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Aims: In patients with obstructive hypertrophic cardiomyopathy (HCM) and mild septal thickness undergoing myectomy, resecting fibrotic anterior mitral leaflet (AML) secondary chordae moves the mitral valve (MV) away from the outflow tract and ejection flow, reducing the need for a deep septal excision. Aim of the present study was to assess whether chordal resection has similarly favourable effects in patients with important hypertrophy, who represent the majority of patients with obstructive HCM., Methods and Results: The MV position in the ventricular cavity, assessed from echocardiography as AML-annulus ratio, was compared before and after chordal resection in 150 consecutive HCM patients with important (≥20 mm) and 62 with mild (≤19 mm) septal thickness undergoing myectomy. Preoperatively, MV position was displaced towards the septum to a similar extent in both groups. Postoperatively, AML-annulus ratio increased of an equal degree in both groups, from 0.43 ± 0.05 to 0.55 ± 0.06 (P < 0.001) a 28% increase, and from 0.43 ± 0.06 to 0.55 ± 0.06 (P < 0.001) a 26% increase, respectively, indicating a similar MV shift away from the outflow tract. When AML-annulus ratio was compared in the study cohort and 124 normal subjects, MV position was within normal range in <4% of patients preoperatively and normalized in >50% postoperatively., Conclusions: In obstructive HCM, displacement of the MV apparatus into the outflow tract interferes with the ejection flow. Resection of fibrotic secondary chordae moves the MV apparatus away from the outflow tract and enlarges the outflow area independently of septal thickness, facilitating septal myectomy by reducing the need for a deep muscular excision., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

High normal blood pressure (HNBP) is associated with an increased risk of incident high blood pressure (HBP) and of cardiovascular diseases (CVD). To estimate the prevalence of HNBP and related cardiovascular risk factors, a representative sample of 1970 Romanian adults was enrolled in SEPHAR III survey (Study for the Evaluation of Prevalence of Hypertension and Cardiovascular Risk in Romania). All were evaluated for blood pressure values and by a 71-item questionnaire, anthropometric measurements, together with extensive evaluation for target organ damage, blood, and urine sample collection. Prevalence of HNBP was 11% [45.1% had HBP, 43.9% normal BP (NBP)]. HNBP individuals were older (51.14 ± 17.13 years) than subjects with NBP (40.5 ± 15.96 years) but younger than those with HBP (55.79 ± 15.68 years), p < 0.0001 (95% CI 18-85, respectively 18-91). Values of weight, waist circumference, body mass index, total and LDL cholesterol, triglycerides, fasting blood glucose, glycosylated hemoglobin (HbA1c), uric acid, serum creatinine, glomerular filtration rate estimate by CKD-EPI equation, urinary albumin to creatinine ratio, intimae-media thickness, arterial stiffness measurements and diastolic dysfunction, indexed left ventricular mass, interventricular septum and posterior left ventricle wall thickness, left atrial volume, and LA dilatation were significantly higher in HNBP subjects than in NBP. Our study showed that individuals with HNBP represent ~11% and most of them had an elevated total cardiovascular risk. It is essential to educate the public and health care providers to be aware of these individuals and of steps that should be taken to treat modifiable cardiovascular risk factors., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

