Influence of ultrasound transmit frequency on measurement of global longitudinal strain on 2D speckle tracking echocardiography.

The reproducibility of longitudinal strain measured by 2D speckle tracking echocardiography (2DSTE) may be affected by ultrasound settings. This study investigated the effect of transmit ultrasound frequency on global longitudinal strain (GLS) by 2DSTE. Apical, 2- and 4-chamber, and long-axis views were obtained in consecutive 162 patients using Philips ultrasound devices. Three different frequency presets were used sequentially: high resolution (HRES, 1.9 to 2.1 MHz), general (HGEN, 1.6 to 1.8 MHz), and penetration mode (HPEN, 1.3 to 1.6 MHz). GLS values were determined for each preset using the Philips Q-station software, resulting in GLS-HRES, GLS-HGEN, and GLS-HPEN. Among the 151 patients with successfully measured GLS, a significant difference in GLS was observed among the three presets (p < 0.0001). GLS-HRES (- 17.9 ± 4.4%) showed a slightly smaller magnitude compared to GLS-HGEN (- 18.8 ± 4.5%, p < 0.0001) and GLS-HPEN (- 18.8 ± 4.5%, p < 0.0001), with absolute differences of 1.1 ± 1.0% and 1.1 ± 1.2%, respectively. This variation in GLS with frequency was evident in patients with both optimal (n = 104) and suboptimal (n = 47) image quality and remained consistent regardless of ultrasound devices, ischemic etiology, or ejection fraction. In conclusion, ultrasound frequency had only a modest effect on GLS measurements. GLS may be reliably assessed in most cases regardless of the ultrasound frequency used.

Sleep apnea severity in patients undergoing atrial fibrillation ablation: Home sleep apnea-test and polysomnography comparison.

Background: Sleep apnea (SA) is highly prevalent and should be treated in patients referred for catheter ablation (CA) of atrial fibrillation (AF). Watch-type peripheral arterial tonometry (WP) for home SA testing has demonstrated a high correlation of the apnea-hypopnea index (AHI) with Polysomnography (PSG), but the evidence of its accuracy in AF patients is not adequate. Methods: This study was conducted under a retrospective, single-center, observational design. We included 464 consecutive AF patients (age 65 ± 11 years, 76.5% male, 45.0% paroxysmal-AF) who received both WP and PSG during the periprocedural period of the CA. We compared the AHI using the WP (WP-AHI) to that using PSG (PSG-AHI). Results: The WP-AHI was 25.9 ± 12.7 and PSG-AHI 31.4 ± 18.9 (r = .48). Among 325 patients with a WP-AHI < 30, 116 (35.7%) exhibited a PSG-AHI ≥ 30. Only 12.5% of the patients were indicated for continuous positive airway pressure (CPAP) treatment only by the WP-AHI, while 70.9% were indicated for CPAP by the PSG-AHI according to the Japanese health insurance system. The best cut-off value of the WP-AHI was 18.1 to predict a PSG-AHI ≥ 20 with an area under the curve of 0.72 (95% confidence interval, 0.67-0.76). Conclusions: The WP-AHI and PSG-AHI were weakly correlated in AF patients receiving CA. About one-third of the patients with moderate SA using the WP was diagnosed with severe SA evaluated by PSG. The majority required PSG for the CPAP indication.

Efficacy of Intravascular Ultrasound-Based 3D Wiring Using the Tip Detection Method for CTO Intervention.

To perform intravascular ultrasound (IVUS)-based real-time 3-dimensional wiring in chronic total occlusion percutaneous coronary intervention, we devised a tip detection method and developed AnteOwl WR (AO)-IVUS, which is an upgraded version of Navifocus WR (Navi)-IVUS with an added pull back transducer system. We compared the procedural outcomes of AO-IVUS-based 3-dimensional wiring using the tip detection method (n = 30) and Navi-IVUS-based conventional wiring (n = 17) in chronic total occlusion percutaneous coronary intervention. The success rate of IVUS-guided wiring was markedly improved in the AO-IVUS group compared with the Navi-IVUS group (93% vs 59% of cases, respectively; P = 0.007). In cases of successful IVUS-guided wiring, the IVUS-guided wiring time was markedly improved in the AO-IVUS group compared with the Navi-IVUS group (9 ± 8 minutes vs 24 ± 26 minutes, respectively; P = 0.001). There were 2 successful cases of tip detection-antegrade dissection and re-entry in the AO-IVUS group.

