD. The study aimed to review the safety and efficacy of NOACs in ACHD. METHODS: Retrospective evaluation of ACHD patients started on NOACs from 2014 to 2020, with the primary endpoints of bleeding or thromboembolic events (TE). CHA2DS2-VASc and HAS-BLED scores were calculated, mortality was assessed, and risk factors for bleeding were identified. RESULTS: A total of 93 patients were included, the mean age was 52 ± 15 years, 58% were female, 55.9% had moderate CHD, and 23.7% had severe CHD (3.2% Fontan). Most (66%) had a CHA2DS2-VASc score ≥ 2 and 82% HAS-BLED ≤ 2. In a median follow-up of 41 (IQR 21) months (400.4 patient-years), there were TE in two patients. The annual risk for TE was 0.49%/patient/year. The cardiovascular mortality was 2% and all-cause mortality 5%; there were no fatal TE or bleeding events. Minor (n = 6, 6.5%) and major (n = 3, 3.2%) bleeding events were observed, a median of 12 (IQR 15) months after starting NOAC therapy. The annual risk for bleeding was 2.2%/patient/year. Renal disease (HR 14.6 [95% CI 1.23-73.6], p = 0.033) and the HAS-BLED score were predictors of major (adjusted HR 6.97 [95% CI 1.69-28.78], p = 0.007) and minor (adjusted HR 3.80 [95% CI 1.48-9.78], p = 0.006) bleeding complications. CONCLUSION: In this real-life cohort of selected ACHD, the use of NOACs was safe and effective, with a low incidence of bleeding events.

Outcomes and predictors of periprocedural stroke after transcatheter aortic valve implantation.

BACKGROUND: Risk factors for stroke after transcatheter aortic valve implantation (TAVI) are currently incompletely understood. PURPOSE: To identify possible predictors of early post-TAVI stroke and explore its short-term outcomes. METHODS: Retrospective analysis of consecutive patients (pts) submitted to TAVI between 2009 and 2020 in a tertiary center. Baseline characteristics, procedural information and stroke in first 30 days after TAVI were collected. In-hospital and 12 months outcomes were analyzed. RESULTS: A total of 512pts (56,1% female, mean age of 82 ± 6years.) were included. In the first 30 days after TAVI 19pts (3,7%) had a stroke. In univariate analysis stroke was associated with higher body mass index (29 vs 27kg/m2, p=0.035), higher triglyceridemia (> 117,5mg/dL, p=0,002), lower high-density lipoprotein (< 38,5mg/dL, p=0,009) and porcelain aorta (36,8% vs 15,5%, p=0,014) and more frequent use of post-dilatation (58,8% vs 32%, p=0,021). In multivariate analysis, triglycerides > 117,5mg/dL (p=0,032, OR = 3,751) and post-dilatation (p=0,019, OR = 3,694) were the independent predictors. Stroke after TAVI was associated with longer intensive care unit stay (12 vs 4 days, p<0,001) and post-TAVI hospital stay (25 vs 10 days, p<0,0001), higher intra-hospital mortality (21,1% vs 4,3%, p=0,003), cardiovascular 30-day mortality (15,8% vs 4,1%, p=0,026) and 1-year stroke (13,2% vs 1,1%, p=0,003). CONCLUSION: Periprocedural and 30-day stroke is a relatively uncommon but potentially devastating complication after TAVI. In this cohort, 30-day stroke rate after TAVI was 3.7%. Hypertriglyceridemia and post-dilatation were found to be the only independent risk predictors. Outcomes after stroke, including 30-day mortality, were significantly worse.

Bioconjugate Supramolecular Pd2+ Metallacages Penetrate the Blood Brain Barrier In Vitro and In Vivo.

The biomedical application of discrete supramolecular metal-based structures, specifically self-assembled metallacages, is still an emergent field of study. Capitalizing on the knowledge gained in recent years on the development of 3-dimensional (3D) metallacages as novel drug delivery systems and theranostic agents, we explore here the possibility to target [Pd2L4]4+ cages (L = 3,5-bis(3-ethynylpyridine)phenyl ligand) to the brain. In detail, a new water-soluble homoleptic cage (CPepH3) tethered to a blood brain barrier (BBB)-translocating peptide was synthesized by a combination of solid-phase peptide synthesis (SPPS) and self-assembly procedures. The cage translocation efficacy was assessed by inductively coupled mass spectrometry (ICP-MS) in a BBB cellular model in vitro. Biodistribution studies of the radiolabeled cage [[99mTcO4]- ⊂ CPepH3] in the CD1 mice model demonstrate its brain penetration properties in vivo. Further DFT studies were conducted to model the structure of the [[99mTcO4]- ⊂ cage] complex. Moreover, the encapsulation capabilities and stability of the cage were investigated using the [ReO4]- anion, the "cold" analogue of [99mTcO4]-, by 1H NMR spectroscopy. Overall, our study constitutes another proof-of-concept of the unique potential of supramolecular coordination complexes for modifying the physiochemical and biodistribution properties of diagnostic species.

