BackgroundMyostatin (Mstn) is a key regulator of heart metabolism and cardiomyocyte growth interacting tightly with insulin-like growth factor I (IGF-I) under physiological conditions. The pathological role of Mstn has also been suggested since Mstn protein was shown to be upregulated in the myocardium of end-stage heart failure. However, no data are available about the regulation of gene expression of Mstn and IGF-I in different regions of healthy or pathologic human hearts, although they both might play a crucial role in the pathomechanism of heart failure.MethodsIn the present study, heart samples were collected from left ventricles, septum and right ventricles of control healthy individuals as well as from failing hearts of dilated (DCM) or ischemic cardiomyopathic (ICM) patients. A comprehensive qRT-PCR analysis of Mstn and IGF-I signaling was carried out by measuring expression of Mstn, its receptor Activin receptor IIB (ActRIIB), IGF-I, IGF-I receptor (IGF-IR), and the negative regulator of Mstn miR-208, respectively. Moreover, we combined the measured transcript levels and created complex parameters characterizing either Mstn- or IGF-I signaling in the different regions of healthy or failing hearts.ResultsWe have found that in healthy control hearts, the ratio of Mstn/IGF-I signaling was significantly higher in the left ventricle/septum than in the right ventricle. Moreover, Mstn transcript levels were significantly upregulated in all heart regions of DCM but not ICM patients. However, the ratio of Mstn/IGF-I signaling remained increased in the left ventricle/septum compared to the right ventricle of DCM patients (similarly to the healthy hearts). In contrast, in ICM hearts significant transcript changes were detected mainly in IGF-I signaling. In paralell with these results miR-208 showed mild upregulation in the left ventricle of both DCM and ICM hearts.ConclusionsThis is the first demonstration of a spatial asymmetry in the expression pattern of Mstn/IGF-I in healthy hearts, which is likely to play a role in the different growth regulation of left vs. right ventricle. Moreover, we identified Mstn as a massively regulated gene in DCM but not in ICM as part of possible compensatory mechanisms in the failing heart.

The incidence of cardiac perforation related to pacing and defibrillation leads is low. The use of active fixation leads is associated with an increased risk of cardiac perforation. We did not find any correlation between the perforation rate and any particular model of the implanted lead.

Ablation can be performed safely with no or minimal radiation exposure during pregnancy. In the setting of malignant, drug-resistant arrhythmia, ablation may be considered a therapeutic option in selected cases.

MVRS ePTFE cordal implantation can reduce the invasiveness and morbidity of conventional MV surgery. The device's safety profile is promising and prospective trials comparing the outcomes of the MVRS to conventional MV repair surgery are warranted. (CE Mark Study for the Harpoon Medical Device [TRACER]; NCT02768870).

BackgroundCell loss and subsequent deterioration of contractile function are hallmarks of chronic heart failure (HF). While apoptosis has been investigated as a participant in the progression of HF, it is unlikely that it accounts for the total amount of non-functional tissue. In addition, there is evidence for the presence of necrotic cardiomyocytes in HF. Therefore, the objective of this study was to investigate the necroptotic proteins regulating necroptosis, a form of programmed necrosis, and thereby assess its potential role in human end-stage HF.MethodsLeft ventricular samples of healthy controls (C) and patients with end-stage HF due to myocardial infarction (CAD) or dilated cardiomyopathy (DCM) were studied. Immunoblotting for necroptotic and apoptotic markers was performed. Triton X-114 fractionated samples were analyzed to study differences in subcellular localization.ResultsElevated expression of RIP1 (receptor-interacting protein), pSer227-RIP3 and its total levels were observed in HF groups compared to controls. On the other hand, caspase-8 expression, a proapoptotic protease negatively regulating necroptosis, was downregulated suggesting activation of necroptosis signaling. Total mixed-lineage kinase domain-like protein (MLKL) expression did not differ among the groups; however, active cytotoxic forms of MLKL were present in all HF samples while they were expressed at almost undetectable levels in controls. Interestingly, pThr357-MLKL unlike pSer358-MLKL, was higher in DCM than CAD. In HF, the subcellular localization of both RIP3 and pThr357-MLKL was consistent with activation of necroptosis signaling. Expression of main apoptotic markers has not indicated importance of apoptosis.ConclusionsThis is the first evidence showing that human HF of CAD or DCM etiology is positive for markers of necroptosis which may be involved in the development of HF.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1189-5) contains supplementary material, which is available to authorized users.

