The effect of an initial catheter ablation with an adjunctive ethanol infusion into the vein of Marshall on persistent atrial fibrillation.

INTRODUCTION: Some previous studies have reported that a first-step ethanol infusion into the vein of Marshall (EIVOM) with touch-up radiofrequency (RF) ablation can facilitate mitral isthmus (MI) block and improves the ablation outcomes in persistent atrial fibrillation (PeAF) patients. However, the effect of an initial RF ablation with an adjunctive EIVOM has not been fully investigated. METHODS: This study enrolled 233 PeAF patients undergoing pulmonary vein isolation and linear ablation including an MI, roof line, and cavotricuspid isthmus ablation. An EIVOM was performed when endocardial ablation with or without coronary sinus ablation failed to create MI block. RESULTS: Bidirectional MI block was achieved in 224 patients (96.1%). Among them, MI block was obtained by only RF ablation in 174/224 patients (77.7%) (RF group) and an adjunctive EIVOM was needed in 50/224 (22.3%) (EIVOM group). During the follow-up, 113 (64.9%) RF group patients were free from AF/atrial tachycardia compared to 41 (82.0%) EIVOM group patients (log-rank p = .045). In a multivariate Cox regression analysis, an adjunctive EIVOM was associated with a lower recurrence rate (hazard ratio = 0.39, 95% confidence interval = 0.17-0.78, p = .006). CONCLUSION: An initial RF ablation with an adjunctive EIVOM strategy improved MI ablation's acute success rate and was associated with better clinical outcomes.

Post-contrast Acute Kidney Injury After Emergent and Elective Percutaneous Coronary Intervention (from the CREDO-Kyoto PCI/CABG Registry Cohort 3).

Post-contrast acute kidney injury (PC-AKI) is a common complication after percutaneous coronary intervention (PCI). However, it is unclear whether or not the effects of PC-AKI on long-term clinical outcomes were different between emergent and elective procedures. Among patients enrolled in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort 3, we identified 10,822 patients treated using PCI (emergent PCI stratum: n = 5,022 [46%] and elective PCI stratum: n = 5,860 [54%]). PC-AKI was defined as ≥0.3 mg/100 ml absolute or 1.5-fold relative increase of serum creatinine within 72 hours after PCI. The incidence of PC-AKI was significantly higher after emergent PCI than after elective PCI (10.5% vs 3.7%, p <0.001). In the multivariable logistic regression model, emergent PCI was the strongest independent risk factor for PC-AKI in the entire study population. The excess adjusted risk of patients with PC-AKI relative to those without remained significant for all-cause death in both the emergent and elective PCI strata (hazard ratio 1.87, 95% confidence interval 1.59 to 2.21, p <0.001 and hazard ratio 1.31, 95% confidence interval 1.03 to 1.68, p = 0.03, respectively). There was a significant interaction between the PCI setting (emergent and elective) and the effect of PC-AKI on all-cause death, with a greater magnitude of effect in the emergent PCI stratum than in the elective PCI stratum (p for interaction = 0.01). In conclusion, the incidence of PC-AKI was 2.8 times higher after emergent PCI than after elective PCI. The excess mortality risk of PC-AKI relative to no PC-AKI was greater after emergent PCI than after elective PCI.

Iatrogenic Atrial Septal Defect Requiring Transcatheter Closure Following Transcatheter Mitral Valve Repair.

