Effects of Ivabradine on Patients with Depressed Left Ventricular Function after Cardiac Resynchronization Therapy.

Background: The potential synergistic effect of ivabradine and cardiac resynchronization therapy (CRT) in heart failure (HF) patients has rarely been studied. We aimed to evaluate the clinical benefits of ivabradine in patients with left ventricular dysfunction following CRT implantation. Methods: Two hundred and thirty-one patients receiving CRT were consecutively enrolled between January 2014 and December 2018 from two HF centers. A total of 123 patients had left ventricular ejection fraction (LVEF) < 40% and resting sinus heart rate (HR) ≥ 75 bpm after six months of CRT implantation. Among these patients, 45 were treated with ivabradine (Group 1), and 78 did not receive ivabradine treatment (Group 2). Results: Baseline characteristics and prescription rates of HF medications other than ivabradine were similar between the two groups. In Group 1, the mean HR decreased from 82.2 ± 11.4 bpm to 76.3 ± 10.5 bpm (p = 0.012), and the mean LVEF increased from 29.9 ± 6.5% to 38.8 ± 12.4% (p < 0.001). Atrial pacing percentage, biventricular pacing percentage, and burden of atrial fibrillation (AF) were not significantly different between the two groups during the study period. The patients' daily physical activity increased significantly in Group 1 compared to Group 2 (Δ daily activity 0.4 ± 0.7 hours/day vs. -0.1 ± 7.2 hours/day, p < 0.001). Conclusions: Ivabradine could effectively reduce HR and improve physical activity. It was safe to use and did not increase AF burden or affect biventricular pacing percentage in CRT recipients.

The Characteristics and Outcomes of Patients with Heart Failure and Reduced Ejection Fraction: The Eligibility of Novel Heart Failure Medications.

BACKGROUND: Renin-angiotensin system inhibitors and beta-blockers are the initial treatment of choice for heart failure with reduced ejection fraction (HFrEF), whereas sacubitril/valsartan (SAC/VAL) and ivabradine are considered to second-line therapies. The eligibility of SAC/VAL and ivabradine according to the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) labels, Taiwan National Health Insurance (TNHI) reimbursement regulations, and European Society of Cardiology (ESC) heart failure (HF) guidelines are diverse, and they may not fulfill the needs of real-world HFrEF patients. METHODS: Patients hospitalized for HF with left ventricular ejection fraction (LVEF) ≤ 40% were recruited from 21 hospitals in Taiwan between 2013 and 2014. The criteria for SAC/VAL and ivabradine according to the different regulations were applied. RESULTS: Of 1,474 patients, 86.8%, 29.4%, and 9.5% met the EMA/FDA label criteria, TNHI-regulation, and ESC guidelines for SAC/VAL, compared to 47.1%, 37.2%, and 45.6% for ivabradine, respectively. Ineligible reasons for the TNHI regulations included LVEF > 35% (19.9%, for SAC/VAL and ivabradine) and sinus rate < 75 beats per minute (bpm) (29.9%, for ivabradine). Although not meeting the TNHI regulations, patients with LVEF 35-40% had a similar 1-year mortality rate (15.6% vs. 15.8%, p = 0.876) to those with LVEF ≤ 35%, whereas patients with a sinus rate 70-74 bpm had a similar 1-year mortality rate (15.3% vs. 16.1%, p = 0.805) to those with a sinus rate ≥ 75 bpm. CONCLUSIONS: Approximately 70% and 63% of TSOC-HFrEF registry patients were ineligible for SAC/VAL and ivabradine, respectively, according to current TNHI regulations. Regardless of the eligibility for novel HFrEF medications, the high incidence of adverse events suggests that all patients should be treated cautiously.

Observational study of dronedarone in Taiwanese patients with atrial fibrillation.

