Experience with cascade screening: A comprehensive family pedigree analysis of two index patients with Fabry disease.

The wide range of clinical symptoms observed in patients with Fabry disease (FD) often leads to delays in diagnosis and initiation of treatment. Delayed initiation of therapy may result in end-organ damage, such as chronic renal failure, hypertrophic cardiomyopathy, and stroke. Although some tools are available to identify undiagnosed patients, new comprehensive screening methods are needed. In this study, the outcomes of the cascade screening applied to three index cases with FD from 2 familes were investigated. In the pedigree analysis, 280 individuals were included; out of them, 131 individuals underwent genetic testing and cascade screening for FD. During the screening program, a total of 45 individuals were diagnosed, with a diagnostic ratio of 1:15. The average age at diagnosis for all individuals was 30.9 ± 17.7 years, and %25 were pediatric cases (mean age 9.5 ± 5.9 years). Thirty affected relatives were diagnosed from the two index cases in Family 1 and 15 individuals were diagnosed from one index case in Family 2. There were 13 consanguineous marriages observed among 2 pedigres, in two both spouses  were affected, leading to two homozygous affected daughters in one couple. In regions where there is a high prevalence of consanguineous marriages, implementing the cascade screening approach to identify all individuals at risk can be beneficial for patients with FD, specifically women and children.

Tricuspid regurgitation and infective endocarditis as a cause of lead dislodgement in left bundle branch area pacing.

BACKGROUND: According to the current literature, there is no difference between left bundle brunch area pacing (LBBAP) and right ventricular apical pacing in terms of lead dislodgement and capture threshold elevation. However, there are no large-scale studies reporting the data about long-term lead stability in patients with severe tricuspid regurgitation. METHODS AND RESULTS: We present a case of lead dislodgement with possible infective endocarditis six months after implantation in a patient with severe tricuspid regurgitation who underwent LBBAP. CONCLUSIONS: We concluded that severe preoperative tricuspid regurgitation may cause lead dislodgement, and infective endocarditis may be a facilitator or main reason of lead dislodgement in cases of LBBAP.

The effect of idiopathic premature ventricular complexes on left ventricular ejection fraction.

AIM: Current literature lacks a definitive threshold of idiopathic premature ventricular complex (PVC) burden for predicting cardiomyopathy (CMP). The main objective of the present study was to evaluate relationship between the PVC burden and left ventricular ejection fraction (LVEF). METHOD: This multicenter, cross-sectional study included 341 consecutive patients with more than 1,000 idiopathic PVC in 24 hr of Holter monitoring admitted to the cardiology clinics between January 2019 and May 2019 in the nineteen different centers. The primary outcome was the LVEF measured during the echocardiographic examination. RESULT: Overall, the median age was 50 (38-60) and 139 (49.4%) were female. Percentage of median PVC burden was 9% (IQR: 4%-17.4%). Median LVEF was found 60% (55-65). We used proportional odds logistic regression method to examine the relationship between continuous LVEF and candidate predictors. Increase in PVC burden (%) (regression coefficient (RE) -0.644 and 95% CI -1.063, -0.225, p < .001), PVC QRS duration (RE-0.191 and 95% CI -0.529, 0.148, p = .049), and age (RE-0.249 and 95% CI -0.442, -0.056, p = .018) were associated with decrease in LVEF. This inverse relationship between the PVC burden and LVEF become more prominent when PVC burden was above 5%. A nomogram developed to estimate the individual risk for decrease in LVEF. CONCLUSION: Our study showed that increase in PVC burden %, age, and PVC QRS duration were independently associated with decrease in LVEF in patients with idiopathic PVC. Also, inverse relationship between PVC burden and LVEF was observed in lower PVC burden than previously known.

Monitoring the response to treatment of acute heart failure patients by ultrasonographic inferior vena cava collapsibility index.

OBJECTIVE: Our aim was to determine if N-terminal pro-brain natriuretic peptide (NT-proBNP) or sonographic measurements of inferior vena caval (IVC) diameters and collapsibility index (IVC-CI) have a role in the monitoring of acute heart failure (AHF) therapy. METHODS: Inferior vena caval diameters of 50 healthy people (control group) were measured to determine the normal values of the IVC parameters. We then prospectively enrolled patients who were admitted to the emergency department (ED) with a primary diagnosis of AHF. At presentation, IVC diameters were measured during expiration and inspiration, and blood was drawn for NT-proBNP. We repeated the measurement of the IVC parameters and collected a second blood sample 12 hours after the therapy was administered. The data were analyzed in SPSS 15.0 (IBM, Armonk, NY) using the Student t test and Mann-Whitney U test. RESULTS: A total of 97 subjects were enrolled: 47 in the patient group and 50 in the control group. The mean IVC during expiration was 2.10 ± 0.37 cm before and 1.57 ± 0.24 cm after the therapy (P < .001). The mean IVC during inspiration was 1.63 ± 0.40 cm before and 0.90 ± 0.26 cm after the therapy (P < .001). The mean IVC-CI rose from 22.80% ± 10.97% to 43.09% ± 13.63% (P < .001). After the therapy, there was no difference between the IVC-CI of the patients and controls (P = .246). There was no significant change in the mean NT-proBNP levels after the therapy. CONCLUSION: Inferior vena caval collapsibility index may be helpful in monitoring AHF patients' responses to therapy in the ED.

