DAPagliflozin for the attenuation of albuminuria in Patients with hEaRt failure and type 2 diabetes (DAPPER study): a multicentre, randomised, open-label, parallel-group, standard treatment-controlled trial.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the urinary albumin-to-creatinine ratio (UACR) in patients with elevated levels of albuminuria in the presence or absence of heart failure (HF) or type 2 diabetes mellitus (T2D). However, these effects have not yet been reported in the presence of both HF and T2D. This lack of evidence prompted us to conduct a clinical trial on the effects of dapagliflozin on UACR in patients with HF and T2D. Methods: DAPPER is a multicentre, randomised, open-labeled, parallel-group, standard treatment-controlled trial that enrolled patients at 18 medical facilities in Japan. Eligible participants with both HF and T2D and aged between 20 and 85 years were randomly assigned to a dapagliflozin or control (anti-diabetic drugs other than SGLT 2 inhibitors) group with a 1:1 allocation. The primary outcome was changes in UACR from baseline after a two-year observation, and secondary endpoints were cardiovascular (CV) events and parameters related to HF. This trial was registered with the UMIN-CTR registry, UMIN000025102 and the Japan Registry of Clinical Trials, jRCTs051180135. Findings: Between 12 May 2017 and 31 March 2020, 294 patients were randomly assigned to the dapagliflozin group (n = 146) or control group (n = 148). The mean age of patients was 72.1 years and 29% were female. The mean glycated hemoglobin value was 6.9%, mean NT-proBNP was 429.1 pg/mL, mean estimated GFR was 65.7 mL/min/1.73 m2, and median UACR was 25.0 (8.8-74.6) mg/g Cr in the dapagliflozin group and 25.6 (8.2-95.0) mg/g Cr in the control group. Of the 146 patients in the dapagliflozin group, 122 completed the study, and 107 (87.7%) were taking 5 mg of dapagliflozin daily at the end of the observation period. The primary outcome did not significantly differ between the dapagliflozin and control groups. Among the secondary endpoints, the mean decrease in left ventricular end-diastolic dimensions as one of the echocardiographic parameters was larger in the dapagliflozin group than in the control group. The composite endpoint, defined as CV death or hospitalisation for CV events, hospitalisation for HF events, hospitalisation for all causes, and an additional change in prescriptions for heart failure in a two-year observation, was less frequent in the dapagliflozin group than in the control group. Interpretation: Although dapagliflozin at a dose of 5 mg daily did not reduce urinary albumin excretion in patients with HF and T2D from that in the controls, our findings suggest that dapagliflozin decreased CV events and suppressed left ventricular remodeling. Funding: AstraZeneca KK, Ono Pharmaceutical Co., Ltd.

A randomized controlled trial to evaluate the safety and efficacy of transluminal injection of foam sclerotherapy compared with ultrasound-guided foam sclerotherapy during endovenous catheter ablation in patients with varicose veins.

OBJECTIVE: We compared the safety, need for additional foam sclerotherapy, and 1-year venous clinical severity score (VCSS) improvement in the limbs of patients with chronic venous disease and great saphenous vein (GSV) reflux. These patients had undergone endovenous laser ablation (EVLA) using a 1470-nm diode laser and concurrent foam sclerotherapy (1% polidocanol) through the access sheath (transluminal injection of foam sclerotherapy [TLFS]) or EVLA and concurrent direct-puncture ultrasound-guided foam sclerotherapy (UGFS). METHODS: In the present study, we screened 467 patients (577 legs) with symptomatic primary GSV reflux for randomization to either TLFS with EVLA (n = 103 legs; TLFS group) or UGFS with EVLA (n = 94 legs; UGFS group). The exclusion criteria were (1) recurrent varicose veins after previous intervention; (2) hypersensitivity reaction to sclerotherapy; (3) acute deep vein thrombosis; (4) serious lower limb ischemic disease; (5) a coagulation disorder; and (6) simultaneous EVLA of both GSVs and small saphenous veins. The correlations of the VCSS changes with the clinical features, such as age, sex, CEAP (clinical, etiologic, anatomic, pathophysiologic) classification, total amount of sclerosant used at the original procedure, multiple punctures (more than two) for sclerotherapy at the original procedure, the use of TLFS, and linear endovenous energy density, were estimated using logistic regression. RESULTS: No significant differences in the distribution of the CEAP classification were observed between the two groups. After 12 months of follow-up, all truncal veins were occluded. The VCSS had significantly improved in the TLFS group compared with the UGFS group (UGFS, -7.4 ± 1.8; TLFS, -8.7 ± 1.5; P < .0001). Multivariate analysis revealed that TLFS was the only significant factor for an improved VCSS (hazard ratio, 0.63; 95% confidence interval, 0.32-0.96; P < .0001). The need for additional second-stage sclerotherapy was significantly avoided in the TLFS group (n = 10; 10%) compared with the UGFS group (n = 51; 54%; P < .0001). CONCLUSIONS: TLFS combined with EVLA is a safe and feasible procedure that improves the VCSS and reduces the need for additional second-stage interventions compared with UGFS combined with EVLA.