BACKGROUND/PURPOSE: Currently, data on the real-world use of dronedarone, an antiarrhythmic drug for atrial fibrillation (AF), are contradictory and often based on patient populations comprised of Caucasians. We prospectively investigated the efficacy and safety of dronedarone and risk factors related to treatment outcomes in a real-world use setting. METHODS: The prospective, observational, single-arm, multi-center study included a total of 824 Taiwanese patients with a diagnosis of paroxysmal or persistent AF and receiving dronedarone treatment. Risk factors analysis, efficacy, and safety of dronedarone were assessed with a follow-up of six months. RESULTS: Of the 824 patients enrolled (mean age, 75.3 ± 7.2 years), 95.2% had at least one cardiovascular risk factor. An increase in the proportion of patients with sinus rhythm following treatment was seen (52.1% at baseline vs. 67.4% at 6 months). A decrease in the mean duration of AF episodes (388.4 min vs. 62.3 min) and an increase in total AFEQT (65.4 ± 16.2 vs. 74.0 ± 11.8) were also observed after 6 months of treatment. Females, those under the age of 75, and those with symptomatic AF had higher odds of treatment success. At 6 months, 10.5% of patients reported treatment-related AEs. However, only 0.2% of the AEs were both severe in nature and causally related to dronedarone. CONCLUSION: This six-month study showed dronedarone to be relatively safe and efficacious and to improve quality-of-life in Taiwanese patients with atrial fibrillation. Odds of treatment success were related to the patient's gender, age, and AF type.

Transcatheter Repair of Iatrogenic Aortic Perforation Complicating Transseptal Puncture for a Catheter Ablation of Atrial Arrhythmia.

UNLABELLED: Aortic root perforation is a potentially life-threatening complication that may occur during transseptal puncture and requires immediate repair. We present a 71-year-old man who was admitted for catheter ablation of persistent atypical atrial flutter. Fluoroscopic-guided transseptal puncture was performed to gain access to the left atrium. An unrecognized puncture of the aortic root by Brockenbrough needle and inadvertent advancement of Mullins sheath resulted in aortic root perforation. We decided to seal the hole transcatheterly with an occluder device. Severe aortic regurgitation (AR) was noted by transesophageal echocardiography after deployment of a 6 mm Amplatzer septal occluder (ASO). Thereafter, we switched to a 6/4-mm Amplatzer duct occluder (ADO) and only minimal AR was noted after deployment. This is because the diameter of the left atrial disc of ASO is larger than the diameter of the retention skirt of ADO to interfere with the movement of aortic valve leaflet. During 6 months of echocardiographic follow-up, the ADO remained in place and no residual shunt was observed. KEY WORDS: Aortic perforation; Transcatheter repair; Transseptal puncture.

[The clinicopathological features of acute fibrinous and organizing pneumonia].

OBJECTIVE: To improve understanding of the clinical, radiological and pathological characteristics of acute fibrinous and organizing pneumonia (AFOP). METHODS: The clinical data of 5 AFOP patients were retrospectively analyzed. AFOP was diagnosed via percutaneous lung biopsy guided by chest computerized tomography (CT) in the Affiliated Drum Tower Hospital of Nanjing University Medical School during March 2011 to June 2012. The clinical, radiological and pathological characteristics of those patients were summarized. RESULTS: Among the 5 patients, 2 were male and 3 were female, aging 43-61 years. They were all subacute onset. The main clinical manifestations were dyspnea, productive cough, fever and chest pain with hypoxemia via blood gas analysis. Bilateral infiltrates with diffuse and pathy distribution were the predominant features in chest HRCT. The pathological examination revealed slightly widened alveolar septa, 1ymphocyte and plasma cell infiltration and the presence of intra-alveolar fibrin in the form of fibrin "balls" (organization) within the alveolar spaces. No neutrophil, and eosinophil infiltration and hyaline membrane formation were detected, which was different from other well-recognized histologic patterns of acute lung injury, such as diffuse alveolar damage, cryptogenic organizing pneumonia and eosinophilic pneumonia. All patients were treated by corticosteroids and showed significant clinical and radiological improvement. CONCLUSIONS: AFOP has nospecific features, and its diagnosis depends on pathological examination. Treatment with corticosteroids is optimal. However, whether it is a unique interstitial disease needs to be further clinically investigated.

Long-term outcome of catheter ablation in patients with atrial fibrillation originating from the superior vena cava.

