Anatomical Variants of the Origin of the Coronary Arteries: A Systematic Review and Meta-Analysis of Prevalence.

PURPOSE: The most common anomaly is an anomalous left coronary artery originating from the pulmonary artery. These variants can be different and depend on the location as well as how they present themselves in their anatomical distribution and their symptomatological relationship. For these reasons, this review aims to identify the variants of the coronary artery and how they are associated with different clinical conditions. METHODS: The databases Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS were researched until January 2024. Two authors independently performed the search, study selection, and data extraction. Methodological quality was evaluated using an assurance tool for anatomical studies (AQUA). Pooled prevalence was estimated using a random effects model. RESULTS: A total of 39 studies met the established selection criteria. In this study, 21 articles with a total of 578,868 subjects were included in the meta-analysis. The coronary artery origin variant was 1% (CI = 0.8-1.2%). For this third sample, the funnel plot graph showed an important asymmetry, with a p-value of 0.162, which is directly associated with this asymmetry. CONCLUSIONS: It is recommended that patients whose diagnosis was made incidentally and in the absence of symptoms undergo periodic controls to prevent future complications, including death. Finally, we believe that further studies could improve the anatomical, embryological, and physiological understanding of this variant in the heart.

Anatomical Variants of the Renal Veins and Their Relationship with Morphofunctional Alterations of the Kidney: A Systematic Review and Meta-Analysis of Prevalence.

Background: Variations in renal veins are quite common, and most people do not experience issues due to them. However, these variations are important for healthcare professionals, especially in surgical procedures and imaging studies, as precise knowledge of vascular anatomy is essential to avoid complications during medical interventions. The purpose of this study was to expose the frequency of anatomical variations in the renal vein (RV) and detail their relationship with the retroperitoneal and renal regions. Methods: A systematic search was conducted in the Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception until January 2024. Two authors independently carried out the search, study selection, and data extraction and assessed methodological quality using a quality assurance tool for anatomical studies (AQUA). Ultimately, consolidated prevalence was estimated using a random effects model. Results: In total, 91 studies meeting the eligibility criteria were identified. This study included 91 investigations with a total of 46,664 subjects; the meta-analysis encompassed 64 studies. The overall prevalence of multiple renal veins was 5%, with a confidence interval (CI) of 4% to 5%. The prevalence of the renal vein trajectory was 5%, with a CI of 4% to 5%. The prevalence of renal vein branching was 3%, with a CI of 0% to 6%. Lastly, the prevalence of unusual renal vein origin was 2%, with a CI of 1% to 4%. Conclusions: The analysis of these variants is crucial for both surgical clinical management and the treatment of patients with renal transplant and hemodialysis.

Identification success rates in the post-Spanish Civil War mass graves located in the cemetery of Paterna, Spain: Meta-research on 15 mass graves with 933 subjects.

Spain suffered a Civil War between 1936 and 1939 that ended with the victory of the National Forces led by General Franco. Once the Spanish Civil War ended, 2238 subjects were executed and buried in several mass graves in the Cemetery of Paterna, one of Spain's largest mass grave sites. Efforts to locate and identify all the victims of the mass graves of the Paterna cemetery are ongoing, but the actual data of the percentage of DNA identifications remains uncertain. Following this, we conducted a meta-research study including 15 mass graves and 933 subjects to determine the DNA identification rates in the mass graves of the Paterna cemetery. We found that the total proportion of identified subjects in the mass graves was 15.9 % (95 % CI: 10.0-22.9). Moreover, we found that the model between the identification success rate (ISR) and the number of relatives that donated DNA (NRTDD) in the mass graves of the cemetery of Paterna was ISR = NRTDD-0.424. Results obtained about the proportion of identified subjects and the model between the ISR and the NRTDD imply the need for a scientific reflection between all the research groups involved in the identification tasks to modify deficiencies and update identification protocols to obtain better future results.

Hypoplastic and Congenital Absence of Coronary Arteries and Its Correlation with Clinical Implications of Cardiac Circulation: A Systematic Review and Meta-Analysis.