The gender effects in arterial hypertension (HT) epidemiology remain poorly clarified to date. We present an up-to-date review of the data regarding gender disparities in HT's prevalence, awareness, treatment, and control. Based on the data from three consecutive national-representative SEPHAR (Study for the Evaluation of Prevalence of Hypertension and Cardiovascular Risk in Romania) surveys conducted between 2005 and 2016, we provide insights into gender differences in HT's epidemiology and their 11- years the evolutionary trend in a high-CV risk European country. Our data displays gender effects in different age-dependent epidemiological patterns in terms of hypertension prevalence, awareness, treatment, and control, mainly due to hormonal status. Hypertension's prevalence is higher in younger men and older women. Although women are more often aware of their hypertensive condition and receive more often antihypertensive treatment, BP control is lower in older women compared to men of the same age, mainly due to a higher treatment side-effect rate. There is no solid evidence that different antihypertensive drugs exhibit different effects in lowering BP values between genders. In high CV risk European countries like Romania, if all the influencing conditions remain similar to those in the past 11 years, gender discrepancies in terms of HT's prevalence will diminish over time, awareness and treatment of hypertension will continue to be higher in females than in men, with an upward trend of BP control predicted only for women, while in men HT treatment control rate is expected to stagnate., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The aim of this study was to explore the rare variants in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM)., Methods: Forty-five unrelated probands with HCM were screened by targeted next generation sequencing (NGS) of 47 core and emerging genes connected with HCM., Results: We identified 95 variants with allele frequency < 0.1% in population databases. MYBPC3 and TTN had the largest number of rare variants (17 variants each). A definite genetic etiology was found in 6 probands (13.3%), while inconclusive results due to either known or novel variants were established in 31 cases (68.9%). All disease-causing variants were detected in sarcomeric genes (MYBPC3 and MYH7 with two cases each, and one case in TNNI3 and TPM1 respectively). Multiple variants were detected in 27 subjects (60%), but no proband carried more than one causal variant. Of note, almost half of the rare variants were novel., Conclusions: Herein we reported for the first time the rare variants identified in core and putative genes associated with HCM in a cohort of Romanian unrelated adult patients. The clinical significance of most detected variants is yet to be established, additional studies based on segregation analysis being required for definite classification.

Background: The mitral valve is often structurally abnormal in hypertrophic cardiomyopathy (HCM). However, the mechanisms responsible for these abnormalities remain controversial. In 2016 we identified, at myectomy, muscular mitral-aortic discontinuity in 5 young patients with obstructive HCM., Objectives: This study sought to confirm our preliminary findings and assess the prevalence of muscular mitral-aortic discontinuity in obstructive HCM., Methods: At our center, from January 2017 to April 2018, the area between the anterior mitral leaflet and aortic valve was inspected at myectomy in 106 consecutive patients with HCM., Results: Muscular mitral-aortic discontinuity was identified in 28 (26%) patients and was significantly more common in younger than older patients (age 39 ± 13 years vs. 58 ± 11 years; p < 0.001). Muscular discontinuity was present in each of 6 patients aged <30 years but only 1 (2.7%) of 37 aged ≥60 years. Pathogenic sarcomere mutations were identified in 22 (79%) of 28 patients with and 24 (31%) of 78 without discontinuity (p < 0.001) and were associated with discontinuity independently of age (p = 0.021). Discontinuity mean length was 7.3 mm and was inversely related to age (p = 0.022). At echocardiography, the anterior mitral leaflet was longer in patients with than those without discontinuity (34 ± 4 mm vs. 29 ± 5 mm; p < 0.001)., Conclusions: We report, for the first time, muscular mitral-aortic discontinuity in HCM. At myectomy, a long muscular discontinuity displaced the anterior mitral leaflet toward the apex in most young patients, was significantly associated with sarcomere mutations independent of age, and was extremely uncommon in older patients. These findings suggest that a long muscular mitral-aortic discontinuity could predispose to the development of outflow obstruction in young patients with sarcomere mutations., Competing Interests: Author Relationship With Industry The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is a genetic disease and the most frequent primary cardiomyopathy, affecting 1:500 of the general population. Integrated multimodality imaging, including transthoracic echocardiography, 2- and 3‑dimensional transesophageal echocardiography, stress echocardiography, and cardiac magnetic resonance, has provided answers to questions on the management of HCM, leading to standardized protocols. The late 1990s brought the news of a nonsurgical treatment of obstruction in HCM. It is now increasingly evident that septal ablation cannot address all the mechanisms of the left ventricular outflow tract (LVOT) gradient, especially mitral valve involvement. According to American and European guidelines, surgical septal myectomy is the current gold standard treatment. However, deep septal myectomy requires specific operator and institutional experience; therefore, it should not be performed in small community hospitals but only in centers of excellence for HCM treatment. The so-called Ferrazzi technique involves cutting the fibrotic secondary chordae of the mitral valve (MV) and thus helps avoid a deep myectomy by moving the anterior mitral leaflet and the coaptation point of the MV posteriorly away from the septum. This technique, together with careful mobilization of the papillary muscles, helped us achieve excellent results since November 2015, with no mortality, resolution of the LVOT gradient, and MV preservation in all 72 patients. Owing to recent advances in the surgical treatment of hypertrophic obstructive cardiomyopathy, addressing not only the septum but also the MV, the procedure of a deep myectomy has been simplified and mitral regurgitation adequately corrected.

