Early Detection of Cardiac Amyloidosis in Transthyretin Mutation Carriers.

Diagnostic strategies for symptomatic transthyretin (ATTR) cardiac amyloidosis showing typical morphological features such as increased ventricular wall thickness and myocardial injury such as an elevation in serum troponin T level have been established, but those for subclinical cardiac amyloidosis are limited. In the era when effective therapies to suppress/delay progression of ATTR cardiac amyloidosis are available, early detection of cardiac involvement plays a crucial role in appropriate decision-making for treatment in TTR mutation carriers who have a family history of heart failure and death due to ATTR amyloidosis. Findings of three cases with known pathogenic transthyretin (TTR) mutations (p.Ser70Arg, p.Phe53Val, and p.Val50Met) and family histories of death for amyloidosis were presented. Two cases were asymptomatic, and a case carrying p.Phe53Val had gastrointestinal symptoms and autonomic neuropathy. Levels of plasma N-terminal fragment of pro-B-type natriuretic peptide and troponin T were within normal ranges in all cases, but results of cardiac magnetic resonance (CMR) and bone scintigraphy clearly revealed the presence of cardiac involvement in all cases, even in a case without echocardiographic abnormalities including left ventricular hypertrophy and relative apical sparing of longitudinal strain shown by two-dimensional speckle-tracking echocardiography. Electrocardiography revealed modest abnormalities including reduced R wave amplitude in V2 and a trend toward left axis deviation in all cases. In conclusion, CMR, bone scintigraphy, and electrocardiography are useful for early detection of ATTR cardiac amyloidosis in TTR mutation carriers. The role of comprehensive cardiac assessment in the early detection of cardiac amyloidosis in TTR mutation carriers is discussed.

Conduction time from left bundle branch pacing to the left ventricular lateral wall in two patients in whom cardiac resynchronization therapy pacemaker was implanted.

The efficacy of left bundle branch pacing (LBBP) as cardiac resynchronization therapy (CRT) has been reported, but LBBP may not always improve conduction disturbance in the left ventricle (LV). To evaluate LV electrical conduction delay during LBBP, we measured conduction time from the pacing at left bundle branch to LV lead sensing (LBBP-LV) in two patients in whom left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT) was attempted. Case 1 was a 77-year-old female with dilated cardiomyopathy (DCM) and left bundle branch block. The QRS duration during LBBP was 160 ms and the interval between the stimulus artifact and peak of the R wave in lead V6 (Stim-V6RWPT) was 74 ms. LBBP-LV at the LV mid-lateral wall and LV mid-posterolateral wall were 112 ms and 102 ms, respectively. Case 2 was a 75-year-old female with DCM and nonspecific intraventricular conduction delay. The QRS duration during LBBP was 156 ms and Stim-V6RWPT was 66 ms. LBBP-LV at the LV mid-anterolateral wall, LV mid-lateral wall, and LV mid-posterolateral wall were 96 ms, 107 ms, and 121 ms, respectively. In conclusion, LBBP-LV at the LV mid-lateral area was relatively long. If LBBP does not improve LV conduction disturbances, LOT-CRT may be more effective. Learning objective: The efficacy of left bundle branch pacing (LBBP) for cardiac resynchronization therapy (CRT) has been reported. However, if the conduction time from pacing to the left ventricular (LV) lateral area during LBBP is long, LBBP may not improve LV conduction disturbance, resulting in ineffective CRT. In such cases, more effective CRT would be expected with LV lead implantation at the area of the LV conduction delay during LBBP.

A screw-type pacemaker lead implanted in the right atrium perforated the ascending aorta.

BACKGROUND: Perforation by pacemaker leads, although rare, is a complication reported since the introduction of pacemaker therapy. Although historically reported frequencies were as high as 5%, recent reports have cited frequencies ranging from 1 to 2%. We report a case where a screw-type atrial lead slightly penetrated the right atrial wall, causing chronic abrasion of the ascending aorta, resulting in shock. CASE PRESENTATION: A 54-year-old male presented with dilated cardiomyopathy diagnosed at 40 years of age when he developed decompensated heart failure. Despite ongoing treatment, his heart failure worsened, leading to hospitalization at the age of 54. During his hospital stay, he experienced cardiac arrest that required cardiopulmonary resuscitation, followed by a return of spontaneous circulation. He was subsequently transferred to our institution after initiation of venoarterial extracorporeal membrane oxygenation (VA-ECMO) and an intra-aortic balloon pump (IABP). Echocardiography revealed an ejection fraction of 25%, left ventricular end-diastolic diameter of 60 mm, and severe mitral regurgitation (MR). Transcatheter mitral valve repair was performed to treat severe MR, followed by implantation of a cardiac resynchronization therapy defibrillator (CRT-D). Three months later, the patient was brought to our emergency department by ambulance because of hypotension. Contrast-enhanced computed tomography revealed pericardial effusion causing cardiac tamponade, necessitating emergency pericardial decompression via left fourth intercostal mini-thoracotomy and drain placement. Upon transfer to the intensive care unit, 1200 mL of blood was drained from the chest tube, prompting a return to the operating room for a median sternotomy. It was discovered that the pacemaker lead on the left side of the right atrium had slowly eroded into the aorta, leading to perforation. The ascending aorta was repaired and hemostasis was achieved; the patient recovered uneventfully and was discharged on postoperative day 18. CONCLUSIONS: The pacemaker lead perforated the right atrium; chronic abrasion of the lead against the ascending aorta resulted in bleeding from the ascending aorta 3 months later.

