Effect of Catheter Ablation for Atrial Fibrillation in Heart Failure With Mid-Range or Preserved Ejection Fraction　- Pooled Analysis of the AF Frontier Ablation Registry and Hokuriku-Plus AF Registry.

BACKGROUND: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group. CONCLUSIONS: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

Impact of the timing of first appropriate shock on outcomes in patients with an implantable cardioverter-defibrillator: Early versus late.

BACKGROUND: Appropriate implantable cardioverter-defibrillator (ICD) shocks are associated with an increased risk of mortality and heart failure (HF) events. The first appropriate shock may occur late after implantation. However, whether the timing of the first appropriate shock influences prognosis is unknown. This study aimed to evaluate the clinical significance of the timing of the first appropriate shock in patients with ICD. METHODS: This retrospective and observational study enrolled 565 consecutive ICD patients. Patients who received an appropriate shock were divided into the early group (first appropriate shock <1 year after ICD implantation) and late group (first appropriate shock ≥1 year after ICD implantation). All-cause mortality was compared between the two groups. RESULTS: Over a median follow-up of 5.6 years, 112 (19.8%) patients received an appropriate shock, including 32 patients (28.6%) in the early group and 80 patients (71.4%) in the late group. Comparisons of baseline characteristics at ICD implantation revealed that the late group was more likely to receive cardiac resynchronization therapy (66.3% vs. 31.3%, p < 0.001), ICD for primary prevention (60.0% vs. 31.3%, p = 0.001), and angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker treatment (88.8% vs. 71.9%, p = 0.028). Survival after shock was significantly worse in the late group than in the early group (p = 0.027). In multivariable Cox proportional hazards analysis, the late group had an increased risk of all-cause mortality compared with the early group (HR: 2.22; 95% CI 1.01-4.53; p = 0.029). In both groups, the most common cause of death was HF. CONCLUSIONS: Late occurrence of the first appropriate ICD shock was associated with a worse prognosis compared with early occurrence of the first appropriate shock. Cardiac death was the most common cause of death in patients who experienced late occurrence of the first appropriate ICD shock, resulting from HF in most cases.

Implication of modified MELD scores for postdischarge prognosis in hospitalized patients with heart failure.

We evaluated whether modified Model for End-Stage Liver Disease (MELD) scores are useful for predicting the postdischarge prognosis in hospitalized patients with heart failure (HF) who are discharged alive. The MELD-XI and MELD-Na scores were calculated at discharge for a total of 1156 patients in the HIJ-HF II study. We also studied 3 groups on the basis of the left ventricular ejection fraction (LVEF): the HFrEF (LVEF < 40%), HFmrEF (LVEF 40-49%) and HFpEF (LVEF ≥ 50%) groups. The primary outcome was all-cause mortality, and the secondary outcome was rehospitalization due to worsening HF. The median MELD-XI and MELD-Na scores were 12 and 14, respectively. After a median follow-up of 19 months, there were significantly higher rates of all-cause mortality in patients with MELD-XI scores ≥ 12 than in those with MELD-XI scores < 12; there were also higher rates of all-cause mortality in patients with MELD-Na scores ≥ 14 than in those with MELD-Na scores < 14 (both log-rank p < 0.001). The cumulative incidence function based on a competing risks model showed a higher rate of rehospitalization due to worsening HF in patients with MELD-XI scores ≥ 12 than in those with MELD-XI scores < 12 and a higher rate of rehospitalization due to worsening HF in those with MELD-Na scores ≥ 14 than in those with MELD-Na scores < 14 (both Gray's test p < 0.001). The adjusted hazard ratios (HRs) of all-cause mortality for patients with MELD-XI scores ≥ 12 and those with MELD-Na scores ≥ 14 were 2.07 [95% confidence interval (CI) 1.25-3.44] and 2.79 [95% CI 1.63-4.79], respectively, in the HFrEF group; however, the HRs were not significant in the HFmrEF or HFpEF groups. Thus, MELD-XI and MELD-Na scores may be useful for predicting prognosis in hospitalized HF patients who are discharged alive, especially for those in the HFrEF group.

Prognostic significance of cardiorenal dysfunction within 1 year after atrial fibrillation ablation in patients with systolic dysfunction.