UNLABELLED: Long-Term Outcome of SVC AF Ablation. INTRODUCTION: Data of the long-term clinical outcome after superior vena cava (SVC) isolation are limited. We aimed to evaluate the long-term outcome in patients with atrial fibrillation (AF) who had triggers originating from the SVC and received catheter ablation of AF. METHODS AND RESULTS: The study consisted of 68 patients (age 56 ± 12 years old, 32 males) who underwent the ablation procedure for drug-refractory, symptomatic paroxysmal AF originating from the SVC since 1999. Group 1 consisted of 37 patients with AF initiated from the SVC only, and group 2 consisted of 31 patients with both SVC and pulmonary vein (PV) triggers. During a follow-up period of 88 ± 50 months, the AF recurrence rate was 35.3% after a single procedure. The freedom-from-AF rates were 85.3% at 1 year and 73.3% at 5 years. In the baseline study, group 2 had larger left atrium (38 ± 4 mm vs 36 ± 5 mm, P = 0.04), left ventricle (50 ± 5 mm vs 46 ± 5 mm, P = 0.003), and PV diameters. Kaplan-Meier survival analysis showed a higher AF recurrence rate in group 2 compared to that in group 1 (P = 0.012). The independent predictor of an AF recurrence was a larger SVC diameter (P = 0.02, HR 1.4, 95% CI 1.1-1.8). CONCLUSION: Among the patients with paroxysmal AF originating from the SVC, 73% remained free of AF for 5 years after a single catheter ablation procedure. Superior vena cava isolation without PV isolation is an acceptable therapeutic strategy in those patients with AF originating from the SVC only. The SVC diameter was an independent predictor of AF recurrence. (J Cardiovasc Electrophysiol, Vol. 23, pp. 955-961, September 2012).

Using QRS loop descriptors to characterize the risk of sudden cardiac death in patients with structurally normal hearts.

The predictive value of non-invasive electrocardiographic examination findings for the risk of sudden cardiac death (SCD) in populations with structurally normal hearts remains unclear. This study aimed to investigate the characteristics of the QRS vectorcardiography of surface electrocardiography in patients with structurally normal hearts who experienced SCD. We consecutively enrolled patients who underwent vectorcardiography between March 2017 and December 2018 in a tertiary referral medical center. These patients didn't have structural heart diseases, histories of congestive heart failure, or reduced ejection fraction, and they were classified into SCD (with aborted SCD history and cerebral performance category score of 1) and control groups (with an intervention for atrioventricular node reentrant tachycardia and without SCD history). A total of 162 patients (mean age, 54.3±18.1 years; men, 75.9%), including 59 in the SCD group and 103 in the control group, underwent propensity analysis. The baseline demographic variables, underlying diseases, QRS loop descriptors (the percentage of the loop area, loop dispersion, and inter-lead QRS dispersion), and other electrocardiographic parameters were compared between the two groups. In the univariate and multivariate analyses, a smaller percentage of the loop area (odds ratio, 0.0003; 95% confidence interval, 0.00-0.02; p<0.001), more significant V4-5 dispersion (odds ratio, 1.04; 95% confidence interval, 1.02-1.07; p = 0.002), and longer QRS duration (odds ratio, 1.05; 95% confidence interval, 1.00-1.10; p = 0.04) were associated with SCD. In conclusion, the QRS loop descriptors of surface electrocardiography could be used as non-invasive markers to identify patients experiencing aborted SCD from a healthy population. A decreased percentage of loop area and elevated V4-5 QRS dispersion values assessed using vectorcardiography were associated with an increased risk of SCD in patients with structurally normal hearts.

Predictive value of predischarge spectral tissue doppler echocardiography and n-terminal pro-B-type natriuretic peptide in patients hospitalized with acute heart failure.

