Possibility of steroid therapy without pacemaker implantation in patients with sarcoidosis presenting atrioventricular block.

Atrioventricular Block (AVB) is one of the common manifestations in cardiac sarcoidosis (CS). Although pacemaker implantation is generally recommended in patients with CS complicated by symptomatic AVB, some case reports have shown that they can be managed by steroid therapy without pacemaker implantation. The aim of this study was to evaluate the feasibility and effectiveness of steroid therapy without pacemaker implantation in patients with CS complicated by symptomatic AVB. We performed medical record review of consecutive ten CS patients who admitted Nippon Medical School Hospital for symptomatic second or third degree AVB between April 2015 and March 2021. Of the studied population, steroid therapy before pacemaker implantation was feasible in three patients with second degree AVB. Two of them showed subsequent recovery of atrioventricular conduction to 1:1, and they were managed by steroid therapy without pacemaker. The remaining one patient showed no improvement of atrioventricular conduction and required pacemaker implantation. Seven patients with third degree AVB required device implantation (pacemaker; n = 7, cardiac resynchronization therapy defibrillator; n = 1) before steroid therapy mainly because of hemodynamic instability. Steroid therapy without pacemaker implantation might be feasible, and possibly be effective in patients with CS presenting second degree AVB. However, the feasibility is limited in patients with third degree AVB.

Characteristics of patients with atrial flutter and spontaneous 1:1 atrioventricular conduction with and without anti-arrhythmic drug treatment.

Atrial flutter (AFL) is a large reentrant circuit located in the right atrium. Anti-arrhythmic drugs (AADs) can provoke AFL with 1:1 atrioventricular conduction (AVC) to cause hemodynamic collapse. We elucidated the characteristics of patients with AFL exhibiting spontaneous 1:1 AVC. Fifteen patients (1:1 AFL group; 11 males, 52.4 ± 13.7 years old) who documented AFL with 1:1 AVC were enrolled and compared to 153 patients without 1:1 AVC (Control group; 137 males, 68.9 ± 11.2 years old). AFL cycle length during maximum AVC was significantly longer in the 1:1 AFL group than in the control group (274.7 ± 37.0 vs. 216.2 ± 25.6 ms, p < 0.001). Among 1:1 AVC group, 9 patients had AADs, and AFL cycle length was significantly longer during 1:1 AVC as compared with 2:1 AVC documented the other day (284.4 ± 41.3 vs. 233.3 ± 26.0 ms, p < 0.001), suggesting enhancement effect of the AADs during 1:1 AVC. Remaining 6 patients who did not take AADs, 2 patients showed enlargement of the tricuspid annulus and 3 patients developed 1:1 AVC during exercise. Multivariate analysis revealed that younger age and the use of AADs was independent risk factors for the development of 1:1 AFL group. Prolonged AFL cycle length associated with the class Ia/Ic AAD use, slower heart rate during sinus rhythm and younger age were important risk factors for the development of 1:1 AVC during AFL.

Localization of Late Gadolinium Enhancement and Its Association with Ventricular Tachycardia in Patients with Cardiac Sarcoidosis.

Sustained ventricular tachycardia (sVT), leading to sudden cardiac death, is one of the common manifestations in cardiac sarcoidosis (CS). Although late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) has been reported to be associated with sVT, the relationships of its localization to sVT have not been fully evaluated.To evaluate the localization of LGE and its relationships to sVT in patients with CS, we reviewed medical record of consecutive 31 patients with CS who underwent CMR. The localization of LGE was divided into four categories: Left ventricular (LV) septum, LV free wall, right ventricular (RV) septum, and RV free wall. We investigated the association of sVT with localization of LGE and other parameters including serum biomarkers LV ejection fraction on echocardiography and Fluorine-18-fluorodeoxyglucose (FDG) accumulation on positron emission tomography (PET) -CT.Of the studied population, 8 patients (25.8%) were known to present with sVT among 31 CS patients. LGE was observed in the RV free wall in 6 patients with sVT, whereas it was in 5 patients without sVT (75.0% versus 21.7%, P = 0.022). Univariate analysis showed that only LGE in the RV free wall was associated with sVT (odds ratio [OR]: 10.80; 95% confidence interval [CI]: 1.64-70.93, P = 0.013).LGE in the RV free wall was associated with sVT in patients with CS.

Prognostic impact of newly detected atrial fibrillation in patients with hypertrophic cardiomyopathy following cardiac implantable electronic device implantation.

Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). The present study aimed to investigate the incidence and prognostic impact of newly detected AF after cardiac implantable electronic device (CIED) implantation with HCM patients. Fifty-six patients (33 men, age 57 ± 17 years) with HCM who underwent CIED implantations with no previous history of AF at the time of implantation (ICD n = 46, Pacemaker n = 10) were retrospectively enrolled. During 5.7 ± 3.6 years of follow-up, AF was newly detected in 20 (36%) of 56 patients after the CIED implantation (AF group) and the rest of the patients had no newly detected AF (non-AF group). The presence of mitral regurgitation (HR 8.49; 95% CI 2.29-30.6 P < 0.01) and concomitant NYHA II-IV (HR 3.37; 95% CI 1.30-8.86 P = 0.01) were the independent predictors of newly detected AF. During the follow-up, all patients in the AF group started anticoagulation mean 21 days after detection of AF, and none had a stroke during the follow-up period. The rate of appropriate ICD therapy (log-rank P = 0.95), inappropriate ICD therapy (log-rank P = 0.78), and all-cause death (log-rank P = 0.23) were similar between the two groups. However, the incidence of hospitalizations due to heart failure was higher in the AF group (55% vs. 6% log-rank P < 0.01). In conclusion, the incidence of newly detected AF after CIED implantations in HCM patients was high. The newly detected AF was associated with worsening heart failure and careful follow-up is recommended.

Differential diagnosis between LQT1 and LQT2 by QT/RR relationships using 24-hour Holter monitoring: A multicenter cross-sectional study.

BACKGROUND: The clinical course and therapeutic strategies in the congenital long QT syndrome (LQTS) are genotype-specific. However, accurate estimation of LQTS genotype is often difficult from the standard 12-lead ECG. OBJECTIVES: This study aims to evaluate the utility of QT/RR slope analysis by the 24-hour Holter monitoring for differential diagnosis of LQTS genotype between LQT1 and LQT2. METHODS: This cross-sectional study enrolled 54 genetically identified LQTS patients (29 LQT1 and 25 LQT2) recruited from three medical institutions. The QT-apex (QTa) interval and the QT-end (QTe) interval at each 15-second were plotted against the RR intervals, and the linear regression (QTa/RR and QTe/RR slopes, respectively) was calculated from the entire 24-hour and separately during the day or night-time periods of the Holter recordings. RESULTS: The QTe/RR and QTa/RR slopes at the entire 24-hour were significantly steeper in LQT2 compared to those in LQT1 patients (0.262 ± 0.063 vs. 0.204 ± 0.055, p = .0007; 0.233 ± 0.052 vs. 0.181 ± 0.040, p = .0002, respectively). The QTe interval was significantly longer, and QTe/RR and QTa/RR slopes at daytime were significantly steeper in LQT2 than in LQT1 patients. The receiver operating curve analysis revealed that the QTa/RR slope of 0.211 at the entire 24-hour Holter was the best cutoff value for differential diagnosis between LQT1 and LQT2 (sensitivity: 80.0%, specificity: 75.0%, and area under curve: 0.804 [95%CI = 0.68-0.93]). CONCLUSION: The continuous 24-hour QT/RR analysis using the Holter monitoring may be useful to predict the genotype of congenital LQTS, particularly for LQT1 and LQT2.

Prevalence and characteristics of portopulmonary hypertension in cirrhotic patients who underwent both hepatic vein and pulmonary artery catheterization.

Portopulmonary hypertension (PoPH) is a well-known complication of liver cirrhosis. The aim of this study was to clarify the pulmonary hemodynamics and the prevalence and characteristics of PoPH in patients with portal hypertension. METHODS: The subjects were 335 patients with portal hypertension diagnosed by hepatic vein pressure gradient (HVPG). Among them, 186 patients received measurements of pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR). PoPH was diagnosed by PAP >20 mmHg, PVR ≥3 Wood units (WU) and PAWP ≤15 mmHg. RESULTS: The Child-Pugh classification was class A in 53, B in 92 and C in 41 patients. Median (range) values of HVPG, PAP, PVR and PAWP were 18.4 (5.5-39.0) mmHg, 12.9 (6.6-40.8) mmHg, 0.8 (0.1-4.5) WU and 7.5 (2.2-15.4) mmHg, respectively. Of six patients with PAP >20 mmHg, four had autoimmune hepatitis or primary biliary cholangitis, with the prevalence being significantly higher than that in patients with PAP ≤20 mmHg. Meanwhile, no significant difference was noted in the hepatic functional reserve or HVPG between patients with PAP >20 mmHg and ≤20 mmHg. Only two patients met the diagnostic criteria of PoPH and both patients were Child-Pugh B. The Child-Pugh score and HVPG were not associated with PoPH. CONCLUSIONS: Our study demonstrated that only two patients were complicated by PoPH. High PAP values were noted in patients with primary biliary cholangitis or autoimmune hepatitis. However, the presence of PoPH and high PAP were not associated with the degree of hepatic functional reserve or HVPG.

