Familial Hypertrophic Cardiomyopathy With Fasciculoventricular Accessory Pathway.

Hypertrophic cardiomyopathy (HCM) is a common but an underdiagnosed condition. Fasciculoventricular bypass tract (FVBT) is rare. Concomitant presence of both conditions is well described in Danon disease. We report a case of familial HCM with FVBT linked to a heterozygous pathogenic variant, c.655G>C (p.Val219Leu), in the cardiac myosin binding protein C3 (MYBPC3) gene. (Level of Difficulty: Advanced.).

Catheter ablation of premature ventricular contractions originating from kissing papillary muscles.

Very thick left ventricular papillary muscles (PAMs) may kiss each other and premature ventricular contractions (PVCs) can originate from the sides of the PAMs facing each other. In such a setting, mapping of those PVCs is confusing and rendering catheter ablation challenging.

Leadless solution for arrhythmia-related sudden unexpected death in epilepsy.

A leadless pacemaker is a recently approved pacing technology that helps mitigate lead-related complications, but it has several limitations. Careful candidate selection is needed. Here, we demonstrate leadless pacing as the solution for prolonged postictal bradycardia/asystole; there is no consensus regarding pacemaker implantation for seizure patients with such a risk of sudden cardiac death.

Twenty-five-year-old woman with palpitations and hypertrophic cardiomyopathy.

CLINICAL INTRODUCTION: A 25-year-old woman with a diagnosis of hypertrophic cardiomyopathy (HCM) and pre-excitation on ECG presented with unexplained syncope and daily palpitation. Genetic testing was positive for lysosome-associated membrane protein 2 (LAMP2) mutation which confirmed the diagnosis of Danon disease. Her younger sister was diagnosed with a similar condition and received a defibrillator implantation. Her 12-lead ECG (figure 1) and a long strip tracing (figure 2) are shown below.Figure 112-lead ECG. QUESTION: Where is the location of the accessory pathway and what is the next appropriate management?Anteroseptal pathway and catheter ablationMid-septal pathway and pacemaker/defibrillator implantationRight lateral pathway and catheter ablationFasciculoventricular pathway and electrophysiological studyLeft lateral pathway and electrophysiological study.

Successful treatment of a cardiac resynchronization therapy nonresponder by identifying lead malpositioning.

This case describes some of the commonly overlooked device-related issues in patients who have reportedly failed to respond to cardiac resynchronization therapy (CRT). The case demonstrates voltage-dependent right ventricular capture instead of right atrial capture by a subtly malpositioned right atrial lead. CRT therapy failed to improve symptoms of heart failure and the diagnosis of "CRT nonresponder" was made. With a detailed fact-finding approach, the mechanism behind this nonresponse was identified, and the outcome of CRT was significantly improved with rectification of the problems.

Atrial Fibrillation Monitoring in Cryptogenic Stroke: the Gaps Between Evidence and Practice.

Identifying occult paroxysmal atrial fibrillation as the etiology of cryptogenic stroke has been a top research priority in the past decade. This is because prompt initiation of anticoagulation has significantly decreased subsequent stroke risk. Available evidence suggests that prolonged cardiac monitoring after stroke increases the likelihood of detecting atrial fibrillation. However, further research is required to fill in the gaps in regard to the optimal period of monitoring, candidates for monitoring, etc. Here, we review the current evidence supporting the use of prolonged monitoring for cryptogenic stroke patients and discuss the directions of future research.

Subclinical and clinical contrast-induced acute kidney injury: data from a novel blood marker for determining the risk of developing contrast-induced nephropathy (ENCINO), a prospective study.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is produced in response to tubular injury. Contrast-induced acute kidney injury (CI-AKI) is associated with adverse outcomes in chronic kidney disease (CKD) patients. We sought to characterize blood NGAL level and the degree of kidney injury in CKD patients who underwent coronary angiography. METHODS: This study was a prospective, blinded assessment of blood samples obtained from patients with estimated glomerular filtration rates (eGFRs) between 15 and 90 mL/min/1.73 m2 undergoing elective coronary angiography with iodinated contrast. Blood NGAL and serum creatinine were measured at baseline, 1, 2, 4, 6, 12, 24 and 48 h after contrast administration. RESULTS: A total of 63 subjects with a mean eGFR of 48.17±16.45 mL/min/1.73 m2 were enrolled. There was a graded increase in baseline NGAL levels across worsening stages of CKD (p=0.0001). Post-procedure NGAL increased from baseline in each stage of CKD. Eight (12.7%) patients were diagnosed with CI-AKI by diagnostic criteria of 2012 KDIGO definition of CI-AKI, and seven (11.1%) patients developed subclinical CI-AKI defined by a twofold or greater rise in NGAL. There was no relationship between baseline eGFR and diabetes on the composite outcome of subclinical and clinical CI-AKI. CONCLUSIONS: Baseline and post-procedure NGAL are progressively elevated according to the baseline stage of CKD. Using a twofold rise in NGAL, 46.7% of composite CI-AKI is detected and complements the 53.3% of cases identified using KDIGO criteria. Traditional risk predictors were not independently associated with this composite outcome.

