ACTN1-related thrombocytopenia: Homozygosity for an ACTN1 variant results in a more severe phenotype.

ACTN1-related thrombocytopenia is a rare disorder caused by heterozygous variants in the ACTN1 gene characterized by macrothrombocytopenia and mild bleeding tendency. We describe for the first time two patients affected with ACTN1-RT caused by a homozygous variant in ACTN1 (c.982G>A) with mild heart valve defects unexplained by any other genetic variants investigated by WES. Within the reported family, the homozygous sisters have moderate thrombocytopenia and marked platelet macrocytosis with giant platelets, revealing a more severe haematological phenotype compared to their heterozygous relatives and highlighting a significant effect of allelic burden on platelet size. Moreover, we hypothesize that some ACTN1 variants, especially when present in the homozygous state, may also contribute to the cardiac abnormalities.

Cardiac MRI-Enriched Phenomapping Classification and Differential Treatment Outcomes in Patients With Ischemic Cardiomyopathy.

BACKGROUND: Significant controversy continues to confound patient selection and referral for revascularization and mitral valve intervention in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance (CMR) enables comprehensive phenotyping with gold-standard tissue characterization and volumetric/functional measures. Therefore, we sought to determine the impact of CMR-enriched phenomapping patients with ICM to identify differential outcomes following surgical revascularization and surgical mitral valve intervention (sMVi). METHODS: Consecutive patients with ICM referred for CMR between 2002 and 2017 were evaluated. Latent class analysis was performed to identify phenotypes enriched by comprehensive CMR assessment. The primary end point was death, heart transplant, or left ventricular assist device implantation. A multivariable Cox survival model was developed to determine the association of phenogroups with overall survival. Subgroup analysis was performed to assess the presence of differential response to post-magnetic resonance imaging procedural interventions. RESULTS: A total of 787 patients were evaluated (63.0±11.2 years, 24.8% women), with 464 primary events. Subsequent surgical revascularization and sMVi occurred in 380 (48.3%) and 157 (19.9%) patients, respectively. Latent class analysis identified 3 distinct clusters of patients, which demonstrated significant differences in overall outcome (P<0.001). Latent class analysis identified differential survival benefit of revascularization in patients as well as patients who underwent revascularization with sMVi, based on phenogroup classification, with phenogroup 3 deriving the most survival benefit from revascularization and revascularization with sMVi (hazard ratio, 0.61 [0.43-0.88]; P=0.0081). CONCLUSIONS: CMR-enriched unsupervised phenomapping identified distinct phenogroups, which were associated with significant differential survival benefit following surgical revascularization and sMVi in patients with ICM. Phenomapping provides a novel approach for patient selection, which may enable personalized therapeutic decision-making for patients with ICM.

Large Animal Translational Validation of 3 Mitral Valve Repair Operations for Mitral Regurgitation Using a Mitral Valve Prolapse Model: A Comprehensive In Vivo Biomechanical Engineering Analysis.