BACKGROUND: Transcatheter mitral valve repair with the MitraClip system has been established in selected high-risk patients. The MitraClip procedure results in a relatively large iatrogenic atrial septal defect (iASD). This study aimed to investigate the prevalence and clinical course of iASD requiring transcatheter closure following the MitraClip procedure.Methods and Results: This study was conducted at all 59 institutions that perform transcatheter mitral valve repair with the MitraClip system in Japan. The data of patients on whom transcatheter iASD closure was performed were collected. Of the 2,722 patients who underwent the MitraClip procedure, 30 (1%) required transcatheter iASD closure. The maximum iASD size was 9±4 mm (range, 3-18 mm). The common clinical course of transcatheter iASD closure was hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt. Of the 30 patients, 22 (73%) required transcatheter closure within 24 h following the MitraClip procedure, including 12 with hypoxemia and 5 with right-sided heart failure complicated with cardiogenic shock. Of the 5 patients, 2 required mechanical circulatory support devices. Twenty-one patients immediately underwent transcatheter iASD closure, and hemodynamic deteriorations were resolved; however, 1 patient died without having undergone transcatheter closure. CONCLUSIONS: Transcatheter iASD closure was required in 1% of patients who underwent the MitraClip procedure. Many of these patients immediately underwent transcatheter iASD closure because of hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt.

Efficacy of treat-and-repair strategy for atrial septal defect with pulmonary arterial hypertension.

OBJECTIVE: Therapeutic strategies for atrial septal defect (ASD) with severe pulmonary arterial hypertension (PAH) are controversial. This study aimed to evaluate the efficacy of PAH-specific medications and subsequent transcatheter closure (ie, treat-and-repair strategy) on clinical outcomes. METHODS: We enrolled 42 patients who were referred to 13 institutions for consideration of ASD closure with concomitant PAH and underwent the treat-and-repair strategy. The endpoint was cardiovascular death or hospitalisation due to heart failure or exacerbated PAH. RESULTS: At baseline prior to PAH-specific medications, pulmonary to systemic blood flow ratio (Qp:Qs), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (PAP) were 1.9±0.8, 6.9±3.2 Wood units and 45±15 mm Hg. Qp:Qs was increased to 2.4±1.2, and PVR and mean PAP were decreased to 4.0±1.5 Wood units and 35±9 mm Hg at the time of transcatheter ASD closure after PAH-specific medications. Transcatheter ASD closure was performed without any complications. During a median follow-up period of 33 months (1-126 months) after transcatheter ASD closure, one older patient died and one patient was hospitalised due to heart failure, but the other patients survived with an improvement in WHO functional class. PAP was further decreased after transcatheter ASD closure. CONCLUSIONS: The treat-and-repair strategy results in low complication and mortality rates with a reduction in PAP in selected patients with ASD complicated with PAH who have a favourable response of medical therapy.

Comparative pathological findings between coronary bare-metal stent implantation and balloon angioplasty over 16 years.

A 68-year old man underwent bare metal stent (BMS; Palmaz-Shatz stent) implantation in the distal right coronary artery (RCA; #4PL) and balloon angioplasity (BA) in the proximal left circumflex coronary artery (LCX; #11) for stable angina. After 5 years after initial stent implantation, de novo lesion located in mid RCA was treated by BMS (NIR stent) implantation additionally. After 16 years from first BMS implantation, the patient died from heart failure due to cardiac amyloidosis, and pathologic examination was performed for the specimen of stented RCA segment and LCX BA segment. An autopsy demonstrated that the lesions of stented site at RCA and BA site LCX were histopathologically different. In the stented segment, severe luminal stenosis is observed due to marked proliferation of the neointima in all stented sites. In addition, neovascularization and spotty calcification with mild lymphocyte infiltration were observed especially around the struts. In contrast, at the BA site of the proximal LCX lesion, in the neointima, the smooth muscle cells were rather atrophic and abundant collagen fibers were evident in the intercellular spaces, which showed very stable findings. Compared with these BMS implanted portions, the site of BA was associated with a trend for smaller late lumen loss. These findings suggested that in the stented site, chronic inflammatory reaction to the stent struts could evoke continuous proliferation of neointima resulting in severe late lumen loss. .

Utility of copeptin for predicting long-term clinical outcomes in patients with heart failure.

