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BACKGROUND In patients with severe primary mitral regurgitation (MR), the indication for surgery is currently based on the presence of symptoms, left ventricular dilatation and dysfunction, atrial fibrillation, and pulmonary hypertension.OBJECTIVES The aim of this study was to evaluate the prognostic impact of the presence of extra-mitral valve cardiac involvement (including known risk factors but also severe left atrial [LA] dilatation and right ventricular [RV] dysfunction) in a large multicenter study of patients with primary MR.METHODS Patients with severe primary MR undergoing surgery were included and categorized according to the extent (highest) of cardiac involvement: group 0, no cardiac involvement; group 1, left ventricular involvement; group 2, LA involvement; group 3, pulmonary vasculature or tricuspid valve involvement; or group 4, RV involvement. The outcome was all-cause mortality.RESULTS A total of 1,106 patients were included (mean age 63 +/- 12 years, 68% male). In total, 377 patients (34%) were classified in group 0, 239 (22%) in group 1, 213 (19%) in group 2, 180 (16%) in group 3, and 97 (9%) in group 4. Kaplan-Meier curve analysis revealed significantly worse survival (log-rank chi-square 1/4 43.4; P < 0.001) with higher group. On multivariable analysis, age, male sex, chronic obstructive pulmonary disease, kidney function, and group of cardiac involvement were independently associated with all-cause mortality. For each increase in group, a 17% higher risk for all-cause mortality was observed (95% CI: 1.051-1.313; P 0.005) during a median follow-up time of 88 months.CONCLUSIONS In patients with severe primary MR, a novel classification system based on extra-mitral valve cardiac involvement may help refine risk stratification and timing of surgery, particularly including severe LA dilatation and RV dysfunction in the assessment. (C) 2022 by the American College of Cardiology Foundation.

Background: Noninvasive left ventricular (LV) pressure-strain loop analysis is emerging as a new echocardiographic method to evaluate LV function, integrating longitudinal strain by speckle-tracking analysis and sphygmomanometrically measured blood pressure to estimate myocardial work. The aims of this study were (1) to describe global and segmental myocardial work in patients with hypertrophic cardiomyopathy (HCM), (2) to assess the correlation between myocardial work and other echocardiographic parameters, and (3) to evaluate the association of myocardial work with adverse outcomes.Methods: One hundred ten patients with nonobstructive HCM (mean age, 55 +/- 15 years; 66% men), with different phenotypes (apical, concentric, and septal hypertrophy), and 35 age- and sex-matched healthy control subjects were included. The following myocardial work indices were included: myocardial work index, constructive work (CW), wasted work, and cardiac efficiency. The combined end point included all-cause mortality, heart transplantation, heart failure hospitalization, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator therapy.Results: Mean global CW (1,722 +/- 602 vs 2,274 +/- 574 mm Hg%, P < .001), global cardiac efficiency (93% [89%-95%] vs 96% [96%-97%], P < .001), and global MWI (1,534 +/- 551 vs 1,929 +/- 473 mm Hg%) were significantly reduced, while global wasted work (104 mm Hg% [66-137 mm Hg%] vs 71 mm Hg% [49-92 mm Hg%], P < .001) was increased in patients with HCM compared with control subjects. Segmental impairment in CW colocalized with maximal wall thickness (HCM phenotype), and global CW correlated with LV wall thickness (r = -0.41, P < .001), diastolic function (r = -0.27, P = .001), and QRS duration (r = -0.28, P = .001). Patients with global CW > 1,730 mm Hg% (the median value) experienced better event-free survival than those with global CW < 1,730 mm Hg% (P < .001).Conclusions: Myocardial work, assessed noninvasively using echocardiography and blood pressure measurement, is reduced in patients with nonobstructive HCM; it correlates with maximum LV wall thickness and is significantly associated with a worse long-term outcome.

ObjectiveMitral valve prolapse (MVP) has been associated with ventricular arrhythmias (VA), but little is known about VA in patients with significant primary mitral regurgitation (MR). Our aim was to describe the prevalence of symptomatic VA in patients with MVP (fibro-elastic deficiency or Barlow’s disease) referred for mitral valve (MV) surgery because of moderate-to-severe MR, and to identify clinical, electrocardiographic, standard and advanced echocardiographic parameters associated with VA.Methods610 consecutive patients (64±12 years, 36% female) were included. Symptomatic VA was defined as symptomatic and frequent premature ventricular contractions (PVC, Lown grade ≥2), non-sustained or sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) without ischaemic aetiology.ResultsA total of 67 (11%) patients showed symptomatic VA, of which 3 (4%) had VF, 3 (4%) sustained VT, 27 (40%) non-sustained VT and 34 (51%) frequent PVCs. Patients with VA were significantly younger, more often female and showed T-wave inversions; furthermore, they showed significant MV morphofunctional abnormalities, such as mitral annular disjunction (39% vs 20%, pConclusionIn patients with MVP with moderate-to-severe MR, symptomatic VA are relatively frequent and associated with significant MV annular abnormalities, subtle left ventricular function impairment and heterogeneous contraction. Assessment of these parameters might help decision-making over further diagnostic analyses and improve risk-stratification.