Guide extension proximal locking method: standardization of maximum backup force in percutaneous coronary intervention.

We developed the smallest diameter guide-extension catheter (GUIDE PLUS® 5Fr) to enable a new technique, the guide-extension proximal locking method (GP-Lock), and assessed its efficacy in the present experimental and clinical study. Sufficient guide catheter backup is sometimes crucial for PCI. We developed the KIWAMI-Lock direct anchoring method to obtain the strongest backup force by locking a Kiwami® 4Fr child catheter (Terumo Corp. Tokyo, Japan) directly to the coronary artery by ballooning from outside the child catheter. However, this method is complicated due to the requirement for a child catheter. We compared the backup power of the GP-Lock method and other conventional methods in an experimental study and compared the procedural outcomes of 17 cases treated using the initial GP-Lock method with 17 cases using the recent KIWAMI-Lock method before GP-Lock. The GP-Lock method had the highest backup force among the methods examined (GP-Lock: 293.7 ± 10.2 g force (gf), KIWAMI-Lock: 270.4 ± 12.9 gf, side branch balloon anchoring technique: 182.7 ± 8.1 gf, respectively, P < 0.0001). The preparation time was significantly shorter for the GP-Lock group than the KIWAMI-Lock group (5.0 [4.0, 5.0] min vs. 11.0 [8.0, 13.0] min, respectively, P < 0.001). The GP-Lock method makes it possible to easily obtain the strongest backup force, which can overcome situations where devices cannot pass through, especially in complex PCI procedures.

Impact of Residual Functional Mitral Regurgitation After Atrial Fibrillation Ablation on Clinical Outcomes in Patients With Left Ventricular Systolic Dysfunction.

Functional mitral regurgitation (FMR) negatively impacts the prognosis in patients with atrial fibrillation (AF) and reduced left ventricular (LV) ejection fraction (LVEF). Although structural reverse remodeling after AF ablation can reduce FMR severity, the prognostic impact of FMR and its evolution remain unclear. Of 491 patients with baseline LVEF <50% who underwent first-time AF ablation, 134 patients (27%) had grade 2 to 4 FMR at baseline. Among them, 88 patients (66%) exhibited FMR improvement to grade 0 to 1 FMR 6 months after AF ablation. Conversely, among 357 with baseline grade 0 to 1 FMR, 13 patients (3.6%) exhibited FMR worsening to grade 2 to 4 FMR despite AF ablation. Assessment with multidetector computed tomography revealed that an increase in the left atrial emptying fraction (odds ratio 3.55 per 10% increase; 95% confidence interval 2.12 to 5.95) and a reduction in the LV end-diastolic volume index (1.35 per 10-ml/m2 decrease; 1.04 to 1.76) were identified as contributors to the FMR improvement. During a follow-up of 43 months, patients with postprocedural grade 2 to 4 FMR more frequently experienced hospitalizations for heart failure or cardiovascular death than those with grade 0 to 1 FMR (30.5% vs 4.6%, log-rank p <0.001). An age-adjusted multivariate Cox regression analysis including baseline and postprocedural FMR revealed that postprocedural grade 2 to 4 FMR (hazard ratio, 3.24; 95% confidence interval 1.43 to 7.35) was significantly associated with unfavorable events. In conclusion, AF ablation modified and often improved FMR severity in patients with reduced LVEF. Residual grade 2 to 4 FMR 6 months after AF ablation was associated with a poor prognosis.

Impact of pericardial fluid glucose level and computed tomography attenuation values on diagnosis of malignancy-related pericardial effusion.

BACKGROUND: We evaluated malignancy according to the characteristics of pericardial fluid in symptomatic Japanese patients undergoing pericardiocentesis and computed tomography (CT). METHODS: This was a retrospective, single-center, observational study of 125 symptomatic patients undergoing pericardiocentesis. The patients were classified into two groups: a malignancy group and a non-malignancy group, according to the primary disease and cytology of the pericardial effusion (PE). We compared the pericardial fluid sample and CT measurements between both groups. RESULTS: All patients were diagnosed as having exudative PE by Light's criteria. PE with malignant cells was demonstrated in 76.8% of the malignancy group patients. Pericardial to serum lactate dehydrogenase (LDH) ratio > 0.6, as one of Light's criteria, was associated with malignancy (p = 0.017). Lower serum brain natriuretic peptide (BNP) concentration was also associated with malignancy (BNP: 126.9 ± 89.8 pg/ml vs 409.2 ± 97.7 pg/ml, malignancy vs non-malignancy groups, respectively; p = 0.037). A significant difference was observed in pericardial fluid glucose level between the malignancy and non-malignancy groups (pericardial fluid glucose: 78.24 ± 48.29 mg/dl vs 98.41 ± 44.85, respectively; p = 0.048). Moreover, CT attenuation values (Hounsfield units (HU)) tended to be higher in the malignancy group vs the non-malignancy group (22.7 [interquartile range (IQR), 17.4-26.0] vs 17.4 [IQR, 13.7-26.4], respectively; p = 0.08). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy (p = 0.012). CONCLUSIONS: Lower pericardial fluid glucose level with higher CT attenuation values may suggest malignancy-related PE.

