Application of first-generation high- and low-dose drug-coated balloons to the femoropopliteal artery disease: a sub-analysis of the POPCORN registry.

BACKGROUND: Drug-coated balloons (DCBs) have significantly changed endovascular therapy (EVT) for femoropopliteal artery (FPA) disease, in terms of the expansion of indications for EVT for symptomatic lower extremity arterial disease (LEAD). However, whether there is a difference in the performance among individual DCBs has not yet been fully discussed. The present sub-analysis of real-world data from a prospective trial of first-generation DCBs compared the clinical outcomes between high- and low-dose DCBs using propensity score matching methods. The primary endpoint was the restenosis-free and revascularization-free rates at 1 year. RESULTS: We compared 592 pairs matched for patient and lesion characteristics using propensity score matching among a total of 2,507 cases with first-generation DCBs (592 and 1,808 cases in the Lutonix low-dose and In.PACT Admiral high-dose DCB groups, respectively). There were no differences in patient/lesion characteristics, procedural success rates, or complications between the two groups. First-generation low-dose DCB had significantly lower patency (73.3% [95% confidence interval, 69.6%-77.3%] in the low-dose DCB group versus 86.2% [84.1%-88.3%] in the high-dose DCB group; P < 0.001) and revascularization-free (84.9% [81.9%-88.1%] versus 92.5% [90.8%-94.1%]; P < 0.001) rates. Chronic kidney disease on dialysis, cilostazol use, anticoagulant use, and severe calcification had a significant interaction effect in the association (all P < 0.05). CONCLUSIONS: EVT to FPA with first-generation DCBs had inferior low-dose patency outcomes as compared with high-dose outcomes in the present cohort. LEVEL OF EVIDENCE: Sub analysis of a prospective multicenter study.

Optical frequency domain imaging of the scoring balloon elements shift.

Here, we report a case of endovascular treatment in which optical frequency domain imaging evaluated the scoring balloon elements shift when three inflations without shaft rotation performed with a scoring balloon.

Association between home-based exercise using a pedometer and clinical prognosis after endovascular treatment in patients with peripheral artery disease.

BACKGROUND: Exercise therapy following endovascular treatment (EVT) is important for patients with peripheral artery disease (PAD); however, continuous exercise therapy is difficult to be performed in clinical practice. This study aimed to investigate the association between the implementation of home-based exercise using pedometers after EVT and 1-year clinical outcomes. METHODS: This multicenter observational prospective cohort registry included patients with PAD complaining of intermittent claudication who underwent EVT for aortoiliac and/or femoropopliteal artery lesions between January 2016 and March 2019. Patients were instructed to perform home-based exercises using a specific pedometer after EVT. The study population was divided into good and poor recording groups according to the frequency of the pedometer measurements. The good recording group was defined as those who completed ≥50 % of the prescribed daily pedometer recording during the follow-up period. The poor recording group was defined as those with an inability to use a pedometer and/or who completed <50 % of the prescribed daily pedometer recordings. The primary outcome was 1-year major adverse events (MAE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, target vessel revascularization, and major amputation of the target limb. RESULTS: The mean age was 74.4 years; 78 % were male. A total of 623 lesions were analyzed (58.7 % aortoiliac, 41.3 % femoropopliteal). At 1 year, a lower cumulative incidence of MAE was observed in the good recording group compared to that in the poor recording group [10/233 (4.3 %) vs. 35/267 (13.7 %) patients, respectively; p < 0.001]. Multivariate Cox regression analysis showed that patients in the good recording group had a lower hazard ratio for 1-year MAE (0.33; 95 % confidence interval, 0.16-0.68; p = 0.004) than that in the poor recording group. CONCLUSIONS: Good self-recording of pedometer measurements was associated with favorable prognosis in patients with PAD following EVT.

A novel initial wiring technique for chronic total occlusion of the superficial femoral artery using the structural features of a polymer jacket guidewire.