Frequent coexistence of early repolarization pattern, J-point elevation, and high Sokolow-Lyon voltage in young men.

Background: Earlier studies have shown male dominance of an early repolarization (ER) pattern and frequent coexistence with high Sokolow-Lyon voltage. Although possible involvement of androgen is speculated, the underlying mechanism has not been clarified yet. Previous studies were conducted in adult populations or only in children, and there has been no study in which the ER pattern was investigated in a series of individuals ranging from children before puberty to adults. Methods: We included 600 individuals comprising six groups according to age: 10-14 years old, 15-19 years old, twenties, thirties, forties, and fifties. Each group had 50 males and 50 females. The distribution of an ER pattern and related ECG parameters were assessed by age and gender. Results: In early teenagers, there was no significant gender difference in the prevalence of an ER pattern (24% in men vs. 28% in women, p = .82). The prevalence of an ER pattern increased after puberty and reached a peak in men in their twenties (42%). With further advance of age, the prevalence of an ER pattern decreased. On the other hand, the prevalence of an ER pattern in women peaked at 28% in teenagers, and it decreased through twenties (20%) to thirties (10%). Similar male dominance after puberty was observed in Sokolow-Lyon voltage and J-point elevation but not in P-wave amplitude. Conclusion: The prevalence of an ER pattern, Sokolow-Lyon voltage, and J-point elevation are all augmented after puberty and decrease with aging, leading to frequent coexistence of these ECG findings in young men.

High defibrillation threshold with right-sided ICD implantation was resolved by a dual coil lead via persistent left superior vena cava.

Persistent left superior vena cava (PLSVC) can be problematic when device implantation is scheduled from the left side because of the technical difficulty in delivering leads. Right-sided implantation is an alternative method, but there is a risk of a high defibrillation threshold (DFT). Transvenous implantation of an implantable cardioverter defibrillator (ICD) was scheduled for a 54-year-old man with idiopathic dilated cardiomyopathy and monomorphic non-sustained ventricular tachycardia, but computed tomography revealed the presence of a PLSVC. Right-sided ICD implantation was performed first; however, an ICD shock at 35 J failed to terminate the induced ventricular fibrillation (VF). Re-implantation via the PLSVC by a left subclavian approach with a dual coil lead was performed next. The dual coil right ventricular lead was successfully implanted via the PLSVC, and the induced VF was terminated by a single shock at 25 J. In the present case, the proximal coil was located in the coronary sinus (CS) and it enabled an antero-posterior defibrillation vector across the left ventricle. In addition to the re-location of the ICD generator from the right side to the left side, the new positioning of the proximal coil inside the CS is likely to have contributed to the great improvement of the DFT. .

Enhanced nuclear localization of phosphorylated MLKL predicts adverse events in patients with dilated cardiomyopathy.

AIMS: The role of necroptosis in dilated cardiomyopathy (DCM) remains unclear. Here, we examined whether phosphorylation of mixed lineage kinase domain-like protein (MLKL), an indispensable event for execution of necroptosis, is associated with the progression of DCM. METHODS AND RESULTS: Patients with DCM (n = 56, 56 ± 15 years of age; 68% male) were enrolled for immunohistochemical analyses of biopsies. Adverse events were defined as a composite of death or admission for heart failure or ventricular arrhythmia. Compared with the normal myocardium, increased signals of MLKL phosphorylation were detected in the nuclei, cytoplasm, and intercalated discs of cardiomyocytes in biopsy samples from DCM patients. The phosphorylated MLKL (p-MLKL) signal was increased in enlarged nuclei or nuclei with bizarre shapes in hypertrophied cardiomyocytes. Nuclear p-MLKL level was correlated negatively with septal peak myocardial velocity during early diastole (r = -0.327, P = 0.019) and was correlated positively with tricuspid regurgitation pressure gradient (r = 0.339, P = 0.023), while p-MLKL level in intercalated discs was negatively correlated with mean left ventricular wall thickness (r = -0.360, P = 0.014). During a median follow-up period of 3.5 years, 10 patients (18%) had adverse events. To examine the difference in event rates according to p-MLKL expression levels, patients were divided into two groups by using the median value of nuclear p-MLKL or intercalated disc p-MLKL. A group with high nuclear p-MLKL level (H-nucMLKL group) had a higher adverse event rate than did a group with low nuclear p-MLKL level (L-nucMLKL group) (32% vs. 4%, P = 0.012), and Kaplan-Meier survival curves showed that the adverse event-free survival rate was lower in the H-nucMLKL group than in the L-nucMLKL group (P = 0.019 by the log-rank test). Such differences were not detected between groups divided by a median value of intercalated disc p-MLKL. In δ-sarcoglycan-deficient (Sgcd-/- ) mice, a model of DCM, total p-MLKL and nuclear p-MLKL levels were higher than in wild-type mice. CONCLUSION: The results suggest that increased localization of nuclear p-MLKL in cardiomyocytes is associated with left ventricular diastolic dysfunction and future adverse events in DCM.