In Vivo Pretargeting Based on Cysteine-Selective Antibody Modification with IEDDA Bioorthogonal Handles for Click Chemistry.

Pretargeted imaging has emerged as an effective multistep strategy aiming to improve imaging contrast and reduce patient radiation exposure through decoupling of the radioactivity from the targeting vector. The inverse electron-demand Diels-Alder (IEDDA) reaction between a trans-cyclooctene (TCO)-conjugated antibody and a labeled tetrazine holds great promise for pretargeted imaging applications due to its bioorthogonality, rapid kinetics under mild conditions, and formation of stable products. Herein, we describe the use of functionalized carbonylacrylic reagents for site-specific incorporation of TCO onto a human epidermal growth factor receptor 2 (HER2) antibody (THIOMAB) containing an engineered unpaired cysteine residue, generating homogeneous conjugates. Precise labeling of THIOMAB-TCO with a fluorescent or radiolabeled tetrazine revealed the potential of the TCO-functionalized antibody for imaging the HER2 after pretargeting in a cellular context in a HER2 positive breast cancer cell line. Control studies with MDA-MD-231 cells, which do not express HER2, further confirmed the target specificity of the modified antibody. THIOMAB-TCO was also evaluated in vivo after pretargeting and subsequent administration of an 111In-labeled tetrazine. Biodistribution studies in breast cancer tumor-bearing mice showed a significant activity accumulation on HER2+ tumors, which was 2.6-fold higher than in HER2- tumors. Additionally, biodistribution studies with THIOMAB without the TCO handle also resulted in a decreased uptake of 111In-DOTA-Tz on HER2+ tumors. Altogether, these results clearly indicate the occurrence of the click reaction at the tumor site, i.e., pretargeting of SK-BR-3 HER2-expressing cells with THIOMAB-TCO and reaction through the TCO moiety present in the antibody. The combined advantages of site-selectivity and stability of TCO tagged-antibodies could allow application of biorthogonal chemistry strategies for pretargeting imaging with minimal side-reactions and background.

Stakeholders' perceptions of appropriate nature-based solutions in the urban context.

The concept of nature-based solutions (NBSs) has become increasingly popular among urban policymakers and planners to help them tackle the urban challenges arising from urban expansion and climate change. Stakeholders' involvement is a fundamental step, and stakeholders' perceptions and preferences can affect the development of NBS projects. This study aims to identify stakeholders' perceptions of the most critical urban challenges, the priority interventions, the preferred NBSs and the benefits of the NBSs, and to identify the determinants of these perceptions. A survey was administered to assess stakeholders' perceptions and views on implementing NBSs in two Portuguese cities with distinct urban, geographical, and socio-economic contexts. A binary logistic regression model was used to understand the determinants of the likelihood of the stakeholders' answers. According to the stakeholders, climate change is one of the main concerns in the urban context. It is usually associated with the incidence of heatwaves and water scarcity. Additionally, stakeholders are concerned about the low quantity and poor management of green spaces (GSs). They believe that it will be necessary to increase the GS, to recover some degraded areas, and to increase mobility. The preferred NBSs were planting more urban trees, making green shaded areas, and rehabilitating riverbanks. The main expected benefits were benefits for leisure and relaxation, reductions in air temperature, purer air, and improvements in public health. The results showed mostly coherent connections between the main concerns/priorities of the stakeholders and the perceived NBS benefits; however, some stakeholders did not present coherent connections, indicating low awareness of the current policy for implementing NBSs to overcome existing and future urban challenges.

Improved Fmoc-solid-phase peptide synthesis of an extracellular loop of CFTR for antibody selection by the phage display technology.

