RATIONALE:Subcellular Ca indicators have yet to be developed for the myofilament where disease mutation or small molecules may alter contractility through myofilament Ca sensitivity. Here, we develop ...and characterize genetically encoded Ca indicators restricted to the myofilament to directly visualize Ca changes in the sarcomere.
OBJECTIVE:To produce and validate myofilament-restricted Ca imaging probes in an adenoviral transduction adult cardiomyocyte model using drugs that alter myofilament function (MYK-461, omecamtiv mecarbil, and levosimendan) or following cotransduction of 2 established hypertrophic cardiomyopathy disease-causing mutants (cTnT Troponin T R92Q and cTnI Troponin I R145G) that alter myofilament Ca handling.
METHODS AND RESULTS:When expressed in adult ventricular cardiomyocytes RGECO-TnT (Troponin T)/TnI (Troponin I) sensors localize correctly to the sarcomere without contractile impairment. Both sensors report cyclical changes in fluorescence in paced cardiomyocytes with reduced Ca on and increased Ca off rates compared with unconjugated RGECO. RGECO-TnT/TnI revealed changes to localized Ca handling conferred by MYK-461 and levosimendan, including an increase in Ca binding rates with both levosimendan and MYK-461 not detected by an unrestricted protein sensor. Coadenoviral transduction of RGECO-TnT/TnI with hypertrophic cardiomyopathy causing thin filament mutants showed that the mutations increase myofilament Ca in systole, lengthen time to peak systolic Ca, and delay Ca release. This contrasts with the effect of the same mutations on cytoplasmic Ca, when measured using unrestricted RGECO where changes to peak systolic Ca are inconsistent between the 2 mutations. These data contrast with previous findings using chemical dyes that show no alteration of Ca transient amplitude or time to peak Ca.
CONCLUSIONS:RGECO-TnT/TnI are functionally equivalent. They visualize Ca within the myofilament and reveal unrecognized aspects of small molecule and disease-associated mutations in living cells.
Objective: The metabolic and cardiovascular risk of obesity is predominantly defined through the amount of intra-abdominal fat (IAF). Regarding this risk and the benefits of weight reduction ...gender-specific differences have been described. The aim of this study was to examine the gender-specific relationship between IAF assessed via ultrasound and the cardiometabolic risk profile in extremely obese adolescents before and after weight loss. Methods: In 107 consecutively admitted adolescents (n = 59 girls, mean age 15.4 ± 2.6 years boys and 15.1 ± 2.1 years girls, mean BMI z-score 3.2 ± 0.6 boys and 3.5 ± 0.6 girls) anthropometric and fasting laboratory chemical parameters were measured before and after an in-patient long-term therapy (mean durance 5.6 ± 2.3 months). IAF was determined by measuring the intra-abdominal depth (IAD) via ultrasound. Results: IAD was higher in boys as compared to girls (58.0 ± 22.4 mm vs. 51.3 ± 16.0 mm). IAD values were positively associated with BMI-z scores, waist circumferences, HOMA-IR and serum levels of γGT, hs-CRP and IL-6 in both genders. In boys, but not in girls, IAD was significantly correlated with systolic and diastolic blood pressure, serum levels of triglycerides, ALT as well as adiponectin and HDL-cholesterol. After a marked mean weight loss of -27.1 ± 16.2 kg (-20.1 ± 7.9%) in boys and of -20.5 ± 11.5 kg (-17.3 ± 7.1%) in girls, IAD decreased by -20.7 ± 16.2 mm (--32.4 ± 16.9%) in boys and by -18.4 ± 12,7 mm (-34.3 ± 18.4%) in girls, resulting in more pronounced ameliorations of cardiovascular risk factors in boys than in girls. Conclusions: The present study indicates that IAF assessed by ultrasound is a good indicator for the cardiometabolic risk factor profile in extremely obese adolescents. Associations between IAF and risk factors are more pronounced in boys than in girls.
Acute ischemic stroke is a feared complication during cardiovascular procedures associated with high morbidity and mortality if not immediately recognized and treated. We conducted a review of cases ...at our center where patients experienced an acute, procedure‐related ischemic stroke and underwent immediate endovascular stroke treatment by the interventional cardiologists trained in acute endovascular stroke intervention. Baseline demographics, procedural and follow‐up data were collected. Three patients were identified in whom the percutaneous procedure (peripheral arterial intervention, transapical NeoChord NeoChord Inc, Minnesota, USA implantation and transcatheter aortic valve implantation, respectively) was complicated by an acute embolic ischemic stroke. In all cases, cerebral vessel re‐canalization was technically successful with thrombolysis in cerebral infarction (TICI) IIB/III flow. Follow‐up computed tomography scans showed no infarct demarcation, oedema or intracranial hemorrhage. One patient survived with no neurological symptoms at 6‐month follow‐up whereas the two other patients died of unrelated intensive care complications and decompensated heart failure. We conclude that endovascular stroke treatment during cardiovascular interventions can be performed by interventional cardiologists with appropriate training. It offers the unique opportunity to treat cerebral embolization in a time‐efficient manner, potentially improving morbidity and mortality of affected patients.
Left atrial appendage closure aims to eliminate the stasis component of Virchow triad by eliminating a cul-de-sac that favors thrombosis, particularly when atrial contractility becomes inefficient, ...such as in atrial fibrillation. Left atrial appendage closure devices have a common objective of sealing the appendage completely, with device stability and avoidance of device thrombosis. Two main device designs have been used to perform left atrial appendage closure: those that use a pacifier design (lobe + disk) and those that use a plug (single lobe) design. This review highlights the potential features and benefits of the single-lobe devices.
A large, prospective international registry was developed to evaluate the initial clinical applications of transcatheter tricuspid valve intervention (TTVI) with different devices.
TTVI for native ...tricuspid valve dysfunction has been emerging during the last few years as an alternative therapeutic option to serve a large high-risk population of patients with severe symptomatic tricuspid regurgitation (TR).
The TriValve Registry included 312 high-risk patients with severe TR (76.4 ± 8.5 years of age; 57% female; EuroSCORE II 9 ± 8%) at 18 centers. Interventions included repair at the level of the leaflets (MitraClip, Abbott Vascular, Santa Clara, California; PASCAL Edwards Lifesciences, Irvine, California), annulus (Cardioband, Edwards Lifesciences; TriCinch, 4tech, Galway, Ireland; Trialign, Mitraling, Tewksbury, Massachusetts), or coaptation (FORMA, Edwards Lifesciences) and replacement (Caval Implants, NaviGate, NaviGate Cardiac Structures, Lake Forest, California). Clinical outcomes were prospectively determined during mid-term follow-up.
A total of 108 patients (34.6%) had prior left heart valve intervention (84 surgical and 24 transcatheter, respectively). TR etiology was functional in 93%, and mean annular diameter was 46.9 ± 9 mm. In 75% of patients the regurgitant jet was central (vena contracta 1.1 ± 0.5; effective regurgitant orifice area 0.78 ± 0.6 cm
). Pre-procedural systolic pulmonary artery pressure was 41 ± 14.8 mm Hg. Implanted devices included: MitraClip in 210 cases, Trialign in 18 cases, TriCinch first generation in 14 cases, caval valve implantation in 30 cases, FORMA in 24 cases, Cardioband in 13 cases, NaviGate in 6 cases, and PASCAL in 1. In 64% of the cases, TTVI was performed as a stand-alone procedure. Procedural success (defined as the device successfully implanted and residual TR ≤2+) was 72.8%. Greater coaptation depth (odds ratio: 24.1; p = 0.002) was an independent predictor of reduced device success. Thirty-day mortality was 3.6% and was significantly lower among patients with procedural success (1.9% vs. 6.9%; p = 0.04); Actuarial survival at 1.5 years was 82.8 ± 4% and was significantly higher among patients who had procedural success achieved.
TTVI is feasible with different technologies, has a reasonable overall procedural success rate, and is associated with low mortality and significant clinical improvement. Mid-term survival is favorable in this high-risk population. Greater coaptation depth is associated with reduced procedural success, which is an independent predictor of mortality.
Transcatheter aortic valve replacement (TAVR) use is increasing in patients with longer life expectancy, yet robust data on the durability of transcatheter heart valves (THVs) are limited. Redo-TAVR ...may play a key strategy in treating patients in whom THVs fail.