BACKGROUND: Various mitral repair techniques have been described. Though these repair techniques can be highly effective when performed correctly in suitable patients, limited quantitative biomechanical data are available. Validation and thorough biomechanical evaluation of these repair techniques from translational large animal in vivo studies in a standardized, translatable fashion are lacking. We sought to evaluate and validate biomechanical differences among different mitral repair techniques and further optimize repair operations using a large animal mitral valve prolapse model. METHODS: Male Dorset sheep (n=20) had P2 chordae severed to create the mitral valve prolapse model. Fiber Bragg grating force sensors were implanted to measure chordal forces. Ten sheep underwent 3 randomized, paired mitral valve repair operations: neochord repair, nonresectional leaflet remodeling, and triangular resection. The other 10 sheep underwent neochord repair with 2, 4, and 6 neochordae. Data were collected at baseline, mitral valve prolapse, and after each repair. RESULTS: All mitral repair techniques successfully eliminated regurgitation. Compared with mitral valve prolapse (0.54±0.18 N), repair using neochord (0.37±0.20 N; P=0.02) and remodeling techniques (0.30±0.15 N; P=0.001) reduced secondary chordae peak force. Neochord repair further decreased primary chordae peak force (0.21±0.14 N) to baseline levels (0.20±0.17 N; P=0.83), and was associated with lower primary chordae peak force compared with the remodeling (0.34±0.18 N; P=0.02) and triangular resectional techniques (0.36±0.27 N; P=0.03). Specifically, repair using 2 neochordae resulted in higher peak primary chordal forces (0.28±0.21 N) compared with those using 4 (0.22±0.16 N; P=0.02) or 6 neochordae (0.19±0.16 N; P=0.002). No difference in peak primary chordal forces was observed between 4 and 6 neochordae (P=0.05). Peak forces on the neochordae were the lowest using 6 neochordae (0.09±0.11 N) compared with those of 4 neochordae (0.15±0.14 N; P=0.01) and 2 neochordae (0.29±0.18 N; P=0.001). CONCLUSIONS: Significant biomechanical differences were observed underlying different mitral repair techniques in a translational large animal model. Neochord repair was associated with the lowest primary chordae peak force compared to the remodeling and triangular resectional techniques. Additionally, neochord repair using at least 4 neochordae was associated with lower chordal forces on the primary chordae and the neochordae. This study provided key insights about mitral valve repair optimization and may further improve repair durability.

A Case of Gemella morbillorum Causing Multi-valvular Endocarditis.

This is the case of a 31-year-old man with no significant past medical history who presented to the emergency department experiencing persistent fevers, chills, and malaise for the past 2-3 weeks. During this period, he had multiple urgent care visits for possible left-sided otitis media which was treated with short a course of Augmentin. While on antibiotics his symptoms would improve, but they would reappear once he had finished treatment. The patient also had significant dental carries with a chronic right molar infection. At the emergency department, blood cultures grew two out of two Gemella morbillorum. Transthoracic echocardiography showed a 1 cm x 0.5 cm mobile density on the left coronary cusp of the aortic valve with moderate-severe aortic insufficiency. The patient was started on empiric IV vancomycin. Further workup revealed that the source of infection was dental carries. While proceeding with a transesophageal echocardiogram, the patient went into flash pulmonary edema requiring ICU admission. Imaging revealed an elongated 1.7 cm x 0.6 cm vegetation attached to the base of the left coronary cusp on the left ventricular outflow tract side with severe aortic regurgitation and a small 0.8 cm x 0.8 cm vegetation on the atrial side of the anterior mitral leaflet at A2 associated with mitral leaflet perforation with severe mitral regurgitation. Oral surgery removed the infected teeth. Cardiothoracic surgery performed open heart valve replacement which revealed a completely destroyed aortic valve, droplet vegetation, and destruction of the mitral valve leading to mechanical valve replacement. The patient received a two-week course of gentamycin while in the ICU with meropenem. Once sensitivities were back, he was switched to IV penicillin therapy for a total of six weeks.

[Conservative treatment of valvular heart disease in adults]. / Konservative Therapie von Herzklappenvitien im Erwachsenenalter.

Currently, there is no specific medication approved for the treatment of valvular heart disease per se. Except for secondary mitral valve insufficiency and tricuspid valve insufficiency in pulmonary hypertension, drug therapy for higher-grade valvular heart disease is limited to diuretic therapy for symptom control. Conservative therapy for comorbidities and potential heart failure can be beneficial regardless of the specific valve lesion. In cases of aortic valve stenosis or insufficiency, controlling arterial hypertension is important. Patients with mitral valve stenosis benefit from rhythm and rate control. Diuretics can help reduce regurgitant volume in patients with primary mitral valve insufficiency and tricuspid valve insufficiency. In addition to drug therapy, maintaining functional capacity is crucial for the outcome of patients. Therefore, it is recommended to engage in active physical activity whenever possible, despite the presence of valvular heart disease.

Our 10-Year Experience with Atrial Myxomas: Is Concurrent Valve Intervention Really Warranted?