A flow cytometric analysis of the inhibition of platelet reactivity due to nitrite reduction by deoxygenated erythrocytes.

Nitric oxide (NO), a small gas molecule, has long been known to be a potent inhibitor of platelet function but the physiological and pathological implications of platelet inhibition by NO have not been well clarified. We recently showed that the addition of nitrite to platelet-rich plasma in the presence of erythrocytes could inhibit platelet aggregation and this inhibitory effect of nitrite + erythrocytes was enhanced by deoxygenation of erythrocytes as measured by P-selectin expression and cGMP production. In order to study the nitrite effect on platelets at different oxygen levels, we used the flow cytometric assays to detect platelet membrane surface markers upon activation. The P-selectin and activated gpIIb/IIIa expression on platelet membranes in response to ADP, collagen and thrombin stimulation was measured at various hematocrit and oxygen levels. Nitrite (0.1 to 1.0 µM) significantly decreased the percentage of these surface markers on the platelet membrane at the hematocrit values above 23% and oxygen levels lower than 49 mmHg. The inhibitory effect of nitrite was augmented by increasing hematocrit values and decreasing oxygen saturation. C-PTIO (an NO scavenger) prevented the platelet inhibition by nitrite + erythrocytes whereas the inhibitors of NO synthase and xanthine oxidoreductase had no effect. These results support the proposal that circulating nitrite decreases platelet reactivity in the presence of partially deoxygenated erythrocytes through its reduction to NO, which may also explain certain differences between arterial and venous thrombosis and support directly the role of deoxyhemoglobin in this process. We believe that our flow cytometric assays offer a possibility to identify the individual molecular process involved in these effects.

Urine catalytic iron and neutrophil gelatinase-associated lipocalin as companion early markers of acute kidney injury after cardiac surgery: a prospective pilot study.

BACKGROUND: Open heart surgery with cardiopulmonary bypass is recognized as a common cause of acute kidney injury (AKI). The conventional biomarker creatinine is not sensitive enough to detect AKI until a significant decline in renal filtration has occurred. Urine neutrophil gelatinase-associated lipocalin (NGAL), part of an acute response to the release of tissue iron from cells, is an early biomarker and a predictor of AKI in a variety of clinical settings. We sought to evaluate the relationship between urine catalytic iron (unbound iron) and NGAL over the course of AKI due to cardiac surgery. METHODS: FOURTEEN PATIENTS WHO UNDERWENT OPEN HEART SURGERY HAD THE FOLLOWING MEASURED: serum creatinine (0, 12, 24, 48 and 72 h postoperatively), urine NGAL and urine catalytic iron (0, 8, 24 and 48 h postoperatively). Urine NGAL and urine catalytic iron were quantified by immunoassay and bleomycin-detectable iron assay, respectively. AKI was defined by the Acute Kidney Injury Network (AKIN) criteria. RESULTS: Urine catalytic iron increased significantly (p < 0.05) within 8 h and peaked at 24 h postoperatively in patients who developed AKI (n = 8, baseline 101.96 ± 177.48, peak 226.35 ± 238.23 nmol/l, p = 0.006), but not in non-AKI patients (n = 6, baseline 131.08 ± 116.21, peak 163.99 ± 109.62 nmol/l, p = 0.380). Urine NGAL levels also peaked at 24 h with significant increase observed only in AKI patients: AKI - baseline 34.88 ± 26.47, peak 65.50 ± 27.03 ng/ml, p = 0.043; non-AKI - baseline 59.33 ± 31.72, peak 71.00 ± 31.76 ng/ml, p = 0.100. The correlation between baseline levels of urine catalytic iron and NGAL and peak levels of urine catalytic iron and NGAL was r = 0.86, p < 0.0001. CONCLUSION: Urine catalytic iron appears to rise and fall in concert with NGAL in patients undergoing cardiac surgery and may be indicative of early AKI. Future research into the role that catalytic iron plays in acute organ injury syndromes and its potential diagnostic and therapeutic implications is warranted.

Effectiveness of deferiprone in transfusion-independent beta-thalassemia/HbE patients.

Beta-thalassemia/HbE (beta-thal/HbE) is a thalassemia intermedia (TI) which encompasses a broad spectrum of severity. Here, we used deferiprone (DFP) as an iron chelating agent in TI patients receiving intermittent blood transfusion who are asymptomatic for cardiovascular disease in order to evaluate the effectiveness in iron overload and reduce the possibility of cardiovascular complications. Thirty transfusion-independent beta-thal/HbE patients with iron overload were treated with DFP for 1 year. Hematological, biochemical, oxidative stress and echocardiographic parameters were determined. Serum ferritin, non-transferrin-bound iron, and malondialdehyde decreased significantly (P<0·05) after 1-year treatment with DFP. For echocardiographic results, mean pulmonary arterial pressure and pulmonary vascular resistance were diminished significantly (P<0·05). All those parameters were still improved after subgroup analysis was done for the high ferritin group (>2500 ng/ml). DFP therapy alone improved iron overload and oxidative stress and compliance was good. We propose that prevention of pulmonary hypertension is also possible for TI undergoing intermittent blood transfusion.