Mitral Valve Surgery for Mitral Regurgitation Results in Reduced Left Ventricular Ejection Fraction in Barlow's Disease as Compared with Fibro-Elastic Deficiency.

Surgical correction of severe mitral regurgitation (MR) can reverse left ventricular (LV) remodeling in patients with mitral valve prolapse (MVP). However, whether this process is similar to the case in Barlow's Disease (BD) and Fibro-elastic Deficiency (FED) is currently unknown. The aim of this study is to evaluate post-operative LV reverse remodeling and function in patients with BD versus FED. In this study, 100 MVP patients (BD = 37 and FED = 63) with severe MR who underwent mitral valve surgery at three Belgian centers were retrospectively included. Transthoracic echocardiography was used to assess MR severity, LV volumes and function before surgery and 6 months thereafter. Baseline MR severity, LV ejection fraction (LVEF), indexed LV end-diastolic (LVEDVi) and end-systolic volumes (LVESVi) were not different between the groups. After a median follow-up of 278 days, there was a similar decrease in LVEDVi, but a trend towards a smaller decrease in LVESVi in BD compared to FED (-3.0 ± 11.2 mL/m2 vs. -5.3 ± 9.0 mL/m2; p = 0.154). This resulted in a significantly larger decrease in LVEF in BD (-8.3 ± 9.6%) versus FED (-3.9 ± 6.9%) after adjusting for baseline LVEF (p < 0.001) and type of surgical intervention (p = 0.01). These findings suggest that LV (reverse) remodeling in BD could be affected by other mechanisms beyond volume overload, potentially involving concomitant cardiomyopathy.

Bleeding and thrombotic risk of different antiplatelet regimens posttranscatheter edge-to-edge mitral valve repair in patients with an indication for oral anticoagulation: Results from an all-comers national registry.

BACKGROUND: Evidence-based recommendations for antithrombotic treatment in patients who have an indication for oral anticoagulation (OAC) after transcatheter edge-to-edge mitral valve repair (TEER) are lacking. AIMS: To compare bleeding and thrombotic risk for different antithrombotic regimens post-TEER with MitraClip in an unselected population with the need for OACs. METHODS: Bleeding and thrombotic complications (stroke and myocardial infarction) up to 3 months after TEER with mitraclip were evaluated in 322 consecutive pts with an indication for OACs. These endpoints were defined by the Mitral Valve Academic Research Consortium criteria and were compared between two antithrombotic regimens: single antithrombotic therapy with OAC (single ATT) and double/triple ATT with a combination of OAC and aspirin and/or clopidogrel (combined ATT). RESULTS: Collectively, 108 (34%) patients received single ATT, 203 (63%) received double ATT and 11 (3%) received triple ATT. Bleeding events occurred in 67 patients (20.9%), with access site related events being the most frequent cause (37%). Bleeding complications were observed more frequently in the combined ATT group than in the single ATT group: 24% versus 14% [p = 0.03, adjusted RR: 0.55 (0.3-0.98)]. Within the combined group, the bleeding risk was 23% in the double ATT and 45% in the triple ATT group. Thrombotic complications occurred in only three patients (0.9%), and all belonged to the combined ATT group. CONCLUSIONS: In patients with an indication for OACs, withholding of antiplatelet therapy post-TEER with Mitraclip was associated with a 45% reduction in bleeding and without a signal of increased thrombotic risk.

Cardiovascular implantable electronic device therapy in patients with left ventricular assist devices: insights from TRAViATA.

BACKGROUND: There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs. METHODS: Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111). RESULTS: A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D. CONCLUSION: In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV­lead pacing post LVAD implantation.

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).

BACKGROUND: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. METHODS: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. RESULTS: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. CONCLUSIONS: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.

Natural Growth of Left Atrial Myxoma.