Background The indication for surgery in patients with severe primary mitral regurgitation (MR) is currently based on the presence of symptoms, left ventricular (LV) dilatation and dysfunction, atrial fibrillation and pulmonary hypertension. The aim of this study was to evaluate the prognostic impact of a new staging classification based on cardiac damage including the known risk factors but also including global longitudinal strain (GLS), severe left atrial (LA) dilatation and right ventricular (RV) dysfunction. Methods In total 614 patients who underwent surgery for severe primary MR with available baseline transthoracic echocardiograms were included. Patients were classified according to the extent of cardiac damage (Figure): Stage 0-no cardiac damage, Stage 1-LV damage, Stage 2-LA damage, Stage 3-pulmonary vasculature or tricuspid valve damage and Stage 4-RV damage. Patients were followed for all-cause mortality. Results Based on the proposed classification, 172 (28%) patients were classified as Stage 0, 102 (17%) as Stage 1, 134 (21%) as Stage 2, 135 (22%) as Stage 3 and 71 (11%) as Stage 4. The more advanced the stage, the older the patients were with worse kidney function, more symptoms and higher EuroScore. Kaplan-Meier curve analysis revealed that patients with more advanced stages of cardiac damage had a significantly worse survival (log-rank chi-square 35.2; p Conclusion In patients with severe primary MR, a novel staging classification based on the extent of cardiac damage, may help refining risk stratification, particularly including also GLS, LA dilatation and RV dysfunction in the assessment. Funding Acknowledgement Type of funding source: None

OBJECTIVES Barlow’s disease (BD) is characterized by thick, redundant mitral valve (MV) leaflets, which can lead to prolapse and significant mitral regurgitation (MR). MV annular abnormalities are also commonly observed and increasingly recognized as possible primary pathology, with leaflet thickening being secondary to increased stress on the MV apparatus. To provide more insights into this hypothesis, the evolution of MV abnormalities over time in patients with BD was assessed. METHODS A total of 64 patients (54 ± 12 years, 72% male) with BD who underwent MV surgery and had multiple transthoracic echocardiograms (TTE) before surgery were included. In total, 186 TTE were analysed (median time interval 4.2, interquartile range 2.2–6.5 years) including specific MV characteristics. RESULTS At baseline, MV leaflet length, thickness, billowing height and annular diameter were larger in patients with BD compared to 59 healthy subjects. Systolic outward motion (curling) of the annulus was observed in 77% and severe mitral annular disjunction (≥5 mm) in 38% of patients with BD. Forty (63%) patients had MR grade I–II and 24 (37%) MR grade III–IV; at baseline, the 2 groups only differed in left atrial volume and in thickness and billowing height of the posterior leaflet, showing comparable MV annular abnormalities and dilatation despite different grades of MR. Over time, MV annulus diameter, leaflet length and billowing height increased significantly along with MR grade. CONCLUSIONS In patients with BD, MV annulus abnormalities are present at an early stage and precede the development of significant MR, suggesting their substantial role in the pathophysiology of this disease and as an important target for surgical treatment.

Only few studies aimed at identifying predictors of heart failure (HF) in hypertrophic cardiomyopathy (HC) patients. Furthermore, serial echocardiographic analyses are lacking in these patients and little is known about the natural progression of left ventricular (LV) abnormalities and their association with HF development. Aim of this study was to assess the prognostic value of LV global longitudinal strain (GLS) and other clinical and echocardiographic characteristics for the development of HF in patients with nonobstructive HC; furthermore, changes in echocardiographic parameters over time were correlated with HF development. Echocardiography was performed in 236 HC patients (68% men, age: 50 ± 14 years) at their initial visit and during follow-up (6.5(4.1 to 9.8) years). The end point of new HF development or progression to New York Heart Association class III/IV was noted and echocardiographic changes over time were compared among patients with and without HF using linear mixed model analysis. In total, 40 patients reached the HF end point. Multivariable cox regression analysis showed that age (HR 1.04(1.01 to 1.06), p = 0.016), New York Heart Association class (HR 2.30(1.07 to 4.95), p = 0.033), GLS (HR 1.15(1.05 to 1.22), p = 0.001), and left atrial volume (LAVI, HR 2.22(1.10 to 4.50), p = 0.027) were independently associated with the HF end point. Echocardiographic parameters, including GLS and LAVI, remained stable over time in patients without HF end point, but changed significantly in patients who developed HF (group-time interaction, p = 0.042 for GLS and p = 0.027 for LAVI). In conclusion, LV dysfunction is a progressive phenomenon in nonobstructive HC patients which can be detected by repeated echocardiography. Importantly, GLS and LAVI at baseline as well as their changes over time are associated with HF.