Cystic fibrosis (CF), a life-shortening genetic disease, is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that codes for the CFTR protein, the major chloride channel expressed at the apical membrane of epithelial cells. The development of an imaging probe capable of non-invasively detect CFTR at the cell surface could be of great advantage for the management of CF. With that purpose, we synthesized the first extracellular loop of CFTR protein (ECL1) through fluorenylmethyloxycarbonyl (Fmoc)-based microwave-assisted solid-phase peptide synthesis (SPPS), according to a reported methodology. However, aspartimide formation, a well-characterized side reaction in Fmoc-SPPS, prompted us to adopt a different side-chain protection strategy for aspartic acid residues present in ECL1 sequence. The peptide was subsequently modified via PEGylation and biotinylation, and cyclized through disulfide bridge formation, mimicking the native loop conformation in CFTR protein. Herein, we report improvements in the synthesis of the first extracellular loop of CFTR, including peptide modifications that can be used to improve antigen presentation in phage display for selection of novel antibodies against plasma membrane CFTR.

Causal effect of prolificacy on milk yield in dairy sheep using propensity score.

In animal production, it is often important to investigate causal relationships among variables. The gold standard tool for such investigation is randomized experiments. However, randomized experiments may not always be feasible, possible, or cost effective or reflect real-world farm conditions. Sometimes it is necessary to infer effects from farm-recorded data. Inferring causal effects between variables from field data is challenging because the association between them may arise not only from the effect of one on another but also from confounding background factors. Propensity score (PS) methods address this issue by correcting for confounding in different levels of the causal variable, which allows unbiased inference of causal effects. Here the objective was to estimate the causal effect of prolificacy on milk yield (MY) in dairy sheep using PS based on matched samples. Data consisted of 4,319 records from 1,534 crossbred ewes. Confounders were lactation number (first, second, and third through sixth) and dairy breed composition (<0.5, 0.5-0.75, and >0.75 of East Friesian or Lacaune). The causal variable prolificacy was considered as 2 levels (single or multiple lambs at birth). The outcome MY represented the volume of milk produced in the whole lactation. Pairs of single- and multiple-birth ewes (1,166) with similar PS were formed. The matching process diminished major discrepancies in the distribution of prolificacy for each confounder variable indicating bias reduction (cutoff standardized bias = 20%). The causal effect was estimated as the average difference within pairs. The effect of prolificacy on MY per lactation was 20.52 L of milk with a simple matching estimator and 12.62 L after correcting for remaining biases. A core advantage of causal over probabilistic approaches is that they allow inference of how variables would react as a result of external interventions (e.g., changes in the production system). Therefore, results imply that management and decision-making practices increasing prolificacy would positively affect MY, which is important knowledge at the farm level. Farm-recorded data can be a valuable source of information given its low cost, and it reflects real-world herd conditions. In this context, PS methods can be extremely useful as an inference tool for investigating causal effects. In addition, PS analysis can be implemented as a preliminary evaluation or a hypothesis generator for future randomized trials (if the trait analyzed allows randomization).

Isostructural Re(I)/(99m)Tc(I) tricarbonyl complexes for cancer theranostics.

Merging classical organic anticancer drugs with metal-based compounds in one single molecule offers the possibility of exploring new approaches for cancer theranostics, i.e. the combination of diagnostic and therapeutic modalities. For this purpose, we have synthesized and biologically evaluated a series of Re(I)/(99m)Tc(I) tricarbonyl complexes (Re1­Re4 and Tc1­Tc4, respectively) stabilized by a cysteamine-based (N,S,O) chelator and containing 2-(4'-aminophenyl)benzothiazole pharmacophores. With the exception of Re1, all the Re complexes have shown a moderate cytotoxicity in MCF7 and PC3 cancer cells (IC50 values in the 15.9­32.1 µM range after 72 h of incubation). The cytotoxic activity of the Re complexes is well correlated with cellular uptake that was quantified using the isostructural (99m)Tc congeners. There is an augmented cytotoxic effect for Re3 and Re4 (versusRe1 and Re2), and the highest cellular uptake for Tc3 and Tc4, which display a long ether-containing linker to couple the pharmacophore to the (N,S,O)-chelator framework. Moreover, fluorescence microscopy clearly confirmed the cytosolic accumulation of the most cytotoxic compound (Re3). Biodistribution studies of Tc1­Tc4 in mice confirmed that these moderately lipophilic complexes (logDo/w = 1.95­2.32) have a favorable bioavailability. Tc3 and Tc4 presented a faster excretion, as they undergo metabolic transformations, in contrast to complexes Tc1 and Tc2. In summary, our results show that benzothiazole-containing Re(I)/(99m)Tc(I) tricarbonyl complexes stabilized by cysteamine-based (N,S,O)-chelators have potential to be further applied in the design of new tools for cancer theranostics.