Assessment of the correlation between Doppler derived dP/dt and aortic velocity-time integral during cardiac resynchronization therapy optimization.

PURPOSE: Suboptimal response to cardiac resynchronization therapy (CRT) may be improved by optimization of device parameters using echocardiography. For this purpose, the aortic velocity-time integral (aVTI) has been used as a target metric to define optimal velocity timings for each ventricle. dP/dt is a parameter used for the assessment of myocardial contractility. In this study, we aimed to evaluate the effectiveness of Doppler-derived dP/dt in optimization by assessing the possible correlation between aVTI and dP/dt. METHODS: Patients with CRT admitted for routine follow-up were included in the study. Aortic VTI and dP/dt measurements were recorded in four different standard pacing configurations during reprogramming. RESULTS: A total of 45 patients were included in the final analysis. No correlation was found between the aVTI and the delta dP/dt value in the two configurations where the change in dP/dt was maximum (p = 0.894). In the two configurations where the change in aVTI was maximum, there was also no correlation between the delta dP/dt and the delta aVTI (p = 0.715). When patients were dichotomized according to the median value of dP/dt, there were no differences in aVTI, NYHA classes, LVEF, and mitral regurgitation (MR) severity (p = 0.4; p = 0.5; p = 0.7; p = 0.3; respectively). The change in both dP/dt and aVTI was statistically significant when switching from RV-only to QRS width-targeted configuration (p = 0.001; p = 0.041; respectively). CONCLUSION: In conclusion, aVTI recorded at different pacing configurations did not correlate with dP/dt during interventricular optimization. However, both parameters consistently showed a positive effect of biventricular pacing on contractile synchronization and stroke volume.

A long-standing conundrum: an unusual case of 2:1 atrioventricular block with conflicting findings.

A 2:1 atrioventricular (AV) block can occur anywhere within the conduction system, and noninvasive measurements may not always predict the exact site of the block. Although localization of the block is critical for deciding any treatment, patients should also be carefully questioned about symptoms both at rest and during exertion. A case of 2:1 AV block that was symptomatic only during exertion, appeared infranodal by noninvasive diagnostic methods, but was found to be intranodal on electrophysiological study is reported.

Evaluation of the Impact of Body Position on Primary Central Sleep Apnea Syndrome.

OBJECTIVE: To evaluate the impact of the body position on primary central sleep apnea syndrome. METHODS: Fifty-five subjects diagnosed with central sleep apnea (CSA) through polysomnographic examinations were prospectively enrolled in the study. All patients underwent cardiologic and neurologic examinations. Primary positional central sleep apnea (PCSA) was determined when the supine Apnea-Hypopnea Index (AHI) was greater than two times the non-supine AHI. The primary PCSA and non-PCSA groups were compared in terms of demographic characteristics, sleep parameters, and treatment approaches. RESULTS: Overall, 39 subjects diagnosed with primary CSA were included in the study; 61.5% of the subjects had primary PCSA. There were no differences between the primary PCSA and non-PCSA groups regarding age, sex, body mass index (BMI), co-morbidities, and history of septoplasty. In terms of polysomnography parameters, AHI (P=.001), oxygen desaturation index (P=.002), the time spent under 88% saturation during sleep (P=.003), number of obstructive apnea (P=.011), mixed apnea (P=.009), and central apnea (P=.007) was lower in the primary PCSA group than in the non-PCSA group. Twenty-nine percent of the patients in the primary PCSA group were recommended position treatment and 71% were recommended positive airway pressure (PAP) therapy; all patients in the non-PCSA group were recommended PAP therapy. CONCLUSIONS: Our results demonstrated that the rate of primary PCSA was high (61.5%) and primary PCSA was associated with milder disease severity compared with non-PCSA. The classification of patients with primary CSA regarding positional dependency may be helpful in terms of developing clinical approaches and treatment recommendations.

Association of cardiac adaptations with NT-proBNP levels after percutaneous closure of atrial septal defect.