OBJECTIVES The risk factors and clinical effect of elevated mitral valve (MV) gradients after valve repair for degenerative valve disease remain insufficiently understood. METHODS Between January 2004 and December 2015, a total of 484 patients underwent valve repair for degenerative disease. A true-sized full annuloplasty ring was implanted in all cases. We analysed the effect of preoperative and intraoperative factors on the postrepair gradient. Additionally, we explored the effect of postrepair gradients on long-term outcomes. RESULTS On linear regression analysis, postrepair MV gradients were associated with patient age (coefficient = −0.110, standard error = 0.005, P = 0.034), body surface area (coefficient = 0.905, standard error = 0.340, P = 0.008), implanted annuloplasty ring size (coefficient = −0.181, standard error = 0.018, P CONCLUSIONS Following valve repair for degenerative MV disease, elevated gradients occur even when true-sized annuloplasty is performed. The late clinical results of valve repair with elevated postrepair gradient are impaired and further studies are needed to explore preventive measures aimed at resolving the issue.

OBJECTIVES This study sought to investigate whether left ventricular (LV) global longitudinal strain (GLS) is associated with long-term outcome after mitral valve (MV) surgery for primary mitral regurgitation (MR) and assess the differences in outcome according to MR etiology: Barlow's disease (BD), fibroelastic deficiency (FED), and forme fruste (FF).BACKGROUND Appropriate timing of MV surgery for primary MR is still challenging and may differ according to the etiology. In these patients, LV-GLS has been proposed as more sensitive measure to detect subtle LV dysfunction as compared with LV ejection fraction.METHODS Echocardiography was performed in 593 patients (64% men, age 65 +/- 12 years) with severe primary MR who underwent MV surgery, including assessment of LV-GLS. The etiology (BD, FED, or FF) was defined based on surgical observation. During follow-up, primary endpoint was all-cause mortality and a secondary endpoint included cardiovascular death, heart failure hospitalizations, and cerebrovascutar accidents.RESULTS During a median follow-up of 6.4 (interquartile range: 3.6 to 10.4) years, 146 patients died (16 within 30 days after surgery), 46 patients were hospitalized for heart failure, and 13 patients had a cerebrovascutar accident. Age (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.05 to 1.11; p < 0.001) and LV-GLS (HR: 1.13; 95% CI: 1.06 to 1.21; p < 0.001) were independently associated with all-cause mortality. Patients with LV-GLS >-20.6% (more impaired) showed significant worse survival than did patients with LV-GLS

To the Editor: Fibroelastic deficiency (FED) and Barlow disease (BD) are 2 phenotypes of degenerative mitral valve regurgitation characterized by excessive movement of the mitral leaflets and the saddle-shaped mitral annulus [(1,2)][1]. Compared with FED, BD exhibits more pronounced excessive

PurposeAlthough a familial distribution has been documented, the genetic aetiology of mitral valve prolapse (MVP) is largely unknown, with only four genes identified so far: FLNA, DCHS1, DZIP1 and PLD1. The aim of this study was to evaluate the genetic yield in known causative genes and to identify possible novel genes associated with MVP using a heart gene panel based on exome sequencing.MethodsPatients with MVP were referred for genetic counselling when a positive family history for MVP was reported and/or Barlow’s disease was diagnosed. In total, 101 probands were included to identify potentially pathogenic variants in a set of 522 genes associated with cardiac development and/or diseases.Results97 (96%) probands were classified as Barlow’s disease and 4 (4%) as fibroelastic deficiency. Only one patient (1%) had a likely pathogenic variant in the known causative genes (DCHS1). However, an interesting finding was that 10 probands (11%) had a variant that was classified as likely pathogenic in six different, mostly cardiomyopathy genes: DSP (1×), HCN4 (1×), MYH6 (1×), TMEM67 (1×), TRPS1 (1×) and TTN (5×).ConclusionExome slice sequencing analysis performed in MVP probands reveals a low genetic yield in known causative genes but may expand the cardiac phenotype of other genes. This study suggests for the first time that also genes related to cardiomyopathy may be associated with MVP. This highlights the importance to screen these patients and their family for the presence of arrhythmias and of ‘disproportionate’ LV remodelling as compared with the severity of mitral regurgitation, unravelling a possible coexistent cardiomyopathy.

