Acute mitral regurgitation with and without acute heart failure.

Acute severe mitral regurgitation (MR) is rare, but often leads to cardiogenic shock, pulmonary edema, or both. Most common causes of acute severe MR are chordae tendineae (CT) rupture, papillary muscle (PM) rupture, and infective endocarditis (IE). Mild to moderate MR is often seen in patients with acute myocardial infarction (AMI). CT rupture in patients with floppy mitral valve/mitral valve prolapse is the most common etiology of acute severe MR today. In IE, native or prosthetic valve damage can occur (leaflet perforation, ring detachment, other), as well as CT or PM rupture. Since the introduction of percutaneous revascularization in AMI, the incidence of PM rupture has substantially declined. In acute severe MR, the hemodynamic effects of the large regurgitant volume into the left atrium (LA) during left ventricular (LV) systole, and in turn back into the LV during diastole, are profound as the LV and LA have not had time to adapt to this additional volume. A rapid, but comprehensive evaluation of the patient with acute severe MR is essential in order to define the underline cause and apply appropriate management. Echocardiography with Doppler provides vital information related to the underlying pathology. Coronary arteriography should be performed in patients with an AMI to define coronary anatomy and need for revascularization. In acute severe MR, medical therapy should be used to stabilize the patient before intervention (surgery, transcatheter); mechanical support is often required. Diagnostic and therapeutic steps should be individualized, and a multi-disciplinary team approach should be utilized.

Mitral commissural prolapse.

Mitral commissural prolapse or flail, either isolated or combined with more extensive degenerative valve disease, imposes several challenges both on its diagnosis and management while being a risk factor for valve reoperation after mitral valve repair. Accurate identification of the prolapsing segment is often not feasible with transthoracic 2D echocardiography, with transesophageal 3D imaging then required for correct diagnosis and surgical planning. Various surgical techniques employed alone or in combination have yielded good results in the repair of commissural prolapse. Herein, we analyze the specific characteristics of commissural disease focusing our attention on 2D and 3D echocardiographic findings and we briefly comment on techniques employed for surgical correction of the disease.

Matrix Metalloproteinase Polymorphisms in Patients with Floppy Mitral Valve/Mitral Valve Prolapse (FMV/MVP) and FMV/MVP Syndrome.

BACKGROUND: It has been suggested that collagen abnormalities of the mitral valve are present in patients with floppy mitral valve (FMV)/mitral valve prolapse (MVP). Genetic factors determining collagen synthesis and degradation have not been well defined in these patients. This study was undertaken to determine whether selective polymorphisms of matrix metalloproteinase-2 (MMP2) or transforming growth factor-ß (TGFß), with known or putative effects on collagen turnover, are more frequent in FMV/MVP. METHODS: Single nucleotide polymorphisms (SNPs) in select genes related to collagen turnover, including MMP2 rs2285053, MMP2 rs243865, TGFß1 rs1800469, and TGFß2 rs900, were determined in 98 patients with FMV/MVP who had severe mitral regurgitation and compared to 99 controls. RESULTS: MMP2 rs243865 was the only SNP significantly associated with FMV/MVP as compared to the control (odds ratio 2.07, 95% CI 1.23-3.50, p = 0.006). MMP2 rs228503 was the only SNP significantly associated with the FMV/MVP syndrome as compared to patients with FMV/MVP without the syndrome (odds ratio 2.41, 95% CI 1.08-5.40, p = 0.032). CONCLUSION: The frequency of certain MMP2 polymorphisms is higher in patients with the FMV/MVP syndrome and patients with FMV/MVP without the syndrome. The data suggest that a genetic predisposition that alters collagen turnover may play a role in the pathogenesis and development of FMV/MVP.

Implementation of Endoscopic Minimally Invasive Mitral Valve Replacement Surgery With Automated Suturing Technology.

