Computed Simulation of Transcatheter Edge-to-Edge Mitral Valve Repair - A Proof of Concept Study.

AIMS: As transcatheter mitral valve (MV) interventions are expanding and more device types and sizes become available, a tool supporting operators in preprocedural planning and the clinical decision-making process is highly desirable. We sought to develop a finite element (FE) computational simulation model to predict results of transcatheter edge-to-edge (TEER) interventions. METHODS AND RESULTS: We prospectively enrolled patients with secondary mitral regurgitation (MR) referred for a clinically indicated TEER. Three-dimensional (3D) transesophageal echocardiograms performed at the beginning of the procedure were used to perform the simulation. On the 3D dynamic model of the MV that was first obtained, we simulated the clip implantation using the same clip(s) type, size, number, and implantation location that was used during the intervention. The 3D model of the MV obtained after simulation of the clip implantation was compared to the clinical results obtained at the end of the intervention. We analyzed the degree and location of residual MR and the shape and area of the diastolic mitral valve area. We performed computational simulation on 5 patients. Overall, the simulated models predicted well the degree and location of the residual regurgitant orifice(s) but tended to underestimate the diastolic mitral orifice area. CONCLUSIONS: In this proof-of-concept study, we present preliminary results on our algorithm simulating clip implantation in 5 patients with functional MR. We show promising results regarding the feasibility and accuracy in terms of predicting residual MR and the need to improve the estimation of the diastolic mitral valve area.

Femoral Versus Nonfemoral Peripheral Access for Transcatheter Aortic Valve Replacement.

BACKGROUND: Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Guidelines recommend reconsidering surgery when this access is not feasible. However, alternative peripheral accesses exist, although they have not been accurately compared with femoral access. OBJECTIVES: This study compared nonfemoral peripheral (n-FP) TAVR with femoral TAVR. METHODS: Using the data from the national prospective French registry (FRANCE TAVI [French Transcatheter Aortic Valve Implantation]), this study compared the characteristics and outcomes of TAVR procedures according to whether they were performed through a femoral or a n-FP access, using a pre-specified propensity score-based matching between groups. Subanalysis during 2 study periods (2013 to 2015 and 2016 to 2017) and among low/intermediate-low and intermediate-high/high volume centers were performed. RESULTS: Among 21,611 patients, 19,995 (92.5%) underwent femoral TAVR and 1,616 (7.5%) underwent n-FP TAVR (transcarotid, n = 914 or trans-subclavian, n = 702). Patients in the n-FP access group had more severe disease (mean logistic EuroSCORE 19.95 vs. 16.95; p < 0.001), with a higher rate of peripheral vascular disease, known coronary artery disease, chronic pulmonary disease, and renal failure. After matching, there was no difference in the rate of post-procedural death and complications according to access site, except for a 2-fold lower rate of major vascular complications (odds ratio: 0.45; 95% confidence interval: 0.21 to 0.93; p = 0.032) and unplanned vascular repairs (odds ratio: 0.41; 95% confidence interval: 0.29 to 0.59; p < 0.001) in those who underwent n-FP access. The comparison of outcomes provided similar results during the second study period and in intermediate-high/high volume centers. CONCLUSIONS: n-FP TAVR is associated with similar outcomes compared with femoral peripheral TAVR, except for a 2-fold lower rate of major vascular complications and unplanned vascular repairs. n-FP TAVR may be favored over surgery in patients who are deemed ineligible for femoral TAVR and may be a safe alternative when femoral access risk is considered too high.

Management and research in cancer treatment-related cardiovascular toxicity: Challenges and perspectives.

Cardiovascular toxicity is a potentially serious complication that can result from the use of various cancer therapies and can impact the short- and long-term prognosis of treated patients as well as cancer survivors. In addition to their potential acute cardiovascular adverse events, new treatments can lead to late toxicity even after their completion because patients who survive longer generally have an increased exposure to the cancer therapies combined to standard cardiovascular risk factors. These complications expose the patient to the risk of cardiovascular morbi-mortality, which makes managing cardiovascular toxicity a significant challenge. Cardio-oncology programs offer the opportunity to improve cardiovascular monitoring, safety, and management through a better understanding of the pathogenesis of toxicity and interdisciplinary collaborations. In this review, we address new challenges, perspectives, and research priorities in cancer therapy-related cardiovascular toxicity to identify strategies that could improve the overall prognosis and survival of cancer patients. We also focus our discussion on the contribution of cardio-oncology in each step of the development and use of cancer therapies.