Background Mitral valve prolapse (MVP) is known to be associated with ventricular arrhythmias (VA), from symptomatic premature ventricular contractions (PVCs) to malignant ventricular tachycardia (VT) and sudden cardiac death (SCD). Previous studies identified risk factors for VA in these patients such as young woman, bileaflet prolapse and inverted T-waves, but they included only specific cohort of patients who experienced SCD or who had only trivial or mild mitral regurgitation (MR). The prevalence of VA and their potential risk factors in a population of MVP patients with severe MR are unknown. Purpose The aim of our study was to describe the prevalence of VA in patients who underwent mitral valve surgery for moderate to severe MR due to MVP and to identify clinical, electrocardiographic and echocardiographic parameters associated with VA. Methods 797 patients (65±12 years, 65% male) who underwent surgery for MVP were included from 2000 until 2018. The presence of VA was defined as symptomatic and frequent PVCs (Lown grade ≥2), non-sustained ventricular tachycardia (nsVT), VT or ventricular fibrillation (VF) documented before surgery and without an ischemic cause. The echocardiogram and electrocardiogram (ECG) prior to operation were used for the specific analysis. ECGs were checked for rhythm, conduction times, QRS morphology and inferior T-wave inversion. The origin of the PVCs was derived from a 12-lead ECG when available and divided in 5 groups; mitral annulus, papillary muscle (PM), left ventricle (LV, including outflow tract), right ventricle (including outflow tract) and other. By echocardiography, several parameters such as LV thickness and volumes, LV ejection fraction (EF), global longitudinal strain (GLS) and MR grade were obtained. Results A total of 99 (12%) patients showed VA; 70% (69/99) of the patients had symptomatic PVCs, 36% (36/99) had nsVT, 12% (12/99) VT and 3% (3/99) VF. 21 patients had more than one type of VA, of which the combination PVCs and nsVT was the most common (19/99, 19%). In addition, 6 patients experienced an out of hospital cardiac arrest of a non-ischemic cause. When comparing the clinical characteristics (Table), patients with VA were significantly younger (and with better renal function), more frequently diagnosed with Barlow's disease and experienced more palpitations as compared to patients without VA. The ECG analysis showed that patients with VA more often had inferior T-wave inversions and that the PVCs predominantly originated from the PM whereas in patients without VA the PVCs originated from different regions. Echocardiography showed that patients with VA had a thinner posterior wall, reduced LV EF and worse GLS; more severe MR was not associated with VA. Conclusion In MVP patients with moderate to severe MR undergoing surgery, Barlow's disease, inferior T-wave inversions, thinner posterior wall and LV systolic dysfunction are associated with the presence and development of VA.

Background Several studies have suggested a familial clustering of mitral valve prolapse (MVP), especially for Barlow disease (BD), which is regarded as the effect of genetic or developmental errors. However, the genetic etiology of MVP, in particular BD, is largely unknown. So far only three genes have been identified: FLNA, DCHS1 and PLD1. Purpose The aim of this study was to identify genes associated with MVP using whole exome sequencing (WES). Methods Patients with MVP, who were classified as BD and/or had a positive family history for MVP, were referred for genetic counseling and WES. In total, 106 unrelated probands were included to identify potentially pathogenic variants in a set of 551 genes associated with cardiovascular development and/or diseases. The population databases Genome Aggregation and WES data from 110 parents of children with mental retardation were used as controls. Variants were analyzed using prediction programs, frequency in the population database and literature search. Variants were divided into the following categories: likely benign, variant of unknown significance or likely pathogenic. Results Thirteen percent (14/106) of the probands had a likely pathogenic variant in seven different genes: DCHS1 (1x), DSP (1x), HCN4 (2x), MYH6 (1x), TMEM67 (1x), TRPS1 (1x) and TTN (7x); the DSP, MYH6 and HCN4 variants cosegregated in affected relatives. None of the 110 parents of children with mental retardation had a likely pathogenic variant in these seven genes. In addition, 31% (33/106) of the probands harbored a variant of unknown significance in 23 different genes, including the genes DSP, FLNA, MYH6 and TTN (Fig). Remarkable, one variant of unknown significance in the FBN2 gene was shared among three unrelated probands and did not occur in population databases. Conclusion WES analysis conducted in probands with MVP using a large panel of genes associated with cardiac development and/or disease confirmed previously known causative genes (DCHS1) and expanded the cardiac phenotype of genes originally associated with cardiomyopathy (DSP, HCN4, MYH6 and TTN). This study is the first study that described the association between MVP and the genes DSP, MYH6 and TTN although the pathogenesis is still unknown. This high yield of likely pathogenic variants emphasizes the importance of genetic screening in MVP patients.

Background Left atrial remodelling in hypertrophic cardiomyopathy (HCM) is recognized as the main contributor to the development of atrial fibrillation (AF). It is well reported that the occurrence of AF in HCM increases both morbidity and mortality. Therefore, early recognition of AF is essential. Due to its often silent and paroxysmal nature, the diagnosis can be missed. Purpose PA-TDI, representing total atrial conduction time, reflects the left atrial structural and electrical remodelling. We sought to evaluate the association between this novel non-invasive echocardiographic parameter and AF in patients with HCM. Methods The electronic charts of patients with HCM and no previous history of AF from 1993 to 2018 were retrospectively analysed. PA-TDI was measured offline using pulsed wave tissue Doppler imaging with the sample volume placed on the lateral wall of the left atrium just above the mitral annulus in an apical 4-chamber view. The time interval was determined from the onset of P wave on surface ECG to the peak of the a' wave of the left atrial tissue Doppler tracing. Results There were 208 patients (64% male) with a mean age of 53±14 years in this study. The incidence of AF was 20% over a median follow-up of 56.3 (IQR 18.4–84.5) months. Patients who developed AF, had higher baseline PA-TDI intervals when in sinus rhythm (134±23 ms vs 111±30 ms, P Conclusion A prolonged PA-TDI was strongly associated with the development of AF in patients with HCM. This parameter may be useful to risk-stratify patients with HCM who are at risk of having AF.