Differential Effectiveness of Landiolol Between Atrial Fibrillation and Atrial Flutter/Atrial Tachycardia Patients With Left Ventricular Dysfunction.

BACKGROUND: Landiolol, an ultra-short acting ß1-selective blocker, is more effective for controlling the heart rate (HR) than digoxin in patients with atrial tachyarrhythmias and left ventricular (LV) dysfunction. The impact of the type of atrial tachyarrhythmias on the effectiveness of landiolol is uncertain. We evaluated the efficacy and safety of landiolol on tachycardiac atrial fibrillation (AF) and tachycardiac atrial flutter/atrial tachycardia (AFl/AT) in patients with reduced LV function. Methods and Results: Seventy-seven patients treated with landiolol were retrospectively analyzed. There were no significant differences in the baseline characteristics between the AF group (n=65) and AFl/AT group (n=12). Despite a higher dosage, the %change in HR from baseline to 12 and 24 h was only -10.2±12.7% and -16.1±19.4% in the AFl/AT group, while it was -28.3±13.2% and -31.3±11.3% in the AF group (P<0.02), respectively. The prevalence of the responders to landiolol treatment was much greater in the AF group than in the AFl/AT group (P<0.001). Alternative treatments such as i.v. amiodarone and electrical cardioversion were required in 83% of the AFl/AT patients. CONCLUSIONS: Landiolol was ineffective in the majority of AFl/AT patients. An alternative management to prevent any worsening of heart failure might be considered in those patients.

Electrocardiographic characteristics in the patients with a persistent left superior vena cava.

A persistent left superior vena cava (PLSVC) is a congenital venous abnormality and is usually asymptomatic and does not cause hemodynamic disturbances. Therefore, it is difficult to identify it by routine examinations in clinical practice. This study aimed to elucidate the electrocardiographic characteristics for the prediction of a PLSVC. Twelve patients (9 males, 56.2 ± 18.3 years) who were diagnosed with a PLSVC were enrolled. The electrocardiographic parameters, including the P-wave duration, axis, and morphology of the P waves, were automatically measured and compared to 150 controls (77 males, 57.3 ± 14.6 years). There were no significant differences in the P-wave duration. Negative or positive/negative P waves in lead III predicted a PLSVC with a sensitivity of 100% and specificity of 81%. The P-wave axis in PLSVC exhibited a significant leftward deviation as compared to the controls (14.8 ± 21.1 vs. 54.0 ± 17.4°, p < 0.001). A receiver operating characteristic curve analysis of the P-wave axis for predicting a PLSVC exhibited an area under curve of 0.93 [CI 95% (0.87-0.98), p < 0.001), and identified a P-wave axis of less than 37.5° to have a 92% sensitivity and 83% specificity in predicting a PLSVC. A negative or positive/negative P-wave morphology in lead III was a useful finding for suggesting the presence of a PLSVC.

Validating vignette and conjoint survey experiments against real-world behavior.

Survey experiments, like vignette and conjoint analyses, are widely used in the social sciences to elicit stated preferences and study how humans make multidimensional choices. However, there is a paucity of research on the external validity of these methods that examines whether the determinants that explain hypothetical choices made by survey respondents match the determinants that explain what subjects actually do when making similar choices in real-world situations. This study compares results from conjoint and vignette analyses on which immigrant attributes generate support for naturalization with closely corresponding behavioral data from a natural experiment in Switzerland, where some municipalities used referendums to decide on the citizenship applications of foreign residents. Using a representative sample from the same population and the official descriptions of applicant characteristics that voters received before each referendum as a behavioral benchmark, we find that the effects of the applicant attributes estimated from the survey experiments perform remarkably well in recovering the effects of the same attributes in the behavioral benchmark. We also find important differences in the relative performances of the different designs. Overall, the paired conjoint design, where respondents evaluate two immigrants side by side, comes closest to the behavioral benchmark; on average, its estimates are within 2% percentage points of the effects in the behavioral benchmark.

Blanking Period Phenomenon After a Second Atrial Fibrillation Ablation Session: The Application and Factors Related to It.