Seasonality of soil erosion under mediterranean conditions at the Alqueva Dam watershed.

The Alqueva reservoir created the largest artificial lake of Western Europe in 2010. Since then, the region has faced challenges due to land-use changes that may increase the risk of erosion and shorten the lifetime of the reservoir, increasing the need to promote land management sustainability. This paper investigates the aspect of seasonality of soil erosion using a comprehensive methodology that integrates the Revised Universal Soil Loss Equation (RUSLE) approach, geographic information systems, geostatistics, and remote-sensing. An experimental agro-silvo pastoral area (typical land-use) was used for the RUSLE factors update. The study confirmed the effect of seasonality on soil erosion rates under Mediterranean conditions. The highest rainfall erosivity values occurred during the autumn season (433.6 MJ mm ha(-1) h(-1)), when vegetation cover is reduced after the long dry season. As a result, the autumn season showed the highest predicted erosion (9.9 t ha(-1)), contributing 65 % of the total annual erosion. The predicted soil erosion for winter was low (1.1 t ha(-1)) despite the high rainfall erosivity during that season (196.6 MJ mm ha(-1) h(-1)). The predicted annual soil loss was 15.1 t ha(-1), and the sediment amount delivery was 4,314 × 10(3) kg. Knowledge of seasonal variation would be essential to outline sustainable land management practices. This model will be integrated with World Overview of Conservation Approaches and Technologies methods to support decision-making in that watershed, and it will involve collaboration with both local people and governmental institutions.

Permanent pacemaker implantation after alcoholic septal ablation induced complete heart block: Long-term impact.

INTRODUCTION AND OBJECTIVES: Patients with hypertrophic obstructive cardiomyopathy (HOCM) that remain symptomatic despite optimized medical therapy often undergo alcohol septal ablation (ASA). One of the most frequent complications is complete heart block (CHB), requiring a permanent pacemaker (PPM) in variable rates of up to 20% of patients. The long-term impact of PPM implantation in these patients remains unclear. This study aimed to evaluate the long-term clinical outcomes in patients who implant PPM after ASA. METHODS: Patients who underwent ASA at a tertiary center were consecutively and prospectively enrolled. Patients with previous PPM or implantable cardio-defibrillator were excluded from this analysis. Patients with and without PPM implantation after ASA were compared based on their baseline characteristics, procedure data and three-year primary endpoint of composite of all-cause mortality and hospitalization and secondary endpoint of composite of all-cause mortality and cardiac cause hospitalization. RESULTS: Between 2009 and 2019, 109 patients underwent ASA, 97 of whom were included in this analysis (68% female, mean age 65.2 years old). 16 patients (16.5%) required PPM implantation for CHB. In these patients, no vascular access, pacemaker pocket or pulmonary parenchyma complications were noted. The baseline characteristics of comorbidities, symptoms, echocardiographic and electrocardiographic findings were identical in the two groups, with higher mean age (70.6±10.0 years vs. 64.1±11.9 years) and lower beta-blocker therapy rate (56% vs. 84%) in the PPM group. Procedure-related data showed higher creatine kinase (CK) peaks in the PPM group (1692 U/L vs. 1243 U/L), with no significant difference in the alcohol dose. At three years after ASA procedure, there were no differences in the primary and secondary endpoints between the two groups. CONCLUSIONS: Permanent pacemaker after ASA induced CHB do not affect long term prognosis in hypertrophic obstructive cardiomyopathy patients.

Intranasal Multiepitope PD-L1-siRNA-Based Nanovaccine: The Next-Gen COVID-19 Immunotherapy.

The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are nanotechnology-based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, stressing the global demand for novel preventive vaccine technologies. Bearing this in mind, we set out to develop a flexible nanovaccine platform for nasal administration to induce mucosal immunity, which is fundamental for optimal protection against respiratory virus infection. The next-generation multiepitope nanovaccines co-deliver immunogenic peptides, selected by an immunoinformatic workflow, along with adjuvants and regulators of the PD-L1 expression. As a case study, we focused on SARS-CoV-2 peptides as relevant antigens to validate the approach. This platform can evoke both local and systemic cellular- and humoral-specific responses against SARS-CoV-2. This led to the secretion of immunoglobulin A (IgA), capable of neutralizing SARS-CoV-2, including variants of concern, following a heterologous immunization strategy. Considering the limitations of the required cold chain distribution for current nanotechnology-based vaccines, it is shown that the lyophilized nanovaccine is stable for long-term at room temperature and retains its in vivo efficacy upon reconstitution. This makes it particularly relevant for developing countries and offers a modular system adaptable to future viral threats.