Background: Coronary arteries originate from the first portion of the aorta, emerging from the right and left aortic sinuses. They traverse through the subepicardium and coronary sulcus to supply the myocardium during diastolic function. The objective of this review was to understand how the hypoplasia and agenesis of the coronary arteries are associated with cardiac pathologies. Methods: The databases Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS were researched until January 2024. An assurance tool for anatomical studies (AQUA) was used to evaluate methodological quality. The pooled prevalence was estimated using a random effects model. Results: A total of three studies met the established selection criteria for inclusion in this meta-analysis. The prevalence of coronary artery variants was 3% (CI = 2% to 8%), with a heterogeneity of 77%. The other studies were analyzed descriptively, along with their respective clinical considerations in the presence of the variant. Conclusions: Hypoplasia and the congenital absence of the coronary arteries are often incidental findings and understanding these variants is crucial to prevent misdiagnosis. Additionally, it is essential to exercise caution when considering surgical management for hearts with these variants.

Association between the Anatomical Location of Glioblastoma and Its Evaluation with Clinical Considerations: A Systematic Review and Meta-Analysis.

Background: Glioblastoma is a primary malignant brain tumor; it is aggressive with a high degree of malignancy and unfavorable prognosis and is the most common type of malignant brain tumor. Glioblastomas can be located in the brain, cerebellum, brainstem, and spinal cord, originating from glial cells, particularly astrocytes. Methods: The databases MEDLINE, Scopus, Web of Science, Google Scholar, and CINAHL were researched up to January 2024. Two authors independently performed the search, study selection, and data extraction. Methodological quality was evaluated with an assurance tool for anatomical studies (AQUA). The statistical mean, standard deviation, and difference of means calculated with the Student's t-test for presence between hemispheres and presence in the frontal and temporal lobes were analyzed. Results: A total of 123 studies met the established selection criteria, with a total of 6224 patients. In relation to the mean, GBM between hemispheres had a mean of 33.36 (SD 58.00) in the right hemisphere and a mean of 34.70 (SD 65.07) in the left hemisphere, due to the difference in averages between hemispheres. There were no statistically significant differences, p = 0.35. For the comparison between the presence of GBM in the frontal lobe and the temporal lobe, there was a mean in the frontal lobe of 23.23 (SD 40.03), while in the temporal lobe, the mean was 22.05 (SD 43.50), and for the difference in means between the frontal lobe and the temporal lobe, there was no statistically significant difference for the presence of GBM, p = 0.178. Conclusions: We believe that before a treatment, it will always be correct to know where the GBM is located and how it behaves clinically, in order to generate correct conservative or surgical treatment guidelines for each patient. We believe that more detailed studies are also needed to show why GBM is associated more with some regions than others, despite the brain structure being homologous to other regions in which GMB occurs less frequently, which is why knowing its predominant presence in brain regions is very important.

Morphological Characteristics of the Double Mental Foramen and Its Relevance in Clinical Practice: An Observational Study.

The mental foramen (MF) is an opening found bilaterally on the anterolateral aspect of the mandible; it can be round or oval and have different diameters. One of the anatomical variants of the jaw is the presence of an accessory mental foramen (AMF). These are usually smaller than the MF and can be located above, below, or to the sides of the main MF. The objective of this study was to recognize the presence of AMF in dry jaws of the Chilean population and collect information about its clinical relevance reported in the literature. In this descriptive observational study, we have collected dried jaws obtained from three higher education institutions in Santiago de Chile, from the Department of Morphology of the Andrés Bello University, the Normal Human Anatomy Unit of the University of Santiago, and the Human Anatomy pavilion from the Faculty of Medicine of the Finis Terrae University. The samples for this research were obtained by convenience, and the observation of the jaws was carried out in the human anatomy laboratories of each institution by three evaluators independently, and a fourth evaluator was included to validate that each evaluation was correct. The sample for this research came from 260 dry jaws, showing the following findings from the total jaws studied, and to classify as an accessory MF, it will be examined and measured so that it complies with what is declared in the literature as the presence of AMF, which is between 0.74 mm. and 0.89 mm. There were 17 studies included with a sample that fluctuated between 1 and 4000, with a cumulative total of 7946 and an average number of jaws analyzed from the studies of 467.4, showing statistically significant differences between the means with the sample analyzed in this study; p = 0.095. For the cumulative prevalence of the presence of AMF, this was 3.07 in this study, and in the compared studies, the average of AMF was 8.01%, which did not present a statistically significant difference; p = 0.158. Regarding the presence of variants of unilateral AMF, this occurred in five jaws, which is equivalent to 1.84% in the sample of this study, while in previous studies, it was 7.5%, being higher on the left side than on the right. The presence of AMF is a variant with high prevalence if we compare it with other variants of the jaw. Knowledge of the anatomy and position of the AMF is crucial to analyze different scenarios in the face of surgical procedures or conservative treatments of the lower anterior dental region.