Impact of Neointimal Condition and Platelet Reactivity on Intrastent Thrombus at Long-Term Follow-up After 2nd- and 3rd-Generation Drug-Eluting Stent Implantation　- Insights From a Coronary Angioscopy and Pharmacodynamic Study.

BACKGROUND: Although the incidence of very late stent failure (VLSF) is reduced with newer generation drug-eluting stent (DES), the mechanism of VLSF has not been fully explored.Methods and Results:This study evaluated both local vascular healing using coronary angioscopy and systemic factors determined by platelet reactivity at long-term follow-up after 2nd- and 3rd-generation DES implantation in patients with acute coronary syndrome. Coronary angioscopy was performed to assess neointimal coverage (NIC), yellow color (YC) grade and presence of thrombus. The obtained findings were compared with 2nd- and 3rd-DES. Platelet aggregation was assessed by light transmittance aggregometry. 100 consecutive patients were prospectively enrolled: 2nd- (n=50) and 3rd-DES (n=50). 3rd-DES patients had significantly higher NIC grade and lower YC grade compared with 2nd-DES. The presence of thrombus was tended to be lower with 3rd-DES than with 2nd-DES (8% vs. 18%, P=0.11). Patients with thrombus had significantly higher maximum platelet aggregation and higher prevalence of high on-treatment platelet reactivity (HPR) than those without thrombus. Multivariable analysis showed stent strut exposure and HPR as independent predictors of thrombus. CONCLUSIONS: Newer generation DES contribute to better vascular healing depending on the degree of neointimal coverage. In addition to local factors at the stented lesion, systemic factors such as degree of platelet reactivity might also contribute to VLSF.

Long-term effects of non-retrieved inferior vena cava filters on recurrences of venous thromboembolism in cancer and non-cancer patients: From the COMMAND VTE registry.

BACKGROUND: There is a paucity of data comparing the long-term outcomes after inferior vena cava (IVC) filters placement for patients with acute venous thromboembolism (VTE) between those with and without active cancer. METHODS: In the COMMAND VTE Registry, we evaluated the effects of IVC filter use on the long-term clinical outcomes stratified by the presence and absence of active cancer. RESULTS: Among 2,626 patients with acute symptomatic VTE, there were 604 patients with active cancer, and 2022 patients without active cancer. IVC filters were placed and not retrieved in 455 patients (17%) in the entire cohort, in 150 patients (24.8%) in the active cancer stratum, and in 305 patients (15.1%) in the non-cancer stratum. In the entire cohort, non-retrieved IVC filter placement was not associated with a lower adjusted risk for PE recurrence (HR 0.59, 95% CI 0.30-1.15, P = 0.122), but with an increased adjusted risk for DVT recurrence (HR 2.27, 95% CI 1.43-3.60, P<0.001). In the non-cancer stratum, the non-retrieved IVC filter placement was associated with a decreased risk for PE (HR 0.29, 95% CI 0.09-0.93, P = 0.037), but not with an increased risk for DVT (HR 1.73, 95% CI 0.89-3.38, P = 0.108), while in the active cancer stratum, it was associated with an increased risk for DVT (HR 2.47, 95% CI 1.24-4.91, P = 0.010), but not with a decreased risk for PE (HR 0.82, 95% CI 0.34--1.96, P = 0.650). CONCLUSIONS: There were some differences in the risk-benefit balance between VTE patients with and without active cancer.

Determinants and prognostic implications of instantaneous wave-free ratio in patients with mild to intermediate coronary stenosis: Comparison with those of fractional flow reserve.