BACKGROUND: To evaluate the efficacy of the GLadIus MG drilLINg technique (GLIMGLIN), a novel initial wiring technique using the Gladius MG™ structural features, for crossing the superficial femoral artery (SFA) with chronic total occlusion (CTO). METHODS: This retrospective, single-center study enrolled 27 symptomatic patients (mean age 77.4 ± 8.5 years; 20 men) with de novo SFA CTO (mean CTO length 16.1 ± 8.9 cm) who underwent GLIMGLIN as the initial wiring between January 2020 and December 2021. The success of GLIMGLIN was defined when the wire crossing was completed using a Gladius MG™ and a microcatheter without any additional devices and techniques. RESULTS: The success rate of GLIMGLIN was 48.1%. Intravascular ultrasound findings showed complete true lumen passage in the GLIMGLIN success group. Compared to the failure group, the proximal (6.3 ± 0.8 vs. 5.5 ± 0.9 mm, p = 0.02) and distal (5.9 ± 0.5 vs. 5.4 ± 0.6 mm, p = 0.02) reference vessel diameters were significantly larger, and the rate of calcium angle > 180° was significantly lower (30.8 vs. 71.4%, p = 0.04) in the success group. No significant difference was shown in the CTO length between two groups. Total wiring time, total procedure time, and fluoroscopic time were significantly shorter in the success group. CONCLUSIONS: GLIMGLIN may enable operators to perform CTO wiring easily and efficiently in selected cases.

Three-Year Clinical Outcomes of the Innova™ Self-Expanding Nitinol Stent for the Treatment of Femoropopliteal Lesions.

PURPOSE: To report the 3-year results of Innova™ stent implantation for the treatment of femoropopliteal (FP) lesions in a real-world setting. METHODS: This single-arm, retrospective, multicenter clinical study analyzed 481 lesions from 453 consecutive patients with symptomatic peripheral artery diseases (Rutherford category 1-6) who underwent endovascular therapy with implantation of Innova™ self-expanding nitinol stent for FP lesions. The primary outcome measure was the 3-year restenosis rate based on doppler-ultrasound or angiographic criteria. The secondary outcome measures included the rates of 3-year major amputation and major adverse limb events. RESULTS: Restenosis following Innova™ implantation was found in 61% of the cases at 3 years. At the end of 3 years, the rates of major amputations and major adverse limb events were 3 and 31%, respectively. In cases free from restenosis at 1 year, no predictive factors for restenosis at 3 years could be determined. CONCLUSION: The present study demonstrated mid-term clinical outcomes after Innova™ stent implantation for the treatment of FP lesions in a real-world population. The Innova™ stent demonstrated acceptable clinical outcomes in a real-world setting.

Usefulness of the "Non-Slip Element" Percutaneous Transluminal Angioplasty Balloon in the Treatment of Femoropopliteal Arterial Lesions.

Purpose: To evaluate a new scoring balloon, the non-slip element (NSE) percutaneous transluminal angioplasty (PTA) balloon, in the treatment of femoropopliteal lesions by comparing angiographic dissection patterns to those of a conventional balloon. Methods: This retrospective, single-center study included 71 symptomatic patients (mean age 77.4±8.8 years; 33 men) with de novo femoropopliteal lesions <20 cm long treated with balloon angioplasty between January 2017 and May 2018. Thirty-four patients were treated with 3 inflations of an NSE balloon and 37 patients were treated with a conventional balloon. Results: Severe dissections were fewer (8.8% vs 29.7%, p=0.027) and the total dissection length was shorter (11.5±12.8 vs 35.7±24.1 mm, p=0.027) in the NSE group. The bailout stenting rate was also lower in the NSE group (17.6% vs 40.5%, p=0.035). There were no significant differences between the groups regarding lesion length (70.3±50.4 vs 77.8±56.6 mm, p=0.28), inflation time (294±162 vs 353±179 seconds, p=0.08), or inflation pressure (10.6±5.0 vs 11.3±5.3 atm, p=0.31). Conclusion: Three NSE balloon inflations may reduce severe dissections induced by balloon angioplasty in femoropopliteal lesions.