Absence of first-pass isolation is associated with poor pulmonary vein isolation durability and atrial fibrillation ablation outcomes.

BACKGROUND: Pulmonary vein (PV) reconnection is the main cause of atrial fibrillation (AF) recurrence. This study aimed to examine the effect of first-pass PV isolation (PVI) on PV reconnection frequency during the procedure and on AF ablation outcomes. METHODS: This retrospective study included 446 patients with drug-refractory AF (370 men, aged 64 ± 10 years) who underwent initial PVI using an open-irrigated contact force catheter between January 2015 and October 2016. We investigated the effect of first-pass PVI on PV reconnection during spontaneous PV reconnection and dormant conduction after an adenosine triphosphate challenge. RESULTS: First-pass PVI was achieved in 69% (617/892) of ipsilateral PVs, of which we observed PV reconnection during the procedure in 134 (22%) PVs. This value was significantly lower than that observed in those without first-pass PVI (50%, 138/275) (P < .0001). We divided the subjects into two groups based on the presence or absence of first-pass PVI in at least one of two ipsilateral PVs: first-pass (n = 383, 86%) and non-first-pass groups (n = 63, 14%). The 2-year AF recurrence-free rate was significantly higher in the first-pass group than in the other group (75% vs 59%, log-rank P = .032). In 78 patients with repeat AF ablation, the PV reconnection rate in the second procedure was significantly lower in PVs that had first-pass isolation in the first procedure (34% vs 73%, P < .0001). CONCLUSIONS: Absence of first-pass PVI was associated with a higher frequency of spontaneous PV reconnection and dormant conduction and poor ablation outcomes. First-pass isolation may be a useful marker for better PVI durability.

Comparison of the Safety and Efficacy of Automated Annotation-Guided Radiofrequency Ablation and 2nd-Generation Cryoballoon Ablation in Paroxysmal Atrial Fibrillation.

BACKGROUND: Automated ablation lesion annotation with optimal settings for parameters including contact force (CF) and catheter stability may be effective for achieving durable pulmonary vein isolation. Methods and Results: We retrospectively examined 131 consecutive patients who underwent initial catheter ablation (CA) for paroxysmal atrial fibrillation (PAF) by automatic annotation system (VISITAG module)-guided radiofrequency CA (RFCA) (n=61) and 2nd-generation cryoballoon ablation (CBA) (n=70) in terms of safety and long-term efficacy. The automatic annotation criteria for the RFCA group were as follows: catheter stability range of motion ≤1.5 mm, duration ≥5 s, and CF ≥5 g. We ablated for >20 s with a force-time integral >150 gs at each site, before moving to the next site. Each interlesion distance was <6 mm. Procedural complications were more frequent in the CBA group (1.6% vs. 10.0%, P=0.034). Across a median follow-up of 2.98 years, 88.5% and 70.0% of patients in the RFCA and CBA groups, respectively, were free from recurrence (log-rank test, P=0.0039). There was also a significant difference in favor of RFCA with respect to repeat ablations (3.3% vs. 24.3%, log-rank test, P=0.0003). CONCLUSIONS: RF ablation guided by an automated algorithm that includes CF and catheter stability parameters showed better long-term outcomes than CBA in the treatment of patients with PAF without increasing complications.

Calcified amorphous tumor of the heart with mitral annular calcification: a case report.