Prediction of symptomatic embolism in infective endocarditis: construction and validation of a risk calculator in a multicenter cohort.

OBJECTIVES: The aim of this study was to develop and validate a simple calculator to quantify the embolic risk (ER) at admission of patients with infective endocarditis. BACKGROUND: Early valve surgery reduces the incidence of embolism in high-risk patients with endocarditis, but the quantification of ER remains challenging. METHODS: From 1,022 consecutive patients presenting with definite diagnoses of infective endocarditis in a multicenter observational cohort study, 847 were randomized into derivation (n = 565) and validation (n = 282) samples. Clinical, microbiological, and echocardiographic data were collected at admission. The primary endpoint was symptomatic embolism that occurred during the 6-month period after the initiation of treatment. The prediction model was developed and validated accounting for competing risks. RESULTS: The 6-month incidence of embolism was similar in the development and validation samples (8.5% in the 2 samples). Six variables were associated with ER and were used to create the calculator: age, diabetes, atrial fibrillation, embolism before antibiotics, vegetation length, and Staphylococcus aureus infection. There was an excellent correlation between the predicted and observed ER in both the development and validation samples. The C-statistics for the development and validation samples were 0.72 and 0.65, respectively. Finally, a significantly higher cumulative incidence of embolic events was observed in patients with high predicted ER in both the development (p < 0.0001) and validation (p < 0.05) samples. CONCLUSIONS: The risk for embolism during infective endocarditis can be quantified at admission using a simple and accurate calculator. It might be useful for facilitating therapeutic decisions.

Infectious endocarditis detected by PET/CT in a patient with a prosthetic knee infection: case report and review of the literature.

We report a case illustrating the potential use of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET/CT) for the diagnosis of infective endocarditis (IE) in an 84-y-old woman who had a history of chronic left knee osteitis and a mitral cardiac valve bioprosthesis replacement and a pacemaker. She developed a polymicrobial knee infection 15 days after her total knee replacement. Transoesophageal echocardiography showed a new mitral regurgitation, but no vegetation or abscess. PET/CT showed hypermetabolic hyperactivity around the mitral cardiac valve prosthesis and the intracardiac pacemaker leads. We found 17 case reports and 2 case series of IE in which PET/CT showed encouraging results for the detection of IE. PET/CT may be used in patients with a suspicion of IE who do not have echocardiographic evidence of IE. It may also be useful for identifying the portal of entry of an infection and for identifying secondary foci (mycotic aneurysm).

Excess mortality and morbidity in patients surviving infective endocarditis.

BACKGROUND: Mortality and morbidity associated with infective endocarditis may extend beyond successful treatment. The primary objective was to analyze rates, temporal changes, and predictors of excess mortality in patients surviving the acute phase of endocarditis. The secondary objective was to determine the rate of recurrence and the need for late cardiac surgery. METHODS: An observational cohort study was conducted at a university-affiliated tertiary medical center, among 328 patients who survived the active phase of endocarditis. We used age-, sex-, and calendar year-specific mortality hazard rates of the Bouches-du-Rhone French district population to calculate expected survival and excess mortality. The risk of recurrence and late valve surgery was also assessed. RESULT: Compared with expected survival, patients surviving a first episode of endocarditis had significantly worse outcomes (P = .001). The relative survival rates at 1, 3, and 5 years were 92% (95% CI, 88%-95%), 86% (95% CI, 77%-92%), and 82% (95% CI, 59%-91%), respectively. This excess mortality was observed during the entire follow-up period but was the highest during the first year after hospital discharge. Most of the recurrences and late cardiac surgeries also occurred during this period. Women exhibited a higher risk of age-adjusted excess mortality (adjusted excess hazard ratio, 2.0; 95% CI, 1.05-3.82; P = .03). Comorbidity index, recurrence of endocarditis, and history of an aortic valve endocarditis in women were independent predictors of excess mortality. CONCLUSIONS: These results justify close monitoring of patients after successful treatment of endocarditis, at least during the first year. Special attention should be paid to women with aortic valve damage.

Long-term outcomes following infection of cardiac implantable electronic devices: a prospective matched cohort study.