Aims In mitral valve prolapse (MVP), leaflet thickening has recently been suggested to be due, in addition to a myxomatous degeneration, to the presence of a superimposed tissue (SIT), defined as an additional fibrous layer on top of the original leaflet. The mechanisms of SIT formation are currently unknown. We hypothesized that SIT formation would result from excessive leaflet stress and we used a unique ex vivo model to assess the correlation between leaflet remodelling and the type and location of mechanical stress and to elucidate the mechanisms underlying SIT formation. Methods and results Human diseased mitral valves (MVs; n = 21) were histologically analysed for SIT formation and original leaflet thickening. The SIT comprised of various compositions of extracellular matrix and could reach more than 50% of total leaflet thickness. Original leaflet and SIT thickness did not show significant correlation (r = −0.27, P = 0.23), suggesting different regulatory mechanisms. To study the role of the mechanical environment on MV remodelling, mouse MV were cultured in their natural position in the heart and subjected to various haemodynamic conditions representing specific phases of the cardiac cycle and the MVP configuration. SIT formation was induced in the ex vivo model, mostly present on the atrial side, and clearly dependent on the duration, type, and extent of mechanical stress. Specific stainings and lineage tracing experiments showed that SIT comprises of macrophages and myofibroblasts and is associated with the activation of the transforming growth factor-beta and bone morphogenetic protein signalling pathways. Migration of valvular interstitial cells and macrophages through breakages of the endothelial cell lining contributed to SIT formation. Conclusions Mechanical stresses induce specific cellular and molecular changes in the MV that result in SIT formation. These observations provide the first insights in the mechanism of SIT formation and represent an initial step to identify potential novel and early treatment for MVP.

Background Initial studies have suggested the familial clustering of mitral valve prolapse, but most of them were either community based among unselected individuals or applied non-specific diagnostic criteria. Therefore little is known about the familial distribution of mitral regurgitation in a referral-type population with a more severe mitral valve prolapse phenotype. The objective of this study was to evaluate the presence of familial mitral regurgitation in patients undergoing surgery for mitral valve prolapse, differentiating patients with Barlow's disease, Barlow forme fruste and fibro-elastic deficiency. Methods A total of 385 patients (62 ± 12 years, 63% men) who underwent surgery for mitral valve prolapse were contacted to assess cardiac family history systematically. Only the documented presence of mitral regurgitation was considered to define ‘familial mitral regurgitation’. In the probands, the aetiology of mitral valve prolapse was defined by surgical observations. Results A total of 107 (28%) probands were classified as having Barlow's disease, 85 (22%) as Barlow forme fruste and 193 (50%) patients as fibro-elastic deficiency. In total, 51 patients (13%) reported a clear family history for mitral regurgitation; these patients were significantly younger, more often diagnosed with Barlow's disease and also reported more sudden death in their family as compared with ‘sporadic mitral regurgitation’. In particular, ‘familial mitral regurgitation’ was reported in 28 patients with Barlow's disease (26%), 15 patients (8%) with fibro-elastic deficiency and eight (9%) with Barlow forme fruste (P Conclusions In a large cohort of patients operated for mitral valve prolapse, the self-reported prevalence of familial mitral regurgitation was 26% in patients with Barlow's disease and still 8% in patients with fibro-elastic deficiency, highlighting the importance of familial anamnesis and echocardiographic screening in all mitral valve prolapse patients.

Right ventricular (RV) dysfunction is a well-known prognostic factor in several cardiac diseases. However, the prevalence of RV dysfunction in hypertrophic cardiomyopathy (HC) is unclear and its prognostic value is unknown. This study aims at addressing these issues assessing RV function with speckle tracking echocardiography. In 267 HC patients (52 +/- 15 years, 68% male), standard and advanced echocardiographic measurements of RV function were performed including RV 4-chamber longitudinal strain (RV4CLS) and RV free wall longitudinal strain (RVFWLS). The primary end point was all-cause mortality and heart failure development. RV dysfunction was observed in 9% of patients based on tricuspid annular plane systolic excursion (=-19%, 39% based on RVFWLS >=-23%, and 55% based on RV4CLS >=-20%. In total 59 (22%) patients reached the primary end point during a median follow-up of 6.7 (interquartile range 4.2 to 9.8) years. Kaplan-Meier survival curve showed a significant worse survival free of the end point for patients with impaired RV4CLS >=-20% versus patients with preserved RV4CLS =-19% versus patients with preserved RVFWLS