Essentials of cardio-oncology.

Cardio-oncology is a subspecialty that provides cardiac care for patients with cancer. Newer oncological agents have not only increased survivorship, but also sprouted novel cardiovascular toxicity (CVT) involving any component of the cardiovascular system, albeit with some preferential targets. Patients with cancer should undergo a baseline cardiovascular risk assessment and have individualised surveillance planned during cancer therapy and post treatment. The early diagnosis of CVT, by clinical history and examination along with imaging and laboratory analysis, is paramount. Management includes cardioprotective strategies and multidisciplinary decision-making regarding the risk-benefit ratio of oncological treatment based on CVT.

Threading the needle: a case report of double-wiring technique and double intracoronary imaging guidance for a multifenestrated iatrogenic coronary artery dissection.

Background: Iatrogenic coronary artery dissection (ICAD) may represent a serious complication of percutaneous coronary intervention. Stenting the dissected segment is recommended in large dissections with compromised distal blood flow, although wiring the true lumen is often difficult. Case summary: A 64-year-old woman with effort angina was submitted to invasive coronary angiography that revealed a severe stenosis in the distal right coronary artery. A large spiral ICAD occurred after pre-dilatation and guidewire position is lost. We report the treatment of this multifenestrated dissection using combined intracoronary imaging guidance with angiographic co-registered optical coherence tomography and real-time intravascular ultrasound, which were crucial to achieve a successful outcome. Discussion: A double-wiring technique with double intracoronary imaging guidance enables a comprehensive depiction of the compromised artery and should be considered in selected cases to guide true lumen wiring and stent implantation.

Initial single-center experience of a standardized protocol for invasive assessment of ischemia and non-obstructive coronary artery disease.

INTRODUCTION: Coronary vasomotion disorders (CVDs), including microvascular angina (MVA) and vasospastic angina (VSA), account for significant morbidity among patients with non-obstructive coronary artery disease (NOCAD). However, protocols for CVD assessment in clinical practice are seldom standardized and may be difficult to implement. PURPOSE: To assess the safety and feasibility of a comprehensive coronary function test (CFT) protocol for assessment of CVD and the prevalence of different phenotypes of CVD in patients with angina and NOCAD (ANOCA). METHODS: Patients with persistent angina referred for invasive coronary angiogram and found to have NOCAD were prospectively recruited and underwent a CFT. Functional parameters (fractional flow reserve, coronary flow reserve and index of myocardial resistance) and coronary vasoreactivity were assessed in all patients. RESULTS: Of the 20 patients included, the mean age was 63±13 years and 50% were females. Most patients had persistent typical angina and evidence of ischemia in noninvasive tests (75%). The CFT was successfully performed in all subjects without serious complications. Isolated MVA was found in 25%, isolated VSA in 40%, both MVA and VSA in 10% and noncardiac chest pain in 25% of patients. Antianginal therapy was modified after the results of CFT in 70% of patients. CONCLUSION: A coronary function test was feasible and safe in a cohort of patients with ANOCA. CVD were prevalent in this selected group of patients, and some presented mixed CVD phenotypes. CFT may provide a definitive diagnosis in patients with persistent angina and prompt the stratification of pharmacological therapy.

Outcomes in Pregnant Women with Valvular Heart Disease from Portuguese-Speaking African Countries Treated in Portugal through an International Agreement of Health Cooperation.