In the evolving landscape of cardiac surgery, this article explores the potential of minimally invasive mitral valve replacement procedures as a viable alternative to conventional surgical techniques. Leveraging advancements in automated suturing devices and video endoscopy, our work aims to demonstrate that minimally invasive approaches can be applied across a broad spectrum of surgical scenarios. Herein we highlight preoperative diagnostics and operative techniques, with a focus on infra-axillary anterolateral minithoracotomy as the access point. Our technique utilizes technology from LSI SOLUTIONS® (Victor, NY, USA), including the RAM® Device for automated suturing, which has an ergonomic design and safety features. The device's capabilities are further enhanced by the SEW-EASY® Device, the RAM® RING, and the COR-KNOT MINI® Device, which streamline suture management and securement. This work outlines how these technological advancements can mitigate concerns about technical complexity and learning curves, thereby encouraging wider adoption of minimally invasive techniques. Clinical benefits may include reduced surgical trauma, quicker recovery, and cost-effectiveness, making it a compelling option in an era of aggressively promoted transcatheter interventions.

Pacemaker implantation after concomitant tricuspid valve repair in patients undergoing minimally invasive mitral valve surgery: Results from the Mini-Mitral International Registry.

Objective: Randomized evidence suggests a high risk of pacemaker implantation for patients undergoing mitral valve (MV) surgery with concomitant tricuspid valve repair (cTVR). We investigated the impact of cTVR on outcomes in the Mini-Mitral International Registry. Methods: From 2015 to 2021, 7513 patients underwent minimally invasive MV with or without cTVR in 17 international centers (MV: n = 5609, cTVR: n = 1113). Propensity matching generated 1110 well-balanced pairs. Multivariable analysis was applied. Results: Patients with cTVR were older and had more comorbidities. Propensity matching eliminated most differences except for more TR in patients who underwent cTVR (77.2% vs 22.1% MV, P < .001). Mean matched age was 71 years, and 45% were male. European System for Cardiac Operative Risk Evaluation II was still 2.68% (interquartile range [IQR], 0.80-2.63) vs 1.9% (IQR, 1.12-3.9) in matched MV (P < .001). MV replacement (30%) and atrial fibrillation surgery (32%) were similar in both groups. Cardiopulmonary bypass (161 minutes [IQR, 133-203] vs MV: 130 minutes [IQR, 103-166]; P < .001) and crossclamp times (93 minutes [IQR, 66-123] vs MV: 83 minutes [IQR, 64-107]; P < .001) were longer with cTVR. Although in-hospital mortality was similar (cTVR: 3.3% vs MV: 2.2%; P = .5), postoperative pacemaker implantations (9% vs MV: 5.8%; P = .02), low cardiac output syndrome (7.7% vs MV: 4.4%; P = .02), and acute kidney injury (13.8% vs MV: 10%; P = .01) were more frequent with cTVR. cTVR eliminated relevant TR in most patients (greater-than-moderate TR: 6.8%). Multivariable analysis identified MV replacement, atrial fibrillation, and cTVR as risk factors of postoperative pacemaker implantation. Conclusions: cTVR in minimally invasive MV surgery is an independent risk factor for pacemaker implantation in this international registry. It is also associated with more bleeding, low output syndrome, and acute kidney injury. It remains unclear whether technical or patient factors (or both) explain these differences.

Periostin is overexpressed, correlated with fibrosis and differs among grades of cardiomyocyte hypertrophy in myectomy tissue of patients with hypertrophic cardiomyopathy.