BACKGROUND: Calcified amorphous tumor of the heart is a rare, non-neoplastic cardiac mass characterized by nodular calcium in the background of amorphous degenerating fibrinous material. Clinical diagnosis of calcified amorphous tumor can be difficult, and current single imaging techniques do not specifically differentiate calcified amorphous tumor from other cardiac tumors such as calcified atrial myxoma, calcified thrombi, or vegetation. Complete surgical resection is the treatment of choice for both symptom improvement and prevention of embolization, as well as for pathological diagnosis. CASE PRESENTATION: A 70-year-old Asian man with end-stage renal disease complained of chest discomfort during exercise. He had no history of thromboembolism or endocarditis. A transthoracic echocardiogram revealed mitral annular calcification as well as a highly mobile mass (8 × 6 mm) attached to the ventricular side of the posterior mitral valve leaflet. As the mass was highly mobile, suggesting a high risk of embolization, he underwent surgical resection. A histopathological examination revealed multiple nodular amorphous calcifications, along with fibrous connective tissue. There were no identifiable myxoma or malignancy cells. Consequently, the diagnosis of calcified amorphous tumor was confirmed. CONCLUSIONS: In the present case, a calcified amorphous tumor arose from mitral annular calcification. A characteristic of mitral annular calcification-related calcified amorphous tumor is its highly mobile nature, with a high risk of stroke or other systemic embolism. Therefore, surgical therapy should be considered for treatment of calcified amorphous tumors.

Chronic total occlusion treated with coronary intervention by three-dimensional guidewire manipulation: an experimental study and clinical experience.

Three-dimensional (3D) wiring is one method for accurate guidewire control in chronic total occlusion (CTO) lesions during manipulation of CTO-specific stiff guidewires. However, the construction of a mental 3D image is difficult. We propose the idea of image patterns to allow immediate construction of 3D images from the two perpendicular angles of the X-ray system detector and report a case of CTO treated with 3D wiring.

Regional difference of optimal contact force to prevent acute pulmonary vein reconnection during radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Regional differences in optimal contact force (CF) to prevent acute pulmonary vein reconnection (APVR) during catheter ablation for atrial fibrillation (AF) remain unclear. OBJECTIVE: The purpose of this study was to evaluate regional difference in optimal CF during AF ablation. METHODS: This single-center observational study evaluated data from 57 consecutive drug-refractory AF patients (mean age, 62 ± 11 years; 43 males) who underwent initial pulmonary vein isolation (PVI) using the THERMOCOOL® SMARTTOUCH™ (Biosense Webster, Diamond Bar, CA, USA) catheter from June to August 2013. APVR was defined as the time-dependent reconnection >20 minutes after initial PVI and/or reconnection evoked by intravenous adenosine administration (20 mg). Point-by-point relationships between the reconnected points and their CF values were evaluated. RESULTS: Total 72 gaps causing APVR were observed. Of a total of 4,421 ablation points, 285 (6.4%) were associated with APVR. The average CF value of the points with APVR was significantly lower than that of those without (APVR vs. no APVR; 7.5 ± 6.7 g vs. 9.9 ± 8.4 g; P < 0.0001). The areas under the curve and optimal CF values differed between segments (range 0.593-0.761 and 10-22 g, respectively). The optimal CF value was highest in bottom of the right PV and posterosuperior right PV segments (22 g) and lowest in posteroinferior right PV segment (10 g). CONCLUSIONS: There was a regional difference in optimal CF values to prevent APVR, and the optimal CF value to prevent APVR with >95% probability was 10-22 g, depending on the individual peri-PV segments.

The impact of systemic vascular resistance on the accuracy of the FloTrac/Vigileo™ system in the perioperative period of cardiac surgery: a prospective observational comparison study.

FloTrac/Vigileo™ system is based on arterial pressure waveform analysis arterial pressure-based CO (APCO). Therefore, systemic vascular resistance (SVR) can influence the accuracy of APCO. The purpose of this study is to evaluate the relationship between SVR and the accuracy of APCO. We managed 50 consecutive patients in the perioperative period of cardiac surgery with FloTrac/Vigileo™ system (v. 3.02) and Swan-Ganz catheter/Vigilance™ system pulmonary artery catheter-based CO (PAC-CO) simultaneously. Continuous hemodynamic measurement using both methods was performed every 20 s from the induction of anesthesia to PAC removal 4 h after extubation. A total of 11,092 (intraoperative), 38,455 (postoperative, pre-extubation), and 44,235 (postoperative, post-extubation) data pairs were finally analyzed. Bland-Altman analysis revealed that in the intraoperative [postoperative pre-extubation, post-extubation] period, the bias was 0.5 [0.1, 0.0] L/min and the limits of agreement ranged from -2.4 to 3.3 [-2.2 to 2.4, -2.4 to 2.3] L/min. The percentage error was 60.3 [54.5, 48.5] %. Regression analysis of the systemic vascular resistance index (SVRI) and the bias between APCO and PAC-CO showed that the bias was positively correlated to the SVRI. Subanalysis based on SVR with Lin's concordance correlation coefficient revealed that relatively satisfactory concordance was found in the normal-SVR group (concordance correlation coefficient ρ c = 0.51-0.56) regardless of vasoactive agent use. The accuracy of the FloTrac/Vigileo™ System (v. 3.02) is relatively satisfactory in the condition with normal SVR regardless of vasoactive agent use. Positive correlation between the bias and SVR can be the clue to the more effective use of FloTrac/Vigileo™ system.