The instantaneous wave-free ratio (iFR) is used for assessing the hemodynamic severity of a lesion, as an alternative to the fractional flow reserve (FFR). We evaluated the relationship between iFR and FFR in detail and the clinical significance of iFR in patients with mild to intermediate coronary artery stenosis. We recruited consecutive 323 patients (421 lesions) with lesions exhibiting 30% to 80% diameter stenosis on angiography in whom FFR and iFR were measured. In the total lesions, mean diameter stenosis was 48.6% ± 9.0%, and physiological significance, defined by FFR of 0.80 or less or by iFR of 0.92 or less, was observed in 32.5% or 33.5%, respectively. Mismatch between iFR and FFR was observed in 18.1% of the lesions. Clinical factors did not predict FFR value; however, gender, diabetes mellitus, aortic stenosis, anemia, high-sensitivity CRP value, and renal function predicted iFR value. In multivariate logistic analysis after adjustment for FFR value, gender (p < 0.001), diabetes mellitus (p = 0.005), aortic stenosis (p = 0.016), high-sensitivity CRP (p < 0.001), and renal function (p = 0.003) were all independent predictors of iFR value. In Kaplan-Meier analysis, the baseline iFR predicted the subsequent major cardiovascular events (MACE) (hazard ratio, 2.40; 95% CI, 1.16-4.93; p = 0.018) and the results of the iFR-guided strategy for predicting rates of MACE and myocardial infarction/revascularization were superior to those of the FFR-guided strategy. In conclusion, significant clinical factors predicted iFR value, which affected the prognostic capacity. The iFR-guided strategy may be superior in patients with mild to intermediate stenosis.

Clinical and angiographic factors predicting fractional flow reserve and explaining the visual-functional mismatch in patients with intermediate coronary artery stenosis.

BACKGROUND: Visual-functional mismatch between coronary angiography and fractional flow reserve (FFR) has been reported, and the underlying reason remains poorly understood. Therefore, the relationship between angiographic measurements and FFR was evaluated, and predictors for FFR in intermediate coronary artery stenosis were determined. METHODS: Consecutive 314 patients (405 lesions) with a lesion of 30-80% angiographic diameter stenosis who underwent invasive FFR were recruited. The myocardial area supplied by the coronary artery distal to the stenosis was evaluated using a modified version of the Bypass Angioplasty Revascularization Investigation (BARI) score. Participants underwent follow-up, and major cardiovascular events (MACE), including all-cause death, myocardial infarction (MI), and unplanned revascularization were recorded. RESULTS: Although % diameter stenosis was correlated with FFR (R = 0.279, P < 0.001), diameter stenosis-FFR mismatch was observed in 37.8% of the lesions. Although FFR values were not associated with clinical factors, such as age, sex, and comorbidities, it was correlated with minimal lumen diameter (MLD), diffuse lesion, presence of proximal lesion, and BARI score. In addition, the lesions in left anterior descending (LAD) coronary artery showed low FFR values compared with those in the left circumflex coronary artery or right coronary artery. In multivariate logistic analysis, MLD (ß coefficient = 0.330), diffuse lesion (ß coefficient = -0.266), proximal lesion (ß coefficient = -0.144), BARI score (ß coefficient = -0.219), and LAD lesion (ß coefficient = -0.293) were all independent predictors for FFR value. The estimated FFR value based on these factors showed smaller mismatch and higher sensitivity. No difference was observed in the event rates for MACE and MI or revascularization between the FFR-guided and estimated FFR-guided strategies. CONCLUSIONS: MLD, diffuse lesion, proximal lesion, BARI score, and lesion vessel were independent predictors for FFR in intermediate coronary stenosis. Not only the extent of local lesion stenosis but also the amount of myocardial supply and the lesion location may determine the physiological significance and explain the visual-functional mismatch. The estimation of FFR by these factors may be useful in clinical practice.

Modulation of Sympathetic Activity and Innervation With Chronic Ivabradine and ß-Blocker Therapies: Analysis of Hypertensive Rats With Heart Failure.

