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.

QRS analysis using wavelet transformation for the prediction of response to cardiac resynchronization therapy: a prospective pilot study.

BACKGROUND: Wider QRS and left bundle branch block morphology are related to response to cardiac resynchronization therapy (CRT). A novel time-frequency analysis of the QRS complex may provide additional information in predicting response to CRT. METHODS: Signal-averaged electrocardiograms were prospectively recorded, before CRT, in orthogonal leads and QRS decomposition in three frequency bands was performed using the Morlet wavelet transformation. RESULTS: Thirty eight patients (age 65±10years, 31 males) were studied. CRT responders (n=28) had wider baseline QRS compared to non-responders and lower QRS energies in all frequency bands. The combination of QRS duration and mean energy in the high frequency band had the best predicting ability (AUC 0.833, 95%CI 0.705-0.962, p=0.002) followed by the maximum energy in the high frequency band (AUC 0.811, 95%CI 0.663-0.960, p=0.004). CONCLUSIONS: Wavelet transformation of the QRS complex is useful in predicting response to CRT.

Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials.

AIM: The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. METHODS AND RESULTS: The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. CONCLUSION: Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.

Clinical characteristics and natural history of hypertrophic cardiomyopathy with midventricular obstruction.

BACKGROUND: The prevalence, clinical characteristics and natural history of patients with hypertrophic cardiomyopathy (HCM) and midventricular obstruction (MVO) have not been adequately studied. METHODS AND RESULTS: A single-center cohort consisting of 423 patients (mean age, 49.3±17.2 years; 66.2% male) was thoroughly followed up for a median of 84 months (7 years; range, 6-480 months). MVO, characterized by the echocardiographic appearance of midventricular muscular apposition with a simultaneous mid-cavitary gradient ≥30mmHg, was identified in 34 patients (8%). Patients with MVO tended to be more symptomatic during their initial evaluation (>90% presented with NYHA class ≥II) compared to the rest of the HCM cohort. Apical aneurysm formation was identified in more than one-fourth of patients with MVO (26.5%), being a characteristic of the group. On multivariate Cox regression hazard analysis, presence of MVO strongly predicted progression to end-stage (burnt out) HCM and related heart failure (HF) deaths (hazard ratio, [HR], 2.62; 95% confidence interval [CI]: 1.2-8.8; P=0.047), as well as sudden death and associated lethal arrhythmic events (HR, 3.3; 95% CI: 1.26-8.85; P=0.016). CONCLUSIONS: MVO is a distinct phenotype of HCM associated with unfavorable prognosis in terms of end-stage HCM, sudden death and lethal arrhythmic events. The high adverse outcome rate necessitates early recognition of MVO and appropriate therapeutic interventions.

Quinidine: an "endangered species" drug appropriate for management of electrical storm in brugada syndrome.

Brugada syndrome is an inherited channelopathy associated with an increased risk of syncope and sudden cardiac death. In rare cases it can be manifested with electrical storm. We report two cases of Brugada syndrome that presented with electrical storm and were treated successfully with oral quinidine, an "endangered species" drug.

The use of the GuideLiner™ catheter as a child-in-mother technique: an initial single-center experience.

Recently, a new interventional guide catheter, the GuideLiner™ catheter, was introduced into the market as a strategy for tackling the problem of stent delivery failure. We implemented this simplified child-in-mother technique in a series of 16 challenging coronary interventions. Balloon and stent delivery was successfully achieved in all cases and the device was both simple to deploy and remove. Apart from two cases of vessel dissection that were managed successfully with stent implantation, no other serious procedural complications were reported.

Radial versus femoral access for orally anticoagulated patients.

OBJECTIVES: To prospectively compare the efficacy and procedural safety of the radial versus femoral route for cardiac catheterization during uninterrupted warfarin therapy. BACKGROUND: The optimal treatment strategy for cardiac catheterization in patients receiving long-term oral anticoagulation has not been defined. Increasing evidence suggests the feasibility and safety of catheterization without warfarin interruption. However, the relative safety and efficacy of the radial and femoral access in fully anticoagulated patients are unknown. METHODS: Fifty-six consecutive patients on chronic warfarin treatment with international normalized ratio (INR) between 1.8 and 3.5 were randomized to undergo coronary angiography, alone, or followed by percutaneous coronary intervention (PCI), via the femoral (n = 29) or radial route (n = 27). Procedural success, in-hospital major adverse cardiac and cerebrovascular events, access-site, and bleeding complications were recorded. RESULTS: The two groups were well balanced with similar clinical characteristics at baseline. There were no significant differences in preprocedural antiplatelet therapy or in INR levels between the radial and femoral group (2.62 ± 0.7 vs. 2.48 ± 0.6, respectively, P = 0.63). Procedural success was achieved in all femoral patients, whereas one patient in the radial group (3.7%) required crossover to femoral access. Eight patients from the femoral and 10 patients from the radial group successfully underwent PCI. Access-site complications occurred only in patients who underwent PCI: three (37.5%) in the femoral versus none in the radial group (P = 0.034). CONCLUSION: The radial access is as efficacious and safe as the femoral route for coronary angiography in fully anticoagulated patients, but is likely to result in fewer access-site complications in patients who also undergo PCI.