INTRODUCTION: Primary cardiac myxomas are rare tumors. Concurrent valvular lesion is a common finding on evaluation which is thought to be due to annular dilatation secondary to tumor movement across the valve, functional obstruction across the valve, and severe pulmonary hypertension secondary to chronic obstruction. A common belief among surgeons is that excision of myxoma leads to abatement of symptoms, and further valve intervention may not be warranted. METHODS: A 10-year retrospective descriptive study was designed to analyze patients who underwent excision of cardiac myxoma at our center. Data was analyzed regarding presenting features, echocardiographic findings of myxoma and valve morphology, intraoperative assessment, and postoperative outcome with/without valve repair/replacement in all patients. RESULTS: A total of 22 patients underwent surgery for myxoma. Six patients underwent successful mitral valve repair with ring annuloplasty, two had moderate mitral regurgitation, three had severe mitral regurgitation, and one patient had no mitral regurgitation on preoperative assessment, but moderate mitral regurgitation was found intraoperatively. Four of these patients had no residual mitral regurgitation in follow-up period while two had mild residual mitral regurgitation. One patient had severe mitral stenosis of concurrent rheumatic etiology and successfully underwent mitral valve replacement. CONCLUSION: Cardiac myxomas are rare benign tumors commonly associated with mitral valve insufficiency. Mitral valve should be assessed intraoperatively after excision of mass as preoperative assessment might often be insufficient. Concomitant mitral valve intervention might be needed with a case-specific tailored approach, and mitral valve repair with ring annuloplasty offers best surgical outcome in such cases.

Association of pulmonary hypertension with the outcome in patients undergoing edge-to-edge mitral valve repair.

OBJECTIVES: The association of pulmonary hypertension (PH) with the outcome after mitral transcatheter edge-to-edge repair (M-TEER) focusing on the new ESC/ERS guidelines definition for PH. BACKGROUND: PH is frequently found in patients with mitral regurgitation and is associated with lower survival rates. Recent studies were based on echocardiographic parameters, but results based on invasive haemodynamics differentiating distinct types of PH using the new definition for PH are missing. METHODS: 449 consecutive M-TEER-treated patients from December 2009 to February 2015 were included in this retrospective analysis. All patients were stratified by the distinct types of PH (no PH, precapillary PH, isolated postcapillary PH, combined post-PH and precapillary PH) according to the definitions of the ESC/ERS guidelines for the diagnosis of PH from 2015 (meanPA cut-off <25 mm Hg, pulmonary capillary wedge pressure (PCWP) cut-off ≤15 mm Hg, diastolic pulmonary gradient cut-off ≥7 mm Hg or pulmonary vascular resistance (PVR) >3 WU) and 2022 (meanPA cut-off ≤20 mm Hg, PCWP cut-off ≤15 mm Hg, PVR cut-off ≥3 WU). RESULTS: Patients with any type of PH (2015: meanPA cut-off 25 mm Hg; 2022: meanPA cut-off >20 mm Hg) showed a higher risk of death after M-TEER compared with patients with no PH (2015: HR 1.61 (95% CI 1.25 to 2.07); p<0.001 and 2022: HR 2.09 (95% CI 1.54 to 2.83); p<0.001). Based on the new PH definition, each PH subgroup showed a lower survival after M-TEER compared with patients with no PH. Echocardiographic estimated systolic PAP showed a correlation with invasively measured mean pulmonary artery pressure (mPAP) (r=0.29, p<0.001) and systolic pulmonary arterial pressure (r=0.34,p<0.001). Cox-regression analysis showed higher invasive diastolic, systolic and mean pulmonary pressures were associated with higher all-cause mortality (p<0.001). In addition, invasive measured higher right atrial pressure, lower pulmonary arterial compliance, higher PVR and higher wedge pressure were identified as predictors of all-cause mortality after M-TEER. CONCLUSIONS: The new PH definition discriminates PH groups and mortality better than the old definition. The lower threshold of mPAP of 20mmHg improved prognostication in this cohort of patients.

Implications of Mitral Annular Calcification on Outcomes Following Mitral Transcatheter Edge-to-Edge Repair.