One-Year Clinical Outcomes following Implantation of InnovaTM Self-Expanding Nitinol Stents in Patients with Peripheral Artery Diseases Presenting Femoropopliteal Artery Lesions.

AIM: Although the InnovaTM self-expanding nitinol stent (Boston Scientific, Marlborough, MA) exhibits acceptable performance in long-term safety and efficacy when used for the treatment of femoropopliteal (FP) lesions, clinical outcomes following its implantation have not been systematically studied in real-world settings. We investigated the one-year clinical outcomes after implantation of InnovaTM self-expanding nitinol stents for the treatment of FP lesions in real-world settings. METHODS: In this multicenter study, 481 lesions in 453 consecutive patients with peripheral artery disease (PAD) (74±9 years; male, 70%; diabetes mellitus, 61%; dialysis, 27%; critical limb ischemia, 37%) who underwent endovascular therapy with the implantation of InnovaTM self-expanding nitinol stents for FP lesions were analyzed from February 2016 to April 2017. The primary endpoint was one-year restenosis, whereas the secondary endpoints included one-year major adverse limb events and predictors for one-year restenosis. RESULTS: The mean lesion length was 18±10 cm. One-year restenosis and major adverse limb event rates were 36% and 18%, respectively. Multivariate analysis revealed that the presence of diabetes mellitus (odds ratio [OR]: 1.83; 95% confidence interval [CI]: 1.07-3.13), distal reference vessel diameter (OR: 1.86; 95% CI: 1.09-3.16), spot stenting (OR: 2.27; 95% CI: 1.27-4.06), and lack of one-year cilostazol treatment (OR: 0.58; 95% CI: 0.33-1.00) were independent risk factors for one-year restenosis. CONCLUSION: The current study demonstrated one-year clinical outcomes after InnovaTM self-expanding nitinol stent placement for the treatment of FP lesions, including challenging cases in real-world settings.

Protrusion of a loop-shaped 0.035-inch wire without the fracture of the self-expanding nitinol stent: A case report and experimental study.

We report a case of a loop-shaped 0.035-inch wire protruding through self-expanding nitinol stent struts. Our in vitro experiment suggests that, even if there are no stent fractures, the loop-shaped 0.035-inch wire has a potential to protrude through the struts of the self-expanding nitinol stents.

Ouabain-digoxin antagonism in rat arteries and neurones.

'Classic' cardiotonic steroids (CTSs) such as digoxin and ouabain selectively inhibit Na+, K+ -ATPase (the Na+ pump) and, via Na+ / Ca2+ exchange (NCX), exert cardiotonic and vasotonic effects. CTS action is more complex than previously thought: prolonged subcutaneous administration of ouabain, but not digoxin, induces hypertension, and digoxin antagonizes ouabain's hypertensinogenic effect. We studied the acute interactions between CTSs in two indirect assays of Na+ pump function: myogenic tone (MT) in isolated, pressurized rat mesenteric small arteries, and Ca2+ signalling in primary cultured rat hippocampal neurones. The 'classic' CTSs (0.3-10 nm) behaved as 'agonists': all increased MT70 (MT at 70 mmHg) and augmented glutamate-evoked Ca2+ (Fura-2) signals. We then tested one CTS in the presence of another. Most CTSs could be divided into ouabain-like (ouabagenin, dihydroouabain (DHO), strophanthidin) or digoxin-like CTS (digoxigenin, digitoxin, bufalin). Within each group, the CTSs were synergistic, but ouabain-like and digoxin-like CTSs antagonized one another in both assays: For example, the ouabain-evoked (3 nm) increases in MT70 and neuronal Ca2+ signals were both greatly attenuated by the addition of 10 nm digoxin or 10 nm bufalin, and vice versa. Rostafuroxin (PST2238), a digoxigenin derivative that displaces 3H-ouabain from Na+, K+ -ATPase, and attenuates some forms of hypertension, antagonized the effects of ouabain, but not digoxin. SEA0400, a Na+ / Ca2+ exchanger (NCX) blocker, antagonized the effects of both ouabain and digoxin. CTSs bind to the α subunit of pump αß protomers. Analysis of potential models suggests that, in vivo, Na+ pumps function as tetraprotomers ((αß)4) in which the binding of a single CTS to one protomer blocks all pumping activity. The paradoxical ability of digoxin-like CTSs to reactivate the ouabain-inhibited complex can be explained by de-oligomerization of the tetrameric state. The interactions between these common CTSs may be of considerable therapeutic relevance.