Modulation of individual susceptibility to the no-reflow phenomenon after acute myocardial infarction.

Coronary reperfusion using primary percutaneous coronary intervention (PCI) dramatically reduces morbidity and mortality among patients with acute myocardial infarction (AMI). Nevertheless, inadequate myocardial perfusion, known as the "no-reflow" phenomenon, is observed in approximately 15% of patients and is associated with poor outcomes. No-reflow is caused not only by mechanical occlusion of the microvasculature due to thromboembolism but also by myocardial injury. Transmural myocardial damage before PCI and the size of the associated area are major factors in the development of no-reflow. There is evidence indicating that inflammation, oxidative injury, morphological changes of endothelial cells, hyperglycemia, and absence of ischemic preconditioning also contribute to the development of no-reflow. Several strategies have been attempted to counteract these risk factors. To prevent microembolization related to PCI, thrombus aspiration appears promising, but distal protection devices have failed to demonstrate the expected results among patients with AMI. Most cardioprotective agents developed to modify the risk factors for no-reflow have been effective in animal experiments but have disappointed in clinical trials. Adjunctive treatments using statins, adenosine, atrial natriuretic peptide, nicorandil, or glycoprotein IIb/IIIa antagonists have been effective in reducing the infarct size or improving outcomes after AMI in clinical studies, although some have shown inconsistent results. It is probable that the relevance of each component associated with no-reflow is different for individual patients, and therefore the attempt to indiscriminately apply one treatment to all patients will not be as successful as expected. Individual susceptibility has to be evaluated when selecting an appropriate adjunctive treatment to prevent no-reflow in patients with AMI.

Coronary microcirculatory dysfunction in aortic stenosis: myocardial contrast echocardiography study.

BACKGROUND: The aims of this study were to quantify the microcirculatory dysfunction in aortic stenosis (AS) and to measure the changes in transmural perfusion after aortic valve replacement (AVR), using quantitative myocardial contrast echocardiography. METHODS: Myocardial contrast echocardiography was used to quantify the myocardial blood flow in both the subendocardium and subepicardium in 22 patients with AS (A group), before, 2 weeks after, and 1 year after AVR. Healthy volunteers (C group, n = 10) and patients with mitral regurgitation (M group, n = 10) were included as controls. Triggered myocardial contrast echocardiography was performed, and the endosystolic 1.5 harmonic images were recorded. RESULTS: The myocardial contrast echocardiography study showed that, before AVR, the myocardial blood flow in the subendocardium was significantly lower in the A group than in the other groups (CI = -18.6 +/- 3.0 dB, -11.8 +/- 4.1 dB, and -12.7 +/- 4.1 dB, respectively, in A, M, and C groups; p < 0.05), whereas there was no significant difference in blood flow in the subepicardium. In the A group, the myocardial blood flow in the subendocardium was significantly improved 2 weeks after AVR (-13.1 +/- 3.5 dB after AVR), and this improvement was preserved 1 year after AVR. CONCLUSIONS: In patients with AS, the myocardial blood flow in the subendocardium declined preoperatively, and the coronary microcirculatory function was recovered after AVR in both the short and long term.

Chronic expanding intrapericardial hematoma after coronary artery bypass surgery presenting with congestive heart failure.

We report the successful treatment of a rare case of chronic expanding intrapericardial hematoma that had slowly developed into a large mass after coronary artery bypass surgery. An 85-year-old man with a history of coronary artery bypass surgery presented with dyspnea on exertion and leg edema in 2006. Chest roentgenograph demonstrated right pleural effusion and severe pulmonary edema. An echocardiographic study demonstrated a mass located posterior to the left ventricle that severely compressed the left ventricle toward the ventricular septum. Surgical resection of the mass was planned to release the symptoms and to confirm the diagnosis of the mass. The mass was completely resected through a left thoracotomy, and the histological findings confirmed the diagnosis of a chronic expanding intrapericardial hematoma. The patient's postoperative course was uneventful, and his symptoms improved markedly. There has been no sign of recurrence 1 year after the operation.

Detection and quantification of embolic particles during percutaneous coronary intervention to stable plaque: it correlates to coronary flow dynamics and myocardial damage.