Aims Genetic, dilated cardiomyopathy (DCM) can be caused by a large variety of mutations. Mutation carriers are often asymptomatic until DCM is well established, presenting with heart failure, arrhythmias, or sudden cardiac death. Preventive strategies can only be applied if DCM can be detected early. Echocardiographic, left ventricular (LV) global longitudinal strain (GLS) is a promising tool for early diagnosis, i.e. before a decrease in LV ejection fraction (EF) has occurred. We, therefore, investigated the role of LV GLS as an early disease marker in genetic DCM.Methods and results Genetic DCM patients and genotyped family members were evaluated. The study population was grouped as (i) genotype-positive, phenotype-positive (GPFP) patients with a pathogenic mutation and LVEF = 55%, and (iii) genotype-negative, phenotype-negative (GNFN) individuals without a pathogenic mutation and LVEF >= 55%. One hundred and fifteen individuals (53 +/- 15 years, 51% male) were analysed: 28 (24%) were classified as GNFN, 50 (44%) as GPFN, and 37 (32%) as GPFP. Various mutations were represented: 39 (34%) titin, 14 (12%) lamin A/C, 13 (11%) sarcomeric, and 21 (18%) less frequent mutations (grouped together). The mean LVEF was 58 +/- 14% for all subjects. The mean LV GLS in the GNFN group was -21.7 +/- 1.5% vs. -19.7 +/- 3.5% for the GPFN group (P = 0.036). The mean LV GLS was -12.9 +/- 4.3% for the GPFP category (P < 0.001 vs. GPFN and GNFN).Conclusion Decreased LV GLS discriminates GPFN individuals from normal controls, which may permit early institution of therapy for genetic DCM.

Background. The risk factors for the development of mitral annular calcification (MAC) in degenerative mitral valve disease and the effect it may have on patient-and valve-related outcomes require further evaluation.Methods. Between January 2002 and December 2015, 627 patients underwent mitral valve operations for degenerative disease. MAC was seen in 75 patients (12%); 73 (97%) underwent valve repair (6 without annuloplasty ring implantation) and 2 (3%) underwent valve replacement after an unsuccessful repair attempt.Results. MAC was linked to patient age, female sex, and degenerative disease subtype. Early mortality was comparable between patients with and without MAC (3 of 75 [4%] vs 10 of 552 [2%], p = 0.20]. In patients with MAC, one-third of the deaths were directly related to annular decalcification and reconstruction. Early repair failure was more common in patients with MAC (8 of 75 [11%] vs 17 of 552 [3%], p = 0.006). During follow-up, no differences in overall survival or freedom from late reintervention were observed. However, at 8 years after the operation, freedom from recurrent mitral regurgitation was worse in patients with MAC. In these patients, repair failure was linked to nonuse of ring annuloplasty. For patients with MAC in whom annular decalcification and annuloplasty were performed, repair durability was comparable to patients without MAC.Conclusions. Mitral valve surgery in degenerative disease accompanied by MAC is safe. Optimal surgical strategy includes annular decalcification (when this would prevent implantation of an annuloplasty ring) and ring annuloplasty and will lead to results similar to patients without MAC. However, repair performance is hampered when the annulus is not addressed. For these patients, alternative repair techniques should be explored in the future. (C) 2019 by The Society of Thoracic Surgeons

Implementation of point-of-care HbA1c devices in the preoperative outpatient clinic might facilitate the early diagnosis of glycemic disturbances in overweight or obese patients undergoing surgery, but validation studies in this setting do not exist. We determined the level of agreement between a point-of-care and laboratory HbA1c test in non-diabetic patients visiting the outpatient clinic for preoperative risk profiling. Point-of-care HbA1c levels were measured in whole blood obtained by a finger prick (Siemens DCA Vantage HbA1c analyzer) and in hemolysed EDTA blood in the central laboratory (LAB). Bland Altman and Clarke’s error grid analysis were used to analyze the agreement between the point-of-care and laboratory measurements. Patients (n = 49) were 55 ± 11 years old, 47% were male with a body mass index (BMI) of 30.6 ± 3.4 kg/m2. The mean HbA1c was 38.1 ± 3.7 mmol/mol or 5.6 ± 0.3%. One patient was diagnosed with a HbA1c indicative for diabetes mellitus (6.7%). Bland Altman analysis revealed a bias of − 0.53 ± 1.81 mmol/mol with limits of agreement of − 4.09 to 3.03 mmol/mol and a bias of − 0.05 ± 0.17% with limits of agreement − 0.39 to 0.28%. The percentage error was 9.2% and 5.9% for HbA1c expressed in mmol/mol and %, respectively. Clarke’s error grid analysis showed that 48 out of 49 measurements were located in area A (98%). Point-of-care HbA1c measurements showed a high level of agreement with the laboratory test in the outpatient setting, and may be used for preoperative risk profiling in patients prone to cardiometabolic complications.Trial registration: Netherlands Trial Register NTR3057.