BACKGROUND: Copeptin, a surrogate marker of pro-arginine vasopressin, is expected to be a marker in cardiovascular diseases. Its utility for predicting long-term clinical outcomes in heart failure (HF), however, has not been adequately evaluated in daily clinical practice in Japan. METHODS: To assess the relationship of serum copeptin at admission with long-term clinical outcomes, we evaluated serum copeptin at admission in consecutive 107 patients hospitalized for HF between April 2011 and July 2012. The primary outcome measure was defined as a composite of all-cause death and re-admission for HF (all-cause death/HF). RESULTS: In this study population, median serum copeptin at admission was 15.5 (6.7-32.0)pmol/L. As compared with the low-copeptin group (<18pmol/L, N=60), the high-copeptin group (≥18pmol/L, N=47) included more male patients and those with prior myocardial infarction, prior HF, low left ventricular ejection fraction, and chronic kidney disease. During median 4.5 (1.0-5.5) years of clinical follow-up, the cumulative incidence of all-cause death/HF was significantly higher in the high-copeptin than in the low-copeptin group (63.4% versus 33.0% at 1 year, and 85.2% versus 77.2% at 5 years, log-rank p=0.03). After adjusting for confounders, high-copeptin was still an independent predictor for all-cause death/HF [hazard ratio (95% confidence interval): 1.77 (1.04-3.01), p=0.03]. CONCLUSION: Copeptin was suggested as a useful marker for predicting long-term clinical outcomes in patients with HF.

Nardilysin is a promising biomarker for the early diagnosis of acute coronary syndrome.

BACKGROUND: Biomarkers for detection of transient myocardial ischemia in patients with unstable angina (UA) or for very early diagnosis of acute myocardial infarction (AMI) are not currently available. METHODS AND RESULTS: We performed two sequential screenings of autoantibodies elevated shortly after the onset of acute coronary syndrome (ACS), and focused on metalloendopeptidase nardilysin (NRDC) among 19 identified candidate antigens. In a retrospective analysis among 93 ACS and 117 non-ACS patients, the serum level of NRDC was significantly increased in patients with ACS compared with that in patients with non-ACS (2073.5±189.8pg/ml versus 775.7±63.4pg/ml, P<0.0001). The area under the curve of NRDC for the diagnosis of ACS was 0.822 by the receiver operating characteristic curves analysis. In the time course analysis in 43 consecutive ACS patients (AMI: N=35 and UA: N=8), serum concentration of NRDC was significantly increased even in UA patients with a peak serum NRDC levels reached at admission both in AMI and UA patients. In a mouse model of AMI, we found an acute increase in serum NRDC and reduced NRDC expression in ischemic regions shortly after coronary artery ligation. NRDC expression was also reduced in infarcted regions in human autopsy samples from AMI patients. Moreover, the short treatment of primary culture of rat cardiomyocytes with H2O2 or A23187 induced NRDC secretion without cell toxicity. CONCLUSION: NRDC is a promising biomarker for the early detection of ACS, even in UA patients without elevation of necrosis markers.

Use of extracorporeal membrane oxygenation in complicated transcatheter aortic valve replacement.

OBJECTIVES: Although transcatheter aortic valve replacement (TAVR) is an excellent alternative procedure for high-risk patients with severe symptomatic aortic stenosis, it is often associated with life-threatening complications. We report on the emergency or elective use of veno-arterial extracorporeal membrane oxygenation (ECMO) to manage these complications. METHODS: Between December 2013 and February 2016, 46 patients underwent TAVR at our institution. Of these, 4 patients required emergency ECMO support and another 3 patients were electively placed on ECMO support at the start of the procedure. The mean age of the ECMO patients was 87.3 ± 3.6 years and all were female. The Society of Thoracic Surgeons-predicted risk of mortality score in these patients was 12.2 ± 6.2%. RESULTS: TAVR with ECMO was completed through the transapical approach in 6 patients, and the transfemoral approach in 1 patient. The arterial access route for ECMO was the femoral artery in 5, the external iliac artery in 1, and the subclavian artery in 1. Indications for the use of emergency ECMO were hemodynamic instability in 2, cardiogenic shock in 2, while indications for elective ECMO were severe pulmonary hypertension, impaired left ventricular function and a combination of these. There was no 30-day mortality, and the 1-year survival rate was 83.3% with no significant difference compared to patients without ECMO support. CONCLUSION: The use of ECMO in very high-risk patients undergoing TAVR may increase safety and contribute to excellent outcomes. Although ECMO support is rarely needed in TAVR, a well-prepared treatment strategy by the heart team is mandatory.