BACKGROUND: Limited data exist regarding the impact of mitral annular calcification (MAC) on outcomes of transcatheter edge-to-edge repair for mitral regurgitation (MR). METHODS: We retrospectively analyzed 968 individuals (median age, 79 [interquartile range, 70-86] years; 60.0% males; 51.8% with functional MR) who underwent an isolated, first-time intervention. Stratified by MAC extent per baseline transthoracic echocardiogram, the cohort was assessed for residual MR, functional status, all-cause mortality, heart failure hospitalizations, and mitral reinterventions post-procedure. RESULTS: Patients with above-mild MAC (n=101; 10.4%) were older and more likely to be female, exhibited a greater burden of comorbidities, and presented more often with severe, primary MR. Procedural aspects and technical success rate were unaffected by MAC magnitude, as was the significant improvement from baseline in MR severity and functional status along the first postprocedural year. However, the persistence of above-moderate MR or functional classes III and IV at 1 year and the cumulative incidence of reinterventions at 2 years were overall more pronounced within the above-mild MAC group (significant MR or functional impairment, 44.7% versus 29.9%, P=0.060; reinterventions, 11.9% versus 6.2%, P=0.033; log-rank P=0.035). No link was demonstrated between MAC degree and the cumulative incidence or risk of mortality and mortality or heart failure hospitalizations. Differences in outcomes frequencies were mostly confined to the primary MR subgroup, in which patients with above-mild MAC also experienced earlier, more frequent 2-year heart failure hospitalizations (20.8% versus 9.6%; P=0.016; log-rank P=0.020). CONCLUSIONS: Mitral transcatheter edge-to-edge repair in patients with and without above-mild MAC is equally feasible and safe; however, its postprocedural course is less favorable among those with primary MR.

Cardiogeriatrics: the current state of the art.

It is estimated that by 2050, 17% of the world's population will be greater than 85 years old, which, combined with cardiovascular disease (CVD) being the leading cause of death and disability, sets an unprecedented burden on our health and care systems. This perfect storm will be accompanied by a rise in the prevalence of CVD due to increased survival of patients with pre-existing CVD and the incidence of CVD that is associated with the process of ageing. In this review, we will focus on the diagnosis and management of common CVD conditions in old age, namely: heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF) and valvular heart disease (VHD). Despite limited evidence, clinical guidelines are increasingly considering the complexity of management of these conditions in the older person, which often coexist, for example, AF and HF or CAD and VHD. Furthermore, they, in turn, need specific consideration in the context of comorbidities, polypharmacy, frailty and impaired cognition found in this age group. Hence, the emerging role of the geriatric cardiologist is therefore vital in performing comprehensive geriatric assessment, attending multidisciplinary team meetings and ultimately considering the patient and the sum of their diseases in their totality. There have been recent advances in CVD management but how we apply these to deliver integrated care to the elderly population is key. This review article aims to bring together emerging studies and guidelines on assessment and management of CVD in the elderly, summarising latest definitions, diagnostics, therapeutics and future challenges.

Our 10-Year Experience with Atrial Myxomas: Is Concurrent Valve Intervention Really Warranted?

ABSTRACT Introduction: Primary cardiac myxomas are rare tumors. Concurrent valvular lesion is a common finding on evaluation which is thought to be due to annular dilatation secondary to tumor movement across the valve, functional obstruction across the valve, and severe pulmonary hypertension secondary to chronic obstruction. A common belief among surgeons is that excision of myxoma leads to abatement of symptoms, and further valve intervention may not be warranted. Methods: A 10-year retrospective descriptive study was designed to analyze patients who underwent excision of cardiac myxoma at our center. Data was analyzed regarding presenting features, echocardiographic findings of myxoma and valve morphology, intraoperative assessment, and postoperative outcome with/without valve repair/replacement in all patients. Results: A total of 22 patients underwent surgery for myxoma. Six patients underwent successful mitral valve repair with ring annuloplasty, two had moderate mitral regurgitation, three had severe mitral regurgitation, and one patient had no mitral regurgitation on preoperative assessment, but moderate mitral regurgitation was found intraoperatively. Four of these patients had no residual mitral regurgitation in follow-up period while two had mild residual mitral regurgitation. One patient had severe mitral stenosis of concurrent rheumatic etiology and successfully underwent mitral valve replacement. Conclusion: Cardiac myxomas are rare benign tumors commonly associated with mitral valve insufficiency. Mitral valve should be assessed intraoperatively after excision of mass as preoperative assessment might often be insufficient. Concomitant mitral valve intervention might be needed with a case-specific tailored approach, and mitral valve repair with ring annuloplasty offers best surgical outcome in such cases.

