Zero-fluoroscopy ablation in patients with cardiac electronic implantable devices.

INTRODUCTION: Utilizing a three-dimensional (3-D) mapping system and intracardiac echocardiography (ICE) has allowed ablation procedures with less or without fluoroscopy; however, there is limited data for patients with cardiac electronic implantable device (CIED) leads regarding the suspected risk of lead injury. Therefore, we sought to explore technics to perform safe trans-septal approach and catheter manipulation technique in patients with CIED leads. METHODS AND RESULTS: This study comprised 49 consecutive patients (59% males, median 73 years old) with CIED who underwent catheter ablation for supraventricular tachycardia requiring the trans-septal approach, 15 without fluoroscopy (zero-fluoro group), and 34 with fluoroscopy (conventional-fluoro group), between July 2019 and April 2021. All procedures were performed under a 3-D mapping system and ICE guidance. We compared the differences in treatment and development of complications between the two groups. The procedures were for atrial fibrillation (82%) and atrial tachycardia (76%). Coronary sinus catheter insertion and the trans-septal procedure were successfully performed in all patients. The median time from venipuncture to trans-septal procedure (zero-fluoro vs. conventional-fluoro group: 28 [18-37] min vs. 24 [21-31] min, p = .70), total procedure time (231 [142-274] min vs. 175 [163-225] min, p = .63), and the acute procedural success rate (100% vs. 97%, p = 1.00) did not differ between both groups. No patient showed lead-related complications in both groups. CONCLUSION: This is the first study to show zero-fluoro ablation for supraventricular arrhythmia using 3-D mapping and ICE in patients with CIED leads was feasible under careful catheter manipulation.

An anatomical approach to determine the location of the sinoatrial node during catheter ablation.

INTRODUCTION: The sinoatrial node (SAN) should be identified before superior vena cava (SVC) isolation to avoid SAN injury. However, its location cannot be identified without restoring sinus rhythm. This study evaluated the usefulness of the anatomically defined SAN by comparing it with the electrically confirmed SAN (e-SAN) to predict the top-most position of e-SAN and thus establish a safe and more efficient anatomical reference for SVC isolation than the previously reported reference of the right superior pulmonary vein (RSPV) roof. METHODS AND RESULTS: The e-SAN was identified as the earliest activation site in the electroanatomical map obtained during sinus rhythm. The anatomically defined SAN, the cranial edge of the crista terminalis (CT) visualized with intracardiac echocardiography (CT top), and the RSPV roof, which was obtained from the overlaid electroanatomical image of SVC and RSPV, were tagged on one map. The distance from the e-SAN to each reference was measured. Among 77 patients, the height of the e-SAN from the CT top was a median (interquartile range) of -2.0 (-8.0 to 4.0) mm. The e-SAN existed from 10 mm above the CT top or lower in 74 (96%) patients and from the RSPV roof or below in 73 (95%) patients. The reference of 10 mm above the CT top is more proximal to the right atrium than the RSPV roof and can provide longer isolatable SVC sleeves (30.0 [20.0-35.0] vs. 24.0 [18.0-30.0] mm, p < .001). The e-SAN tended to be found above the CT top when the heart rate during mapping was faster (adjusted odds ratio [95% confidence interval] per 10-bpm increase: 1.71 [1.20-2.43], p < .01). CONCLUSION: The CT top is useful for predicting the upper limit of the e-SAN and can provide a better reference for SVC isolation than the RSPV roof.

Time-to-first appropriate shock in patients implanted prophylactically with an implantable cardioverter-defibrillator: data from the Survey on Arrhythmic Events in BRUgada Syndrome (SABRUS).

