Incomplete stent apposition (ISA) is characterized by the lack of contact of at least 1 stent strut with the vessel wall in a segment not overlying a side branch; it is more commonly found in ...drug-eluting stents than bare-metal stents. The accurate diagnosis of ISA, initially only possible with intravascular ultrasound, can currently be performed with higher accuracy by optical coherence tomography, which also enables strut-level assessment due to its higher axial resolution. Different circumstances related both to the index procedure and to vascular healing might influence ISA occurrence. Although several histopathology and clinical studies linked ISA to stent thrombosis, potential selection bias precluded definitive conclusions. Initial studies usually performed single time point assessments comparing overall ISA percentage and magnitude in different groups (i.e., stent type), thus hampering a comprehensive understanding of its relationship with vascular healing. Serial intravascular imaging studies that evaluated vascular response heterogeneity recently helped fill this gap. Some particular clinical scenarios such as acute coronary syndromes, bifurcations, tapered vessels, overlapping stents, and chronic total occlusions might predispose to ISA. Interventional cardiologists should be committed to optimal stent choices and techniques of implantation and use intravascular imaging guidance when appropriate to aim at minimizing acute ISA. In addition, the active search for new stent platforms that could accommodate vessel remodeling over time (i.e., self-expandable stents) and for new polymers and/or eluting drugs that could induce less inflammation (hence, less positive remodeling) could ultimately reduce the occurrence of ISA and its potentially harmful consequences.
Several applications of pluripotent stem cell (PSC)-derived cardiomyocytes require elimination of undifferentiated cells. A major limitation for cardiomyocyte purification is the lack of easy and ...specific cell marking techniques. We found that a fluorescent dye that labels mitochondria, tetramethylrhodamine methyl ester perchlorate, could be used to selectively mark embryonic and neonatal rat cardiomyocytes, as well as mouse, marmoset and human PSC-derived cardiomyocytes, and that the cells could subsequently be enriched (>99% purity) by fluorescence-activated cell sorting. Purified cardiomyocytes transplanted into testes did not induce teratoma formation. Moreover, aggregate formation of PSC-derived cardiomyocytes through homophilic cell-cell adhesion improved their survival in the immunodeficient mouse heart. Our approaches will aid in the future success of using PSC-derived cardiomyocytes for basic and clinical applications.
Objectives This study sought to evaluate the association between contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention and severity of bleeding estimated from ...periprocedural hemoglobin (Hb) measurement. Background The relationship between CI-AKI and bleeding in contemporary practice remains controversial. Methods In a retrospective analysis of the prospectively maintained Japan Cardiovascular Database-Keio Interhospital Cardiovascular Studies (JCD-KICS) multicenter registry, we divided 2,646 consecutive patients into 5 groups according to the change of Hb level after compared with before percutaneous coronary intervention: patients without a decrease in Hb level (group A) and patients with a decreased Hb level: <1 g/dl (group B); 1 to <2 g/dl (group C); 2 to <3g/dl (group D); and >3 g/dl (group E). CI-AKI was defined as an increase in serum creatinine level ≥0.5 mg/dl or ≥25% above baseline values at 48 h after administration of contrast media. Procedure and outcome variables were compared. Results The mean patient age was 67 ± 11 years. Of the 2,646 patients, CI-AKI developed in 315 (11.9%). The CI-AKI incidence was 6.2%, 7.5%, 10.7%, 17.0%, and 26.2%, in groups A through E, respectively (p < 0.01), whereas the incidence of major bleeding was 0.7%, 1.3%, 2.0%, 4.1%, and 28.3%, respectively (p < 0.01). CI-AKI was associated with higher rates of mortality (5.4% vs. 0.6%, p < 0.01) and of composite of heart failure, cardiogenic shock, and death (16.5% vs. 2.8%, p < 0.01). Conclusions Periprocedural bleeding was significantly associated with CI-AKI, with CI-AKI incidence correlating with bleeding severity.