BACKGROUND: Admission for an acute heart failure (HF) confers an extremely poor prognosis. We aimed at finding out whether simultaneous assessment of multiple plasma-based biomarkers and Doppler echocardiography could provide complementary information and thus enable clinicians to stratify risk more effectively among patients hospitalized with acute HF; hence, untoward events after discharge avoided. METHODS: A comprehensive echocardiographic study and measurements of cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic protein (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) were conducted in 87 patients with symptomatic de novo acute HF or decompensation of chronic HF. Major adverse cardiac events (MACE) regarding cardiac death or hospitalization with worsening HF during a median follow-up period of 191 days were determined. RESULTS: According to the univariate analysis, echocardiographic variables left atrial volume, left atrial volume index, pulmonary artery systolic pressure, E/E' ratio, and the concentrations of NT-proBNP were significantly related to clinical outcomes (all P-values < 0.05). Cox proportional hazard analysis identified two independent prognostic predictors of MACE: E/E' ratio and NT-proBNP. Moreover, the combining of plasma level of NT-proBNP with E/E' ratio provided independent and additional prognostic value in identifying high-risk acute HF patients. CONCLUSIONS: These findings reinforce the necessity of combining the heart hemodynamic variable E/E' ratio and plasma-based neurohormonal biomarker NT-proBNP when clinicians attempt to define the individual risk of patients hospitalized with acute HF.

Transradial approach in myocardial infarction.

OBJECTIVE: This study investigates the feasibility, efficacy, and safety of routine primary percutaneous coronary intervention via transradial approach in patients with acute ST-elevation myocardial infarction. METHODS AND RESULTS: From 2005 to 2007,122 consecutive patients with acute ST-elevation myocardial infarction within 12 hours, including those experiencing cardiogenic shock, were eligible for primary transradial PCI if the radial artery pulse could be felt. Efficacy, safety, and major adverse cardiac events regarding mortality, recurrent non-fatal myocardial infarction, and revascularization were recorded. Eighty-five of 122 patients underwent transradial PCI, and 37 had transfemoral PCI. Older women, haemodynamic instability, and the presence of severe chronic kidney disease (stages 4 and 5) or end-stage renal disease were significantly related to choice of transfemoral approach (P < 0.05). Glycoprotein IIb/IIIa inhibitors were used more often in patients who underwent transradial PCI than in those who underwent transfemoral PCI (37% vs 16%; P = 0.043). The incidence of major bleeding complications requiring blood transfusion was significantly higher in the transfemoral group (P = 0.004). A similar procedural success rate was achieved in both groups (P = 0.737). During follow-up of 580 days, the total major adverse cardiac events were similar in both groups (P = 0.299). CONCLUSIONS: Routine transradial primary PCI can be safely and successfully performed on up to 70% of acute ST-elevation myocardial infarction patients and, compared with transfemoral approach, is associated with a significantly reduced rate of major bleeding complications.

Loeffler's endocarditis in a patient with a new diagnosed Churg-Strauss syndrome (CSS): A case report.

BACKGROUND: Loeffler's endocarditis is a rare disease, caused by endocardial involvement of esosinophils, which damages the heart and leads to endomyocardial fibrosis with consequent restrictive cardiomyopathy, mural thrombi or valvular dysfunction. The association between Loeffler's endocarditis and Churg-Strauss syndrome (CSS) was also reported. Abnormal elevation of peripheral eosinophil counts in a heart failure patient is a hint of disease. Though echocardiography or cardiac magnetic resonance imaging (MRI) facilitates diagnosis, endomyocardial biopsy is still the gold standard. Treatments include immunosuppressive agents, anticoagulant and guideline-directed medical therapy for heart failure. CASE PRESENTATION: A 59-year-old man presented with progressive dyspnea for one week and he was referred to our hospital for surgical treatment evaluation because valve destruction by infective endocarditis has been suspected at the local hospital. Echocardiography revealed biventricular mural thrombus and limited aortic valve opening caused by abutting thrombus. Moreover, eosinophilia, bronchial asthma, lung infiltration, acute kidney injury and positive perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) test implied Churg Strauss syndrome. Eosinophil infiltrate with fibrin thrombus was revealed by endomyocardial biopsy. The patient was diagnosed of cardiac involvement of CSS and recovered after immunosuppressive and anticoagulant treatments. CONCLUSION: Loeffler's endocarditis should be suspected when physicians encounter restrictive cardiomyopathy accompanied by mural thrombus in a patient with eosinophilia. Prompt immunosuppressive and anticoagulant medication can bring the disease under control.