Periostin, a secreted matricellular protein, has been implicated in cardiac extracellular matrix remodeling and fibrosis. Evidence suggest that periostin stimulates cardiomyocyte hypertrophy. The current study aims to investigate the extent of periostin expression in patients with advanced Hypertrophic Cardiomyopathy (HCM) and its correlation with fibrosis and hallmark histopathological features of the disease. Interventricular septal tissue from thirty-nine HCM patients who underwent myectomy and five controls who died from non-cardiac causes was obtained. Staining with Masson's Trichrome and immunohistochemistry were used to localize fibrosis and periostin respectively. The extent of fibrosis and the expression of periostin were defined as the stained percentage of total tissue area using digital pathology software. Periostin expression was higher in HCM patients compared to controls (p<0.0001), positively correlated with the extent of fibrosis (r = 0.82, p<0.001), positively correlated with maximal interventricular septal thickness (Rho = 0.33, p = 0.04) and negatively correlated with LVEF (r = -0.416, p = 0.009). Periostin was approximately co-localized with fibrosis. Mean periostin expression was lower in patients with mild grade cardiomyocyte hypertrophy compared to those with moderate grade (p = 0.049) and lower in patients with mild grade replacement fibrosis compared to moderate grade (p = 0.036). In conclusion, periostin is overexpressed in advanced HCM, correlated with fibrosis and possibly related to cardiomyocyte hypertrophy.

Aortic cross-clamp time correlates with mortality in the mini-mitral international registry.

OBJECTIVES: Minimally invasive access has become the preferred choice in mitral and/or tricuspid valve surgery. Reported outcomes are at least similar to classic sternotomy although aortic cross-clamp times are usually longer. METHODS: We analysed the largest registry of mitral and/or tricuspid valve surgery patients (mini-mitral international registry (MMIR)) for the relationship between aortic cross-clamp times, mortality and other outcomes. From 2015 to 2021, 7513 consecutive patients underwent mini-mitral and/or tricuspid valve surgery in 17 international Heart-Valve-Centres. Data were collected according to Mitral Valve Academic Research Consortium (MVARC) definitions and 6878 patients with 1 cross-clamp period were analysed. Uni- and multivariable regression analyses were used to assess outcomes in relation to aortic cross-clamp times. RESULTS: Median age was 65 years (57% male). Median EuroSCORE II was 1.3% (Inpatient Quality Reporting (IQR): 0.80-2.63). Minimally invasive access was either by direct vision (28%), video-assisted (41%) or totally endoscopic/robotic (31%). Femoral cannulation was used in 93%. Three quarters were repairs with 17% additional tricuspid valve surgery and 19% Atrial Fibrillation (AF)-ablation. Cardiopulmonary bypass and cross-clamp times were 135 min (IQR: 107-173) and 85 min (IQR: 64-111), respectively. Postoperative events were death (1.6%), stroke (1.2%), bleeding requiring revision (6%), low cardiac output syndrome (3.5%) and acute kidney injury (6.2%, mainly stage I). Statistical analyses identified significant associations between cross-clamp time and mortality, low cardiac output syndrome and acute kidney injury (all P < 0.001). Age, low ejection fraction and emergent surgery were risk factors, but variables of 'increased complexity' (redo, endocarditis, concomitant procedures) were not. CONCLUSIONS: Aortic cross-clamp time is associated with mortality as well as postoperatively impaired cardiac and renal function. Thus, implementing measures to reduce cross-clamp time may improve outcomes.

Risk-related clinical outcomes after minimally invasive mitral valve surgery: insights from the Mini-Mitral International Registry.

OBJECTIVES: With the popularization of catheter-based mitral valve procedures, evaluating risk-specific differentiated clinical outcomes after contemporary mitral valve surgery is crucial. In this study, we assessed the operative results of minimally invasive mitral valve operations across different patient risk profiles and evaluated the value of EuroSCORE (ES) II predicted risk of mortality model for risk prediction, in the large cohort of Mini-Mitral International Registry (MMIR). METHODS: The MMIR database was used to analyse mini-mitral operations between 2015 and 2021. Patients were categorized as low (<4%), intermediate (4% to <8%), high (8% to <12%) and extreme risk (≥12%) according to ES II. The observed-to-expected mortality ratio was calculated for each risk group. RESULTS: A total of 6541 patients were included in the analysis. Of those, 5546 (84.8%) were classified as low risk, 615 (9.4%) as intermediate risk, 191 (2.9%) as high risk and 189 (2.9%) as extreme risk. Overall operative mortality and stroke rates were 1.7% and 1.4%, respectively, and were significantly associated with patient's risk. The observed mortality was significantly lower than expected-according to the ES II-in all risk categories (observed-to-expected ratio < 1). CONCLUSIONS: The present study provides an international contemporary benchmark for operative outcomes after minimally invasive mitral surgery. Operative results were excellent in low-, intermediate- and high-risk patients, but were less satisfactory in extreme risk. The ES II model overestimated the in-hospital mortality. We believe that findings from the MMIR may assist surgeons and cardiologists in clinical decision-making and treatment allocation for patients with mitral valve disease.