Myxomas are common benign cardiac tumors that can cause life-threatening events. Urgent surgical excision is needed. Therefore, little is known about their growth rate. We present a peculiar case of an incidental left atrial myxoma offering calculation of a growth curve over more than 6 years. The myxoma was incidentally seen retrospectively on computed tomography scans in follow-up for bladder carcinoma in a 71-year-old patient. The patient underwent surgical resection of the myxoma. The authors emphasize that myxoma can be unnoticed on non-electrocardiogram-gated computed tomography scans. In the presented case, cardiac myxoma appears to grow linearly over time.

Left Ventricular End-Systolic Dimension and Outcome in Patients With Heart Failure Undergoing Percutaneous MitraClip Valve Repair for Secondary Mitral Regurgitation.

Recent MitraClip heart failure (HF) trials suggest that baseline left ventricular (LV) remodeling may be critical for patient selection. We, therefore, investigated whether baseline LV remodeling affects safety, efficacy, and clinical outcomes in HF patients with symptomatic secondary mitral regurgitation (MR) undergoing percutaneous mitral valve repair using MitraClip. LV remodeling was assessed by LV end-systolic dimension index (LVESDi) on transthoracic baseline echocardiography. Early and late outcome was reported using Mitral Valve Academic Research Consortium-criteria. A total of 107 consecutive HF patients (73 ± 10 years, 70% male) who underwent MitraClip intervention for secondary MR were studied. The study population was stratified by median LVESDi between nonadvanced (<28 mm/m², n = 49) and advanced LV remodeling (≥28 mm/m², n = 58). Both groups had similar acute procedural success, in hospital bleeding and nonbleeding complications and significant improvement in MR severity and symptoms, sustained up to 36 months (all p >0.05). LVESDi, but not LV end-diastolic diameter index nor LV ejection fraction, independently related to HF hospitalization (hazard ratio 1.11, 95% confidence interval 1.05 to 1.16, p <0.001) and mortality (hazard ratio 1.11, 95% confidence interval 1.06 to 1.17, p <0.001). At 1 and 3 years, survival free of HF hospitalization was higher in patients without versus with advanced LV remodeling (89% vs 66% and 65% vs 37%, p = 0.002) and mortality was lower (9% vs 24% and 36% vs 47%, p = 0.074), respectively. Annual HF hospitalization rate only decreased in the nonadvanced LV remodeling group (-43%, p = 0.025). Advanced LV remodeling, assessed by LVESDi, in HF patients who underwent MitraClip therapy does not influence therapeutic safety nor efficacy, but implies increased HF hospitalization and mortality risk. This parameter may be valuable for MitraClip therapy patient selection.

Afterload Mismatch After MitraClip Implantation: Intraoperative Assessment and Prognostic Implications.

AIM: To evaluate the acute hemodynamic effects after MitraClip implantation and to identify predictors of afterload mismatch and its prognostic implications. METHODS: Acute hemodynamic effects were assessed intraoperatively by right heart catheterization and by transesophageal echocardiography before and after MitraClip implantation in 62 consecutive patients with severe mitral regurgitation (MR) (functional MR, 73.8%; EuroScore 2, 7.1 ± 4.9%; left ventricular ejection fraction [LVEF], 36 ± 15%; New York Heart Association class III/IV, 65%). Afterload mismatch was defined as a >15% decrease in LVEF (acute LV depression) or a >15% increase in LV end-diastolic volume (acute adverse LV remodeling). Patients were followed over a period of 24 months (mean, 18 ± 3 months) with all-cause mortality as the primary endpoint. RESULTS: Successful MitraClip implantation with residual MR ≤2 was achieved in 85% of patients. Acute LV depression was observed in 23% of patients, and acute adverse LV remodeling was observed in 15% of patients. Acute adverse LV remodeling occurred in 40% of patients with EuroScores >12 vs in 10% of patients with EuroScores ≤12 (P=.02). Although acute adverse LV remodeling was well tolerated in the acute phase, it was associated with a higher mortality rate during follow-up (62% vs 26%; log-rank P=.04). In a multivariate model, EuroScore 2, but not afterload mismatch, was the most important prognostic risk factor, with an adjusted hazard ratio of 1.1 (95% confidence interval, 1.0-1.2). CONCLUSION: Afterload mismatch, as assessed intraoperatively, is not uncommon after MitraClip implantation in patients with impaired LV function and is a risk marker of poor clinical outcome.