Prediction of Recurrent Atrial Tachyarrhythmia After Receiving Atrial Flutter Ablation in Patients With Prior Cardiac Surgery for Valvular Heart Disease.

Background: Surgical scars cause an intra-atrial conduction delay and anatomical obstacles that facilitate the perpetuation of atrial flutter (AFL). This study aimed to investigate the outcome and predictor of recurrent atrial tachyarrhythmia after catheter ablation in patients with prior cardiac surgery for valvular heart disease (VHD) who presented with AFL. Methods: Seventy-two patients with prior cardiac surgery for VHD who underwent AFL ablation were included. The patients were categorized into a typical AFL group (n = 45) and an atypical AFL group (n = 27). The endpoint was the recurrence of atrial tachyarrhythmia during follow-up. A multivariate analysis was performed to determine the predictor of recurrence. Results: No significant difference was found in the recurrence rate of atrial tachyarrhythmia between the two groups. Patients with concomitant atrial fibrillation (AF) had a higher recurrence of typical AFL compared with those without AF (13 vs. 0%, P = 0.012). In subgroup analysis, typical AFL patients with concomitant AF had a higher incidence of recurrent atrial tachyarrhythmia than those without it (53 vs. 14%, P = 0.006). Regarding patients without AF, the typical AFL group had a lower recurrence rate of atrial tachyarrhythmia than the atypical AFL group (14 vs. 40%, P = 0.043). Multivariate analysis showed that chronic kidney disease (CKD) and left atrial diameter (LAD) were independent predictors of recurrence. Conclusions: In our study cohort, concomitant AF was associated with recurrence of atrial tachyarrhythmia. CKD and LAD independently predicted recurrence after AFL ablation in patients who have undergone cardiac surgery for VHD.

Role of the N-terminus in human 4-hydroxyphenylpyruvate dioxygenase activity.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a key enzyme in tyrosine catabolism, catalysing the oxidation of 4-hydroxyphenylpyruvate to homogentisate. Genetic deficiency of this enzyme causes type III tyrosinaemia. The enzyme comprises two barrel-shaped domains formed by the N- and C-termini, with the active site located in the C-terminus. This study investigated the role of the N-terminus, located at the domain interface, in HPPD activity. We observed that the kcat/Km decreased ∼8-fold compared with wild type upon removal of the 12 N-terminal residues (ΔR13). Interestingly, the wild-type level of activity was retained in a mutant missing the 17 N-terminal residues, with a kcat/Km 11-fold higher than that of the ΔR13 mutant; however, the structural stability of this mutant was lower than that of wild type. A 2-fold decrease in catalytic efficiency was observed for the K10A and E12A mutants, indicating synergism between these residues in the enzyme catalytic function. A molecular dynamics simulation showed large RMS fluctuations in ΔR13 suggesting that conformational flexibility at the domain interface leads to lower activity in this mutant. These results demonstrate that the N-terminus maintains the stability of the domain interface to allow for catalysis at the active site of HPPD.

Recovery of left ventricular dysfunction after sacubitril/valsartan: predictors and management.