The concepts underlying hypertrophic cardiomyopathy (HCM) pathogenesis have evolved greatly over the last 60 years since the pioneering work of the British pathologist Donald Teare, presenting the autopsy findings of "asymmetric hypertrophy of the heart in young adults". Advances in human genome analysis and cardiac imaging techniques have enriched our understanding of the complex architecture of the malady and shaped the way we perceive the illness continuum. Presently, HCM is acknowledged as "a disease of the sarcomere", where the relationship between genotype and phenotype is not straightforward but subject to various genetic and nongenetic influences. The focus of this review is to discuss key aspects related to molecular mechanisms and imaging aspects that have prompted genotype-phenotype correlations, which will hopefully empower patient-tailored health interventions.

In obstructive hypertrophic cardiomyopathy (HC), extreme heterogeneity of septal morphology makes septal myectomy particularly challenging. Although cardiovascular magnetic resonance (CMR) reconstructs ventricular anatomy with high spatial resolution, CMR is not used systematically to plan preoperatively septal myectomy. In this study, we report our results with using CMR to plan the extent of septal excision in 112 consecutive HC patients who subsequently underwent myectomy. Depth and length of the myectomy planned at CMR were compared with those of the septal muscle excised in a single piece in all patients. Anterior septum maximal thickness at CMR was 22 ± 5 mm and excised muscle thickness 9 ± 3 mm. Planned myectomy length was 35 ± 11 mm (range 17 to 65) and excised muscle length 38 ± 10 mm (range 10 to 70), indicating extension of septal resection to mid-cavity. Thickness and length of the planned myectomy showed a significant correlation with the excised muscle (R 2  = 0.345; p <0.001; and R 2  = 0.358; p <0.001, respectively). Deep septal crypts were identified at CMR in 12(11%) patients, preventing muscle excision from areas at increased risk of iatrogenic septal defect. Large aberrant muscle bundles that could decrease mid-cavity dimension were identified at CMR and excised in 26(23%) patients. In the 55 patients with postoperative CMR, qualitative comparison of pre and postoperative ventricular morphology showed a smooth and apically extended myectomy. In conclusion, CMR planning of septal myectomy provided high resolution images of septal morphology and allowed us to perform a standardized and apically extended septal excision that was associated with favorable outcome. Our novel approach could make myectomy more accessible to cardiovascular surgeons., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Diagnostic screening for Anderson-Fabry cardiomyopathy (AFC) is performed in the presence of specific clinical red flags in patients with hypertrophic cardiomyopathy (HCM) older than 25 years. However, left ventricular outflow tract obstruction (LVOTO) has been traditionally considered an exclusion criteria for AFC., Objective: To examine a series of patients diagnosed with HCM and severe basal LVOTO undergoing myectomy in whom the diagnosis of AFC was suspected by the cardiac surgeon intraoperatively and confirmed by histological and genetic examinations., Design, Setting, and Participants: This retrospective analysis of patients undergoing surgical septal reduction strategies was conducted in 3 European tertiary referral centers for HCM from July 2013 to December 2016. Patients with a clinical diagnosis of obstructive HCM referred for surgical management of LVOTO were observed for at least 18 months after the procedure (mean [SD] follow-up, 33 [14] months)., Main Outcomes and Measures: Etiology of patients with HCM who underwent surgical myectomy., Results: From 2013, 235 consecutive patients with a clinical diagnosis of HCM underwent septal myectomy. The cardiac surgeon suspected a storage disease in 3 patients (1.3%) while inspecting their heart samples extracted from myectomy. The mean (SD) age at diagnosis for these 3 patients was 42 (4) years; all were male. None of the 3 patients presented with extracardiac features suggestive of AFC. All patients showed asymmetrical left ventricular hypertrophy, with maximal left ventricular thickness in the basal septum (19-31 mm), severe basal LVOTO (70-120 mm Hg), and left atrial dilatation (44-57 mm). Only 1 patient presented with late gadolinium enhancement on cardiovascular magnetic resonance at the right ventricle insertion site. The mean (SD) age at surgical procedure was 63 (5) years. On tactile sensation, the surgeon felt a spongy consistency of the surgical samples, different from the usual stony-elastic consistency typical of classic HCM, and this prompted histological examinations. Histology showed evidence of intracellular storage, and genetic analysis confirmed a GLA A gene mutation (p.Asn215Ser) in all 3 patients., Conclusions and Relevance: Screening for AFC should be performed even in the absence of red flags in patients with HCM older than 25 years.