The Diagnostic Challenge of Extrapulmonary Tuberculosis: Esophageal Perforation, Mediastinitis, Pneumopericardium, and Pericardial Abscess Formation.

We describe the case of extrapulmonary tuberculosis complicated by esophageal perforation, pneumopericardium, and pericardial abscess formation. This case illustrates the difficulty in diagnosing extrapulmonary tuberculosis, as the occurrence of tuberculosis is rare in the developed world. The appropriate treatment strategy and 6-month follow-up results are discussed. (Level of Difficulty: Advanced.).

Safety of centrifugal left ventricular assist device in patients previously treated with MitraClip system.

INTRODUCTION: No data regarding the safety of continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with previous MitraClip have been reported. Thus, it remains unknown whether an initial treatment strategy with MitraClip therapy might complicate future heart failure management in patients who are also considered for CF-LVAD. METHODS: We retrospectively identified 6 patients (median age of 62 years; 2 women) who had been treated with MitraClip, that were eventually implanted with a CF-LVAD (all Heartware HVAD) in 3 hospitals between 2013 and 2018. RESULTS: Patients were treated in 4 cases with 2 clips, and in 2 cases with 1 clip. Median time from MitraClip implantation to CF-LVAD implant was 282 days (interquartile range 67 to 493), and median time on CF-LVAD support was 401 days (interquartile range 105 to 492 days). Two patients underwent a heart transplant, 3 patients died on support, and 1 is alive on support. In all cases, there was a reduction of functional mitral regurgitation without MitraClip-related complications. CONCLUSIONS: Based on this small case series, implantation of a CF-LVAD appears safe in patients with a previously positioned MitraClip system, at least, with 1 or 2 clips in place, with no need for additional mitral valve surgery.

Left ventricular remodelling patterns after MitraClip implantation in patients with severe mitral valve regurgitation: mechanistic insights and prognostic implications.

AIMS: The effect of MitraClip implantation on left ventricular (LV) remodelling has been shown to be highly variable. The present study wants to assess patterns of LV remodelling and its relationship with outcome. METHODS AND RESULTS: Serial echocardiography before, 1 and 6 months after MitraClip implantation was performed in 79 pts with severe mitral regurgitation (MR) (age 74 ± 10 years, New York Heart Association III/IV 80%, LV ejection fraction 38 ± 13%, logistic EuroSCORE 21 ± 15, and functional MR 81%). LV reverse/adverse remodelling was defined as a >15% decrease/>10% increase in LV end-diastolic volume (LVEDV), respectively. Patients were followed over a period of 32 ± 16 months with all-cause mortality as the primary endpoint. A sustained (6 month) reduction of MR ≤ 2 post-MitraClip implantation was observed in 83% of patients. The average decrease in LVEDV 6 months after intervention was 13% ± 16%. Reverse remodelling at 6 months occurred in 40 patients (51%), and adverse remodelling occurred in 6 patients (8%). Patients with adverse remodelling showed a 38% increase of LVEDV at 1 month vs. no early change in LVEDV in patients with reverse remodelling. During follow-up, a total of 25 patients (32%) died. Patients with adverse remodelling died more frequently than patients with reverse remodelling [67% vs. 27%, adjusted odds ratio of 5.6 (95% CI 1.5-21)]. CONCLUSION: The majority of patients undergoing MitraClip implantation for severe MR showed LV reverse remodelling. However, there was a small group in whom afterload mismatch resulted in sustained adverse remodelling with subsequent high mortality.