Neurological outcomes in minimally invasive mitral valve surgery: risk factors analysis from the Mini-Mitral International Registry.

OBJECTIVES: The aim of this study was to examine the incidence and predictors of stroke after minimally invasive mitral valve surgery (mini-MVS) and to assess the role of preoperative CT scan on surgical management and neurological outcomes in the large cohort of Mini-Mitral International Registry. METHODS: Clinical, operative and in-hospital outcomes in patients undergoing mini-MVS between 2015 and 2021 were collected. Univariable and multivariable analyses were used to identify predictors of stroke. Finally, the impact of preoperative CT scan on surgical management and neurological outcomes was assessed. RESULTS: Data from 7343 patients were collected. The incidence of stroke was 1.3% (n = 95/7343). Stroke was associated with higher in-hospital mortality (11.6% vs 1.5%, P < 0.001) and longer intubation time, ICU and hospital stay (median 26 vs 7 h, 120 vs 24 h and 14 vs 8 days, respectively). On multivariable analysis, age (odds ratio 1.039, 95% confidence interval 1.019-1.060, P < 0.001) and mitral valve replacement (odds ratio 2.167, 95% confidence interval 1.401-3.354, P < 0.001) emerged as independent predictors of stroke. Preoperative CT scan was made in 31.1% of cases. These patients had a higher risk profile and EuroSCORE II (median 1.58 vs 1.1, P < 0.001). CT scan influenced the choice of cannulation site, being ascending aorta (18.5% vs 0.5%, P < 0.001) more frequent in the CT group and femoral artery more frequent in the no CT group (97.8% vs 79.7%, P < 0.001). No difference was found in the incidence of postoperative stroke (CT group 1.5, no CT group 1.4%, P = 0.7). CONCLUSIONS: Mini-MVS is associated with a low incidence of stroke, but when it occurs it has an ominous impact on mortality. Preoperative CT scan affected surgical cannulation strategy but did not led to improved neurological outcomes.

Floppy mitral valve/mitral valve prolapse and sudden cardiac death.

It is well appreciated today that sudden cardiac death (SCD) occurs in patients with floppy mitral valve (FMV)/mitral valve prolapse (MVP) without significant mitral regurgitation . Data from studies most likely represent a heterogeneous population and probably underestimate the true incidence of SCD in this group of patients. SCD in patients with FMV/MVP occurs mostly in young individuals without comorbidities. Over the last decade, the phenotypic expression of patients with FMV/MVP at risk for SCD (bileaflet prolapse, redundant mitral leaflets, symptomatic young women) have been defined, possible pathophysiologic mechanisms leading to SCD have been proposed, and appropriate steps to prevent the catastrophic event, though in evolution, have been suggested. In this review, state-of-the-art knowledge related to SCD in patients with FMV/MVP is summarized.

Totally endoscopic aortic valve replacement with concomitant trans-aortic mitral valve repair for mitral regurgitation.

BACKGROUND: Minimally invasive aortic valve procedures through a hemi-sternotomy or a right anterior mini-thoracotomy have gained popularity over the last several years. Totally endoscopic aortic valve replacement (TEAVR) is an innovative and a less invasive (incision-wise) surgical aortic valve replacement technique. The operative steps of TEAVR have been reported previously from our group. Mitral regurgitation (MR) frequently accompanies aortic valve disease that at times may also require repair. Totally endoscopic surgery in such cases has not been tested. PRESENTATION OF THE TECHNIQUE: We present a surgical technique for a totally endoscopic approach to aortic valve replacement and concomitant mitral valve repair for primary and secondary MR. An aortotomy incision was used avoiding an atriotomy, which results in an increase in cross-clamp (XC) and cardiopulmonary bypass (CPB) times that could be associated with higher mortality and morbidity. Neochords (artificial chordae tendineae) were used for primary MR and an edge-to-edge approach for secondary MR. CONCLUSION: TEAVR and concomitant mitral valve repair can be performed successfully with reasonable XC and CPB times with excellent short-term results.