BACKGROUND:Degenerative mitral valve (MV) disease is a common cause of severe mitral regurgitation (MR) and accounts for the majority of MV operations. Conventional MV surgery requires cardiopulmonary bypass, aortic cross-clamping, cardioplegia, and a thoracotomy or sternotomy and, therefore, is associated with significant disability, risks, and unpredictable rates of MV repair. Transesophageal echocardiography-guided beating-heart MV repair with expanded polytetrafluoroethylene cordal insertion has the potential to significantly reduce surgical morbidity. We report the first-in-human clinical experience with a novel preformed expanded polytetrafluoroethylene knot implantation device (Harpoon TSD-5) designed to treat degenerative MR. METHODS:Through a small left thoracotomy, the device was inserted into the heart and guided by transesophageal echocardiography to the ventricular surface of the prolapsed leaflet. Multiple expanded polytetrafluoroethylene cords were anchored in the leaflet and then adjusted to the correct length to restore MV leaflet coaptation and secured at the epicardium. RESULTS:Eleven patients with posterior leaflet prolapse and severe MR, with mean±SD age of 65±13 years and mean ejection fraction of 69±7%, were treated with 100% procedural success. Immediate postprocedural mean MR grade was trace. At 1 month, the mean MR grade was mild with significant decreases in end-diastolic volume (139 to 107 mL; P=0.03) and left atrial volume (118 to 85 mL; P=0.04). CONCLUSIONS:A novel device used for beating-heart image-guided MV repair demonstrates a significant reduction in MR with favorable left ventricular and left atrial reverse remodeling. This approach has the potential to decrease invasiveness and surgical morbidity. Further follow-up is necessary to assess long-term efficacy. CLINICAL TRIAL REGISTRATION: 190M itral valve disease is the most prevalent heart valve disorder and is 3 to 4 times more common than aortic valve disease. Significant mitral regurgitation (MR) affects ≈2% of the total population and 9% of the population >75 years of age.1 MR causes volume overload of the left ventricle (LV), which in turn can progress to ventricular dilation, decreased ejection performance, pulmonary hypertension, congestive heart failure, atrial fibrillation (AF), right ventricular dysfunction, and eventually death. Degenerative MR is the most common indication for mitral valve surgery in North America.2 Introduced clinically in 1986, mitral valve repair with expanded polytetrafluoroethylene (ePTFE) artificial cords has been shown to be equivalent to leaflet resection techniques 3 and is increasingly being used in conventional mitral valve repair operations. 4 Although effective, conventional mitral valve surgery requires cardiopulmonary bypass, aortic crossclamping, cardioplegia, and a thoracotomy or sternotomy. It is therefore associated with significant disability and risks, including stroke, renal failure, widely variable rates of mitral valve repair versus replacement, and death.5 As a result, the...

Objectives The aim of the study was to compare the usefulness of cardiac CT to transthoracic (TTE) and transesophageal (TEE) echocardiography in the diagnosis of infective endocarditis (IE) and perivalvular complications using surgical inspection as the gold standard. Material and methods Fifty-three consecutive patients (42 men, mean age 58.3 ± 12.5) with IE requiring surgical procedures were enrolled in the study. All patients underwent preoperative TTE, TEE, and CT. The presence of vegetations, perivalvular abscess/pseudoaneurysm, leaflet perforation, inflammatory infiltration, and prosthesis dehiscence was assessed. Results We analyzed 71 affected valves (58 native, 13 prosthetic). Intraoperative assessment revealed 11 abscesses/pseudoaneurysms. Sensitivity and specificity of echocardiography (TTE + TEE) and CT were 63%, 90% and 81%, 90%, respectively. The combination of CT and echocardiography allowed diagnosing all abscesses/pseudoaneurysms. Inflammatory infiltration was found intraoperatively in 15 patients. Sensitivity and specificity of TEE and CT were 53%, 94% and 46%, 100%, respectively. Intraoperative assessment revealed leaflet perforation in 16 patients. Sensitivity and specificity of TEE and CT were 75%, 79% and 43%, 89%. The sensitivity of the combination of TTE + TEE + CT was 81%. Perivalvular leakage was found in eight patients with a prosthetic valve. Sensitivity and specificity of echocardiography and CT were 100%, 100% and 88%, 100%, respectively. TEE showed higher sensitivity (97%) than CT (89%) in the diagnosis of vegetations. Conclusions The combination of TTE, TEE, and CT increased the sensitivity for the detection of valvular and perivalvular complications of IE. Key Points • CT is a useful modality in the diagnosis of IE and its local complications in addition to echocardiography. • For the detection of abscesses and pseudoaneurysms, CT is superior to echocardiography. Combining these two modalities can increase the sensitivity of diagnosing abscess/pseudoaneurysm up to 100%. • Adding CT to TEE increases the sensitivity for detection of inflammatory infiltrate. CT is not superior to echocardiography in diagnosing vegetations, valvular leaflet perforations, and perivalvular leaks, but it can be a useful tool when echocardiography is indeterminate.

TTN gene truncating variants are common in dilated cardiomyopathy (DCM), although data on their clinical significance is still limited. We sought to examine the frequency of truncating variants in TTN in patients with DCM, including familial DCM (FDCM), and to look for genotype-phenotype correlations. Clinical cardiovascular data, family histories and blood samples were collected from 72 DCM probands, mean age of 34 years, 45.8% FDCM. DNA samples were examined by next generation sequencing (NGS) with a focus on the TTN gene. Truncating mutations were followed up by segregation study among family members. We identified 16 TTN truncating variants (TTN trunc) in 17 probands (23.6% of all cases, 30.3% of FDCM, 17.9% of sporadic DCM). During mean 63 months from diagnosis, there was no difference in adverse cardiac events between probands with and without TTN truncating mutations. Among relatives 29 mutation carriers were identified, nine were definitely affected (31%), eight probably affected (27.6%) one possibly affected (3.4%) and eleven were not affected (37.9%). When relatives with all affected statuses were combined, disease penetrance was still incomplete (62.1%) even after exclusion of unaffected relatives under 40 (82%) and was higher in males versus females. In all mutation carriers, during follow-up, 17.4% had major adverse cardiac events, and prognosis was significantly worse in men than in women. In conclusion, TTN truncating variants were observed in nearly one fourth of young DCM patient population, in vast majority without conduction system disease. Incomplete penetrance suggests possible influence of other genetic and/or environmental factors on the course of cardiotitinopathy. Counseling should take into account sex and incomplete penetrance.