In patients with severe primary mitral regurgitation (MR), the indication for surgery is currently based on symptoms, left ventricular (LV) function, occurrence of atrial fibrillation and pulmonary hypertension. The aim of this study was to evaluate the prognostic impact of a new staging

Background Chordal replacement techniques are progressively used to treat posterior mitral valve leaflet (PMVL) prolapse while leaflet resection remains commonly in use to address excessive leaflet tissue. For excessive tissue in height, shortening neochords can be used alternatively. Use of chordal replacement techniques has been suggested to result in lower diastolic transvalvular gradients, higher freedom from reoperation and improved left ventricular function. Methods From 1/2005 to 12/2016, 150 patients underwent valve repair for isolated PMVL prolapse with excessive tissue. Excessive tissue in height was treated by leaflet resection (N.=99) or shortening neochords (N.=51). Excessive tissue in width was always resected. Logistic regression was used to generate propensity scores for risk-adjusted comparison. Results Two patients died postoperatively. In the Neochords group, resection of excessive tissue in width was still needed in 28 (55%) cases. Postoperative echocardiography demonstrated residual (≥2+) mitral regurgitation in 2/150 patients (Resect group). No differences in anuloplasty ring size, postoperative diastolic transvalvular gradients or left ventricular function were observed. Median clinical follow-up duration was 4.4 (IQR 2.0-7.0; 98% complete) years. There was no inter-group difference in overall survival or freedom from reintervention. Mean echocardiographic follow-up was 3.0 (IQR 1.2-5.4; 93% complete) years. In the matched population, the 6-year freedom from recurrent mitral regurgitation rates were 91.3% (95% CI: 81.9-100%) and 97.2% (95% CI: 91.9-100%) for the Resect and Neochords group, respectively (P=0.43). Conclusions Both leaflet resection and shortening neochords provide a valuable tool to address excessive PMVL height. Repair durability is excellent regardless of the technique utilized.

Objectives Barlow's disease is the most severe form of degenerative mitral valve disease, commonly characterized by bileaflet prolapse. Abnormal mitral annular dynamics is typically present and results in functional prolapse of the mitral leaflets that may be addressed with annular stabilization alone. Methods Between January 2001 and December 2015, 128 patients with Barlow's disease and bileaflet prolapse underwent valve repair. This included anterior mitral valve leaflet (AMVL) repair in 70 patients, whereas 58 patients were identified as having functional prolapse and underwent no specific AMVL repair. During the course of the study, the proportion of patients undergoing specific AMVL repair decreased (77% in the first and 33% in the second 64 patients). Semirigid ring annuloplasty was performed in all cases. The median clinical and echocardiographic follow-up duration was 6.5 years [interquartile range (IQR) 2.9-10.5 years; 93.9% complete] and 4.7 years (IQR 2.2-10.2 years; 94.4% complete), respectively. Results Early mortality was 1.6%. Postoperative echocardiogram demonstrated no residual mitral regurgitation in all but 1 patient (AMVL repair group). There was no significant difference in the overall survival rate at 6 years after operation between both groups. At 6 years, the freedom from recurrent ≥Grade 2+ mitral regurgitation rate was 90.7% (IQR 82.9-98.5%) and 89.1% (IQR 75.8-100%) for patients with and patients with no AMVL repair, respectively (P = 0.43). Three patients required late mitral valve reintervention, all from the AMVL repair group. Conclusions Annular stabilization can effectively resolve the functional prolapse of the AMVL. Careful discrimination between functional and true AMVL prolapse allows for a technically less challenging operation that provides excellent repair durability.

Background In asymptomatic patients with severe degenerative mitral valve regurgitation (MR), early surgery is often performed in experienced centers. The patient- and valve-related results and the quality of life after surgery in these patients remain insufficiently explored. Methods Between 1/2000 and 12/2015, 83 asymptomatic patients (mean age 56.6 ± 12.6 years, 21 female) without any complications related to long-lasting MR underwent early surgery. Follow-up clinical and echocardiographic data and health-related quality of life assessment (SF-36) were studied and matched to the general population. Results Repair rate was 100% and early mortality was 0%. Residual MR (≥grade 2+) was seen in 1 (1%) patient who underwent a successful re-repair while 4 (5%) patients needed permanent pacemaker implantation. At a median follow-up of 7.6 (IQR 4.1–11.9) years, 6 late deaths occurred. The 10-year overall survival rate was 91.5% (95% CI 84.2–98.8%) and was comparable to the general population. The health-related quality of life (84% complete) did not differ from the general population. One patient underwent late reintervention. Median echocardiography follow-up was 5.2 years (IQR 2.4–10.4; 98% complete). The 10-year freedom from recurrent MR rate (≥grade 2+) was 86.7% (95% CI 76.1–97.3%). The 10-year freedom from any atrial tachycardia rate was 68.7% (95% CI 55.2–82.2%) while 7 (8%) patients underwent late pacemaker implantation. Conclusions Early surgical intervention in asymptomatic patients with severe MR can be performed safely and restores normal life expectancy and quality of life. However, the frequency of late arrhythmias and pacemaker implantation is high and needs further evaluation.