Aims: We performed a clinical audit of maternal and fetal outcomes in pregnant women with valvular heart disease (VHD) from Portuguese-speaking African countries who were transferred for their care, during a twenty-year period, through a memorandum of agreement of international cooperation. Methods and results: A retrospective analysis of 81 pregnancies in 45 patients with VHD (median age 24, interquartile range 22-29 years) from 2000 to 2020 was performed. The main outcome measures were maternal cardiovascular and fetal outcomes. History of rheumatic heart disease was present in 60 (74.1%) pregnancies. Most were in New York Heart Association (NYHA) functional class I or II; at the first evaluation, 35 (43.2%) were on cardiac medication and 49 (60.5%) were anticoagulated. Forty-eight pregnancies had at least one valvular prosthesis, including 38 mechanical heart valves. During pregnancy, deterioration in NYHA functional class occurred in 35 (42.0%), and eight (9.9%) patients required initiation or intensified cardiac medication. Mechanical valve thrombosis complicated four (4.9%) pregnancies, all cases on heparin, and resulted in one maternal death. Haemorrhagic complications happened in 7 (8.6%) anticoagulated patients, in the immediate postpartum or puerperal period. The 81 pregnancies resulted in 56 (69.1%) live births, while miscarriage and fetal malformations occurred in 19 (23.5%) and 12 (14.8%) pregnancies, respectively. In multivariate analysis, vitamin K antagonist therapy was the only independent predictor of an unsuccessful pregnancy (p = 0.048). Conclusion: In a high-income country, successful pregnancy was possible with low rate of maternal events in women with VHD transferred from five low-middle income countries in Africa. The use of anticoagulation with a vitamin K antagonist was associated with an unsuccessful pregnancy.

Dilated Cardiomyopathy: A Comprehensive Approach to Diagnosis and Risk Stratification.

Dilated cardiomyopathy (DCM) represents one of the most common causes of non-ischemic heart failure, characterised by ventricular dilation alongside systolic dysfunction. Despite advances in therapy, DCM mortality rates remain high, and it is one of the leading causes of heart transplantation. It was recently recognised that many patients present minor structural cardiac abnormalities and express different arrhythmogenic phenotypes before overt heart-failure symptoms. This has raised several diagnostic and management challenges, including the differential diagnosis with other phenotypically similar conditions, the identification of patients at increased risk of malignant arrhythmias, and of those who will have a worse response to medical therapy. Recent developments in complementary diagnostic procedures, namely cardiac magnetic resonance and genetic testing, have shed new light on DCM understanding and management. The present review proposes a comprehensive and systematic approach to evaluating DCM, focusing on an improved diagnostic pathway and a structured stratification of arrhythmic risk that incorporates novel imaging modalities and genetic test results, which are critical for guiding clinical decision-making and improving outcomes.

Prognostic Value of Preprocedural LV Global Longitudinal Strain for Post-TAVR-Related Morbidity and Mortality: A Meta-Analysis.

BACKGROUND: Left ventricular ejection fraction (LVEF) demonstrates limited prognostic value for post-transcatheter aortic valve replacement (TAVR) outcomes. Evidence regarding the potential role of left ventricular global longitudinal strain (LV-GLS) in this setting is inconsistent. OBJECTIVES: The aim of this systematic review and meta-analysis of aggregated data was to evaluate the prognostic value of preprocedural LV-GLS for post-TAVR-related morbidity and mortality. METHODS: The authors searched PubMed, Embase, and Web of Science for studies investigating the association between preprocedural 2-dimensional speckle-tracking-derived LV-GLS and post-TAVR clinical outcomes. An inversely weighted random effects meta-analysis was adopted to investigate the association between LV-GLS vs primary (ie, all-cause mortality) and secondary (ie, major cardiovascular events [MACE]) post-TAVR outcomes. RESULTS: Of the 1,130 identified records, 12 were eligible, all of which had a low-to-moderate risk of bias (Newcastle-Ottawa scale). On average, 2,049 patients demonstrated preserved LVEF (52.6% ± 1.7%), but impaired LV-GLS (-13.6% ± 0.6%). Patients with a lower LV-GLS had a higher all-cause mortality (pooled HR: 2.01; 95% CI: 1.59-2.55) and MACE (pooled odds ratio [OR]: 1.26; 95% CI: 1.08-1.47) risk compared with patients with higher LV-GLS. In addition, each percentage point decrease of LV-GLS (ie, toward 0%) was associated with an increased mortality (HR: 1.06; 95% CI: 1.04-1.08) and MACE risk (OR: 1.08; 95% CI: 1.01-1.15). CONCLUSIONS: Preprocedural LV-GLS was significantly associated with post-TAVR morbidity and mortality. This suggests a potential clinically important role of pre-TAVR evaluation of LV-GLS for risk stratification of patients with severe aortic stenosis. (Prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis undergoing Transcatheter Aortic Valve Implantation: a meta-analysis; CRD42021289626).