INTRODUCTION: The concept of a 3-month blanking period is widely accepted after the first radiofrequency catheter ablation (RFCA) session for atrial fibrillation (AF). We sought to investigate whether this phenomenon was also observed after a 2nd session, and which factors were related to it. METHODS AND RESULTS: We conducted a prospective observational study including all AF patients who underwent RFCA since 2010. The patients who underwent a second RFCA were followed without any antiarrhythmic drugs. Their clinical background, laboratory data, echocardiographic parameters, ablation procedures, and arrhythmia recurrences were analyzed. Recurrences were classified into early period recurrences (EPRs) and late period recurrences (LPRs) recorded within and after the first 3 months postablation, respectively. Among 925 patients who underwent an initial AF ablation, 2nd sessions were performed in 250 patients, and EPRs and LPRs occurred in 53 (21.2%) and 54 (21.6%) patients, respectively. Although EPRs were an independent predictor of LPRs (hazard ratio [HR], 8.01; 95% confidence interval [CI] 4.03-15.93, P < 0.001), 20 of the patients with EPRs (37.7%) did not experience LPRs, supporting the concept of a blanking period. Among 53 patients with EPRs, the E/E' ratio on echocardiography (HR, 1.156; 95% CI 1.00-1.33, P = 0.04) was an independent predictor of LPRs, while other parameters including the maximum serum C-reactive protein level after the session and the ablation procedure details were not. CONCLUSION: A 3-month blanking period was also applicable after the 2nd AF ablation session. This phenomenon was related to a lower left atrial pressure demonstrated by the E/E' ratio.

Novel strategy for cystitis glandularis: Oral treatment with cyclooxygenase-2 inhibitor.

Cystitis glandularis, a proliferative disease of the bladder, is resistant to antibiotics, non-steroidal anti-inflammatory drugs, anti-allergy drugs and transurethral resection. Cystectomy or partial cystectomy is occasionally required for refractory cystitis glandularis. It has not been defined if cystitis glandularis is a premalignant lesion. We experienced a case of remission from cystitis glandularis after combination of oral treatment with selective cyclooxygenase-2 inhibitor, celecoxib and transurethral resection. Immunohistochemistry showed positive signals of cyclooxygenase-2 in the epithelium of pretreatment specimens, suggesting the pathophysiological role of cyclooxygenase-2 in cystitis glandularis. Here, we show the effectiveness of celecoxib against cystitis glandularis for the first time. Celecoxib could be one of the therapeutic strategies for cystitis glandularis.

Clinical and Electrocardiographic Characteristics of Electrical Storms Due to Monomorphic Ventricular Tachycardia Refractory to Intravenous Amiodarone.

BACKGROUND: Few reports are available on the characteristics of electrical storms of ventricular tachycardia (VT storm) refractory to intravenous (IV) amiodarone. METHODS AND RESULTS: IV-amiodarone was administered to 60 patients with ventricular tachyarrhythmia between 2007 and 2012. VT storms, defined as 3 or more episodes of VT within 24 h, occurred in 30 patients (68±12 years, 7 female), with 12 having ischemic and 18 non-ischemic heart disease. We compared the clinical and electrocardiographic characteristics of the patients with VT storms suppressed by IV-amiodarone (Effective group) to those of patients not affected by the treatment (Refractory group). IV-amiodarone could not control recurrence of VT in 9 patients (30%). The Refractory group comprised 5 patients with acute myocardial infarctions. Although there was no difference in the VT cycle length, the QRS duration of both the VT and premature ventricular contractions (PVCs) followed by VT was narrower in the Refractory group than in the Effective group (140±30 vs. 178±25 ms, P<0.01; 121±14 vs. 179±22 ms, P<0.01). In the Refractory group, additional administration of IV-mexiletine and/or Purkinje potential-guided catheter ablation was effective. CONCLUSIONS: IV-amiodarone-refractory VT exhibited a relatively narrow QRS tachycardia. The narrow triggering PVCs, suggesting a Purkinje fiber origin, may be treated by additional IV-mexiletine and endocardial catheter ablation.

Refractory urinary fistula with infundibular stenosis after partial nephrectomy.

A 71-year-old male patient who was diagnosed with renal cell carcinoma (cT1aN0M0) underwent a laparoscopic left partial nephrectomy. Because the bleeding could not be controlled, conversion to laparotomy was instigated. A ureteral stent was placed on confirmation of postoperative urine leakage from the drain, but the volume of drainage did not decrease. The findings of retrograde pyelography and computed tomography showed a urinary fistula resulting from isolated calyces caused by infundibular stenosis, for which transurethral dilatation for the stenosis was carried out. However, owing to the severity of stenosis, the guidewire was unable to achieve passage, and endoscopic dilatation was abandoned. Selective embolization of the left renal artery was then carried out. No drainage fluid was observed after embolization, and residual renal function of the left kidney was confirmed.