AIMS: Data on predictors of time-to-first appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with Brugada Syndrome (BrS) and prophylactically implanted ICD's are scarce. METHODS AND RESULTS: SABRUS (Survey on Arrhythmic Events in BRUgada Syndrome) is an international survey on 678 BrS patients who experienced arrhythmic event (AE) including 252 patients in whom AE occurred after prophylactic ICD implantation. Analysis was performed on time-to-first appropriate ICD discharge regarding patients' characteristics. Multivariate logistic regression models were utilized to identify which parameters predicted time to arrhythmia ≤5 years. The median time-to-first appropriate ICD therapy was 24.8 ± 2.8 months. A shorter time was observed in patients from Asian ethnicity (P < 0.05), those with syncope (P = 0.001), and those with Class IIa indication for ICD (P = 0.001). A longer time was associated with a positive family history of sudden cardiac death (P < 0.05). Multivariate Cox regression revealed shorter time-to-ICD therapy in patients with syncope [odds ratio (OR) 1.65, P = 0.001]. In 193 patients (76.6%), therapy was delivered during the first 5 years. Factors associated with this time were syncope (OR 0.36, P = 0.001), spontaneous Type 1 Brugada electrocardiogram (ECG) (OR 0.5, P < 0.05), and Class IIa indication (OR 0.38, P < 0.01) as opposed to Class IIb (OR 2.41, P < 0.01). A near-significant trend for female gender was also noted (OR 0.13, P = 0.052). Two score models for prediction of <5 years to shock were built. CONCLUSION: First appropriate therapy in BrS patients with prophylactic ICD's occurred during the first 5 years in 76.6% of patients. Syncope and spontaneous Type 1 Brugada ECG correlated with a shorter time to ICD therapy.

Impact of premature activation of the right ventricle with programmed stimulation in Brugada syndrome.

BACKGROUND: In Brugada syndrome (BrS), it has been reported that delayed activation in the RV is related to the development of type-1 ECG, which is more critical than type-2. On the other hand, the coexistence of complete right bundle-branch block (CRBBB), which also causes delayed activation in the RV, sometimes makes typical BrS ECG misleading. We hypothesized that premature stimulation of the RV can unmask the influence of delayed activation in the RV and convert the morphology of ECG in BrS patients. METHODS AND RESULTS: In 35 BrS patients with type-1 ECG including 8 patients with concomitant CRBBB and 6 control subjects with CRBBB, progressively premature single stimulations were delivered from the RV apex on electrophysiological study. Then we evaluated QRS morphology of fusion beats created by single premature stimulation in each patient. In 29 (83%) of 35 of the BrS patients, conversion from type-1 to type-2 ECG was observed during the process of single premature stimulation. Additionally, in all 8 BrS patients with concomitant CRBBB, type-1 or type-2 BrS ECG was revealed by premature stimulation with relief of CRBBB. These findings were not observed in any of the control subjects with CRBBB. CONCLUSION: Single premature stimulation of the RV converts ECG from type-1 to type-2 in most BrS cases and unmasks type-1 ECG in all BrS cases with CRBBB. Our results could suggest that type-1 ECG is associated with delayed activation of the RV compared with type-2 ECG.

HCN4-Overexpressing Mouse Embryonic Stem Cell-Derived Cardiomyocytes Generate a New Rapid Rhythm in Rats with Bradycardia.

A biological pacemaker is expected to solve the persisting problems of an artificial cardiac pacemaker including short battery life, lead breaks, infection, and electromagnetic interference. We previously reported HCN4 overexpression enhances pacemaking ability of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) in vitro. However, the effect of these cells on bradycardia in vivo has remained unclear. Therefore, we transplanted HCN4-overexpressing mESC-CMs into bradycardia model animals and investigated whether they could function as a biological pacemaker. The rabbit Hcn4 gene was transfected into mouse embryonic stem cells and induced HCN4-overexpressing mESC-CMs. Non-cardiomyocytes were removed under serum/glucose-free and lactate-supplemented conditions. Cardiac balls containing 5 × 103 mESC-CMs were made by using the hanging drop method. One hundred cardiac balls were injected into the left ventricular free wall of complete atrioventricular block (CAVB) model rats. Heart beats were evaluated using an implantable telemetry system 7 to 30 days after cell transplantation. The result showed that ectopic ventricular beats that were faster than the intrinsic escape rhythm were often observed in CAVB model rats transplanted with HCN4-overexpressing mESC-CMs. On the other hand, the rats transplanted with non-overexpressing mESC-CMs showed sporadic single premature ventricular contraction but not sustained ectopic ventricular rhythms. These results indicated that HCN4-overexpressing mESC-CMs produce rapid ectopic ventricular rhythms as a biological pacemaker.

Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial.

AIMS: Substantial portion of early arrhythmia recurrence after catheter ablation for atrial fibrillation (AF) is considered to be due to irritability in left atrium (LA) from the ablation procedure. We sought to evaluate whether 90-day use of antiarrhythmic drug (AAD) following AF ablation could reduce the incidence of early arrhythmia recurrence and thereby promote reverse remodelling of LA, leading to improved long-term clinical outcomes. METHODS AND RESULTS: A total of 2038 patients who had undergone radiofrequency catheter ablation for paroxysmal, persistent, or long-lasting AF were randomly assigned to either 90-day use of Vaughan Williams class I or III AAD (1016 patients) or control (1022 patients) group. The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of class I or III AAD at 1 year, following the treatment period of 90 days post ablation. Patients assigned to AAD were associated with significantly higher event-free rate from recurrent atrial tachyarrhythmias when compared with the control group during the treatment period of 90 days [59.0 and 52.1%, respectively; adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.73-0.96; P = 0.01]. However, there was no significant difference in the 1-year event-free rates from the primary endpoint between the groups (69.5 and 67.8%, respectively; adjusted HR 0.93; 95% CI 0.79-1.09; P = 0.38). CONCLUSION: Short-term use of AAD for 90 days following AF ablation reduced the incidence of recurrent atrial tachyarrhythmias during the treatment period, but it did not lead to improved clinical outcomes at the later phase.

Prognostic Value of Prothrombin Time International Normalized Ratio in Acute Decompensated Heart Failure　- A Combined Marker of Hepatic Insufficiency and Hemostatic Abnormality.

BACKGROUND: There are limited studies regarding the prognostic value of coagulation abnormalities in heart failure patients. The clinical significance of prothrombin time international normalized ratio (INR), a widely accepted marker assessing coagulation abnormalities, in acute decompensated heart failure (ADHF) remains unclear. METHODS AND RESULTS: Among 561 consecutive patients admitted for ADHF, INR was assessed in 294 patients without prior anticoagulation therapy, acute coronary syndrome, liver disease, or overt disseminated intravascular coagulation. Increased INR on admission was positively associated with increased levels of thrombin-antithrombin complex, C-reactive protein, total bilirubin, γ-glutamyl transpeptidase, inferior vena cava diameter, tricuspid regurgitation severity, markers of neurohormonal activation, and also negatively associated with decreased albumin, cholinesterase, and total cholesterol. In contrast, there was no significant association with left ventricular ejection fraction, serum sodium or blood urea nitrogen. Multivariate analysis showed that increased INR was independently associated with increased all-cause mortality (hazard ratio 1.89 per 0.1 increase, 95% confidence interval 1.14-3.13, P=0.013) during the median follow up of 284 days. Increased INR also had a higher prognostic value compared to risk score models including the Model for End-Stage Liver Disease (MELD) score or the MELD excluding INR (MELD-XI) score. CONCLUSIONS: Increased INR is an independent predictor of all-cause mortality in ADHF patients without anticoagulation, reflecting coagulation abnormalities and hepatic insufficiency, possibly through systemic inflammation, neurohormonal activation and venous congestion.

Utility of High-Resolution Magnetocardiography to Predict Later Cardiac Events in Nonischemic Cardiomyopathy Patients With Normal QRS Duration.

BACKGROUND: Nonischemic dilated cardiomyopathy (NIDCM) patients, even those with a narrow QRS, are at increased risk for major adverse cardiac events (MACE). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect prognostic left intraventricular disorganized conduction (LiDC) by overcoming the limitations of fragmented QRS (fQRS, qualitative definitions, low specificity) and late potential (abnormality undetectable in earlier QRS).Methods and Results:We evaluated LiDC on MCG, defined as significant deviation from a global clockwise left ventricular (LV) activation pattern, and conventional noninvasive predictors of MACE, including fQRS and late potential, in 51 NIDCM patients with narrow QRS (LV ejection fraction, 22±7%; QRS duration, 99±11 ms). MACE was defined as cardiac death, lethal ventricular arrhythmias, or LV assist device (LVAD) implantation. LiDC was present in 22 patients. Baseline characteristics were comparable between patients with and without LiDC, except for the ratio of positive late potential. During a mean follow-up of 2.9 years, MACE developed in 16 NIDCM patients (3 cardiac deaths, 9 lethal ventricular arrhythmias, and 4 LVAD). MACE was more incident in patients with LiDC (13/22) than in those without (3/29, P<0.001). Multivariate analysis revealed LiDC, but not fQRS or late potential, as the strongest independent predictor of MACE (hazard ratio 4.28, 95% confidence interval 1.30-19.39, P=0.015). CONCLUSIONS: MCG accurately depicts LiDC, a promising noninvasive predictor of MACE in patients with NIDCM and normal QRS.

Adenosine triphosphate-guided pulmonary vein isolation for atrial fibrillation: the UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate (UNDER-ATP) trial.

AIMS: Most of recurrent atrial tachyarrhythmias after pulmonary vein isolation (PVI) for atrial fibrillation (AF) are due to reconnection of PVs. The aim of the present study was to evaluate whether elimination of adenosine triphosphate (ATP)-induced dormant PV conduction by additional energy applications during the first ablation procedure could reduce the incidence of recurrent atrial tachyarrhythmias. METHODS AND RESULTS: We randomly assigned 2113 patients with paroxysmal, persistent, or long-lasting AF to either ATP-guided PVI (1112 patients) or conventional PVI (1001 patients). The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of Vaughan Williams class I or III antiarrhythmic drugs at 1 year with the blanking period of 90 days post ablation. Among patients assigned to ATP-guided PVI, 0.4 mg/kg body weight of ATP provoked dormant PV conduction in 307 patients (27.6%). Additional radiofrequency energy applications successfully eliminated dormant conduction in 302 patients (98.4%). At 1 year, 68.7% of patients in the ATP-guided PVI group and 67.1% of patients in the conventional PVI group were free from the primary endpoint, with no significant difference (adjusted hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.74-1.09; P = 0.25). The results were consistent across all the prespecified subgroups. Also, there was no significant difference in the 1-year event-free rates from repeat ablation for any atrial tachyarrhythmia between the groups (adjusted HR 0.83; 95% CI 0.65-1.08; P = 0.16). CONCLUSION: In the catheter ablation for AF, we found no significant reduction in the 1-year incidence of recurrent atrial tachyarrhythmias by ATP-guided PVI compared with conventional PVI.

Incidence and Clinical Significance of Brugada Syndrome Masked by Complete Right Bundle-Branch Block.