Cross talk between plasma membrane Na(+)/Ca (2+) exchanger-1 and TRPC/Orai-containing channels: key players in arterial hypertension.

Arterial smooth muscle (ASM) Na(+)/Ca(2+) exchanger type 1 (NCX1) and TRPC/Orai-containing receptor/store-operated cation channels (ROC/SOC) are clustered with α2 Na(+) pumps in plasma membrane microdomains adjacent to the underlying junctional sarcoplasmic reticulum. This arrangement enables these transport proteins to function as integrated units to help regulate local Na(+) metabolism, Ca(2+) signaling, and arterial tone. They thus influence vascular resistance and blood pressure (BP). For instance, upregulation of NCX1 and TRPC6 has been implicated in the pathogenesis of high BP in several models of essential hypertension. The models include ouabain-induced hypertensive rats, Milan hypertensive rats, and Dahl salt-sensitive hypertensive rats, all of which exhibit elevated plasma ouabain levels. We suggest that these molecular mechanisms are key contributors to the increased vascular resistance ("whole body autoregulation") that elevates BP in essential hypertension. Enhanced expression and function of ASM NCX1 and TRPC/Orai1-containing channels in hypertension implies that these proteins are potential targets for pharmacological intervention.

Increased arterial smooth muscle Ca2+ signaling, vasoconstriction, and myogenic reactivity in Milan hypertensive rats.

The Milan hypertensive strain (MHS) rats are a genetic model of hypertension with adducin gene polymorphisms linked to enhanced renal tubular Na(+) reabsorption. Recently we demonstrated that Ca(2+) signaling is augmented in freshly isolated mesenteric artery myocytes from MHS rats. This is associated with greatly enhanced expression of Na(+)/Ca(2+) exchanger-1 (NCX1), C-type transient receptor potential (TRPC6) protein, and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) compared with arteries from Milan normotensive strain (MNS) rats. Here, we test the hypothesis that the enhanced Ca(2+) signaling in MHS arterial smooth muscle is directly reflected in augmented vasoconstriction [myogenic and phenylephrine (PE)-evoked responses] in isolated mesenteric small arteries. Systolic blood pressure was higher in MHS (145 ± 1 mmHg) than in MNS (112 ± 1 mmHg; P < 0.001; n = 16 each) rats. Pressurized mesenteric resistance arteries from MHS rats had significantly augmented myogenic tone and reactivity and enhanced constriction to low-dose (1-100 nM) PE. Isolated MHS arterial myocytes exhibited approximately twofold increased peak Ca(2+) signals in response to 5 µM PE or ATP in the absence and presence of extracellular Ca(2+). These augmented responses are consistent with increased vasoconstrictor-evoked sarcoplasmic reticulum (SR) Ca(2+) release and increased Ca(2+) entry, respectively. The increased SR Ca(2+) release correlates with a doubling of inositol 1,4,5-trisphosphate receptor type 1 and tripling of SERCA2 expression. Pressurized MHS arteries also exhibited a ∼70% increase in 100 nM ouabain-induced vasoconstriction compared with MNS arteries. These functional alterations reveal that, in a genetic model of hypertension linked to renal dysfunction, multiple mechanisms within the arterial myocytes contribute to enhanced Ca(2+) signaling and myogenic and vasoconstrictor-induced arterial constriction. MHS rats have elevated plasma levels of endogenous ouabain, which may initiate the protein upregulation and enhanced Ca(2+) signaling. These molecular and functional changes provide a mechanism for the increased peripheral vascular resistance (whole body autoregulation) that underlies the sustained hypertension.

Case of atrial tachycardia originating from giant coronary sinus connected to persistent left superior vena cava: successful catheter ablation guided by noncontact mapping.