Anatomy of vertebral artery hypoplasia and its relationship with clinical implications: a systematic review and meta-analysis of prevalence.

PURPOSE: The vertebral artery (VA) is a vital branch of the subclavian artery, coursing through the transverse foramina of the cervical vertebrae, and playing a crucial role in irrigating the posterior region of the arterial cerebral circle, also known as the Polygon of Willis. Among the various possible alterations that can affect the VA, vertebral artery hypoplasia (HAV) emerges as a significant variant. This study aims to discern the anatomical features of HAV and its correlation with the clinical conditions of the posterior cerebral circulation. METHODS: The databases Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS were searched until January 2024. Two authors independently performed the search, study selection, and data extraction. Methodological quality was evaluated with an assurance tool for anatomical studies (AQUA). Pooled prevalence was estimated using a random effects model. RESULTS: A total of 24 studies met the established selection criteria, with a total of 8847 subjects. In this study, 6 articles were included for the meta-analysis with a total of subjects. The average prevalence of VAH reported in each study was 11% (95% CI 10-12%); the studies had a heterogeneity of 41% based on the funnel plot and a low risk of bias. CONCLUSION: The prevalence of VAH is low, but in the presence of this condition, the changes are mainly in diameter rather than morphological. If it is present, some clinical safeguards must be taken to avoid complications such as stroke.

Infraorbital canal variants and its clinical and surgical implications. A systematic review.

BACKGROUND: Recent literature highlights anomalous cranial nerves in the sinonasal region, notably in the sphenoid and maxillary sinuses, linked to anatomical factors. However, data on the suspended infraorbital canal (IOC) variant is scarce in cross-sectional imaging. Anatomical variations in the sphenoid sinuses, including optic, maxillary, and vidian nerves, raise interest among specialists involved in advanced sinonasal procedures. The infraorbital nerve's (ION) course along the orbital floor and its abnormal positioning within the orbital and maxillary sinus region pose risks of iatrogenic complications. A comprehensive radiological assessment is crucial before sinonasal surgeries. Cone-beam computed tomography (CBCT) is preferred for its spatial resolution and reduced radiation exposure. OBJECTIVE: The aim of this study was to describe the prevalence of anatomical variants of the infraorbital canal (IOC) and report its association with clinical condition or surgical implication. METHODS: We searched Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception up to June 2023. Two authors independently performed the search, study selection, data extraction, and assessed the methodological quality with assurance tool for anatomical studies (AQUA). Finally, the pooled prevalence was estimated using a random effects model. RESULTS: Preliminary results show that three types are prevalent, type 1: the IOC does not bulge into the maxillary sinus (MS); therefore, the infraorbital foramen through the anterior wall of MS could be used for identification of the ION. Type 2: the IOC divided the orbital floor into medial and lateral aspects. Type 3: the IOC hangs in the MS and the entire orbital floor lying above the IOC. From which the clinical implications where mainly surgical, in type 1 the infraorbital foramen through the anterior wall of MS could be used for identification of the ION, while in type 2, since the lateral orbital floor could not be directly accessed an inferiorly transposition of ION is helpful to expose the lateral orbital wall directly with a 0 scope; or using angled endoscopes and instruments, however, the authors opinion is that direct exposure potentially facilitates the visualization and management in complex situations such as residual or recurrent mass, foreign body, and fracture located at the lateral aspect of the canal. Lastly, in type 3, the ION it's easily exposed with a 0° scope. CONCLUSIONS: This systematic review identified four IOC variants: Type 1, within or below the MS roof; Type 2, partially protruding into the sinus; Type 3, fully protruding into the sinus or suspended from the roof; and Type 4, in the orbital floor. Clinical recommendations aim to prevent nerve injuries and enhance preoperative assessments. However, the lack of consistent statistical methods limits robust associations between IOC variants and clinical outcomes. Data heterogeneity and the absence of standardized reporting impede meta-analysis. Future research should prioritize detailed reporting, objective measurements, and statistical approaches for a comprehensive understanding of IOC variants and their clinical implications. Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/UGYFZ .

Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry.

BACKGROUND AND AIMS: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

The Association between Anatomical Variants of Musculoskeletal Structures and Nerve Compressions of the Lower Limb: A Systematic Review and Meta-Analysis.