Accelerated cellular senescence as underlying mechanism for functionally impaired bone marrow-derived progenitor cells in ischemic heart disease.

BACKGROUND AND AIMS: Bone marrow (BM)-derived progenitor cells are functionally impaired in patients with ischemic heart disease (IHD), thereby hampering the outcome of autologous stem cell therapy. In search for underlying mechanisms for this BM dysfunction, accelerated cellular senescence was explored. METHODS: We analysed telomere length of BM-derived mononuclear cells (MNC) by MMqPCR in patients with coronary artery disease (n = 12), ischemic heart failure (HF; n = 9), non-ischemic HF (n = 7) and controls (n = 10), and related it to their myeloid differentiation capacity. Expressions of senescence-associated genes p53, p21Cip1 and p16lnk4A; and telomere maintenance genes TERT, TRF1/2, Sirt1 in BM-MNC were evaluated using qPCR. Pro-inflammatory cytokine levels (TNFα, IFNy, IL-6) in BM were measured by MSD. RESULTS: BM-MNC telomere length was shortened in patients with IHD, irrespective of associated cardiomyopathy, and shortened further with increasing angiographic lesions. This telomere shortening was associated with reduced myeloid differentiation capacity of BM-MNC, suggesting accelerated senescence as underlying cause for progenitor cell dysfunction in IHD. Both p16lnk4A and p21Cip1 were activated in IHD and inversely related to myeloid differentiation capacity of BM-MNC; hence, the BM-MNC functional impairment worsens with increasing senescence. While BM-MNC telomere attrition was not related with alterations in TERT, TRF1/2 and Sirt1 expression, IFNy levels were associated with p21Cip1/p16lnk4A upregulation, suggesting a link between inflammation and cellular senescence. Still, the trigger for telomere shortening in IHD needs to be elucidated. CONCLUSIONS: Accelerated replicative senescence is associated with a functional impairment of BM-derived progenitor cells in IHD and could be targeted to improve efficacy of stem cell therapy.

Bone Marrow-Derived Progenitor Cells Are Functionally Impaired in Ischemic Heart Disease.

To determine whether the presence of ischemic heart disease (IHD) per se, or rather the co-presence of heart failure (HF), is the primum movens for less effective stem cell products in autologous stem cell therapy, we assessed numbers and function of bone marrow (BM)-derived progenitor cells in patients with coronary artery disease (n = 17), HF due to ischemic cardiomyopathy (n = 8), non-ischemic HF (n = 7), and control subjects (n = 11). Myeloid and erythroid differentiation capacity of BM-derived mononuclear cells was impaired in patients with underlying IHD but not with non-ischemic HF. Migration capacity decreased with increasing IHD severity. Hence, IHD, with or without associated cardiomyopathy, is an important determinant of progenitor cell function. No depletion of hematopoietic and endothelial progenitor cells (EPC) within the BM was observed, while circulating EPC numbers were increased in the presence of IHD, suggesting active recruitment. The observed myelosuppression was not driven by inflammation and thus other mechanisms are at play.

Bone matrix vesicle-bound alkaline phosphatase for the assessment of peripheral blood admixture to human bone marrow aspirates.

PURPOSE: Peripheral blood (PB) admixture should be minimized during numerical and functional, as well as cytokinetic analysis of bone marrow (BM) aspirates for research purposes. Therefore, purity assessment of the BM aspirate should be performed in advance. We investigated whether bone matrix vesicle (BMV)-bound bone alkaline phosphatase (ALP) could serve as a marker for the purity of BM aspirates. RESULTS: Total ALP activity was significantly higher in BM serum (97 (176-124)U/L, median (range)) compared to PB serum (63 (52-73)U/L, p < 0.001). Agarose gel electrophoresis showed a unique bone ALP fraction in BM, which was absent in PB. Native polyacrylamide gel electrophoresis revealed the high molecular weight of this fraction, corresponding with membrane-bound ALP from bone matrix vesicles (BMV), as evidenced by electron microscopy. A serial PB admixture experiment of bone cylinder supernatant samples, rich in BMV-bound ALP, confirmed the sensitivity of this proposed quality assessment method. Furthermore, a BMV ALP fraction of ≥ 15% is suggested as cut-off value for minimal BM quality. Moreover, the BM purity declines rapidly with larger aspirated BM volumes. CONCLUSION: The exclusive presence of BMV-bound ALP in BM could serve as a novel marker to assess purity of BM aspirates.