OBJECTIVE: To assess long-term outcomes and predictors of mortality in patients treated according to current recommendations for cardiac implantable electronic device (CIED) infection. DESIGN: Two-group matched cohort study. SETTING: Tertiary-care institution. PATIENTS: Consecutive patients admitted for CIED infection between 2004 and 2008 were prospectively enrolled. Study subjects were matched to a cohort of uninfected CIED patients by age, sex and type of device. INTERVENTIONS: In all infected patients, the therapeutic approach consisted of complete hardware removal whenever possible, antimicrobial therapy, and implantation of a new device, if indicated. Patients were systematically followed, with standardised outcomes assessment. MAIN OUTCOME MEASURES: All-cause mortality and predictors of long-term mortality. RESULTS: 197 patients were included and matched 1:1 to controls. Pocket infections were present in 41.1% and definite or suspected infective endocarditis in 58.9%. Total or subtotal hardware removal was achieved in 98.5% of cases. Median follow up was 25 months (12-70). Mortality rates in the study group and controls were 14.3% vs 11.0% (NS) at 1 year and 35.4% vs 27.0% (p=NS) at 5 years. Independent predictors of long-term mortality were older age (HR=1.09, p<0.001), cardiac resynchronisation therapy (HR=3.70, p=0.001), thrombocytopenia (HR=5.10, p=0.003) and renal insufficiency (HR=2.66, p=0.006). In patients with reimplanted devices, epicardial right ventricular pacemakers were associated with higher mortality (HR=2.85, p=0.034). CONCLUSION: In patients with CIED infection managed by recommended therapy, long-term mortality rates are similar to comparable controls. Independent predictors include patient and disease-related factors, in addition to implantation of right ventricular epicardial pacemakers.

Low-flow, low-gradient severe aortic stenosis despite normal ejection fraction is associated with severe left ventricular dysfunction as assessed by speckle-tracking echocardiography: a multicenter study.

BACKGROUND: Low-flow low-gradient (LFLG) is sometimes observed in severe aortic stenosis (AS) despite normal ejection fraction, but its frequency and mechanisms are still debated. We aimed to describe the characteristics of patients with LFLG AS and assess the presence of longitudinal left ventricular dysfunction in these patients. METHODS AND RESULTS: In a multicenter prospective study, 340 consecutive patients with severe AS and normal ejection fraction were studied. Longitudinal left ventricular function was assessed by 2D-strain and global afterload by valvulo-arterial impedance. Patients were classified according to flow and gradient: low flow was defined as a stroke volume index ≤35 mL/m(2), low gradient as a mean gradient ≤40 mm Hg. Most patients (n=258, 75.9%) presented with high-gradient AS, and 82 patients (24.1%) with low-gradient AS. Among the latter, 52 (15.3%) presented with normal flow and low gradient and 30 (8.8%) with LFLG. As compared with normal flow and low gradient, patients with LFLG had more severe AS (aortic valve area=0.7±0.12 cm(2) versus 0.86±0.14 cm(2)), higher valvulo-arterial impedance (5.5±1.1 versus 4±0.8 mm Hg/mL/m(2)), and worse longitudinal left ventricular function (basal longitudinal strain=-11.6±3.4 versus -14.8±3%; P<0.001 for all). CONCLUSIONS: LFLG AS is observed in 9% of patients with severe AS and normal ejection fraction and is associated with high global afterload and reduced longitudinal systolic function. Patients with normal-flow low-gradient AS are more frequent and present with less severe AS, normal afterload, and less severe longitudinal dysfunction. Severe left ventricular longitudinal dysfunction is a new explanation to the concept of LFLG AS.

Valvular heart disease associated with benfluorex therapy: high prevalence in patients with unexplained restrictive valvular heart disease.