BACKGROUND: Whether the reduction of heart rate with ivabradine (IVA) could affect sympathetic activation and cardiac innervation in heart failure (HF) remains unknown. PURPOSE: The present study assessed the chronic effects of IVA and ß-blocker on the systemic and local sympathetic nervous systems of hypertensive animals with HF. METHODS AND RESULTS: The Dahl salt-sensitive rats received chronic IVA, bisoprolol (BIS), or placebo (CTL) therapy. The survival of the animal models with IVA and BIS significantly improved (median; 19.7 in IVA and 19.7 in BIS vs 17.0 weeks in CTL, P < .001). A similar decrease in 24-hour heart rate (mean; 305 in IVA and 329 in BIS vs 388 beats/min in CTL, P < .001) without effect on blood pressure, and an improvement in the left ventricular dysfunction (mean fractional shortening; 56.7% in IVA and 47.8% in BIS vs 39.0% in CTL, P < .001) were observed in the animals with IVA and BIS. However, a negative inotropic effect was only observed in the animals with BIS. Excessive urinary noradrenaline excretion in animals with CTL was only suppressed with the use of IVA (mean; 1.35 µg/d in IVA and 1.95 µg/d in BIS vs 2.27 µg/d in CTL, P = .002). In contrast, atrial noradrenaline and acetylcholine depletion in the animals with CTL improved and the tyrosine hydroxylase expression in the both atria were restored with the use of both IVA and BIS. CONCLUSIONS: IVA therapy improved the survival of hypertensive animals with HF. Furthermore, it was associated with the amelioration of systemic sympathetic activation and cardiac sympathetic and parasympathetic nerve innervations. Chronic ß-blocker therapy with negative inotropic effects had beneficial effects only on cardiac innervations.

Renal denervation mitigates cardiac remodeling and renal damage in Dahl rats: a comparison with ß-receptor blockade.

Chronic activation of the sympathetic nervous system (SNS) contributes to cardiac remodeling and the transition to heart failure (HF). Renal sympathetic denervation (RDN) may ameliorate this damage by improving renal function and sympathetic cardioregulation in hypertensive HF patients with renal injury. The efficacy may be comparable to that of chronic ß-blocker treatment. Dahl salt-sensitive hypertensive rats were subjected to RDN in the hypertrophic stage. Another group of Dahl rats were subjected to sham operations and treated chronically with vehicle (CONT) or ß-blocker bisoprolol (BISO). Neither RDN nor BISO altered the blood pressure; however, BISO significantly reduced the heart rate (HR). Both RDN and BISO significantly prolonged survival (22.2 and 22.4 weeks, respectively) compared with CONT (18.3 weeks). Echocardiography revealed reduced left ventricular (LV) hypertrophy and improved LV function, and histological analysis demonstrated the amelioration of LV myocyte hypertrophy and fibrosis in the RDN and BISO rats at the HF stage. Tyrosine hydroxylase and ß1-adrenergic receptor (ADR) expression levels in the LV myocardium significantly increased only in the RDN rats, whereas the α1b-, α1d- and α2c-ADR expression levels increased only in the BISO rats. In both groups, renal damage and dysfunction were also reduced, and this reduction was accompanied by the suppression of endothelin-1, renin and angiotensin-converting enzyme mRNAs. RDN ameliorated the progression of both myocardial and renal damage in the hypertensive rats independent of blood pressure changes. The overall effects were similar to those of ß-receptor blockade with favorable effects on HR and α-ADR expression. These findings may be associated with the restoration of the myocardial SNS and renal protection.

Effects of Long-term Blockade of Vasopressin Receptor Types 1a and 2 on Cardiac and Renal Damage in a Rat Model of Hypertensive Heart Failure.

The effects of chronic blockade of vasopressin type 1a receptors (V1aR) and the additive effects of a type 2 receptor (V2R) antagonist on the treatment of hypertension-induced heart failure and renal injury remain to be unknown. In this study, Dahl salt-sensitive hypertensive rats were chronically treated with a vehicle (CONT), a V1aR antagonist (OPC21268; OPC), a V2R antagonist (tolvaptan; TOLV), or a combination of OPC21268 and tolvaptan (OPC/TOLV) from the pre-hypertrophic stage (6 weeks). No treatment altered blood pressure during the study. Significant improvements were seen in median survival for the OPC and TOLV, and the OPC/TOLV showed a further improvement in Kaplan-Meier analysis. Echocardiography showed suppressed left ventricular hypertrophy in the OPC and OPC/TOLV at 11 weeks with improved function in all treatment groups by 17 weeks. In all treatment groups, improvements were seen in the following: myocardial histological changes, creatinine clearance, urinary albumin excretion, and renal histopathologic damage. Also, key mRNA levels were suppressed (eg, endothelin-1 and collagen). In conclusion, chronic V1aR blockade ameliorated disease progression in this rat model, with additive benefits from the combination of V1aR and V2R antagonists. It was associated with protection of both myocardial and renal damage, independent of blood pressure.