Atrial fibrillation (AF) ablation can improve left ventricular ejection fraction (LVEF) and renal function and can even reduce mortality in patients with impaired LVEF. However, the effect of post-ablation cardiorenal dysfunction on the prognosis of patients with impaired LVEF who underwent AF ablation remains unclear. Of the 1243 consecutive patients undergoing AF ablation, the prognosis of 163 non-dialysis patients who underwent AF ablation with < 50% LVEF was evaluated. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, and a need for modification of the treatment for heart failure. During the median follow-up of 4.2 years after the first AF ablation procedure, the primary outcome occurred in 30 of 163 patients (18%). The receiver operating characteristic curve analysis demonstrated that the post-LVEF (LVEF within 1 year after the procedure, and before the occurrence of primary outcome) had larger areas under the curve (0.70) than the pre-LVEF (LVEF before the procedure), and the most optimal cutoff value was LVEF ≤ 42%. Multivariate analysis demonstrated that patients with post-LVEF ≤ 42% and worsening renal function (WRF; an absolute increase in serum creatinine [SCr] ≥ 0.3 mg/dL compared with the SCr at baseline within 1 year after the procedure and before the occurrence of primary outcome) had a 3.4- to 4.3-fold and 3.4- to 3.7-fold higher risk of the primary outcome compared with those without these predictors, respectively. Patients were categorized using post-LVEF ≤ 42% and WRF as follows: group 1 (post-LVEF > 42% without WRF), group 2 (post-LVEF ≤ 42% without WRF), group 3 (post-LVEF > 42% with WRF), and group 4 (post-LVEF ≤ 42% with WRF). Group 4 had a 15.8-fold (P = 0.0001) higher risk of the primary outcome compared with group 1 after adjusting for pre-procedural factors. In patients with impaired LVEF undergoing AF ablation, post-LVEF ≤ 42% and WRF were independent predictors of poor prognosis. The combination of post-LVEF ≤ 42% and WRF is strongly associated with a poor prognosis in patients with AF undergoing ablation, who with these post-ablation cardiorenal dysfunction may have to be treated more intensively after AF ablation.

Left Ventricular End-Systolic Diameter May Predict Persistent Heart Failure with Reduced Ejection Fraction.

Patients with persistent heart failure (HF) with reduced ejection fraction (HFrEF) have a poorer prognosis than those with HF with improved ejection fraction (HFimpEF). However, data on the predictive value of echocardiographic parameters for persistent HFrEF are lacking. We retrospectively studied 443 patients who were diagnosed with HFrEF (EF ≤ 40%) during hospitalization and underwent echocardiography at the 1-year follow-up. We divided them into the 2 groups: HFimpEF (EF > 40%) and persistent HFrEF group at 1-year follow-up, and assessed the predictive value of echocardiographic parameters at discharge for persistent HFrEF. In total, 301/443 patients (68%) were diagnosed with persistent HFrEF and 142/443 (32%) with HFimpEF at the 1-year follow-up. Kaplan-Meier analysis revealed that the persistent HFrEF group had a poorer prognosis than the HFimpEF group (log-rank, P < 0.001). Receiver operating characteristic curve analysis revealed that left ventricular end-systolic diameter (LVESD) had the highest area under the curve (AUC) (0.70; 95% confidence interval [CI]: 0.64-0.75; cutoff value: 55 mm) among various echocardiographic parameters. LVESD was an independent predictor of persistent HFrEF at the 1-year follow-up (odds ratio: 1.07, 95%CI: 1.02-1.12) upon multivariable logistic regression analysis. The incidence of persistent HFrEF was higher in patients with an LVESD ≥ 55 mm than in those with an LVESD < 55 mm (81% versus 55%, Fisher's exact test, P < 0.001). In conclusion, an LVESD (≥ 55 mm) was associated with persistent HFrEF. Focusing on LVESD in daily practice may help clinicians with risk stratification for decision-making regarding management in patients with advanced HF refractory to guideline-directed medical therapy.

[Emergent Transcatheter Aortic Valve Implantation for Degenerated Surgical Aortic Valve Under Local Anesthesia:Report of a Case].