Transfemoral transcatheter aortic valve implantation in the presence of a mechanical mitral valve prosthesis using a dedicated TAVI guidewire: utility of a patient-specific three-dimensional heart model.

An 82-year-old woman with severe aortic stenosis was referred. She had previously undergone mitral valve replacement. We planned transcatheter aortic valve implantation (TAVI) with transfemoral approach. We planned to use the Safari-dedicated TAVI guidewire. No studies have reported clinical application of the dedicated TAVI guidewire in a patient with the previous mitral valve replacement. Thus, we conducted a simulation using a three-dimensional heart model to confirm the safety of the procedure. The procedure was successful without any complications. This case is the first to show that the dedicated TAVI guidewire can be safely used in patients with preexisting mitral valve.

Feasibility and diagnostic performance of fractional flow reserve measurement derived from coronary computed tomography angiography in real clinical practice.

Non-invasive fractional flow reserve measured by coronary computed tomography angiography (FFRCT) has demonstrated a high diagnostic accuracy for detecting coronary artery disease (CAD) in selected patients in prior clinical trials. However, feasibility of FFRCT in unselected population have not been fully evaluated. Among 60 consecutive patients who had suspected significant CAD by coronary computed tomography angiography (CCTA) and were planned to undergo invasive coronary angiography, 48 patients were enrolled in this study comparing FFRCT with invasive fractional flow reserve (FFR) without any exclusion criteria for the quality of CCTA image. FFRCT was measured in a blinded fashion by an independent core laboratory. FFRCT value was evaluable in 43 out of 48 (89.6 %) patients with high prevalence of severe calcification in CCTA images [calcium score (CS) >400: 40 %, and CS > 1000: 19 %). Per-vessel FFRCT value showed good correlation with invasive FFR value (Spearman's rank correlation = 0.69, P < 0.001). The area under the receiver operator characteristics curve (AUC) of FFRCT was 0.87. Per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 68.6, 92.9, 52.4, 56.5, and 91.7 %, respectively. Even in eight patients (13 vessels) with extremely severely calcified lesions (CS > 1000), per-vessel FFRCT value showed a diagnostic performance similar to that in patients with CS ≤ 1000 (Spearman's rank correlation = 0.81, P < 0.001). FFRCT could be measured in the majority of consecutive patients who had suspected significant CAD by CCTA in real clinical practice and demonstrated good diagnostic performance for detecting hemodynamically significant CAD even in patients with extremely severe calcified vessels.

Pathological analysis of a case with peri-stent contrast staining after BMS implantation.

A 68-year-old female underwent bare-metal stent (BMS) implantation in the right coronary artery (RCA) for ST-segment elevation myocardial infarction. Recurrent refractory restenosis with peri-stent contrast staining (PSS) formation was observed in the stented lesion at follow-up angiography at 7, 11, and 14 months after the index stent implantation. After 2 repeated interventions, this patient was referred to coronary artery bypass grafting due to occlusion of RCA and progression of proximal left anterior descending coronary artery lesion at 15 months after stent implantation. Pathologic examination of the surgically resected specimen of stented RCA segment revealed total occlusion with dense fibrous collagenous tissue and significant inflammatory cell infiltration including scattered eosinophils. Extensive loss of medial smooth muscle layer was observed in the vessel wall, which was likely to be the cause of PSS. In the course of treatment, this patient was found to have chromium allergy with positive patch test. Allergic reactions to chromium released from the stent might be one of the triggering mechanisms for in-stent restenosis and PSS after BMS implantation. .

Unexpectedly High Prevalence of Acquired von Willebrand Syndrome in Patients with Severe Aortic Stenosis as Evaluated with a Novel Large Multimer Index.

AIM: Severe gastrointestinal bleeding sometimes occurs in patients with aortic stenosis (AS), known as Heyde's syndrome. This syndrome is thought to be caused by acquired von Willebrand syndrome and is characterized by reduced large von Willebrand factor (vWF) multimers. However, the relationship between the severity of AS and loss of large vWF multimers is unclear. METHODS: We examined 31 consecutive patients with severe AS. Quantitative evaluation for loss of large vWF multimers was performed using the conventional large vWF ratio and novel large vWF multimer index. This novel index was defined as the ratio of large multimers of patients to those of controls. RESULTS: Loss of large vWF multimers, defined as the large vWF multimer index ＜80%, was detected in 21 patients (67.7%). The large vWF multimer ratio and the large vWF multimer index were inversely correlated with the peak aortic gradient (R = -0.58, p=0.0007, and R=-0.64, p＜0.0001, respectively). Anemia defined as hemoglobin ＜9.0 g/dl was observed in 12 patients (38.7%), who were regarded as Heyde's syndrome. Aortic valve replacement was performed in 7 of these patients, resulting in the improvement of anemia in all patients from a hemoglobin concentration of 7.5±1.0 g/dl preoperatively to 12.4±1.3 g/dl postoperatively (p＜0.0001). CONCLUSIONS: Acquired von Willebrand syndrome may be a differential diagnosis in patients with AS with anemia. The prevalence of AS-associated acquired von Willebrand syndrome is higher than anticipated.

Patient-Specific Three-Dimensional Aortocoronary Model for Percutaneous Coronary Intervention of a Totally Occluded Anomalous Right Coronary Artery.

Percutaneous coronary intervention (PCI) for anomalous coronary arteries is often difficult because the support provided by the guide catheter is insufficient. We encountered a patient with severe three-vessel coronary disease including a totally occluded anomalous right coronary artery (RCA) originating from the left sinus of Valsalva. Initial PCI for the anomalous RCA via the transradial approach failed. Therefore, we constructed a three-dimensional (3D) aortocoronary model and conducted an in vitro simulation to plan the second PCI and found that a Judkins left (JL) 3.5 guide catheter in the power position yielded maximum backup support for the anomalous RCA. Thus, the second PCI was conducted using an 8 Fr JL 3.5 guide catheter in the power position via the transfemoral approach. The procedure was smooth and successful, without any adverse events. Our experience suggests that case-specific 3D models are useful for strategic planning of complex PCIs.

Clinical impact of left ventricular outflow tract obstruction in takotsubo cardiomyopathy.

BACKGROUND: A hyperdynamic state of the basal left ventricle sometimes results in obstruction of the left ventricular outflow tract (LVOT). However, the prevalence, clinical presentation, and prognostic effect of LVOT obstruction in takotsubo cardiomyopathy (TC) have not been fully evaluated. METHODS AND RESULTS: Among 933 consecutive patients who underwent emergency coronary angiography for suspected acute coronary syndrome, 35 patients (3.8%) were diagnosed as TC. The cumulative 3-year incidence of all-cause death, cardiac death, hospitalization for congestive heart failure (CHF), and recurrent TC was 24.2%, 0.0%, 6.5%, and 12.2%, respectively. Among 27 patients with information of a LVOT pressure gradient, LVOT obstruction was present in 9 (33%). The prevalence of moderate to severe mitral regurgitation (67% vs. 11%, P=0.003), CHF (78% vs. 28%, P=0.02), and hypotension (56% vs. 5.6%, P=0.008) was significantly higher in patients with LVOT obstruction than in those without. Nevertheless, the cumulative 3-year incidence of all-cause death was not significantly different between the 2 groups (49.2% vs. 23.0%, P=0.22) with no cardiac deaths in either group. Hospitalization for CHF and recurrent TC were significantly more frequent in patients with LVOT obstruction (25.0% vs. 0.0%, P=0.04, and 25.0% vs. 6.7%, P=0.02). CONCLUSIONS: In 35 consecutive patients with TC, those with significant LVOT obstruction (33%) had a more serious clinical presentation such as CHF and hypotension, but had similar 3-year mortality rate as compared with those without.