AIMS: Restrictive valvular disease (RVD) has recently been reported in patients after benfluorex exposure. However, little is known about its prevalence and echocardiographic features. The aim of our study was to assess the frequency of benfluorex exposure in patients with RVD and to describe their echocardiographic characteristics. METHODS AND RESULTS: In a single centre study, patients with a final diagnosis of unexplained RVD were studied. Patients were interrogated for their previous use of benfluorex or other appetite-suppressant drugs (ASDs). Forty seven consecutive patients, aged 59 ± 9.6 years, with RVD were found [42 (91%) women]. Among them, 35 (74%) had previous treatment with ASD, including benfluorex in 34 patients. Among the latter, 14 (40%) have been exposed to benfluorex alone, 20 (60%) in combination with another ASD. Echocardiographic features included isolated mitral or aortic restricted valve motion in 19 patients (40%), and combined mitral and aortic involvement in 28 (60%).Twenty-seven (96%) of the latter had been exposed to benfluorex. As compared with the 'no ASD' group (n= 12), patients in the benfluorex group (n= 34) were more frequently female, had more frequent arterial hypertension and hypertriglyceridemia, and presented more frequently with combined mitral and aortic disease (79 vs. 8%, P < 0.001). Valve stenosis and tricuspid involvement were rare in the benfluorex group. CONCLUSION: The frequency of benfluorex exposure is high in patients with unexplained RVD. Combined aortic and mitral restrictive valve regurgitation is highly suggestive of valvular disease associated with benfluorex or other ASD therapy and may alert clinician about the possibility of this diagnosis.

Circulating matrix metalloproteinases in infective endocarditis: a possible marker of the embolic risk.

BACKGROUND: Embolic events (EE) in infective endocarditis (IE) are caused by fragmentation of vegetations or valvular tissue. Vegetation length is considered to be the most potent predictor of EE, but does not take into account the degree of friability of the vegetation and of the surrounded infected tissue. Matrix metalloproteinases (MMPs) are enzymes involved in degradation of matrix extracellular components and play a role in the pathophysiology of IE. We aimed to determine whether, in addition to the vegetation size, circulating MMPs could provide accurate predictive value of embolism in IE. METHODS: Among 145 patients referred for a native valve IE, we prospectively included 16 patients who experienced EE during antibiotic therapy (new-EE) and 30 patients without new-EE and treated without valvular surgery. A control group of 38 patients with a degenerative valvular heart disease was also included. In addition to clinical, microbiological and echocardiographic assessment, blood MMPs and their inhibitors were assayed in all patients at admission. RESULTS: MMP-9 serum level was significantly higher in patients with new-EE compared to controls (median [interquartile range]; 250 ng/mL [175-455] vs. 111 ng/mL [70-144], respectively; p<0.0001) and patients with no new-EE (250 ng/mL [175-455] vs. 138 ng/mL [95-232]; p<0.01). A higher MMP-9 activity in patients who experienced new-EE was further confirmed by gelatin zymography analysis. Circulating MMP-9 remains a predictor of new-EE after adjustment for vegetation length and other potential confounders. This parameter provided incremental predictive value over vegetation measurements. CONCLUSIONS: MMP-9 serum level is associated with the risk of embolism during IE. This marker might help physicians in the management of the disease, but further prospective studies are need to confirm these preliminary results.

Diagnosis of cardiac device-related infective endocarditis after device removal.

OBJECTIVES: We sought to determine the incidence, diagnostic value, and outcome of intracardiac masses observed by echocardiography after device removal. We hypothesized that these "ghosts" of leads could be associated with the diagnosis of cardiac device-related infective endocarditis (CDRIE). BACKGROUND: The echocardiographic appearance of residual floating masses in the right atrium after removal of permanent pacemakers and implantable cardioverter-defibrillators was recently described. However, the significance of these ghosts and their relationship with CDRIE are unknown. METHODS: The pre-operative clinical, microbiological, and echocardiographic conditions; the indication; and the removal technique were analyzed in a retrospective cohort including all consecutive patients who underwent percutaneous lead removal. Three groups were formed according to the final diagnosis: CDRIE, local device infection, and noninfectious indications. The incidence of ghosts was compared among the 3 groups. All clinical, infectious, and extraction-related factors were studied for their association with ghosts. All patients with ghosts were followed after hospitalization. RESULTS: Two hundred twelve patients underwent lead removal. Ghosts were observed in 17 patients (8% incidence), including 14 (16%) of 88 patients with CDRIE and 3 (5%) of 59 patients with local device infection. Ghosts were never observed among the remaining 65 noninfected patients. A significant association was found between CDRIE and the presence of a ghost (odds ratio: 7.63, 95% confidence interval: 2.12 to 27.45, p = 0.001). At 3 months, 2 patients with ghosts died suddenly, 2 underwent surgery, and 1 had a pulmonary embolism. CONCLUSIONS: Ghosts are observed in 8% of patients after percutaneous device extraction. Their presence is suggestive of device infection and seems to be associated with the diagnosis of CDRIE. The prognostic significance of such findings needs further investigation.