An 89-year-old man who had undergone aortic valve replacement with a 21 mm Mosaic bioprosthetic valve at another hospital 14 years ago was admitted to the emergency room for a sudden respiratory distress two days prior and was diagnosed with severe aortic regurgitation( AR) caused by valve insufficiency and acute heart failure secondary to low cardiac function. Upon admission, he was found to have severe hypoxia with PaO2 of 40 mmHg range, and transcatheter aortic valve replacement (TAVI, TAV in SAV) with a 20 mm SAPIEN3 was performed under local anesthesia for fear of hypotension while under general anesthesia. After confirming that AR had completely disappeared, the patient was intubated and discharged from the operating room on a mechanical ventilator. The patient was weaned from the ventilator on the second postoperative day and was transferred to the other hospital for rehabilitation, 48 days postoperatively. Although there is no report on the comparative study of anesthesia methods for emergency transcatheter aortic valve implantation( TAVI), TAVI under regional anesthesia is minimally invasive with a lower risk for hypotension than general anesthesia. Therefore, we believe it is useful for patients with acute heart failure and hypotension. In addition, it is important to use a balloon expandable valve with excellent implantability to complete the procedure in a short time.

Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease.

BACKGROUND: There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease. METHODS: In a multicenter, open-label trial conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority. RESULTS: The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority). CONCLUSIONS: As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease. (Funded by the Japan Cardiovascular Research Foundation; AFIRE UMIN Clinical Trials Registry number, UMIN000016612; and ClinicalTrials.gov number, NCT02642419.).

The impact of kidney function in patients on antithrombotic therapy: a post hoc subgroup analysis focusing on recurrent bleeding events from the AFIRE trial.

BACKGROUND: The success of antithrombotic therapies is assessed based on thrombotic and bleeding events. Simultaneously assessing both kinds of events might be challenging, and recurrent bleeding events are often ignored. We tried to confirm the effects of kidney function on outcome events in patients undergoing antithrombotic therapy. METHODS: As a post hoc subgroup analysis of the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial, a randomized clinical trial with a median follow-up of 36 months, patients were divided into high and low estimated glomerular filtration rate (eGFR) groups with a cutoff value of 50 mL/min. The cumulative incidence of bleeding and crude incidence of recurrent bleeding per 100 patient-years were calculated. We used the Cox regression model with multiple failure time data for recurrent bleeding events. RESULTS: Among 2092 patients, 1386 (66.3%) showed high eGFR. The cumulative bleeding events per 100 patients at 1 year were 5.4 and 6.2 in the high and low eGFR groups, respectively. The difference continued to increase over time. The hazard ratio for time to the first bleeding event in the high eGFR group was 0.875 (95% confidence interval 0.701-1.090, p = .234) and that for the first composite event was 0.723 (95% confidence interval 0.603-0.867, p < .000). The recurrent bleeding events per 100 person-years were 11.3 and 15.3 in the high and low eGFR groups, respectively, with a rate ratio of 0.738 (95% confidence interval 0.615-0.886, p = .001). During the observation period, the risk of bleeding changed with time. It peaked soon after the study enrollment in both groups. It decreased continuously in the high eGFR group but remained high in the low eGFR group. CONCLUSIONS: We reaffirmed that kidney function affects bleeding events in patients on antithrombotic therapy, considering recurrent events. Patients should have detailed discussions with physicians regarding the possible bleeding events when continuing antithrombotic therapy, especially in patients with decreased kidney function. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000016612 . ClinicalTrials.gov, NCT02642419 . Registered on 21 October 2015.

Papillary muscle ischemia on high-resolution cine imaging of nitrogen-13 ammonia positron emission tomography: Association with myocardial flow reserve and prognosis in coronary artery disease.

BACKGROUND: The evaluation of papillary muscle (PM) perfusion through existing perfusion imaging, including single-photon emission computed tomography and magnetic resonance imaging, is not possible. Therefore, this study sought to investigate the detection of PM ischemia in coronary artery disease (CAD) using nitrogen-13 (N-13) ammonia positron emission tomography (NH3 PET) and its association with global myocardial flow reserve (MFR) and major adverse cardiac events (MACE). METHODS: Data of adenosine-stress NH3 PET for 263 consecutive patients with known or suspected CAD were retrospectively analyzed. PM ischemia was defined as the absence of PM accumulation under stress conditions and PM presence at rest on high-resolution cine imaging derived from PET-computed tomography scanner with time-of-flight technology. The primary outcome was MACE. RESULTS: Of 263 patients, 30 experienced mean follow-up period of 910 days (MACE), while 31 (11.8%) presented PM ischemia. Compared to patients without PM ischemia, those with PM ischemia reported a significantly lower global MFR and a significantly higher rate of MACE (P < .0001). CONCLUSION: NH3 PET enables the detection of PM ischemia in approximately 10% of patients with known or suspected CAD. PM ischemia is associated with reduced global MFR and is an important sign in predicting prognosis.