BACKGROUND: Literature describing recovery of left ventricular (LV) function post sacubitril/valsartan treatment and the optimal management of heart failure (HF) patients receiving sacubitril/valsartan remain sparse. METHODS: We recruited 437 consecutive chronic HF patients with baseline left ventricular ejection fraction (LVEF) less than 40%, who were treated with sacubitril/valsartan. All patients underwent routine echocardiographic measurement. RESULTS: During treatment period, recovery of LVEF to 50% or greater was observed in 77 (17.6%) patients. After multivariate analysis, recovery of LV dysfunction was associated with non-ischemic etiology of HF, smaller baseline LV end-diastolic diameter (LVEDD), and higher initial dosage of sacubitril/valsartan. Compared to those without recovery of LV dysfunction, death from cardiovascular causes or first unplanned hospitalization for HF (CVD/HFH) were significantly lower in patients with LVEF recovery [11.7% vs. 24.4%, hazard ratio (HR) 0.42, p = 0.014]. Among patients with recovery of LVEF, 51 patients continued to receive the same dosage of sacubitril/valsartan had higher LVEF and were less likely to have deterioration of LVEF than the other 26 patients who received either tapering dose of sacubitril/valsartan or switching from sacubitril/valsartan to renin-angiotensin-system blockers (LVEF 56.4 ± 5.3% vs. 45.0 ± 12.8%, p < 0.001; ΔLVEF 1.2 ± 5.1% vs. -9.3 ± 12.0%, p < 0.001). CVD/HFH occurred more frequently in the taper group than the maintenance group (23.1% vs. 5.9%, HR 0.22, p = 0.035). CONCLUSIONS: Non-ischemic etiology of HF, smaller baseline LVEDD, and higher initial dosage of sacubitril/valsartan could predict better recovery of LV function. Among patients with functional recovery, tapering sacubitril/valsartan dose was associated with deterioration of recovered heart function and had less favorable prognosis during follow-up.

Prescription patterns of diabetes medications influencing clinical outcomes of heart failure patients with reduced ejection fraction.

AIMS: We collected the different prescription patterns of diabetes medications in a cohort of patients with heart failure with reduced ejection fraction (HFrEF) and analysed the impact of different prescription patterns on clinical outcomes. METHODS AND RESULTS: Consecutive diabetic patients with HFrEF from a heart failure referral centre were retrospectively analysed between 2015 and 2016. Exclusion criteria include being lost to follow-up, not receiving diabetes medications, and having severe renal impairment with a glomerular filtration rate < 30 mL/min/1.73 m2 . Prescription of diabetes medications and the respective clinical outcomes were collected between 2016 and 2018. Among 381 patients (mean age, 64.8 ± 12.8 years; 71.9% male; mean left ventricular ejection fraction, 27.6 ± 7.0%; mean body mass index, 26.1 ± 4.7 kg/m2 ), the prescription rates of sodium-glucose co-transporter 2 inhibitor (SGLT2i) increased from 10.3% in 2016 to 17.6% in 2017 and 26.5% in 2018 (P < 0.001); the prescription rates of metformin, sulfonylurea, insulin, and dipeptidyl peptidase-4 inhibitors did not change significantly over time. The prescription rates of metformin and SGLT2i were significantly higher in patients managed by cardiologists than non-cardiologists (in 2018, 71.1% vs. 44.2% for metformin, 45.4% vs. 9.9% for SGLT2i, both P < 0.001). During the study period, annualized event rates of cardiovascular death or first unplanned HF hospitalization were 19.0 per 100 patient-years. After a multivariate analysis, prescriptions of metformin {odds ratio (OR): 0.49 [95% confidence interval (CI) 0.27-0.51], P < 0.001} and SGLT2i [OR: 0.52 (95% CI 0.28-0.98), P = 0.042] were independently associated with lower annualized event rates of cardiovascular death or unplanned HF hospitalization. CONCLUSIONS: Prescription patterns of diabetes medications in diabetics with HFrEF were diverse among different specialists. Prescriptions of metformin and SGLT2i were associated with favourable clinical outcomes. Our finding indicates the importance of awareness of beneficial effect of different classes of diabetes medications and collaboration between specialists in the management of diabetic HFrEF patients.

Managements and outcomes of hospitalized heart failure patients with paroxysmal vs nonparoxysmal atrial fibrillation in Taiwan.