Revaluation of the Significance of Demonstrable Exit Block After Radiofrequency Pulmonary Vein Isolation.

Background: Demonstration of exit block from the pulmonary vein (PV) to the left atrium after PV isolation (PVI) is not always possible after demonstration of entrance block. We examined factors associated with demonstrable exit block and the relationship between demonstrable exit block and subsequent PV reconnection. Methods and Results: The subjects consisted of 227 patients (908 PV; mean patient age, 59.2±10.8 years; 72.2% male) who underwent radiofrequency PVI, 49 of whom proceeded to the second session after a mean duration of 563.4±456.3 days after the first session. In the first session, exit block was demonstrated in 73.1% of PV, and the predictors were superior PV, longitudinal diameter of the PV, and spontaneous activity in the PV. In the second session (n=49), exit block was demonstrated in 51.0% (33.1% in PV without reconnection vs. 79.7% in PV with reconnection, P<0.0001). Spontaneous activity (OR, 2.74; 95% CI: 1.12-7.03, P=0.0272) and use of a contact force-sensing catheter (OR, 0.42, 95% CI: 0.20-0.85, P=0.0151) were independent predictors of PV reconnection, but demonstrable exit block was not (OR, 1.58; 95% CI: 0.74-3.46, P=0.2377). Conclusions: Inability to demonstrate exit block was not associated with increased risk of future PV reconnection.

A novel scoring system for stroke risk stratification in Japanese patients with low CHADS2 scores: Study using a transesophageal-echocardiogram endpoint.

BACKGROUND: Catheter ablation is an effective treatment for atrial fibrillation (AF), but it carries risk of perioperative thromboembolism even in cases with low CHADS2 scores. Here, we examined whether a combination of clinical variables can predict stroke risk factors that are assessed by transesophageal echocardiography (TEE). METHODS: The study population consisted of 209 consecutive AF patients with a CHADS2 score of 0 or 1 (58.7 ± 10.6 years old; persistent AF, 33.0%). All patients underwent TEE, and TEE-determined stroke risk (TEE risk) was defined as cardiac thrombus/sludge, dense spontaneous echo contrast (SEC), and/or peak left atrial appendage (LAA) flow velocity <0.25 m/s. RESULTS: Transesophageal echocardiography risk was observed in 10.5% of the patients. In multivariate logistic analysis, persistent AF [odds ratio (OR): 11.5, CI: 3.14-42.1, P = .0002], left atrial diameter (LAD) (OR: 1.10, CI: 1.01-1.20, P = .0293), contrast medium defect (CMD) in the LAA detected by computed tomography (OR: 20.2, CI: 6.3-65.0, P < .0001), and serum brain natriuretic peptide (BNP) level (OR: 1.00, CI: 1.00-1.01, P = .0056) were independent predictors of TEE risk. A new scoring system comprising LAD > 41 mm (1 point), BNP > 47 pg/mL (1 point), CMD (2 points), and persistent AF (2 points) was constructed and defined as TEE-risk score. The area under the curve (AUC) for prediction of TEE risk was 0.631 in modified CHADS2 score and it was 0.852 in TEE-risk score. CONCLUSION: Transesophageal echocardiography risk is predictable by TEE-risk score, and its combination with CHADS2 score may improve the stroke risk stratification in AF patients with a low CHADS2 score.

Is Incomplete Left Atrial Posterior Wall Isolation Associated With Recurrence of Atrial Fibrillation After Radiofrequency Catheter Ablation?

Background: Complete left atrial posterior wall isolation (LAPI) is not always achieved. We examined whether incomplete LAPI has an effect on outcomes after catheter ablation (CA). Methods and Results: This study enrolled 75 consecutive patients (mean [±SD] age 62.6±8.9 years, 74.7% male) who underwent LAPI by radiofrequency CA for persistent atrial fibrillation (AF). The median follow-up period was 541 days (interquartile range 338-840 days). Incomplete LAPI was defined as the presence of a successfully created roof or floor linear lesion. The rate of complete LAPI was 41.3% (31/75). Either a roof or floor linear lesion was created in 38 patients, whereas neither was created in 6. Multivariate Cox proportional hazards regression analysis revealed that female sex (hazard ratio [HR] 5.29; 95% confidence interval [CI] 1.81-16.8; P=0.002) and complete or incomplete LAPI (HR 0.17; 95% CI 0.03-0.79; P=0.027) were independent predictors of AF recurrence. Kaplan-Meier curves indicated that better outcome was associated with at least one rather than no successful linear lesion (86.5% vs. 50.0% at 1 year; P=0.043). There were no significant differences in outcomes between the complete LAPI and incomplete LAPI groups. Conclusions: Complete LAPI is unachievable in a significant percentage of patients with persistent AF. However, incomplete LAPI, as a result of aiming for complete LAPI, may have a benefit comparable to that of complete LAPI.