BACKGROUND: Brugada syndrome (BrS)-type electrocardiogram (ECG) is concealed by complete right bundle-branch block (CRBBB) in some cases of BrS. Clinical significance of BrS masked by CRBBB is not well known. METHODS AND RESULTS: We reviewed an ECG database of 326 BrS patients who had type 1 ECG with or without pilsicainide. "BrS masked by CRBBB" was defined on ECG as <2-mm elevation of the J point at the time of CRBBB in the right precordial leads, and BrS-type J-point elevation ≥2 mm at the time of normalized QRS complex on relieved CRBBB. We identified 25 BrS patients (7.7%) with persistent (n=12) or intermittent CRBBB (n=13). Relief of CRBBB by pacing was performed in patients with persistent CRBBB. The prevalence of BrS masked by CRBBB was 3.1% (10/326 patients). Three patients had type 1 ECG, and 7 patients had type 2 or 3 ECG on relief of CRBBB. Two of these 10 patients had lethal arrhythmic events during the follow-up period (mean, 86.4±57.2 months). There was no prognostic difference between BrS masked by CRBBB and other BrS. CONCLUSIONS: In a small BrS population, CRBBB can completely mask typical BrS-type ECG. BrS masked by CRBBB is associated with the same risk of fatal ventricular tachyarrhythmia as other BrS.

Risk stratification in patients with Brugada syndrome without previous cardiac arrest ­ prognostic value of combined risk factors.

BACKGROUND: Risk stratification in patients with Brugada syndrome for primary prevention of sudden cardiac death is still an unsettled issue. A recent consensus statement suggested the indication of implantable cardioverter defibrillator (ICD) depending on the clinical risk factors present (spontaneous type 1 Brugada electrocardiogram (ECG) [Sp1], history of syncope [syncope], and ventricular fibrillation during programmed electrical stimulation [PES+]). The indication of ICD for the majority of patients, however, remains unclear. METHODS AND RESULTS: A total of 218 consecutive patients (211 male; aged 46 ± 13 years) with a type 1 Brugada ECG without a history of cardiac arrest who underwent evaluation for ICD including electrophysiological testing were examined retrospectively. During a mean follow-up period of 78 months, 26 patients (12%) developed arrhythmic events. On Kaplan-Meier analysis patients with each of Sp1, syncope, or PES+ suffered arrhythmic events more frequently (P=0.018, P<0.001, and P=0.003, respectively). On multivariate analysis Sp1 and syncope were independent predictors of arrhythmic events. When dividing patients according to the number of these 3 risk factors present, patients with 2 or 3 risk factors experienced arrhythmic events more frequently than those with 0 or 1 risk factor (23/93 vs. 3/125; P<0.001). CONCLUSIONS: Syncope, Sp1, and PES+ are important risk factors and the combination of these risks well stratify the risk of later arrhythmic events.

Electrocardiographic predictors of response to cardiac resynchronization therapy in patients with intraventricular conduction delay.

BACKGROUND: Little is known about predictors of response to cardiac resynchronization therapy (CRT) in patients with intraventricular conduction delay (IVCD). The purpose of this study was to investigate the benefits of CRT and significant variables on surface electrocardiogram (ECG) to predict response to CRT in those patients. METHODS AND RESULTS: Among the cohort of 152 CRT patients, 40 patients with IVCD were evaluated. Sixteen patients (40%) were responders. At baseline, responders had a wider QRS duration (158±18 vs. 144±18ms, P=0.02) and a higher frequency of left axis deviation (LADEV; 75% vs. 29%, P=0.004) compared with non-responders. After CRT, greater shortening of QRS duration (ΔQRS; 26±24 vs. 7±24ms, P=0.02), axis shift from LADEV to right axis deviation (RADEV; 69% vs. 13%, P<0.001), and both rightward forces in lead I and anterior forces in V1 (56% vs. 13%, P=0.003) were found more frequently in responders. Multivariable logistic regression analysis showed that LADEV at baseline, or ΔQRS and axis shift from LADEV to RADEV after CRT were independent predictors of response to CRT. CONCLUSIONS: Patients with IVCD may not respond to CRT, but LADEV at baseline and reversal of ventricular activation after CRT on surface ECG could be important to predict response to CRT.

Fatal Arrhythmic Risks in Cardiac Sarcoidosis With Mildly Impaired Cardiac Function.