Prognostic Impact of Residual Moderate Mitral Regurgitation Following Valve-in-Valve Transcatheter Aortic Valve Implantation

ABSTRACT Introduction: The impact of mitral regurgitation (MR) on valve-in-valve transcatheter aortic valve implantation (VIV-TAVI) in patients with failed bioprostheses remains unclear. The purpose of this study was to assess the prognostic impact of residual moderate MR following VIV-TAVI. Methods: We retrospectively analyzed 127 patients who underwent VIV-TAVI between March 2010 and November 2021. At least moderate MR was observed in 51.2% of patients before the procedure, and MR improved in 42.1% of all patients. Patients with postoperative severe MR, previous mitral valve intervention, and patients who died before postoperative echocardiography were excluded from further analyses. The remaining 114 subjects were divided into two groups according to the degree of postprocedural MR: none-mild MR (73.7%) or moderate MR (26.3%). Propensity score matching yielded 23 pairs for final comparison. Results: No significant differences were found between groups before and after matching in early results. In the matched cohort, survival probabilities at one, three, and five years were 95.7% vs. 87.0%, 85.0% vs. 64.5%, and 85.0% vs. 29.0% in the none-mild MR group vs. moderate MR-group, respectively (log-rank P=0.035). Among survivors, patients with moderate MR had worse functional status according to New York Heart Association (NYHA) class at follow-up (P=0.006). Conclusion: MR is common in patients with failed aortic bioprostheses, and improvement in MR-status was observed in over 40% of patients following VIV-TAVI. Residual moderate MR after VIV-TAVI is not associated with worse early outcomes, however, it was associated with increased mortality at five years of follow-up and worse NYHA class among survivors.

Respect Versus Resect Approaches for Mitral Valve Repair: A Meta-Analysis of Reconstructed Time-to-Event Data.

Mitral valve repair (MVr) has been associated with superior long-term survival and freedom from valve-related complications compared with mitral valve replacement for primary mitral regurgitation (MR). The 2 main approaches for MVr are chordal replacement ("respect approach") and leaflet resection ("resect approach"). We performed a systematic review and a meta-analysis using 3 search databases to compare the long-term end points between both approaches. The primary end point was long-term survival. The secondary end points were long-term MR recurrence and reoperation. After reconstruction of time-to-event data for the individual survival analysis, pooled Kaplan-Meier curves for the end points were generated. A total of 14 studies (5,565 patients) were included in the analysis. The respect approach was associated with superior survival compared with the resect approach in the overall sample (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.56 to 0.96, p = 0.024, n = 3,901 patients) but not in the risk-adjusted sample (HR 1.00, 95% CI 0.55 to 1.82, p = 0.991, n = 620 patients). There was no difference between the approaches in the rate of MR recurrence in the overall sample (HR 1.39, 95% CI 0.92 to 2.08, p = 0.116, n = 1,882 patients) or in the risk-adjusted sample (HR 1.62, 95% CI 0.76 to 3.47, p = 0.211, n = 288 patients). The data for reoperation were only available in the overall sample and did not reveal a difference (HR 0.92, 95% CI 0.62 to 1.35, p = 0.663, n = 3,505 patients). In conclusion, the current evidence suggests no difference in long-term mortality, MR recurrence, or reoperation between the resect and respect approaches for MVr after adjusting for patient risk factors. More long-term follow-up data are warranted.

[Update on functional mitral regurgitation: a comprehensive review]. / Actualización en insuficiencia mitral funcional: una revisión integral.

In recent decades, the advances in the management of functional mitral regurgitation (MR), makes knowledge of this disease extremely important to the clinical cardiologist, as it has an increasing prevalence in patients older than 50 years. The objective of this article is to review the pathophysiological bases of MR, in order to differentiate its mechanism, and to correlate them with the clinical, hemodynamic, and imaging findings that assess the severity of the disease. These data are relevant for the adequate selection of the patient and the opportune moment of the therapeutic interventions, which involves a multidisciplinary team in decision-making to achieve the greatest benefit within the treatment options of this pathology.

Parameters of the mitral apparatus in patients with ischemic and nonischemic dilated cardiomyopathy.

The mitral valve apparatus is a complex structure consisting of several coordinating components: the annulus, two leaflets, the chordae tendineae, and the papillary muscles. Due to the intricate interplay between the mitral valve and the left ventricle, a disease of the latter may influence the normal function of the former. As a consequence, valve insufficiency may arise despite the absence of organic valve disease. This is designated as functional or secondary mitral regurgitation, and it arises from a series of distortions to the valve components. This narrative review describes the normal anatomy and the pathophysiology behind the mitral valve changes in ischemic and non-ischemic dilated cardiomyopathies. It also explains the value of a complete multiparametric assessment of this structure. Not only must an assessment include quantitative measures of regurgitation, but also various anatomical parameters from the mitral apparatus and left ventricle, since they carry prognostic value and are predictors of mitral valve repair success and durability.

When too much closeness harms: circumflex artery injury during mitral valve surgery.

Occlusion of the left coronary circumflex artery (LCX) during surgical procedures of the mitral valve is an infrequent but potentially life-threatening complication (1-3). Due to its close anatomical relationship to the posterior mitral valve annulus, there is a relevant risk of causing a stenosis or an occlusion of the left circumflex artery, especially by surgical annular sutures. The perioperative clinical course is heterogeneous, ranging from-initially-asymptomatic or solely electrocardiographic abnormalities to cardiogenic shock. Both severely impaired ventricular contractility or malignant arrhythmia may potentially lead to a weaning failure from cardiopulmonary bypass (CPB) and eventually result in chronic heart failure with persistently reduced ejection fraction. Possible therapeutic strategies include the immediate reopening of causal sutures, aortocoronary bypass grafting or percutaneous coronary intervention (PCI), yet PCI seems to be the preferred method at present.

Morphology of the mural and commissural atrioventricular junction of the mitral valve.

OBJECTIVE: This study investigates mitral annular disjunctions (MAD) in the atrial wall-mitral annulus-ventricular wall junction along the mural mitral leaflet and commissures. METHODS: We examined 224 adult human hearts (21.9% females, 47.9±17.6 years) devoid of cardiovascular diseases (especially mitral valve disease). These hearts were obtained during forensic medical autopsies conducted between January 2018 and June 2021. MAD was defined as a spatial displacement (≥2 mm) of the leaflet hinge line towards the left atrium. We provided a detailed morphometric analysis (disjunction height) and histological examination of MADs. RESULTS: MADs were observed in 19.6% of all studied hearts. They appeared in 12.1% of mural leaflets. The P1 scallop was the primary site for disjunctions (8.9%), followed by the P2 scallop (5.4%) and P3 scallop (4.5%). MADs were found in 9.8% of all superolateral and 5.8% of all inferoseptal commissures. The average height for leaflet MADs was 3.0±0.6 mm, whereas that for commissural MADs was 2.1±0.5 mm (p<0.0001). The microscopical arrangement of MADs in both the mural leaflet and commissures revealed a disjunction shifted towards left atrial aspect, filled with connective tissue and covered by elongated valve annulus. The size of the MAD remained remarkably uniform and showed no correlation with other anthropometric factors (all p>0.05). CONCLUSIONS: In the cohort of the patients with healthy hearts, MAD is present in about 20% of all studied hearts. The MADs identified tend to be localised, confined to a single scallop. Moreover, MADs in the commissures are notably smaller than those in the mural leaflet.