Oxidative stress in the levator aponeurosis in Asian involutional blepharoptosis.

PURPOSE: To analyze the histopathology and expression of 8-hydroxydeoxyguanosine (OHdG), a marker of oxidative stress, in the levator aponeurosis tissues of involutional aponeurotic and congenital blepharoptosis patients, and adult subjects with no history of blepharoptosis. METHODS: Fourteen and 4 levator aponeurosis tissues obtained from Asian patients with involutional and congenital blepharoptosis and 3 normal adult tissues were examined. All tissues were fixed in 4% paraformaldehyde, embedded in paraffin, and then submitted for hematoxylin and eosin staining and immunohistochemistry with anti-8-OHdG antibody. RESULTS: The levator aponeurosis tissues contained spindle smooth muscle fibers and striated muscles. Nuclear immunoreactivity for 8-OHdG was noted in striated and smooth muscle cells in all the tissues. The 8-OHdG-positive rate was significantly lower in congenital blepharoptosis than involutional blepharoptosis (p < 0.05). Moreover, the number of 8-OHdG-positive striated muscle cells was significantly higher in the involutional blepharoptosis than normal tissues (p < 0.05). In contrast, there was a rare positive 8-OHdG-immunoreactivity of smooth muscle cells in the aponeurotic tissues of the involutional blepharoptosis patients. CONCLUSIONS: Levator aponeurosis in involutional aponeurotic blepharoptosis tissues showed oxidative stress in the muscle, indicating that oxidative stress plays a potential role in the pathologic study of the disease.

Electrophysiological and Histopathological Characteristics of Ventricular Tachycardia Associated With Primary Cardiac Tumors.

BACKGROUND: Ventricular tachycardia (VT) associated with primary cardiac tumors (PCTs) originating from the ventricles is rare, but lethal, in young patients. OBJECTIVES: This study aimed to clarify the mechanisms underlying primary cardiac tumor-related ventricular tachycardia (PCT-VT) and establish a therapeutic strategy for this form of VT. METHODS: Among 67 patients who underwent surgery for VT at our institute between 1981 and 2020, 4 patients aged 1 to 34 years, including 3 males, showed PCT-VT (fibroma, 2; lipoma, 1; and hamartoma, 1), which was investigated using a combination of intraoperative electroanatomical mapping and histopathological studies. RESULTS: All 4 patients developed electrical storms of sustained VTs refractory to multiple drugs and repetitive endocardial ablations. The VT mechanism was re-entry, and intraoperative electroanatomical mapping showed a centrifugal activation pattern originating from the border between the tumor and healthy myocardium, where fractionated potentials were detected during sinus rhythm. Histopathological studies of serial sections of specimens acquired from these areas revealed tumor infiltration into the surrounding myocardium with cell disorganization, exhibiting myocardial disarray. Several myocardia entrapped in the tumor edges contributed to the development and sustainment of re-entrant VT activation. In the 2 patients in whom complete resection was unfeasible, encircling cryoablation to entirely isolate the unresectable tumor was effective in suppressing VT occurrence. CONCLUSIONS: The mechanism underlying PCT-VT involves re-entry localized at the tumor edges. Myocardial disarray associated with tumor infiltration is a substrate for this form of VT. Cryoablation along the border between the tumor and myocardium is a promising therapeutic option for unresectable PCT-VT.

Spontaneous regression of IgG4-related dacryoadenitis.

This is the first report showing the clinical course of a patient with bilateral IgG4-related dacryoadenitis, which spontaneously regressed after excision of the left lacrimal gland. A 65-year-old female had been aware of bilateral eyelid swelling without pain for 5 years. Magnetic resonance imaging revealed enlargement of bilateral lacrimal gland. Laboratory tests showed high IgG4 concentrations, measuring 394 mg/dl. The biopsied specimen of the left lacrimal gland revealed marked lymphoplasmacytic infiltration with mild fibrosis. Marked IgG and IgG4-positive plasma cells surrounded the lymphoid follicles. Although the patient did not wish to undergo any treatments, lacrimal gland lesions showed gradual remission. This case highlights the potential of spontaneous improvement in IgG4-related dacryoadenitis, indicating that careful observation may be one of the therapeutic options for such patients.

Conjunctival lymphoma arising from reactive lymphoid hyperplasia.

Extra nodal marginal zone B-cell lymphoma (EMZL) of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH) of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU). Specimens from conjunctival tumors in the right eye, oculus dexter (OD), revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig) light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS), and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH) region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy.