Association between coronary flow and aortic stenosis during transcatheter aortic valve implantation.

AIMS: In patients with aortic stenosis (AS), the coronary flow reserve decreases even in the absence of epicardial coronary artery stenosis. Systolic coronary flow reversal (SFR) reflecting reduced coronary microcirculation, often seen in patients with severe AS, has a potential negative impact on the pathogenesis of cardiac dysfunction. However, there are limited data on the relationship between the severity of AS and SFR, as well as on the benefits of transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the relationship between the severity of AS and efficacy of TAVI in improving SFR. METHODS AND RESULTS: Consecutive patients with AS who had undergone TAVI using transoesophageal echocardiography (TEE) from November 2020 to February 2022 were prospectively enrolled. Coronary flow in the left anterior descending artery as well as the aortic valve peak velocities, and the mean aortic valve pressure gradients (AVPGs), indicating the severity of AS, were measured using intraprocedural TEE before and after TAVI. The following parameters were measured as coronary flow: systolic and diastolic peak velocity (cm/s) and systolic and diastolic velocity-time integral (VTI) (cm). SFR was defined as the presence of a reversal coronary flow component in systole. The enrolled patients were classified into two groups according to the presence or absence of SFR before TAVI. A total of 25 patients were included: 13 had SFR and 12 who had no SFR, before TAVI. Patients with SFR had significantly higher aortic valve peak velocities (451.1 ± 45.9 vs. 372.1 ± 52.1 cm/s; P < 0.001) and mean AVPGs (49.2 ± 14.5 vs. 30.3 ± 11.6 mmHg; P = 0.002) than those without. The optimal binary cut-off aortic valve peak velocity values and the mean AVPG associated with the presence of SFR before TAVI were >410.0 cm/s (specificity, 75.0%; sensitivity, 92.3%) and >37.4 mmHg (specificity, 83.3%; sensitivity, 92.3%), respectively. After TAVI, SFR immediately disappeared in 11 of 13 patients with SFR (84.6%). Overall, the systolic coronary VTI significantly increased after TAVI (2.0 ± 4.7 vs. 6.4 ± 3.2 cm, P < 0.001), and this increase was greater in patients with SFR than in those without SFR before TAVI (interaction P = 0.035). CONCLUSIONS: SFR was found to be associated with the severity of AS and with a greater increase in systolic coronary flow immediately after TAVI.

Impact of vascular access site on procedural time of endomyocardial biopsy.

Endomyocardial biopsy (EMB) is widely used for the diagnosis of unexplained ventricular dysfunction and for assessment of cardiac allograft rejection. But, the impact of vascular access site on procedural time of EMB is not well-known. From February 2014 to May 2016, consecutive patients requiring EMB were prospectively enrolled in this study. Vascular access, by either the jugular or femoral vein, was randomly assigned. EMB was randomly performed by 3 pre-identified physicians based on practical experience in EMB. Each case was required to obtain at least 3 samples. The primary endpoint was to compare the total time spent in acquiring EMB from the right ventricular septum between the jugular and femoral vein access groups. The secondary endpoints were evaluation of each set (1st to 3rd attempt) of EMB times and safety. In addition, factors affecting the EMB procedural times were evaluated. A total of 49 consecutive patients requiring EMB (3.9 attempts/patient) were enrolled (the jugular group: 23, the femoral group: 26), and 156 myocardial samples (3.2 samples/patient) were obtained. There were no significant differences in total biopsy procedural time between the 2 groups (16.3 ± 7.4 vs. 20.8 ± 9.9 min, p = 0.075). Independent predictors for longer procedural time of the 1st attempt included femoral access, non-expert operators, and larger right atrium according to multiple linear regression analysis. The complication rates were not significantly different between the 2 groups, except for catheter kinking as a technical factor. Total biopsy time was not significantly different between the jugular and femoral venous access groups. However, the 1st attempt EMB procedural time by non-expert operators was longer when using the femoral approach, especially in cases involving a larger right atrium diameter.

Impact of Continuous Administration of Tolvaptan on Preventing Medium-Term Worsening Renal Function and Long-Term Adverse Events in Heart Failure Patients with Chronic Kidney Disease.

Tolvaptan (TLV) has an inhibiting effect for worsening renal function (WRF) in acute decompensated heart failure (HF) patients. However, there are limited data regarding the effect of continuous TLV administration on medium-term WRF.This was a retrospective observational study in hospitalized HF patients with chronic kidney disease (CKD). TLV was administered to those patients with fluid retention despite standard HF therapy. We compared 34 patients treated with TLV (TLV group) to 33 patients treated with conventional HF therapy with high-dose loop diuretics (furosemide ≥ 40 mg) (Loop group). Clinical outcomes, including the incidence of medium-term WRF, defined as increase of serum creatinine > 0.3 mg/dL, at 6 months after discharge and adverse events rate, were evaluated.Baseline patient characteristics were not different between the TLV and Loop group. The TLV group consisted of less frequent use of loop diuretics and carperitide compared with the Loop group. The incidence of medium-term WRF was significantly lower in the TLV group than in the Loop group (3.2% versus 31.0%, P = 0.002). Multivariate logistic analysis showed that the TLV non-user was an independent predictor of medium-term WRF. Kaplan-Meier analysis revealed that the long-term event-free survival was significantly higher in the TLV group (log-rank P = 0.01).Continuous administration of TLV may reduce the risk of medium-term WRF, resulting possibility in improvement of long-term adverse outcomes in HF patients with CKD.

Predictability of tricuspid annular plane systolic excursion for the effectiveness of tolvaptan in patients with heart failure.

BACKGROUND: There is no echocardiographic predictor of the effectiveness of tolvaptan in patients with heart failure (HF). The aim of this study was to investigate the echocardiographic predictor of responders to tolvaptan in patients with HF. METHODS: This observational study consisted of 62 consecutive in-hospital patients with HF who received tolvaptan with volume overload despite standard therapies. The echocardiography data were obtained within 1 week before the administration of tolvaptan. Tolvaptan responders were defined as those having a body weight decrease from baseline >1 kg on the morning of day 8. RESULTS: The mean age of the 62 patients was 75.1 ± 13.9 years, and 45 patients (72.6%) were considered to be responders. Tricuspid annular plane systolic excursion (TAPSE) was significantly higher (17.1 ± 3.8 vs. 13.0 ± 3.9 mm; p = 0.0004) and the tricuspid valve regurgitation pressure gradient (33.3 ± 14.6 vs. 44.9 ± 12.2 mmHg; p = 0.007) and estimated right atrium pressure (7.8 ± 4.2 vs. 10.3 ± 4.5 mmHg; p = 0.043) were significantly lower in the Responder group than in the Non-responder group. In a multivariate logistic regression analysis, TAPSE was found to be an independent predictor of response (odds ratio 1.28; 95% confidence interval 1.03-1.60). According to the receiver operating characteristics analysis, the area under the curve of TAPSE was the largest among the parameters measured by echocardiography. The cut-off value for TAPSE to predict responders was determined to be 17.0 mm (sensitivity = 56.8%, specificity = 94.1%). CONCLUSIONS: TAPSE is a simple predictor of the effectiveness of tolvaptan in patients with HF.

Intravascular ultrasound-guided percutaneous coronary intervention for total occlusion of the proximal left anterior descending artery caused by spontaneous coronary dissection in a young woman.

A 35-year-old woman was admitted to our hospital because of a sudden cardiac arrest caused by an acute anterior myocardial infarction. Emergency coronary angiography showed total occlusion of the proximal left anterior descending artery (LAD). We performed an intravascular ultrasound (IVUS) to detect the LAD orifice and successfully inserted the guidewire to the occluded LAD. An IVUS revealed coronary dissection and no atheromatous plaque from the orifice to the mid-portion of the LAD and the guidewire was in the true lumen. Two bare metal stents were implanted in the proximal and mid portion of the LAD. After stenting to the LAD, coronary dissection retrogradely extended to the left circumflex artery (LCx). Therefore, we performed additional stent implantation from the left main trunk (LMT) to the proximal LCx and the just proximal LAD. An IVUS guided percutaneous coronary intervention (PCI) enabled complete revascularization to spontaneous coronary artery dissection.

Phosphorylation of a heme-regulated eukaryotic initiation factor 2α kinase enhances the interaction with heat-shock protein 90 and substantially upregulates kinase activity.

Heme-regulated eukaryotic initiation factor 2α kinase (HRI) functions under conditions of heme shortage caused by blood diseases such as erythropoietic protoporphyria and ß-thalassemia, and retains the heme:globin ratio at 1:1 by sensing the heme concentration in reticulocytes. This HRI function is regulated by various factors including autophosphorylation and protein-protein interactions. A heat-shock protein controls HRI function, however, the molecular mechanism of catalytic regulation of HRI by the heat-shock protein is unclear. In the present study, we examined the interactions of HRI with a heat-shock protein, Hsp90, under various conditions, using a pull-down assay and measuring catalytic activity. It was found that [1] an interaction between Hsp90 and phosphorylated HRI was evident, whereas no interaction was observed between Hsp90 and HRI dephosphorylated by treatment with λ protein phosphatase; [2] Hsp90 enhanced the kinase activity of phosphorylated HRI but not dephosphorylated HRI, but this enhancement was not observed in the presence of heme; and, [3] autophosphorylation of HRI was not influenced by Hsp90. Therefore, we propose that autophosphorylation of HRI is critical for catalytic regulation by Hsp90 under heme-shortage conditions.