The authors sought to examine outcomes following redo-TAVR.
The Redo-TAVR registry collected data on consecutive patients who underwent redo-TAVR at 37 centers. Patients were classified as probable TAVR failure or probable THV failure if they presented within or beyond 1 year of their index TAVR, respectively.
Among 63,876 TAVR procedures, 212 consecutive redo-TAVR procedures were identified (0.33%): 74 within and 138 beyond 1 year of the initial procedure. For these 2 groups, TAVR-to-redo-TAVR time was 68 (38 to 154) days and 5 (3 to 6) years. The indication for redo-TAVR was THV stenosis in 12 (16.2%) and 51 (37.0%) (p = 0.002) and regurgitation or combined stenosis–regurgitation in 62 (83.8%) and 86 (62.3%) (p = 0.028), respectively. Device success using VARC-2 criteria was achieved in 180 patients (85.1%); most failures were attributable to high residual gradients (14.1%) or regurgitation (8.9%). At 30-day and 1-year follow-up, residual gradients were 12.6 ± 7.5 mm Hg and 12.9 ± 9.0 mm Hg; valve area 1.63 ± 0.61 cm2 and 1.51 ± 0.57 cm2; and regurgitation ≤mild in 91% and 91%, respectively. Peri-procedural complication rates were low (3 stroke 1.4%, 7 valve malposition 3.3%, 2 coronary obstruction 0.9%, 20 new permanent pacemaker 9.6%, no mortality), and symptomatic improvement was substantial. Survival at 30 days was 94.6% and 98.5% (p = 0.101) and 83.6% and 88.3% (p = 0.335) at 1 year for patients presenting with early and late valve dysfunction, respectively.
Redo-TAVR is a relatively safe and effective option for selected patients with valve dysfunction after TAVR. These results are important for applicability of TAVR in patients with long life expectancy in whom THV durability may be a concern.
Display omitted
Left atrial appendage closure aims to eliminate the stasis component of Virchow triad by eliminating a cul-de-sac that favors thrombosis, particularly when atrial contractility becomes inefficient, ...such as in atrial fibrillation. Left atrial appendage closure devices have a common objective of sealing the appendage completely, with device stability and avoidance of device thrombosis. Two main device designs have been used to perform left atrial appendage closure: those that use a pacifier design (lobe + disk) and those that use a plug (single lobe) design. This review highlights the potential features and benefits of the single-lobe devices.
The aim of this study was to evaluate the technical and clinical success of acute stroke interventions performed in our interventional cardiology center.
Dedicated interventional stroke centers ...remain limited. Interventional cardiologists have established networks of catheterization laboratories and the necessary infrastructure to provide around the clock interventional therapy. These networks may also provide the currently lacking universal rapid access to prompt stroke intervention.
Between July 2012 and July 2018, 70 consecutive patients underwent acute stroke intervention for large-vessel occlusions. Seventeen patients (24%) had tandem or multiple vessel occlusions. The majority (n = 63, 90%) were admitted via our local stroke unit, and 7 (10%) patients were transferred from other regional referral centers.
In 43 (61%) patients, systemic fibrinolytic therapy was started after baseline imaging. Mean time between symptom onset and arrival to the cath lab was 138 min; mean door-to-vascular access time was 64 min; mean time between cath lab activation and its operational readiness was 13 min. In all cases, access to supra-aortic vessels was achieved. Mean time between femoral arterial puncture and lesion crossing was 26 min. Stent implantation for extracranial stenosis or dissection was performed in 14 (20%) cases. Thrombectomy of intracranial occlusions was done with a stent retriever (n = 64, 91%) or an aspiration system (n = 14, 20%). In 20 (28%) cases, a combination of techniques was used. Recanalization was technically successful (Thrombolysis In Cerebral Infarction flow grade 2b or 3) in 65 (93%) patients. The 30-day mortality was 18% (n = 13). Favorable clinical outcome, defined as a modified Rankin Scale score of 0 to 2, was achieved in 61% at 3-month follow-up.
Acute stroke interventions can be performed safely and with high technical and clinical success by experienced interventional cardiologists.
PDF