OBJECTIVE: The aim of this study was to evaluate the early effects of transcatheter closure of secundum atrial septal defect (ASD) on atrial and ventricular diameters and functions evaluated by transthoracic echocardiography, and to assess the relation of morphological changes to N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. METHODS: Twenty-two patients with secundum-type ASD referred for percutaneous closure were included in the study as well as 22 healthy individuals who served as a control group. TTE and concurrent blood sampling were performed prior to and 24 hours and 30 days after the closure procedure. RESULTS: At follow-up 24 hours and 30 days after the closure, the right atrial (RA) area, right ventricular (RV) area, RV end-diastolic volume (EDV), and RV end-systolic volume (ESV) decreased, while left ventricle (LV) EDV (LVEDV), LVESV, and LV stroke volume (LVSV) increased. Global RV systolic and diastolic function indices, such as the tricuspid annular plane systolic excursion, the tricuspid E/A and E/e' ratio decreased immediately after the closure. The NT-proBNP value increased in the 24 hours following closure, and after 30 days, it was still higher than the measurement recorded before the transcatheter closure. The LV structural and functional parameters were significantly correlated with the NT-proBNP value (LVEDV: r=0.37, p=0.02; LVESV: r=0.38, p=0.01; left atrium area: r=0.46, p=0.002; mitral E/e': r=0.28, p=0.04). CONCLUSION: Percutaneous ASD closure can lead to both early and sustained changes in cardiac anatomy and function involving both sides of the heart. The NT-proBNP level had increased at 24 hours post procedure, and was also notably increased 30 days after the percutaneous ASD closure, which is associated with increased LV diameter and volume.

Central venous obstruction and clinical predictors in patients with permanent pacemaker.

OBJECTIVE: This study investigated the proportion of silent venous obstruction in patients who underwent pacemaker or lead reimplantation for various reasons. We also investigated independent predictors or risk factor of venous obstruction in this patient population. METHODS: Seventy-three patients who underwent pacemaker pulse generator and/or lead reimplantation in our institution between 2007 and 2010 were enrolled for this retrospective case-control study. Prior to procedure, patients underwent ipsilateral venography. Patients' venographies were classified as non-significant obstruction (stenosis ≤70%, including normal venogram), significant obstruction (stenosis >70%) and complete obstruction. Continuous and categorical data were compared with Mann-Whitney U test and Chi-square statistics respectively. Logistic regression analysis was used to identify independent predictors of venous obstruction. RESULTS: Complete or significant silent central venous obstruction (CVO) proportion was detected as 9.5% (n=7). Basal characteristics of patients with or without CVO were comparable. Significantly increased pacemaker pocket erosion incidence (57% vs 0%, p=0.001, in groups with and without CVO respectively) and significantly higher mean pacemaker age (15.3 ± 10.2 years vs 10.4 ± 5.1 years, p=0.047, in groups with and without CVO respectively) were found in group with CVO. Pacemaker pocket erosion (OR 3.00; 95% CI 1.024-9.302; p=0.001), higher pacemaker age (OR 1.33; 95% CI 1.026-1.733; p=0.02) were found as independent CVO predictors in multiple logistic regression analysis. Correlation analysis also revealed a significant correlation between previous or current pacemaker pocket erosion and CVO (r=0.80, p=0.001). CONCLUSION: Ipsilateral venography is a useful procedure prior to pacemaker or lead reimplantation to detect CVO. In addition to the increased pacemaker age, current or past history of erosion and infection at pacemaker pocket are probable clinical conditions related to CVO. These clinical conditions create a predisposition to CVO with unknown mechanisms, according to the results of this preliminary study.

An observational study of the effect of coronary artery disease severity on acute pacing threshold and lead impedance in patients with permanent pacemaker.

OBJECTIVE: This study investigated the effect of coronary artery disease (CAD) severity, distribution and left ventricular ejection fraction (LVEF) on acute ventricular pacing threshold and lead impedance at the time of pacemaker implantation. METHODS: One hundred and thirty-two patients who received a ventricular pacemaker or internal cardioverter-defibrilator (ICD) lead in our institution between 2007-2010 were included in this observational study. Patients were divided into ICD and anti-bradycardic pacemaker (PM) groups. Groups were compared for ventricular stimulation threshold, lead impedance and LVEF. Later, groups were sub-grouped according to the severity and distribution of CAD and subgroups were compared in both groups for ventricular stimulation threshold, lead impedance. Quantitative data of groups were compared by means of independent samples t-test. RESULTS: Ventricular pacing thresholds were found significantly higher ICD group compared with PM group (p<0.05). Impedance and LVEF values were significantly lower in ICD group (p<0.05). Impedance and ventricular pacing thresholds were comparable in subgroups of ICD and PM groups. Our study does not confirm any relationship between pacing parameters and severity-distribution of CAD and LVEF. CONCLUSION: Patients with ventricular ICD lead had higher pacing thresholds but lower pacing impedance values comparing with PM group. This study did not find any significant relationship between pacing parameters at implantation and LVEF, severity and distribution of CAD.