OBJECTIVESFollowing mitral valve repair for Barlow’s disease, recurrent mitral regurgitation (MR) is believed to occur frequently and is mainly attributed to disease progression.METHODSBetween January 2000 and December 2015, 180 patients (40% women, mean age 58.7 ± 13.5 years) with Barlow’s disease underwent mitral valve repair. To provide a longitudinal assessment of mitral valve repair durability, a multistate model for interval-censored observations (4 states: 1, Grade 0/1+ MR; 2, Grade 2+ MR; 3, Grade 3+/4+ MR; 4, reintervention/death) was developed. The mechanism of recurrent MR was assessed echocardiographically.RESULTSEarly mortality was 1.7%. After hospital discharge, 6 late reinterventions were performed. With death as a competing risk, the 10-year overall reintervention-free survival and reintervention rates were 79.8% (95% confidence interval 72.7–87.6%) and 4.5% (95% confidence interval 2.0–10.2%), respectively. Echocardiographic follow-up was available for 165 (93%) of hospital survivors with a total of 480 examinations. The incidence of both recurrent Grade 2+ and Grade 3+/4+ MR was relatively low up to 10 years after surgery. Grade 2+ MR did not always progress to higher regurgitation grade during the follow-up period. Grade 3+/4+ regurgitation was highly associated with valve-related morbidity and mortality. Recurrent MR (≥Grade 2+) was predominantly related to the technical aspects of valve repair.CONCLUSIONSDespite the complex valve abnormalities observed in patients with Barlow’s disease, mitral valve repair can be performed with good early and late outcomes and low rates of recurrence of MR up to 10 years after surgery. Early and late valve repair durability is good and remains stable over time, suggesting that underlying disease progression has limited clinical significance.

Background— Current methods for predicting adverse events in patients with hypertrophic cardiomyopathy are still limited. Left ventricular global longitudinal strain (GLS) and left atrial volume index (LAVI) have been recently proposed as novel prognostic factors in several cardiovascular diseases. The objective of this study was to evaluate the prognostic value of GLS and LAVI in patients with hypertrophic cardiomyopathy. Methods and Results— Two-dimensional echocardiography was performed in 427 patients with hypertrophic cardiomyopathy (66% men, age 52±15 years), and LAVI and GLS were assessed. During follow-up, the primary end point of all-cause mortality, heart transplantation, sudden cardiac death, and appropriate implantable cardioverter defibrillator therapy was noted. A total of 103 patients reached the primary end point during a follow-up of 6.7 (interquartile range, 3.3–10.0) years. Multivariable Cox regression analysis revealed GLS and LAVI to be independently associated with the primary end point (hazard ratio GLS, 1.10 [1.03–1.19], P =0.007; hazard ratio LAVI, 4.27 [2.35–7.74], P 2 for LAVI and −15% for GLS, Kaplan–Meier survival curves showed significant better survival for patients with LAVI 2 ( P P P Conclusions— GLS and LAVI are independently associated with adverse outcome in patients with hypertrophic cardiomyopathy and may help to optimize risk stratification in these patients.

Although a familial distribution has been documented, the genetic etiology of mitral valve prolapse (MVP) is largely unknown, with only 3 genes identified so far: FLNA, DCHS1 and PLD1. Patients with MVP were referred for genetic counseling and whole exome sequencing (WES) when reported a family

Background— The value of left atrial (LA) diameter, volume, and strain to risk stratify hypertrophic cardiomyopathy patients for new-onset atrial fibrillation (AF) was explored. Methods and Results— A total of 242 hypertrophic cardiomyopathy patients without AF history were evaluated by (speckle-tracking) echocardiography. During mean follow-up of 4.8±3.7 years, 41 patients (17%) developed new-onset AF. Multivariable analysis showed LA volume (≥37 mL/m 2 ; hazard ratio, 2.68; 95% confidence interval, 1.30–5.54; P =0.008) and LA strain (≤23.4%; hazard ratio, 3.22; 95% confidence interval, 1.50–6.88; P =0.003), but not LA diameter (≥45 mm; hazard ratio, 1.67; 95% confidence interval, 0.84–3.32; P =0.145), as independent AF correlates. Importantly, 59% (n=24) of AF events occurred despite a baseline LA diameter 2 and LA strain >23.4% versus ≤23.4% had superior 5-year AF-free survival of 93% versus 80% ( P =0.003) and 98% versus 74% ( P =0.002), respectively. Importantly, LA volume 2 and strain >23.4% yielded high negative predictive value (93% and 98%, respectively) for new-onset AF. Likelihood ratio test indicated incremental value of LA volume assessment ( P =0.011) on top of LA diameter to predict new-onset AF in hypertrophic cardiomyopathy patients with LA diameter P =0.126). Conclusions— LA diameter, volume, and strain all relate to new-onset AF in hypertrophic cardiomyopathy patients. In patients with normal LA size, however, both LA volume and strain further refine risk stratification for new-onset AF.