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.

Coronary angioplasty post TAVI: Is the solution outside the box?

Transcatheter aortic valve replacement (TAVR) has become the standard option for high risk patients with bioprosthetic valve degeneration. However, percutaneous coronary interventions after TAVR may be challenging as the manipulation and engagement of the guiding catheters is much more limited and difficult, due to the superimposition of the metallic frame of the TAVR valve upon the bioprosthetic cage. We describe a case of percutaneous coronary intervention in a patient with history of transcatheter aortic valve implantation after bioprosthetic valve degeneration and we describe a new method for accessing coronary arteries in cases of TAVR-in-surgical aortic valve replacement with a high-frame TAVR with a supra-annular leaflet position, by using the route outside the frame. 〈Learning objective: We describe a method for accessing coronary arteries in cases of transcatheter aortic valve implantation (TAVI)-in-surgical aortic valve replacement with a high-frame TAVI with a supraannular leaflet position, by using the route outside the frame.〉.

Left atrial strain, intervendor variability, and atrial fibrillation recurrence after catheter ablation: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis is to investigate the capacity of preinterventional left atrial strain (LAS) to predict AF recurrence (AFR) after catheter ablation by using all relative published data. Intervendor variability regarding different ultrasound stations and strain analysis software suites was taken into consideration. The research was performed according to PRISMA guidelines. The Cochrane database, MEDLINE, and EMBASE were searched for studies assessing echocardiography LAS prior to catheter ablation of AF cases. The systematic research yielded 10 studies (2 retrospective and 8 prospective, 880 patients in total). LAS differed significantly between the patients with AFR and those with no AF recurrence (nAFR) during the follow-up period (LASAFR: 17.5 ± 8.7% vs. LASnAFR: 24.1 ± 9.5%, p < 0.00001). A pooled cutoff value of 21.9% for LAS was extracted for the prediction of ablation success. Regarding intervendor variability, subgroup analyses were able to be performed for studies using GE and TomTec software. The difference in LASAFR and LASnAFR remained significant (p < 0.00001 and p < 0.0001 for TomTec and GE, respectively), while significant intervendor difference in absolute strain values was also detected (p < 0.0001 for both AFR and nAFR groups). LAS prior to catheter ablation is consistently lower in patients who experience AF recurrence. Its incorporation in clinical practice would assist physicians detect patients who require closer follow-up. Intervendor variability appears to be considerable and steps must be taken to document it thoroughly and mitigate it if possible.

The clockwise rotation of myocardial fiber orientation from epicardial to endocardial surface in left ventricular free wall in a post-mortem human heart.

Following fixation and MRI imaging a post-mortem human heart was sliced at the sagittal plane. Each anatomical section was then cut into smaller segments and each one was objected to classical histology process. The resulting microscopy slides were digitalized with a scanner. The histological section reconstruction was achieved using Adobe Photoshop CS2(R). Using specific software, called FiberCad, the user can define and draw (with the assistance of optical microscope) those fibers that are parallel and those fibers that are vertical to the slides plane. To better align the histological 3D reconstruction, the software is equipped with an option that allows the user to make best possible fit between histological and MRI slices. We present the consequent sagittal sections of LV free wall (from epicardial to endocardial surface), whereby the clockwise rotation of the mean orientation of the fibers that are on the plane of sectioning is clearly evident. We present a post mortem analysis of the complete LV free wall of a human heart.

One heart, two bodies: a simulation study of body surface potential differences between donor and recipient of heart transplantation.