OBJECTIVES: We detected embolic particles liberated from plaque during percutaneous coronary intervention (PCI) as high-intensity transient signals (HITS) with a Doppler guidewire and studied their impact on coronary flow dynamics and the myocardium in patients with stable angina pectoris. BACKGROUND: These embolic particles during PCI may cause myocardial injury. However, this was difficult to confirm because it was impossible to detect embolic particles. METHODS: We performed balloon angioplasty followed by stenting in 31 patients while monitoring coronary flow velocity. After PCI, we measured average peak velocity at baseline and after infusion of adenosine 5'-triphosphate to calculate coronary flow velocity reserve (CFVR) and coronary resistance index (CRI). In patients with PCI to the left coronary artery (n = 21), we calculated relative CFVR as the ratio of CFVR in the target vessel to that in the reference vessel. We measured cardiac troponin T (cTnT) the day after PCI. RESULTS: HITS were detected in 27 (87%) of 31 patients and the majority were observed after stenting. The total number of HITS was correlated with CRI (r = 0.36, P = 0.049) or relative CFVR (r = 0.65, P = 0.0036) but not with CFVR (r = 0.048, P = 0.82). Thirteen patients showed elevated cTnT (range, 0.05-0.31 ng/ml) and the total number of HITS was greater in those with elevated cTnT than in those without elevated cTnT (24 +/- 9 vs. 10 +/- 7, P = 0.0007). CONCLUSIONS: Embolic particles are frequently observed during PCI to stable plaque and the majority are liberated after stenting. There appears to be a quantitative relationship between amounts of HITS and coronary microvessel dysfunction and minor myocardial injury.

Effect of reactive hyperemia after coronary recanalization on myocardial tissue reperfusion by thrombolysis in myocardial infarction flow grade in acute myocardial infarction.

Thrombolysis In Myocardial Infarction (TIMI) flow grade is widely used to evaluate myocardial tissue reperfusion in acute myocardial infarction (AMI), but the current grading system is incomplete. Therefore, we clarified the regulation of epicardial coronary flow velocity with the progression of microvascular dysfunction in AMI. We studied 36 patients with first anterior AMI. After intervention, we assessed TIMI flow grade and measured average peak velocity (APV) at baseline and after infusion of adenosine triphosphate (48 microg; baseline and hyperemic APVs, respectively) with a Doppler guidewire. We performed myocardial contrast echocardiography after 2 weeks to assess microvascular integrity (good reflow vs no reflow) and left ventriculography at admission and discharge (24 +/- 2 days) to measure regional wall motion (SD/chord). Patients were classified into 3 groups based on TIMI flow grade and microvascular integrity: TIMI grade 3 flow/good reflow (n = 16), TIMI grade 3 flow/no reflow (n = 12), and TIMI grade 2 flow (n = 8). Baseline APV was comparable in the patients with TIMI grade 3 flow but hyperemic APV was higher in patients with TIMI grade 3 flow/good reflow than in those with TIMI grade 3 flow/no reflow (hyperemic APV 59.3 +/- 25.8 vs 32.8 +/- 8.9 cm/s, p <0.01). All patients with TIMI grade 2 flow showed no reflow and the lowest values of baseline and hyperemic APVs. Regional wall motion at discharge was higher in patients with TIMI grade 3 flow/good reflow than in those with TIMI grade 3 flow/no reflow and TIMI grade 2 flow (-1.44 +/- 0.70, -2.69 +/- 0.31, and -2.88 +/- 0.48 SD/chord, respectively, p <0.01). In conclusion, compensatory reactive hyperemia preserves epicardial coronary flow velocity even in patients with microvascular damage, and with the progression of damage, this compensatory hyperemia can no longer preserve epicardial coronary flow velocity, and baseline APV is decreased in TIMI grade 2 flow.

Hemodynamics of microvascular dysfunction in patients with anterior wall acute myocardial infarction.

This study investigated whether the no-reflow phenomenon in acute myocardial infarction (AMI) is associated with an increase in coronary zero flow pressure (ZFP), a decrease in coronary arterial conductance, or both phenomena. Coronary blood flow velocity and pressure were measured with a Doppler guidewire and a pressure wire, respectively, during vasodilation with adenosine triphosphate after coronary intervention. The data indicate that the no-reflow phenomenon is not necessarily associated with a decrease in coronary arterial conductance but with an increase in ZFP. Greater ZFP is associated with more severe microvascular dysfunction and worse functional outcomes in patients with AMI.