Abstract Objectives The purpose of this analysis was to assess 5-year outcomes of transcatheter aortic valve implantation (TAVI) using the current technology of the self-expanding CoreValve ...prosthesis (Medtronic Inc., Minneapolis, Minnesota). Background There is a paucity of evidence on long-term durability of currently available transcatheter heart valves. Methods Starting in June 2007, all consecutive patients with severe aortic stenosis undergoing TAVI with the third-generation 18-F CoreValve device in 8 Italian centers were prospectively included in the ClinicalService Project. For the purposes of this study, we included only consecutive patients with 5-year follow-up data available (n = 353) treated from June 2007 to August 2009. All outcomes were reported according to VARC (Valve Academic Research Consortium)-1 criteria. Results All-cause mortality rates at 1, 2, 3, 4, and 5 years were 21%, 29%, 38%, 48%, and 55.0%, respectively. Cardiovascular mortality rates at 1, 2, 3, 4, and 5 years were 10%, 14%, 19%, 23%, and 28.0%, respectively. The overall neurological event rate at 5 years was 7.5%, of which more than two-thirds occurred early after the procedure. During follow-up, there were 241 rehospitalizations for cardiovascular reasons in 164 (46%) patients. Among all rehospitalizations, acute heart failure was the most frequently reported (42.7%), followed by requirement of permanent pacemaker implantation (17.4%). On echocardiography, mean transaortic gradients decreased from 55.6 ± 16.8 mm Hg (pre-TAVI) to 12.8 ± 10.9 mm Hg (5-year post-TAVI) (p < 0.001). Late prosthesis failure occurred in 5 cases (1.4%); among these, redo TAVI was successfully carried out in 2 patients (0.6%) presenting with symptomatic prosthesis restenosis. The remaining 3 cases of prosthesis failure did not undergo further invasive interventions. Ten patients (2.8%) showed late mild stenosis with a mean transaortic gradient ranging from 20 to 40 mm Hg. No other cases of structural or nonstructural valvular deterioration were observed. Valve thrombosis or late valve embolization were not reported. Conclusions TAVI with the currently adopted CoreValve generation was associated with sustained clinical outcomes up to 5-year follow-up, with a low rate (1.4%) of significant prosthetic valve degeneration. The procedure appears to be an adequate and lasting resolution of aortic stenosis in selected high-risk patients.
Managing right-sided chronic heart failure (CHF) due to tricuspid regurgitation (TR) remains a clinical challenge. Tolvaptan (TLV), a vasopressin V2 receptor inhibitor, is effective in controlling ...decompensated HF. However, its effects on right-sided CHF caused by TR are unclear. We sought to clarify the effects of TLV in CHF patients complicated with TR. The cohort consisted of 33 CHF patients with moderate or severe TR and permanent atrial fibrillation, who required hospitalization for HF. We observed 19 patients treated with TLV plus conventional therapies (TLV group) and 14 patients with conventional therapies alone (conventional group). Clinical characteristics, echocardiographic parameters, and laboratory data were investigated. Baseline characteristics were similar between groups. In the TLV group, the severity of TR at admission was 73.7% moderate and 26.3% severe. In the conventional group, these percentages were 85.7% and 14.3%, respectively. During the follow-up, the severity of TR improved in the TLV group (trivial–mild: 52.6%; moderate: 36.8%; severe: 10.5%) (
p
< 0.01). However, it did not improve in the conventional group (trivial–mild: 21.4%; moderate: 50.0%; severe: 28.6%) (
p
= 0.08). The diameter of the tricuspid annulus (
p
< 0.01), basal (
p
= 0.02), and mid right ventricle (
p
= 0.04) was reduced at follow-up in the TLV group. Nevertheless, these parameters did not change in the conventional group. Serum creatinine levels were maintained (
p
= 0.74) in the TLV group, but deteriorated in the conventional group (
p
= 0.03). TLV reduced right ventricular dimensions and improved TR without deterioration of renal function. Thus, TLV may be a new drug for the treatment of CHF patients with TR.
Objective This study retrospectively compared the outcomes of emergently admitted patients with aortic stenosis (AS) with or without urgent transcatheter aortic valve replacement (TAVR). Methods ...Patients hospitalized between February 2015 and December 2019 for symptomatic AS were retrospectively analyzed by comparing the received conservative management continued medical therapy with or without elective surgical transcatheter replacement (SAVR) or TAVR scheduled after the index hospitalization and urgent TAVR (TAVR during the index hospitalization). Results The cohort comprised 114 patients with symptomatic AS who required emergency admission. Urgent TAVR was performed for 37 patients, while conservative management was provided for 77 patients, including 1 who received urgent SAVR. Urgent TAVR was more likely to be performed in patients with a history of hospitalization for heart failure, high New York Heart Association class scores, a lower clinical frailty scale at admission, and a high aortic valve peak velocity (p=0.01, p<0.001, p<0.01 and p=0.02, respectively). Kaplan-Meier analyses with log-rank test revealed favorable outcomes of urgent TAVR in all-cause mortality and cardiovascular events within 60 days of admission (p<0.01, p<0.01, respectively). Conclusion Urgent TAVR had better short-term outcomes in patients with symptomatic AS who required emergency hospital admission than conservative management. When considering urgent TAVR, patients with typical heart failure symptoms due to AS with a history of heart failure hospitalization and relatively little frailty can be selected.