In cardiac transplantation has been recognized some "abnormalities" in recipient ECG. We investigated the influence of heart geometrical position within the chest cavity as well as somatometric parameters on body surface torso potentials. Two control patients with different Body Mass Index (BMI) were undergone a chest MRI scan. Using specific software we created two tetrahedral meshes that could be applied in our study. A post-mortem human heart was undergone a MRI scan and we also created its tetrahedral mesh. Using second software we extracted the heart mesh of control's torsos and we replaced them with the mesh of the post-mortem heart. The last program also assessed the influence of heart (re)positioning within the thorax, on the body surface potentials. The Finite Elements Method (FEM) was used to solve the forward electrocardiographic problem for both torsos, under the assumption that all the ventricular myocardium of the one post-mortem heart was excited. FEM was also applied in simulating Body Surface Potential Mapping (BSPM) on the first thorax torso for nine different heart positions. For BSPM, FEM has been applied on Poison equation. The results show higher BSPM in patient with lower BMI and significant changes in BSPM when heart was rotated round its long axis. Conversely, the heart shifts (long x- or y- axis) didn't cause significant changes on simulated BSPM.

Mitral valve repair: moving towards a personalized ring.

BACKGROUND: Mitral valve repair with the use of an annuloplasty ring is the procedure of choice in patients with significant mitral regurgitation (MR) due to floppy mitral valve (FMV)/mitral valve prolapse (MVP). The mitral annular size, shape and motion may vary substantially among patients and thus, commercially available rings may not be suitable for each individual patient. METHODS: A "personalized ring" (PR) was easily constructed in the operating room using a Dacron sheet and titanium ligating clips to custom fit to each individual mitral annulus shape and size. There were 127 patients with severe MR due to FMV/MVP that underwent mitral valve repair surgery; 58 patients received a PR and 69 patients received a commercial Carpentier-Edwards Physio II ring. The patient records were retrospectively analysed. RESULTS: There were no surgical deaths. In-hospital length-of-stay and blood transfusions were not statistically different between the two groups. Mitral valve area was greater (p < 0.05) in the PR group (3.78 ± 0.22) compared to the Physio II ring group (3.13 ± 0.21). Mitral annular area changed from systole to diastole by 14.35% ± 3.28% in the PR group and did not change in the Physio II ring group (p < 0.05). Systolic anterior motion (SAM) of the mitral valve occurred in 2 patients with the Physio II ring and no patients with the PR. Up to 8 years follow-up, all patients in both groups were alive with NYHA functional class I-II symptoms and mild or less MR. CONCLUSIONS: The PR is suitable for all patients with significant MR due to FMV/MVP who require MV repair. The precise fit of the PR to the mitral annulus better preserves valve area and sphincter function of the mitral annulus, prevents SAM and provides excellent short and long-term results.

An Unusual Case of Arterial Embolism in an Adolescent With a Mitral Valve Repair With a Ring.

We report a case of an adolescent young man who presented with embolism of both lower legs. The patient had undergone mitral valve repair with a Kalangos biodegradable ring (Bioring SA, Lonay, Switzerland) 9 months earlier. Bilateral embolectomy was performed. Histopathologic examination revealed minute fragments of synthetic material within the embolus, which otherwise consisted of recent thrombus.

Heart transplantation for advanced heart failure due to cardiac sarcoidosis.

BACKGROUND: Selected patients with cardiac sarcoidosis undergo heart transplantation, but outcomes may be adversely affected by recurrent cardiac sarcoidosis or progressive extra-cardiac sarcoidosis. OBJECTIVES: We present our single-center experience of patients with cardiac sarcoidosis who underwent heart transplantation. METHODS: Consecutive patients that underwent heart transplantation between 1990 and 2012 were assessed. Cardiac sarcoidosis was defined by the presence of multiple non-caseating epithelioid cell granulomata in the explanted heart. Baseline characteristics and clinical outcomes were compared with a control group without cardiac sarcoidosis that underwent heart transplantation during this period. RESULTS: 901 patients underwent heart transplantation during the study period, of whom 4 patients had a pre-transplant diagnosis of cardiac sarcoidosis and 8 patients had sarcoidosis identified in the explanted heart. Patients with cardiac sarcoidosis had excellent post-transplant outcomes with survival of 92% at one year and 83% at five years. Survival was similar to patients that underwent heart transplantation for an alternate diagnosis. We did not encounter recurrent cardiac sarcoidosis or progressive extra-cardiac sarcoidosis during 1001 months of follow-up. CONCLUSIONS: Carefully selected patients with advanced heart failure due to cardiac sarcoidosis have an acceptable outcome after transplantation. Cardiologists should be aware that reported experience of transplantation for cardiac sarcoidosis mostly represents isolated cardiac sarcoidosis that was only diagnosed at pathological examination of the explanted heart.