Valvular disease is a frequent cardiac pathology leading to heart failure and, ultimately, death. Mitral regurgitation, defined as the inability of the two mitral leaflets to coapt, is a common valvular disease and a self sustained pathology. A better understanding of the mitral valve histological layers provides a better understanding of the leaflet and chordae changes in mitral valve prolapse. Mitral valve prolapse may occur in myxomatous degenerative abnormalities, connective tissue disorders or in sporadic isolated cases. It is the most common mitral abnormality of non-ischemic cause leading to severe surgery-requiring mitral regurgitation. In addition to standard echocardiographic investigations, newly implemented three-dimensional techniques are being used and they permit a better visualisation, from the so-called 'surgical view', and an improved evaluation of the mitral valve. Hypertrophic cardiomyopathy is the most frequent inherited myocardial disease caused by mutations in various genes encoding proteins of the cardiac sarcomere, leading to a marked left ventricular hypertrophy unexplained by other comorbidities. The pathological echocardiographic hallmarks of hypertrophic cardiomyopathy are left ventricular hypertrophy, left ventricular outflow tract obstruction and systolic anterior motion of the mitral valve. The systolic anterior motion of the mitral valve contributes to the development of mitral regurgitation and further narrows the left ventricular outflow tract, leading to more severe symptomatology. Cardiac magnetic resonance imaging accurately measures the left ventricular mass, the degree of diastolic function and it may also be used to distinguish phenotypic variants. The clinical outcome of patients with these pathologies is mostly determined by the selected option of treatment. The purpose of surgical correction regarding mitral valve involvement is to restore valvular competence. Surgery has proven to be the only useful treatment in preventing heart failure, improving symptomatology and reducing mortality. Our approach wishes to enhance the understanding of the mitral valve's involvement in hypertrophic cardiomyopathy and mitral valve prolapse from genetic, haemodynamic and clinical perspectives, as well as to present novelties in the grand field of treatment., Competing Interests: Conflict of interests: The authors declare no conflicts of interest., (Copyright: © 2016, Popa et al. and Applied Systems.)

Quadricuspid aortic valve is a rare variant of aortic semilunar valve, often being an unexpected discovery during cardiac surgery. We present the case of a 59 years old patient, who was admitted for dyspnea on light exertion and palpitations. The transthoracic echocardiography revealed severe aortic valve regurgitation due to a quadricuspid aortic valve, the result being confirmed by the transesophageal echo examination. The patient had a first class indication for aortic valve replacement and the surgical intervention was uneventful. The operative technique and case particularities are discussed in view of the literature published so far regarding this uncommon condition.

In contrast to the well established multiple cellular roles of membrane vesicles in eukaryotic cell biology, outer membrane vesicles (OMV) produced via blebbing of prokaryotic membranes have frequently been regarded as cell debris or microscopy artifacts. Increasingly, however, bacterial membrane vesicles are thought to play a role in microbial virulence, although it remains to be determined whether OMV result from a directed process or from passive disintegration of the outer membrane. Here we establish that the human oral pathogen Porphyromonas gingivalis has a mechanism to selectively sort proteins into OMV, resulting in the preferential packaging of virulence factors into OMV and the exclusion of abundant outer membrane proteins from the protein cargo. Furthermore, we show a critical role for lipopolysaccharide in directing this sorting mechanism. The existence of a process to package specific virulence factors into OMV may significantly alter our current understanding of host-pathogen interactions.