BACKGROUND: The prognostic significance and the optimal treatment strategy for patients with atrial fibrillation (AF) and heart failure (HF) remain controversial. METHODS: We extracted data from a large prospective national database involving Taiwanese patients with AF who were hospitalized for acute HF with reduced ejection fraction. Baseline characteristics, AF types, medications, and 1-year outcomes of the patients were analyzed. RESULTS: At baseline, 393 (26%) patients had AF, including 117 (29.8%) patients with paroxysmal AF (PAF) and 276 (70.2%) with nonparoxysmal AF (N-PAF). Patients with PAF were more likely to have ischemic cardiomyopathy (47.3% vs 29.7%, p = 0.021), chronic kidney disease (46.2% vs 29.0%, p = 0.001), and higher CHA2DS2-VASc score (4.0 vs 3.6, p = 0.033) compared with patients with N-PAF; however, patients with N-PAF had larger left atrial diameter (50.5 vs 47.3 mm, p = 0.004) than patients with PAF. Patients with PAF were more likely to receive treatment with amiodarone (31.6% vs 13.8%, p < 0.001) and antiplatelet agents (54.1% vs 42.5%, p = 0.041) but less likely to receive treatment with renin-angiotensin system blockers (52.3% vs 64.9%, p = 0.021) and anticoagulants (33.3% vs 50%, p = 0.003) compared with patients with N-PAF at discharge. The 1-year mortality (26.2% vs 16.5%, p = 0.024) and non-HF-related death rates (13.1% vs 5%, p = 0.005) were significantly higher in patients with PAF, whereas HF and arrhythmic death rates were similar in both groups (13.1% vs 11.5%). CONCLUSION: Among patients with HF complicated with AF, those with PAF were more likely to receive antiarrhythmic agents, less likely to receive guideline-recommended therapy, but developed worse 1-year outcome compared with patients with N-PAF. These findings further emphasize the importance of optimal guideline-recommended medical therapy in patients with HF.

Sacubitril/valsartan in heart failure with reduced ejection fraction patients: Real world experience on advanced chronic kidney disease, hypotension, and dose escalation.

BACKGROUND: Angiotensin receptor and neprilysin inhibition (ARNI) has been shown to reduce cardiovascular mortality by 20% as compared with enalapril in a randomized controlled trial. However, there is a paucity of real-world data on the effects of ARNI in heart failure patients with reduced ejection fraction (HFrEF), especially those with concurrent renal impairment or hypotension. METHODS: Between 2016 and 2017, we recruited 466 HFrEF patients treated with sacubitril/valsartan (Group A) and 466 patients managed with standard HF treatment without ARNI (Group B) in a HF referral center. Baseline characteristics and clinical outcomes were collected between both groups. RESULTS: Baseline characteristics were comparable between the two groups. During a follow-up period of 15 months, death from cardiovascular causes or first unplanned hospitalization for HF occurred in 100 patients in Group A (21.5%) and 144 in Group B (30.9%, hazard ratio 0.66; 95% CI 0.51-0.85; p=0.001). The incidences of deaths from any causes, cardiovascular death, sudden death, and HF re-hospitalization were all significantly lower in Group A than Group B patients. Among patients with different chronic kidney disease stages and normotensive patients, treatment with sacubitril/valsartan showed more favorable outcomes than treatment with standard HF care without ARNI. However, in patients with baseline systolic blood pressure lower than 100mmHg, there were no significant differences of outcomes in both groups. Among Group A patients, escalation of sacubitril/valsartan was associated with better outcomes. CONCLUSIONS: Our study demonstrated the effectiveness of sacubitril/valsartan on HFrEF patients in real world practice, including those with advanced renal impairment.

The autonomic neural mechanism of right ventricular outflow tract tachycardia.