U-Shape Kissing Chimney Thoracic Endovascular Aneurysm Repair for a Traumatic Arch Rupture in a Polytraumatized Patient.

An 18-year-old male patient was admitted to our hospital because of a high impact trauma. A computed tomography scan showed massive mediastinal bleeding due to a posteriorly located rupture of the aortic arch with formation of a pseudoaneurysm. Although urgent repair was indicated, open cardiac surgery was not feasible, as this would involve full heparinization in a patient with subarachnoid bleeding. The chosen solution was to perform a percutaneous thoracic endovascular aneurysm repair (TEVAR) and a kissing chimney procedure using a U-shape configuration.

Percutaneous mitral valve repair in high-risk patients: initial experience with the Mitraclip system in Belgium.

AIMS: Treatment with percutaneous edge-to-edge mitral valve repair (Mitraclip) has recently been recommended as an alternative to conventional mitral valve repair for high surgical risk patients with symptomatic severe mitral regurgitation (MR). In this study, we report the first use of Mitraclip therapy in Belgium. METHODS AND RESULTS: This prospective registry includes 41 consecutive patients treated with the Mitraclip in two Belgian centres from October 2010 to June 2013. Acute procedural success, in-hospital safety end points and clinical status were analysed on an intention-to-treat basis up to one year after the procedure. In addition, determinants of major adverse cardiac events (MACE, death, surgical mitral valve intervention, and rehospitalization for heart failure) were analysed. Acute procedural success (successful clip placement and reduction of colour Doppler flow MR to < or = 2) was obtained in 32 patients (78%) and 18 of these patients received two clips. The primary safety end point was reached in 36 pts (88%): one patient died due to intracranial bleeding, there were three urgent surgical interventions and one severe access site bleeding. The MACE rate after one year was 41% (17 patients). There were 11 deaths (27%), six surgical interventions (15%) and 10 rehospitalizations for heart failure (24%). Additional subgroup analysis revealed that the one-year MACE rate was particularly high in patients with left ventricular ejection fraction (LVEF) < 25%: 62% vs. 36% in patients with LVEF > or = 5% (P = 0.05). At one year, MR < or = 2+ and NYHA class < or = 2 was present in 83% of the surviving patients CONCLUSION: In high-risk patients with functional MR, treatment with the Mitraclip-device is a feasible and safe option resulting in improvement of MR severity and clinical symptoms. However, as MACE is high in some subgroups (e.g. LVEF < 25%), careful patient selection is crucial to ensure the maximum benefit from this new technique.

Case report: inadvertent intrathecal placement of a pulmonary artery catheter introducer.

We present a case of unintended intrathecal cannulation by a pulmonary artery catheter introducer in a patient scheduled for coronary surgery. This complication was likely due to multiple attempts of placing the guidewire. Switching to the straight tip of the guidewire may have created a false route, facilitating entrance in the subarachnoid space. A lumbar intrathecal catheter was placed to maintain a low pressure at the cervical dural puncture site by draining 10 mL cerebrospinal fluid per hour. After removal of the lumbar drain, the patient experienced symptoms consistent with postdural puncture headache. Magnetic resonance imaging of the spine could not reveal the location of the possible leak. A lumbar epidural blood patch alleviated all complaints. One month later the patient underwent surgery successfully. We hypothesize that ultrasound imaging may have prevented this complication.