Background: The prognosis and later fatal arrhythmia in cardiac sarcoidosis (CS) with relatively preserved cardiac function were unclear. Objectives: This study aimed to evaluate the prognosis and arrhythmic events in patients with CS and mildly impaired cardiac function. Methods: Data were collected from a nationwide Japanese cohort survey conducted in 57 hospitals (n = 420); 322 patients with CS with left ventricular ejection fraction (LVEF) >35% were investigated. Results: Ventricular tachycardia (VT) manifestation was present in 50 patients (16%) and absent in 272 (84%), of whom 36 (72%) and 46 (17%), respectively, had an implantable cardioverter-defibrillator (ICD). Over a median of 5 years, 23 all-cause deaths and 31 appropriate ICD discharges were observed. In Kaplan-Meier analysis, all-cause death did not differ between patients with and without VT manifestation (P = 0.660), although appropriate ICD therapy was significantly less used in patients without VT manifestation than in those with VT manifestation (P < 0.001). Of the 272 patients without VT manifestation, 18 had ventricular arrhythmic events (VAEs), including 3 sudden cardiac deaths and 15 appropriate ICD discharges. In multivariate analysis, concomitant nonsustained ventricular tachycardia (NSVT) with atrioventricular block (AVB), lower LVEF, abnormal gallium-67 scintigraphy or 18F-fluorodeoxyglucose positron emission tomography of the heart (Ga/PET), and concomitant NSVT with abnormal Ga/PET at CS diagnosis were independent predictors of VAEs (P = 0.008, P = 0.021, P = 0.049, and P = 0.024, respectively). Conclusions: If concomitant NSVT with AVB, concomitant NSVT with abnormal Ga/PET, or abnormal Ga/PET is observed in patients with CS and mildly impaired cardiac function (LVEF >35%), ICD should be considered as primary prevention.

Transcatheter closure of atrial septal defect in a geriatric population.

OBJECTIVES: To evaluate the efficacy and safety of transcatheter closure of atrial septal defects (ASD) in patients over 70 years of age. BACKGROUND: Transcatheter closure of ASD is an established procedure in children and young adults, but the benefits of this procedure in geriatric patients are still unclear. METHODS: Between 2005 and 2010, 430 patients with ASD underwent transcatheter closure in our hospital. Among those patients, 30 consecutive patients older than 70 years of age were prospectively evaluated. RESULTS: Mean age at procedure was 75.8 ± 3.8 years (range: 70-85 years). Mean Qp/Qs was 2.4 ± 0.7 and mean ASD diameter was 20.3 ± 6.4 mm. Nine patients (30%) had a history of hospitalization due to heart failure. ASD closure was successfully performed in 28 patients (93%) without significant complications. During the follow-up period (mean period of 19.1 ± 11.3 months), New York Heart Association (NYHA) functional class was significantly improved in 20 patients (74%). Significant improvements of plasma BNP level, resting heart rate, and systolic pulmonary artery pressure were also observed. Improvement of tricuspid regurgitation was observed in 11 of 17 patients with moderate or severe regurgitation during the follow-up period. Conversely, worsening of mitral regurgitation was observed in 10 of the 27 patients. CONCLUSION: Transcatheter closure of ASD in geriatric patients can be performed safely. This procedure contributes to significant improvement of symptoms and positive cardiac remodeling. Long-term follow-up is mandatory, especially for patients with mitral regurgitation.