Routine histopathology of septal myectomy for hypertrophic obstructive cardiomyopathy in a greek cohort.

Hypertrophic cardiomyopathy (HCM) is a diverse inherited disease affecting 1 in 500 individuals irrespective of gender and ethnicity. A fraction of HCM patients will eventually develop drug refractory dynamic obstruction of the left ventricular outflow tract. For such patients, septal myectomy is the procedure of choice to alleviate their symptoms and improve their quality of life. The current histopathological study, the first from the Greek region, aims to examine the hallmark histopathological characteristics of Hypertrophic Obstructive Cardiomyopathy in a population of patients undergoing septal myectomy at a single center over a ten year period. Medical records and histopathology specimens of thirty nine (n=39) patients were evaluated. The sample comprised 22 males (56.4%) and 17 females (43.6%). Mean patient age at myectomy was 53.9±16.7 years, ranging from 12 to 79 years. Maximal IVS thickness on echocardiography was available for 35 patients with a median value of 2.08cm. Peak resting LVOT Pressure Gradient was available for 33 patients with a mean value of 104.88±44.20 mmHg. Central tendency of each histopathological attribute expressed as the median value was: moderate for myocyte hypertrophy, mild for cytoplasmic vacuolization, moderate for subendocardial fibrosis, moderate for interstitial fibrosis, mild for replacement fibrosis, moderate for myofibrillar disarray and mild for capillary stenosis. Myocyte hypertrophy, present in all specimens, was positively correlated with maximal IVS thickness (tau-b=0.43, p=0.002). Replacement fibrosis was positively correlated with the grade of microvascular stenosis (tau-b=0.45, p=0.004). LVEF was negatively correlated with the grade of interstitial fibrosis (tau-b=-0.43, p=0.035) and with the extent of myocardial fiber disarray (tau-b=-0.42, p=0.034). Histopathological attributes were not correlated with patient gender or age thus proving that HCM has a histological phenotype unique to each patient, mainly depending on each specific sarcomeric mutation.

Epidemiology and Management of Chronic Thromboembolic Pulmonary Hypertension in Greece. Real-World Data from the Hellenic Pulmonary Hypertension Registry (HOPE).

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease with poor prognosis if left untreated, characterized by pulmonary vascular bed obstruction due to unresolving thromboembolic material. The Hellenic pulmonary hypertension registry (HOPE) was launched in Greece in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. In total, 98 patients with CTEPH were enrolled from January 2015 until November 2019. Of these patients, 55.1% represented incident population, 50% were classified in the World Health Organization functional class II and 49% had a history of acute pulmonary embolism. The median values of pulmonary vascular resistance (PVR) and cardiac index were 7.4 (4.8) WU and 2.4 (1.0) L/min/m2, respectively, the mean diffusing capacity for carbon monoxide was 74.8 ± 20.6%, the median 6-minute walk distance was 347 (220) meters and the median value of N Terminal-pro brain natriuretic peptide was 506.0 (1450.0) pg/mL. In total, 60.2% of the patients were under pulmonary arterial hypertension-targeted therapy at the time of enrolment; specifically, riociguat was received by 35.7% of the patients and combination therapy was the preferred strategy for 16% of the patients. In total, 74 patients were evaluated for pulmonary endarterectomy (PEA), 34 (45.9%) were assessed as operable but only 23 of those (31.1%) finally underwent PEA. The remaining 40 patients were ineligible for PEA according to the operability assessment and 13 (17.6%) of them underwent balloon pulmonary angioplasty. The age of the non-operable patients was significantly higher than the operable patients (p < 0.001), while there was no significant difference with regard to the history of coagulopathies between the operable and non-operable patients (p = 0.33).

Preoperative determination of artificial chordae tendineae length by transoesophageal echocardiography in totally endoscopic mitral valve repair.

OBJECTIVES: Artificial chordae tendineae are widely used for surgical repair in patients with mitral regurgitation due to floppy mitral valve/mitral valve prolapse. Expanded polytetrafluoroethylene has been used to construct these artificial chordae; however, the determination of the optimal length of the chordae prior to surgery has been an issue. For this reason, such a method was developed and the results of its use are presented. METHODS: Forty-seven consecutive patients with significant mitral regurgitation due to floppy mitral valve/mitral valve prolapse who underwent totally endoscopic mitral valve surgery were studied. The chordae length was predetermined using transoesophageal echocardiography. The length between the top of the fibrous body of the papillary muscle and the coaptation line of the 2 leaflets of the mitral valve was measured and used to define the length of the chordae to be used for repair. Then under stereoscopic vision, a total endoscopic mitral valve repair was performed. RESULTS: The predicted mean length of chordal loops was 19.76 ± 0.71 mm (median 20, range 16-28) and the actual mean length of chordal loops used was 19.68 ± 0.74 mm (median 20, range 16-26) demonstrating an excellent correlation between the two (r = 0.959). The mean number of chordae loops used per patient was 5.12 ± 0.62 (median 4, range 2-12). All patients at the time of discharge had no or trivial mitral regurgitation on transoesophageal echocardiography. CONCLUSIONS: The chordae length used for mitral valve repair can be determined prior to surgery using transoesophageal echocardiography with a high degree of accuracy. Further, total endoscopic repair in this group of patients provides excellent results. For these reasons, it is expected that this method will replace most traditional approaches to cardiac surgeries in the years to come.

The Use of MitraClip in Secondary Mitral Regurgitation and Heart Failure.

Secondary (also known as functional) mitral regurgitation (MR) has increased substantially over the last several decades due to an increase in the prevalence of dilated cardiomyopathy (ischemic and non-ischemic). Mortality and morbidity in patients with dilated cardiomyopathy is much greater when associated with MR as compared to without MR. MR will result in further left ventricular (LV) volume overload, LV dilation, and pupillary muscle displacement resulting in deterioration of the severity of MR leading to a vicious cycle. Optimization of heart failure medical therapy, and cardiac resynchronization therapy for those that qualify, can improve severity of MR; however, significant MR will persist in certain patients. Transcatheter mitral valve repair to treat significant MR using the MitraClip (Abbott, Menlo Park, California), which grasps and coapts the posterior and anterior mitral valve leaflets, in appropriately selected patients with dilated cardiomyopathy and secondary MR has been shown to improve quality of life and prolong survival.

Floppy mitral valve/mitral valve prolapse: A complex entity with multiple genotypes and phenotypes.

Floppy mitral valve/mitral valve prolapse (FMV/MVP) is a common valvular abnormality affecting 2% to 3% of the general population. It occurs in a heterogeneous group of patients with varying and age dependent expressions. FMV/MVP can be familial or sporadic, isolated (called non-syndromic) or as a part of a well-defined syndrome of heritable connective tissue disorders or other diseases. A wide range of phenotypic expression exists ranging from asymptomatic to non-specific symptoms related to neuroendocrine or autonomic nervous system functional abnormalities, varying degrees of mitral regurgitation that may require interventional therapy, heart failure, infective endocarditis, cardiac arrhythmias and/or sudden cardiac death. FMV/MVP is predominantly considered a heritable disorder with clinical manifestations not present at birth, but appearing later in life. Though a variant gene may initiate the development of FMV/MVP, precise phenotypic expression may be related to multiple other molecular, genetic and epigenetic factors that modify the final expression of the disease. A better understanding of these mechanisms will help to better define the natural history of the disease, inhibit disease progression and even prevent the phenotypic expression of FMV/MVP.