Radiofrequency (RF) catheter ablation is widely applied to tachyarrhythmia associated not only with structurally normal hearts but also with relatively mild cardiac anomalies. We present a case of 35 year-old female complaining of exercise-induced frequent palpitations caused by atrial tachycardia (AT) originating from giant coronary sinus (CS) connected to persistent left superior vena cava. AT was sensitive to intravenous ATP administration. Electrophysiological study partly using noncontact balloon of EnSite system clarified that two foci of AT were located at the orifice and the distal inner lumen of giant CS. After repetitive applications of RF energy to these origins, AT was not induced by drip infusion of isoproterenol. AT was not evoked by exercise without antiarrhythmic drugs 15 months after the RF ablation. This case indicates that RF ablation guided by noncontact mapping technique should be considered as a therapeutic regimen for AT associated with mild cardiac malformations.

Low-dose ouabain constricts small arteries from ouabain-hypertensive rats: implications for sustained elevation of vascular resistance.

Prolonged ouabain administration to normal rats causes sustained blood pressure (BP) elevation. This ouabain-induced hypertension (OH) has been attributed, in part, to the narrowing of third-order resistance arteries (approximately 320 microm internal diameter) as a result of collagen deposition in the artery media. Here we describe the structural and functional properties of fourth-order mesenteric small arteries from control and OH rats, including the effect of low-dose ouabain on myogenic tone in these arteries. Systolic BP in OH rats was 138 +/- 3 versus 124 +/- 4 mmHg in controls (P < 0.01). Pressurized (70 mmHg) control and OH arteries, with only a single layer of myocytes, both had approximately 165-microm internal diameters and approximately 20-microm wall thicknesses. Even after fixation, despite vasoconstriction, the diameters and wall thicknesses did not differ between control and OH fourth-order arteries, whereas in third-order arteries, both parameters were significantly smaller in OH than in controls. Myogenic reactivity was significantly augmented in OH fourth-order arteries. Nevertheless, phenylephrine- (1 microM) and high K(+)-induced vasoconstrictions and acetylcholine-induced vasodilation were comparable in control and OH arteries. Vasoconstrictions induced by 5 microM phenylephrine and by 10 mM caffeine in Ca(2+)-free media indicated that releasable sarcoplasmic reticulum Ca(2+) stores were normal in OH arteries. Importantly, 100 nM ouabain constricted both control and OH arteries by approximately 26 microm, indicating that this response was not downregulated in OH rats. This maximal ouabain-induced constriction corresponds to a approximately 90% increase in resistance to flow in these small arteries; thus ouabain at EC(50) of approximately 0.66 nM should raise resistance by approximately 35%. We conclude that dynamic constriction in response to circulating nanomolar ouabain in small arteries likely makes a major contribution to the increased vascular tone and BP in OH rats.

Emphysematous cystitis with venous bubbles.

An 86-year-old nondiabetic woman with an episode of transient ischemic attack two days earlier was referred to our hospital. She had a history of neurogenic bladder and chronic atrial fibrillation and had been anuric for two days. Bubbles were detected by echocardiography in the right atrium, right ventricle, and inferior vena cava. Computed tomography revealed gas accumulation in the wall and lumen of the bladder. She recovered after urinary drainage and antibiotic therapy, and bubbles were no longer detected. It was suspected that bacterial injury of the bladder wall and high intravesical pressure led gas to enter the venous system.

Systemic vasculitis associated with alphal-antitrypsin deficiency.

We describe a rare case of systemic vasculitis associated with alpha1-antitrypsin (alpha1-AT) deficiency. Mutational analysis of the alpha1-AT gene in this patient revealed a homozygous alpha1-AT Mnichinan variant. Alpha1-AT possesses broad-spectrum inhibitory activity against many serine proteases, including human neutrophil elastase, to help maintaining the crucial balance between proteases and protease inhibitors. The increase in free protease activity in the context of alpha1-AT deficiency may induce exacerbation of the vasculitis. This serious genetic defect severely affects the balance between a protease and a protease inhibitor at the pathological site.