BACKGROUND: Ventricular tachycardia (VT) and ventricular premature complexes (VPCs) originating from the right ventricular outflow tract (RVOT) are generally considered as benign arrhythmias, with ECG morphology showing LBBB pattern and inferior axis. Pathogenic mechanisms in the genesis of RVOT VT/VPC remain largely unknown. We aimed to investigate the neural mechanism in RVOT ventricular arrhythmias in canine model. METHODS: Twelve mongrel dogs (13.7 ±â€¯1.3 kg, 5 male dogs) were studied through midline thoracotomies. High-frequency stimulation (HFS) was applied to the proximal pulmonary artery (PA) to induce RVOT VT/VPC. An EnSite Array and a mapping catheter were used for electroanatomical mapping. The RVOT and PA were surgically excised for immunohistochemistry studies, including tyrosine hydroxylase (TH) stain for sympathetic nerves and choline acetyltransferase (ChAT) stain for parasympathetic nerves. RESULTS: In nine (75%) out of twelve dogs, HFS of the proximal PA induced RVOT VT/VPC. The density of TH-positive nerves was significantly higher than that of ChAT-positive nerves (6803 ±â€¯700 vs. 670 ±â€¯252 µm2/mm2, p < 0.001). Furthermore, the density of TH-positive nerves was also significantly higher in the VT/VPC origin sites than that in the non-origin sites (18,044 ±â€¯2866 vs. 5554 ±â€¯565 µm2/mm2, p = 0.002). Catheter ablation of the proximal PA eliminated the inducibility of RVOT VT/VPC successfully. CONCLUSIONS: HFS of the proximal PA could induce RVOT VT/VPC. The sympathetic nerves were densely innervated to the origin of RVOT VT/VPC, indicating the critical role of sympathetic hyperactivity in the initiation and perpetuation of RVOT VT/VPC.

Role of epithelial-mesenchymal transition markers E-cadherin, N-cadherin, ß-catenin and ZEB2 in laryngeal squamous cell carcinoma.

Epithelial-mesenchymal transition (EMT) allows neoplastic cells to gain the invasive phenotype and become migratory, which is required for cancer progression and metastasis. In the present study, the expression of EMT-associated biomarkers and their association with clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC) was investigated. E-cadherin, N-cadherin, ß-catenin and zinc finger E-box binding homeobox 2 (ZEB2) protein expression was evaluated with immunohistochemistry in a cohort of 76 patients with operable LSCC. The association between these transition markers, clinicopathological parameters and their prognostic impact in LSCC was analyzed. Immunohistochemical analysis revealed that EMT-associated proteins were differentially expressed between LSCC and adjacent non-neoplastic laryngeal tissue. Negative E-cadherin expression and positive N-cadherin, ß-catenin and ZEB2 expression were associated with a later tumor (T) stage, decreasing tumor differentiation and a reduced overall survival (OS) time (OS: E-cadherin, P=0.016; N-cadherin, P=0.003; ß-catenin, P=0.002; ZEB2, P=0.0003). E-cadherin/ß-catenin co-expression was significantly associated with the majority of clinicopathological parameters assessed, including lymph node metastases, T stage and tumor cell differentiation (P=0.004, P=0.005, and P<0.001, respectively). Multivariate analysis indicated that T stage and the positive expression of ß-catenin and ZEB2 were independent risk factors for OS in LSCC (P=0.014, P=0.025 and P=0.003, respectively). It was concluded that EMT mediates tumor progression, and reduces OS time in patients with LSCC. E-cadherin/ß-catenin co-expression may be associated with clinicopathological parameters. T stage, and the positive co-expression of ß-catenin and ZEB2 may be independent predictors of prognosis in LSCC.

Multimarker approach to risk stratification among patients with advanced chronic heart failure.

BACKGROUND: Cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP) each predict adverse cardiac events in chronic heart failure (CHF). However, little is known about the utility of these novel biomarkers of CHF in combination. HYPOTHESIS: : We hypothesized that simultaneous assessment of the three biomarkers would enable clinicians to stratify risk more effectively among patients with advanced CHF. METHODS: Measurements of the biomarkers were performed on 152 patients with symptomatic advanced CHF. Major adverse cardiac events during a median follow-up period of 186 days were determined. RESULTS: Univariate and multivariate analysis revealed that elevations of each biomarker were significant predictors of clinical outcome independently of clinical variables. When patients were categorized on the basis of the number of elevated biomarkers, patients with one, two and three elevated biomarkers respectively had a 2.7-(p = 0.125), 8.6- (p < 0.0001) and 23.4-(p < 0.0001) fold increase in the risk of adverse events. CONCLUSIONS: Simultaneous measurement of cTnI, hsCRP, and NT-proBNP could provide complementary information and a simple multimarker strategy that categorizes the patients with advanced CHF based on the number of elevated biomarkers, allowing rapid risk stratification in these patients.