The lethal ventricular arrhythmia Torsade de pointes (TdP) is the most common reason for the withdrawal or restricted use of many cardiovascular and non-cardiovascular drugs. The lack of an
in vitro ...model to detect pro-arrhythmic effects on human heart cells hinders the development of new drugs. We hypothesized that recently established human induced pluripotent stem (hiPS) cells could be used in an
in vitro drug screening model. In this study, hiPS cells were driven to differentiate into functional cardiomyocytes, which expressed cardiac markers including Nkx2.5, GATA4, and atrial natriuretic peptide. The hiPS-derived cardiomyocytes (hiPS-CMs) were analyzed using a multi electrode assay. The application of ion channel inhibitors resulted in dose-dependent changes to the field potential waveform, and these changes were identical to those induced in the native cardiomyocytes. This study shows that hiPS-CMs represent a promising
in vitro model for cardiac electrophysiologic studies and drug screening.
Long QT syndrome (LQTS) is an inheritable and life-threatening disease; however, it is often difficult to determine disease characteristics in sporadic cases with novel mutations, and more precise ...analysis is necessary for the successful development of evidence-based clinical therapies. This study thus sought to better characterize ion channel cardiac disorders using induced pluripotent stem cells (iPSCs).
We reprogrammed somatic cells from a patient with sporadic LQTS and from controls, and differentiated them into cardiomyocytes through embryoid body (EB) formation. Electrophysiological analysis of the LQTS-iPSC-derived EBs using a multi-electrode array (MEA) system revealed a markedly prolonged field potential duration (FPD). The IKr blocker E4031 significantly prolonged FPD in control- and LQTS-iPSC-derived EBs and induced frequent severe arrhythmia only in LQTS-iPSC-derived EBs. The IKs blocker chromanol 293B did not prolong FPD in the LQTS-iPSC-derived EBs, but significantly prolonged FPD in the control EBs, suggesting the involvement of IKs disturbance in the patient. Patch-clamp analysis and immunostaining confirmed a dominant-negative role for 1893delC in IKs channels due to a trafficking deficiency in iPSC-derived cardiomyocytes and human embryonic kidney (HEK) cells.
This study demonstrated that iPSCs could be useful to characterize LQTS disease as well as drug responses in the LQTS patient with a novel mutation. Such analyses may in turn lead to future progress in personalized medicine.
The aim of this study was to assess the feasibility and the safety of early discharge (within 72 h) after transfemoral transcatheter aortic valve implantation (TAVI) and to identify baseline features ...and/or peri-procedural variables, which may affect post-TAVI length-of-stay (LoS) duration.
Patients discharged within 72 h of TAVI (early discharge group) were compared with consecutive patients discharged after 3 days (late discharge group). Propensity-matched cohorts of patients with a 2:1 ratio were created to better control confounding bias. Among 465 patients, 107 (23.0%) were discharged within 3 days of the procedure. Multivariable regression analysis of unmatched patients demonstrated that baseline New York Heart Association (NYHA) class IV (OR: 0.22, 95% CI 0.05 to 0.96; p=0.045) and any bleeding (OR: 0.31, 95% CI 0.74 to 0.92; p=0.031) were less likely to be associated with early discharge after TAVI. Conversely, the year of procedure (OR: 1.66, 95% CI 1.25 to 2.20; p<0.001) and the presence of a permanent pacemaker (PPM) before TAVI (OR: 2.80, 95% CI 1.36 to 5.75; p=0.005) were associated with a higher probability of early discharge. In matched populations, patients in the early discharge group reported lower incidence of in-hospital bleeding (7.9% vs 19.4%, p=0.014), major vascular complications (2.3% vs 9.1%, p=0.038) and PPM implantation (7.9% vs18.5%, p=0.021), whereas after discharge, at 30-day, no significant differences were reported between groups in terms of death (2.2% vs 1.7%, p=0.540), bleeding (0.0% vs 1.1%, p=0.444), PPM implantation (1.1% vs 0.0%, p=0.333) and re-hospitalisation (1.1% vs 1.1%, p=1.000).
Early discharge (within 72 h) after transfemoral TAVI is feasible and does not seem to jeopardise the early safety of the procedure, when performed in a subset of patients selected by clinical judgement. Patients undergoing TAVI in unstable haemodynamic compensation and patients experiencing bleeding after the procedure demonstrated to be poorly suitable to this approach, whereas increasing experience in post-TAVI management was associated with a reduction of LoS.
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