Safety and efficacy of epoprostenol therapy in pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension. There is no proven medical therapy to treat these diseases, and lung transplantation is thought to be the only cure. Administration of vasodilators including epoprostenol sometimes causes massive pulmonary edema and could be fatal in these patients. METHODS AND RESULTS: Eight patients were treated with epoprostenol for 387.3±116.3 days (range, 102-1,063 days), who were finally diagnosed with PVOD or PCH by pathological examination. The maximum dose of epoprostenol given was 55.3±10.7 ng·kg(-1)·min(-1) (range, 21.0-110.5 ng·kg(-1)·min(-1)). With careful management, epoprostenol therapy significantly improved the 6-min walk distance (97.5±39.2 to 329.4±34.6 m, P<0.001) and plasma brain natriuretic peptide levels (381.3±136.8 to 55.2±14.4 pg/ml, P<0.05). The cardiac index significantly increased from 2.1±0.1 to 2.9±0.3 L·min(-1)·m(-2) (P<0.05). However, pulmonary artery pressure and pulmonary vascular resistance were not significantly reduced. For 4 patients, epoprostenol therapy acted as a bridge to lung transplantation. For the other patients who had no chance to undergo lung transplantation, epoprostenol therapy was applied for 528.0±216.6 days and the maximum dose was 63.9±19.0 ng·kg(-1)·min(-1). CONCLUSIONS: This study data suggest that cautious application of epoprostenol can be considered as a therapeutic option in patients with PVOD and PCH.

Acute vasoreactivity testing with nicardipine in patients with pulmonary arterial hypertension.

Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 µg·kg⁻¹·min⁻¹ for 5 min and 2 µg·kg⁻¹·min⁻¹ for 5 min) followed by bolus injection (5 µg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients.

Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling.

Sonic hedgehog (Shh) is a crucial regulator of organ development during embryogenesis. We investigated whether intramyocardial gene transfer of naked DNA encoding human Shh (phShh) could promote a favorable effect on recovery from acute and chronic myocardial ischemia in adult animals, not only by promoting neovascularization, but by broader effects, consistent with the role of this morphogen in embryogenesis. After Shh gene transfer, the hedgehog pathway was upregulated in mammalian fibroblasts and cardiomyocytes. This resulted in preservation of left ventricular function in both acute and chronic myocardial ischemia by enhanced neovascularization, and reduced fibrosis and cardiac apoptosis. Shh gene transfer also enhanced the contribution of bone marrow-derived endothelial progenitor cells to myocardial neovascularization. These data suggest that Shh gene therapy may have considerable therapeutic potential in individuals with acute and chronic myocardial ischemia by triggering expression of multiple trophic factors and engendering tissue repair in the adult heart.

Echocardiographic predictors of cardioembolic stroke due to underlying atrial fibrillation: Reliable left atrial remodeling signs in acute stroke.

INTRODUCTION: Atrial remodeling due to high-burden atrial fibrillation (AF) is associated with cardioembolic stroke (CES). As not all CESs is caused by AF, we analyzed the diagnostic values of each echocardiographic parameter to distinguish likely AF-related CES in acute stroke patients while in non-AF rhythm. METHODS: The data of consecutive patients with acute ischemic stroke in sinus rhythm between 2012 and 2015 were obtained. The echocardiographic parameters of patients with CES due to underlying AF (n = 61) and control patients (n = 319) with either large artery atherosclerosis or small-vessel occlusion were compared using receiver operating characteristic curves and logistic regression analyses. Each parameter was reassessed in acute stroke patients through a validation study using the same database with different periods of generalization. RESULTS: CES patients with underlying AF showed a significantly larger left atrial volume index (LAVi), higher mitral inflow E wave (E), and lower A wave (A) than the controls. The area under the curve (AUC) (95% confidence interval) for diagnosing CES due to underlying AF was significantly higher for LAVi/A than for LAVi (0.785 versus 0.696, P < 0.01). Among patients aged >60 years, the E/A ratio had the highest AUC (0.857) of the parameters. The cut-off values were ≥ 0.70 (sensitivity, 55.7%; specificity, 90.9%) and ≥ 0.82 (sensitivity, 71.4%; specificity, 84.1%) for LAVi/A and the E/A ratio, respectively, in patients >60 years. The cut-off values of all parameters showed similar trends in a validation study. CONCLUSION: LAVi/A is a useful indicator for distinguishing CES patients with underlying AF regardless of age, and the E/A ratio is reliable among patients aged >60 years in evaluation during acute stroke admission.