Different Determinants of the Recurrence of Atrial Fibrillation and Adverse Clinical Events in the Mid-Term Period After Atrial Fibrillation Ablation.

BACKGROUND: It is unclear whether there are differences in the clinical factors between atrial fibrillation (AF) recurrence and adverse clinical events (AEs), including stroke/transient ischemic attack (TIA), major bleeding, and death, after AF ablation.Methods and Results:We examined the data from a retrospective multicenter Japanese registry conducted at 24 cardiovascular centers between 2011 and 2017. Of the 3,451 patients (74.1% men; 63.3±10.3 years) who underwent AF ablation, 1,046 (30.3%) had AF recurrence and 224 (6.5%) suffered AEs (51 strokes/TIAs, 71 major bleeding events, and 36 deaths) over a median follow-up of 20.7 months. After multivariate adjustment, female sex, persistent and long-lasting persistent AF (vs. paroxysmal AF), and stepwise increased left atrial diameter (LAd) quartiles were significantly associated with post-ablation recurrences. A multivariate analysis revealed that an age ≥75 years (vs. <65 years), body weight <50 kg, diabetes, vascular disease, left ventricular (LV) ejection fraction <40% (vs. ≥50%), Lad ≥44 mm (vs. <36 mm), and creatinine clearance <50 mL/min were independently associated with AE incidences, but not with recurrences. CONCLUSIONS: This study disclosed different determinants of post-ablation recurrence and AEs. Female sex, persistent AF, and enlarged LAd were determinants of post-ablation recurrence, whereas an old age, comorbidities, and LV and renal dysfunction rather than post-ablation recurrence were AEs determinants. These findings will help determine ablation indications and post-ablation management.

Impact of signal-averaged electrocardiography findings on appropriate shocks in prophylactic implantable cardioverter defibrillator patients with nonischemic systolic heart failure.

BACKGROUND: Appropriate shock therapy is associated with subsequent all-cause death in heart failure (HF) patients who receive an implantable cardioverter defibrillator (ICD) for the primary prevention of sudden cardiac death. To evaluate the impact of signal-averaged electrocardiography (SAECG) findings on appropriate shocks in prophylactic ICD patients with nonischemic systolic HF. METHODS: We studied 86 patients with nonischemic HF and a left ventricular ejection fraction ≤ 35% who underwent new ICD implantation for the primary prevention of sudden cardiac death. We excluded patients who had a previously implanted permanent pacemaker and patients who received cardiac resynchronization therapy with an ICD. SAECG was performed before implantation. Abnormal SAECG findings were defined if 2 of the following 3 conditions were identified: filtered QRS duration (fQRS) ≥ 114 ms, root-mean-square voltage during the last 40 ms of the fQRS (RMS 40) < 20 µV, and duration of the low-amplitude potentials < 40 µV (LAS 40) > 38 ms; additionally, patients with a QRS complex ≥ 120 ms who met both the RMS 40 and LAS 40 criteria were also considered to have abnormal SAECG findings. The primary outcome was the first occurrence of appropriate shock after implantation of the ICD. The secondary outcomes were the first occurrence of inappropriate shock and all-cause mortality. RESULTS: Forty-two patients met the criteria for abnormal SAECG findings (49%). During a median follow-up period of 61 months, 17 patients (20%) died, 24 (28%) received appropriate shock therapy, and 19 (22%) received inappropriate shock therapy. There was a significantly higher incidence of appropriate shocks in patients with abnormal SAECG findings than in those with normal SAECG findings (log-rank test, p = 0.025). Multivariate analysis revealed that abnormal SAECG findings were independently associated with the occurrence of appropriate shock (hazard ratio 2.67, 95% confidential interval 1.14-6.26). However, abnormal SAECG findings were not related to inappropriate shock. There was no difference in the incidence of all-cause death between patients with abnormal and normal SAECG findings. CONCLUSIONS: Our results suggest that abnormal SAECG findings are associated with a high probability of appropriate shocks in prophylactic ICD patients with nonischemic systolic HF.

Impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry.

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

Prognostic Impact of Landiolol in Patients with Acute Heart Failure and Atrial Fibrillation with Rapid Ventricular Rates: A Pilot Observational Study.

INTRODUCTION: Guidelines recommend ventricular rate control to <130 bpm during atrial fibrillation (AF) in patients with acute decompensated heart failure (ADHF) to avoid aggravating deteriorations in cardiac outputs. We aimed to evaluate the prognostic impact of landiolol in patients with ADHF and AF. METHODS: This observational study included 60 patients who were urgently hospitalized with ADHF and presented with AF and a heart rate (HR) ≥130 bpm at admission. The patients were assigned to the landiolol group (n = 37) or the reference group (n = 23) based on their intravenous landiolol use within 24 h after admission. The primary endpoint was death from any cause. RESULTS: The groups' baseline characteristics were similar. A significant HR reduction occurred in the landiolol group at 2 h after admission. Compared with the reference group, the HR was significantly lower (111.6 vs. 97.9 bpm, p = 0.02) and the absolute HR reduction was greater (-32.2 vs. -50.0 bpm, p = 0.006) in the landiolol group at 48 h after admission. The landiolol group's mortality rate was significantly lower than that in the reference group (log-rank test, p = 0.032). landiolol use within 24 h after admission was independently associated with lower all-cause mortality (adjusted hazard ratio: 0.15, 95% confidence interval: 0.02-0.92). CONCLUSION: Patients with ADHF and AF who received landiolol for rate control during the acute phase had better prognoses than those who did not receive landiolol.

Increased left atrial volume index is associated with more cardiovascular events in patients with acute coronary syndrome: HIJ-PROPER study findings.

AIM: To investigate the association between the left atrial volume index (LAVI) and the incidence of cardiovascular events in patients with acute coronary syndrome (ACS) who did not have atrial fibrillation (AF). METHODS: In this sub-analysis of the HIJ-PROPER study, 226 ACS patients who did not have a history of AF were enrolled. Participants were divided into two groups according to the LAVI cut-off level calculated by receiver operating characteristic (ROC) curve analysis to predict the primary endpoint, and cardiovascular events were compared between groups. The primary endpoint was the first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure. RESULTS: ROC curve analysis for the occurrence of composite of cardiovascular events indicated a LAVI cut-off point of 34 mL/m2 . Based on this, 131 patients (58.0%) were in the LAVI < 34 mL/m2 group and 95 (42.0%) were in the LAVI ≥ 34 mL/m2 group. Over a median follow-up period of 4.0 years [interquartile range: 3.2, 5.1], cardiovascular events were noted in 7 and 15 patients in the LAVI < 34 mL/m2 and LAVI ≥ 34 mL/m2 groups, corresponding to an incidence rate of 5.3% and 15.8%, respectively. Patients with a LAVI value ≥ 34 mL/m2 had a significantly higher risk of cardiovascular events than those with a LAVI value < 34 mL/m2 (hazard ratio: 2.93; 95% confidence interval: 1.19-7.22; P = .014). The tendency was similar after adjusting for several confounders (P = .025). CONCLUSION: In ACS patients without AF, elevated LAVI was associated with increased cardiovascular events. CLINICAL TRIAL REGISTRATION: International standard randomized controlled trial (URL: https://www.umin.ac.jp; UMIN000002742).

Utility of dobutamine stress echocardiography in aortic valve regurgitation and reduced left ventricular function.

OBJECTIVE: Predictors for post-operative reverse remodeling in patients with severe aortic regurgitation (AR) and reduced left ventricular ejection fraction (LVEF) are unknown. We performed low-dose dobutamine stress echocardiography (DSE) in patients with severe AR and reduced LVEF to evaluate the relationship between contractile reserve (CR) and reverse remodeling after surgery. METHODS: In 31 patients with chronic severe AR and reduced LVEF (LVEF < 50%), we performed pre-operative DSE, assessed CR, and examined whether changes in preoperative DSE were associated with improvement of post-operative LVEF after aortic valve surgery. RESULTS: The pre-operative echocardiographic findings were as follows: left ventricular (LV) end-diastolic dimension: 67 ± 10 mm, LV end-systolic dimension: 52 ± 13 mm, and LVEF: 42 ± 8%. All patients underwent aortic valve surgery. Patients with pre-operative LVEF of ≥45% exhibited a significant increase in LVEF; however, patients with pre-operative LVEF of <45% showed no significant change. When we examined the results of DSE performed in patients with pre-operative LVEF of <45%, ΔLVEF of ≥6% (with CR) during DSE was related to an improvement in post-operative LVEF; ΔLVEF of ≥6% during DSE predicted an improvement in post-operative LVEF, with sensitivity 100%; specificity 78%; and area under curve (AUC) .92. CONCLUSIONS: DSE might be a helpful tool for predicting post-operative reverse remodeling in patients with severe AR and moderately reduced LVEF.

First Validation of Myocardial Flow Reserve Derived from Dynamic 99mTc-Sestamibi CZT-SPECT Camera Compared with 13N-Ammonia PET.

13N-ammonia positron emission tomography (NH3-PET) can evaluate myocardial blood flow (MBF) at rest, stress, and myocardial flow reserve (MFR) as well as the ratio of MBF at stress to that at rest. MFR is useful in predicting the prognoses of patients with various heart diseases. Cadmium-zinc-telluride single photon emission computed tomography (CZT-SPECT) enables us to acquire dynamic images of radiotracer kinetics and measure original MBF and MFR using 99mTc-sestamibi. This study aimed to investigate the utility of CZT-SPECT for quantitative assessment of MBF compared to NH3-PET. We validated the correlation of MBF and MFR between CZT-SPECT and NH3-PET. Fourteen patients using one-day rest/stress CZT-SPECT, D-SPECT followed by NH3-PET within 1 month were enrolled and analyzed prospectively. The reproducibility of the MBF and MFR obtained with these two methods was examined using Spearman's correlation coefficient and Bland-Altman plot analysis. The diagnostic value of D-SPECT for abnormal MFR defined using NH3-PET results as MFR < 2.0 was assessed using receiver-operating characteristic (ROC) analysis. The median duration between D-SPECT and NH3-PET was 20 days. Although MBF was overestimated by D-SPECT compared to NH3-PET at high value (mean difference, 0.43 [0.34-0.53]), MBF and MFR were correlated with the two modalities (MBF: r = 0.71, P < 0.0001, MFR: r = 0.60, P < 0.0001). The ROC curve analysis demonstrated a cutoff of 1.6 for detecting abnormal MFR with D-SPECT (sensitivity, 68%; specificity, 91%; AUC, 0.75). MBF and MFR obtained using D-SPECT and NH3-PET had a good correlation, suggesting that the quantitative MFR evaluation by CZT-SPECT may help understand the trend of NH3-PET MFR.

Functional Evaluation of Human Bioengineered Cardiac Tissue Using iPS Cells Derived from a Patient with Lamin Variant Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is caused by various gene variants and characterized by systolic dysfunction. Lamin variants have been reported to have a poor prognosis. Medical and device therapies are not sufficient to improve the prognosis of DCM with the lamin variants. Recently, induced pluripotent stem (iPS) cells have been used for research on genetic disorders. However, few studies have evaluated the contractile function of cardiac tissue with lamin variants. The aim of this study was to elucidate the function of cardiac cell sheet tissue derived from patients with lamin variant DCM. iPS cells were generated from a patient with lamin A/C (LMNA) -mutant DCM (LMNA p.R225X mutation). After cardiac differentiation and purification, cardiac cell sheets that were fabricated through cultivation on a temperature-responsive culture dish were transferred to the surface of the fibrin gel, and the contractile force was measured. The contractile force and maximum contraction velocity, but not the maximum relaxation velocity, were significantly decreased in cardiac cell sheet tissue with the lamin variant. A qRT-PCR analysis revealed that mRNA expression of some contractile proteins, cardiac transcription factors, Ca2+-handling genes, and ion channels were downregulated in cardiac tissue with the lamin variant.Human iPS-derived bioengineered cardiac tissue with the LMNA p.R225X mutation has the functional properties of systolic dysfunction and may be a promising tissue model for understanding the underlying mechanisms of DCM.

Rivaroxaban monotherapy versus combination therapy according to patient risk of stroke and bleeding in atrial fibrillation and stable coronary disease: AFIRE trial subanalysis.

BACKGROUND: In the AFIRE trial, rivaroxaban monotherapy was noninferior to combination therapy with rivaroxaban and an antiplatelet agent for thromboembolic events or death, and superior for major bleeding in patients with atrial fibrillation (AF) and stable coronary artery disease. Little is known about impacts of stroke and bleeding risks on the efficacy and safety of rivaroxaban monotherapy. METHODS: In this subanalysis of the AFIRE trial, we assessed the risk of stroke and bleeding by the CHADS2, CHA2DS2-VASc, and HAS-BLED scores. The primary efficacy end point was the composite of stroke, systemic embolism, myocardial infarction (MI), unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding defined by the International Society on Thrombosis and Haemostasis. RESULTS: Rivaroxaban monotherapy significantly reduced the primary efficacy and safety end points with no evidence of differential effects by stroke risk (CHADS2, p for interaction = 0.727 for efficacy, 0.395 for safety; CHA2DS2-VASc, p for interaction = 0.740 for efficacy, 0.265 for safety) or bleeding risk (HAS-BLED, p for interaction = 0.581 for efficacy, 0.225 for safety). There was also no evidence of statistical heterogeneity across patient risk categories for other end points; stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, MI, MI or unstable angina, death from any cause, any bleeding, or net adverse clinical events. CONCLUSIONS: The advantages of rivaroxaban monotherapy compared with those of combination therapy with respect to all prespecified end points, including thromboembolism, bleeding, and mortality were similar across patients with AF and stable coronary artery disease, irrespective of their risk for stroke and bleeding. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry number, UMIN000016612, and ClinicalTrials.gov number, NCT02642419.

Efficacy of catheter ablation for patients with atrial fibrillation and atrial septal defect.

INTRODUCTION: Given that few studies investigated the efficacy of catheter ablation (CA) in patients with paroxysmal atrial fibrillation (AF) and atrial septal defect (ASD), this study evaluated its effectiveness in patients with paroxysmal AF and ASD. METHODS AND RESULTS: Of the 216 patients who underwent ASD device closure at two hospitals, 36 patients had paroxysmal AF. After April 2012, CA for AF was performed before ASD device closure (ASD-CA group; n = 20). The ASD-CA group had a significantly higher AF-free survival rate after ASD device closure compared to patients without CA for AF before ASD device closure (ASD-non-CA group; n = 16) (ASD-CA group: 2 patients vs. ASD-non-CA group: 9 patients; follow-up period: 4.2 ± 2.5 years; log-rank p = .01). In addition, the AF-free survival rates were similar between the ASD-CA group and 80 paroxysmal AF patients who underwent CA without any detectable structural heart disease (non-SHD-CA group). The two groups were matched by propensity scores for age, sex, and left atrium dimension (ASD-CA group: 2 patients vs. non-SHD-CA group: 5 patients; follow-up period: 3.3 ± 1.8 years; log-rank p = .28). CONCLUSION: CA for AF before ASD device closure might be an effective treatment option for patients with paroxysmal AF and ASD.

Prognosis and recurrence in cardiac sarcoidosis: Serial assessment of BMIPP SPECT and FDG-PET.

BACKGROUND: We analyzed 18F-Fludeoxyglucose positron emission tomography (FDG-PET) and 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) performed for cardiac sarcoidosis (CS) patients taking prednisolone, identified recurrence by FDG-PET, and investigated BMIPP as a recurrence and prognostic factor in CS. METHODS AND RESULTS: CS patients who underwent BMIPP and FDG-PET within 2 months were enrolled. The recurrence-free group included patients with standardized uptake value (SUVmax) < 4 in the myocardium consecutively for ≥ 2 years. The total BMIPP SPECT defect score (BDS) was used to estimate myocardial damage. The predictability of the initial BDS and SUVmax for major adverse cardiac events (MACE) was analyzed using Kaplan-Meier analysis. Overall, 73 patients and 250 BMIPP and FDG-PET sets were analyzed retrospectively (mean follow-up, 3.5 years). The BDS was significantly greater for the recurrence group (N = 21) vs recurrence-free group (20 ± 13 vs 14 ± 12, P = 0.041). Patients with BDS ≥16 had a significantly higher MACE rate than patients with BDS < 16 (log-rank test, P = 0.016). However, MACE occurrence was comparable between patients with SUVmax ≥ 4 and < 4. CONCLUSIONS: BDS is a predictive marker of recurrence and MACE. SUV is not related to MACE. Recurrence, defined by prednisolone treatment-induced SUV variability, was observed in approximately 30% of CS patients.