Objective: The aim of this study was to describe the main anatomical variants and morphofunctional alterations in the lower limb that compress surrounding nervous structures in the gluteal region, thigh region, and leg and foot region. Methods: We searched the Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception up to October 2023. An assurance tool for anatomical studies (AQUA) was used to evaluate methodological quality, and the Joanna Briggs Institute assessment tool for case reports was also used. Forest plots were generated to assess the prevalence of variants of the gluteal region, thigh, and leg. Results: According to the forest plot of the gluteal region, the prevalence was 0.18 (0.14-0.23), with a heterogeneity of 93.52%. For the thigh region, the forest plot presented a prevalence of 0.10 (0.03-0.17) and a heterogeneity of 91.18%. The forest plot of the leg region was based on seven studies, which presented a prevalence of 0.01 (0.01-0.01) and a heterogeneity of 96.18%. Conclusions: This review and meta-analysis showed that, in studies that analyzed nerve compressions, the prevalence was low in the thigh and leg regions, while in the gluteal region, it was slightly higher. This is mainly due to the PM region and its different variants. We believe that it is important to analyze all the variant regions defined in this study and that surgeons treating the lower limb should be attentive to these possible scenarios so that they can anticipate possible surgical situations and thus avoid surgical complications.

Prevalence of the Bifid Mandibular Condyle and Its Relationship with Pathologies of the Temporomandibular Joint: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to describe the prevalence of anatomical variants in the bifid mandibular condyle (BMC) and report its association with temporomandibular joint (TMJ) pathology. METHODS: We searched the Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception up to September 2023. Two authors independently performed the search, study selection, and data extraction, and they also assessed the methodological quality with an assurance tool for anatomical studies (AQUA). Finally, the pooled prevalence was estimated using a random effects model. RESULTS: A total of 50 studies met the eligibility criteria. Twenty studies, with a total of 88,625 subjects, were included in the meta-analysis. The overall prevalence of the bifid mandibular condyle (BMC) variant was 1% (95% CI = 1% to 2%). CONCLUSIONS: The correlation between the BMC and TMJ pathologies has a relatively low prevalence in studies that present a considerable number of subjects. From a clinical point of view, a direct association cannot be made between the presence of the BMC and TMJ pathologies or symptoms.

Double Transverse Foramina-An Anatomical Basis for Possible Vertebrobasilar Insufficiency Risk and Vertebral Artery Injury.

Cervical vertebrae may exhibit the anomalous presence of a double transverse foramen (DTF) that may impact the anatomy of related structures that traverse the cervical region, such as the vertebral artery (VA). This retrospective anatomical study utilized CT angiography cervical scans to examine the prevalence of DTF, VA, and TF areas. The subjects were separated into two groups: normal TF (NTF group; 26 males and 21 females) and double TF (DTF group; 21 males and 24 females). The males presented significantly higher TF area values (30.31 ± 4.52 mm2) than the females (27.48 ± 1.69 mm2) in the NTF group (p = 0.006). The sex differences disappeared when a DTF was present (p = 0.662). There were no differences in the VA area values between the sexes in both the NTF and DTF groups (p = 0.184). No significant differences in the VA area values between males of the NTF and DTF groups (p = 0.485) were noted. The DTF subjects presented an increased VA/TF area ratio than the NTF subjects (p < 0.001). This study showed that DTF presence reduced the TF area. In contrast, the VA area did not change despite the decreasing TF area. This might be an anatomical risk for transient vertebrobasilar insufficiency in subjects with DTF, especially in females, because VA space in the TF is less in DTF subjects than in NTF subjects. This may lead to easy VA compression in DTF subjects following neck trauma.

A cost-effectiveness analysis of hypertrophic cardiomyopathy sudden cardiac death risk algorithms for implantable cardioverter defibrillator decision-making.

AIMS: To conduct a contemporary cost-effectiveness analysis examining the use of implantable cardioverter defibrillators (ICD) for primary prevention in patients with hypertrophic cardiomyopathy (HCM). METHODS: A discrete-time Markov model was used to determine the cost-effectiveness of different ICD decision-making rules for implantation. Several scenarios were investigated including the reference scenario of implantation rates according to observed real world practice. A 12-year time horizon with an annual cycle length was used. Transition probabilities used in the model were obtained using Bayesian analysis. The study has been reported according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Using a 5-year SCD risk threshold of 6% was cheaper than current practice and has marginally better total quality adjusted life years (QALYs). This is the most cost-effective of the options considered, with an incremental cost effectiveness ratio of £834 per QALY. Sensitivity analyses highlighted that this decision is largely driven by what health related quality of life (HRQL) is attributed to ICD patients and time horizon. CONCLUSION: We present a timely new perspective on HCM ICD cost-effectiveness, using methods reflecting real-world practice. While we have shown that a 6% 5-year SCD risk cut-off provides the best cohort stratification to aid ICD decision-making, this will also be influenced by the particular values of costs and HRQL for subgroups or at a local level. The process of explicitly demonstrating the main factors which drive conclusions from such an analysis will help to inform shared decision-making in this complex area for all stakeholders concerned.

Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants.

BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P<0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.

Lamin A/C Ablation Restricted to Vascular Smooth Muscle Cells, Cardiomyocytes, and Cardiac Fibroblasts Causes Cardiac and Vascular Dysfunction.

Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with a particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with elevated expression of total and phosphorylated (active) Smad3 and cleaved (active) caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries and a switch of aortic VSMCs from the 'contractile' to the 'synthetic' phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases.

Accuracy of the angiography-based quantitative flow ratio in intermediate left main coronary artery lesions and comparison with visual estimation.

BACKGROUND: Revascularization of left main coronary artery (LMCA) stenosis is mostly based on angiography. Indices based on angiography might increase accuracy of the decision, although they have been scarcely used in LMCA. The objective of this study is to study the diagnostic agreement of QFR (quantitative flow ratio) with wire-based fractional flow reserve (FFR) in LMCA lesions and to compare with visual severity assessment. METHODS: In a series of patients with invasive FFR assessment of intermediate LMCA stenoses we retrospectively compared the measured value of QFR with that of FFR and the estimate of significance from angiography. RESULTS: 107 QFR studies were included. The QFR intra-observer and inter-observer agreement was 87% and 82% respectively. The mean QFR-FFR difference was 0.047 ± 0.05 with a concordance of 90.7%, sensitivity 88.1%, specificity 92.3%, positive predictive value 88.1% and negative predictive value 92.3%. All these values were superior to those observed with the visual estimation which showed an intra- and inter-observer agreement of 73% and 72% respectively, besides 78% with the FFR value. The low diagnostic performance of the visual estimation and the acceptable performance of the QFR index measurement were observed in all subgroups analysed. CONCLUSIONS: QFR allows an acceptable estimate of the FFR obtained with intracoronary pressure guidewire in intermediate LMCA lesions, and clearly superior to the assessment based on angiography alone. The decision to revascularize patients with moderate LMCA lesions should not be based solely on the degree of angiographic stenosis.

The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants.

BACKGROUND: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. RESULTS: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). CONCLUSIONS: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.

Current therapies for hypertrophic cardiomyopathy: a systematic review and meta-analysis of the literature.

AIMS: The aim of this study was to synthesize the evidence on the effect of the current therapies over the pathophysiological and clinical characteristics of patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: A systematic review and meta-analysis of 41 studies identified from 1383 retrieved from PubMed, Web of Science, and Cochrane was conducted. Therapies were grouped in pharmacological, invasive and physical exercise. Pharmacological agents had no effect on functional capacity measured by VO2max (1.11 mL/kg/min; 95% CI: -0.04, 2.25, P < 0.05). Invasive septal reduction therapies increased VO2max (+3.2 mL/kg/min; 95% CI: 1.78, 4.60, P < 0.05). Structured physical exercise programmes did not report contraindications and evidenced the highest increases on functional capacity (VO2max + 4.33 mL/kg/min; 95% CI: 0.20, 8.45, P < 0.05). Patients with left ventricular outflow tract (LVOT) obstruction at rest improved their VO2max to a greater extent compared with those without resting LVOT obstruction (2.82 mL/kg/min; 95% CI: 1.97, 3.67 vs. 1.18; 95% CI: 0.62, 1.74, P < 0.05). Peak LVOT gradient was reduced with the three treatment options with the highest reduction observed for invasive therapies. Left ventricular ejection fraction was reduced in pharmacological and invasive procedures. No effect was observed after physical exercise. Symptomatic status improved with the three options and to a greater extent with invasive procedures. CONCLUSIONS: Invasive septal reduction therapies increase VO2max, improve symptomatic status, and reduce resting and peak LVOT gradient, thus might be considered in obstructive patients. Physical exercise emerges as a coadjuvant therapy, which is safe and associated with benefits on functional capacity. Pharmacological agents improve reported NYHA class, but not functional capacity.