scholarly journals South Asian-Specific MYBPC3Δ25bp Deletion Carriers Display Hypercontraction and Impaired Diastolic Function Under Exercise Stress

2021 ◽  
Vol 8 ◽  
Author(s):  
Sholeh Bazrafshan ◽  
Robert Sibilia ◽  
Saavia Girgla ◽  
Shiv Kumar Viswanathan ◽  
Megan J. Puckelwartz ◽  
...  
Keyword(s):  
Right Ventricle ◽  
Late Onset ◽  
Peak Velocity ◽  
South Asians ◽  
Left Ventricular ◽  
Stress Conditions ◽  
Exercise Stress ◽  
Cardiac Monitoring ◽  
Diastolic Compliance ◽  
And Gender

Background: A 25-base pair (25bp) intronic deletion in the MYBPC3 gene enriched in South Asians (SAs) is a risk allele for late-onset left ventricular (LV) dysfunction, hypertrophy, and heart failure (HF) with several forms of cardiomyopathy. However, the effect of this variant on exercise parameters has not been evaluated.Methods: As a pilot study, 10 asymptomatic SA carriers of the MYBPC3Δ25bp variant (52.9 ± 2.14 years) and 10 age- and gender-matched non-carriers (NCs) (50.1 ± 2.7 years) were evaluated at baseline and under exercise stress conditions using bicycle exercise echocardiography and continuous cardiac monitoring.Results: Baseline echocardiography parameters were not different between the two groups. However, in response to exercise stress, the carriers of Δ25bp had significantly higher LV ejection fraction (%) (CI: 4.57 ± 1.93; p < 0.0001), LV outflow tract peak velocity (m/s) (CI: 0.19 ± 0.07; p < 0.0001), and higher aortic valve (AV) peak velocity (m/s) (CI: 0.103 ± 0.08; p = 0.01) in comparison to NCs, and E/A ratio, a marker of diastolic compliance, was significantly lower in Δ25bp carriers (CI: 0.107 ± 0.102; p = 0.038). Interestingly, LV end-diastolic diameter (LVIDdia) was augmented in NCs in response to stress, while it did not increase in Δ25bp carriers (CI: 0.239 ± 0.125; p = 0.0002). Further, stress-induced right ventricular systolic excursion velocity s' (m/s), as a marker of right ventricle function, increased similarly in both groups, but tricuspid annular plane systolic excursion increased more in carriers (slope: 0.008; p = 0.0001), suggesting right ventricle functional differences between the two groups.Conclusions: These data support that MYBPC3Δ25bp is associated with LV hypercontraction under stress conditions with evidence of diastolic impairment.

Abstract 13481: South Asian-specific MYBPC3 25bp Intronic Deletion Carriers Demonstrate Hypercontractility and Impaired Diastolic Function Under Exercise Stress

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sholeh Bazrafshan Kondori ◽  
Robert Sibilia ◽  
Saavia Girgla ◽  
Shiv K Viswanathan ◽  
Megan Puckelwartz ◽  
...  
Keyword(s):  
Diastolic Function ◽  
Risk Allele ◽  
Late Onset ◽  
South Asians ◽  
Left Ventricular ◽  
Exercise Stress ◽  
Cardiac Monitoring ◽  
Exercise Heart Rate ◽  
Lv Dysfunction ◽  
Significant Difference

Introduction: A 25bp intronic deletion in MYBPC3 ( Δ25bp ), present in 6% of US South Asians, is a risk allele for late onset left ventricular (LV) dysfunction and hypertrophy. Hypothesis: Asymptomatic Δ25bp carriers have detectable subclinical pathology to development of LV hypercontractility and impaired relaxation. Methods: To evaluate Δ25bp carriers for changes in cardiac function with bicycle exercise stress echocardiography and continuous cardiac monitoring, 16 Δ25bp male carriers (51±2 years) and 10 age- and sex-matched non-carrier (NCs) controls (50±3 years) participated in this pilot study. Of 16 Δ25bp carriers, six carried an additional pathogenic variant D389V in MYBPC3 . Included subjects had no uncontrolled comorbidities. Regression analysis and two-way ANOVA were performed, and 95% confidence interval (CI) and p values were reported. Results: Baseline echocardiographic parameters as well as baseline and monitored exercise heart rate and blood pressure were similar in both groups. The estimated effect of exercise stress and genotype showed that Δ25bp carriers had significantly higher ejection fraction (%) (CI: 4.03±1.64; p<0.0001) and higher LV outflow tract peak velocity (m/s) (CI: 0.15±0.06; p<0.0001) in comparison to NCs. Additionally, stress-induced LV end diastolic diameter did not increase in Δ25bp carriers as compared to NCs with a significant difference between the groups (CI: 0.22±0.11; p=0.0002). E/A ratio, a marker of diastolic function, significantly decreased with exercise in Δ25bp carriers (slope: -0.002; p=0.005) but showed non-significant change in the NCs (slope: -0.0006; p=0.428). Right ventricular systolic excursion velocity s' (m/s) as a marker of right ventricle function increased similarly in both groups, although tricuspid annular plane systolic excursion (cm) increased more dramatically in carriers (slope: 0.004; p=0.0002). Sub-analysis of Δ25bp vs Δ25bp + D389V did not reveal any differences. Conclusions: LV hypercontractility under exercise stress conditions with evidence of diastolic impairment at high workloads is evident among asymptomatic carriers of MYBPC3 Δ25bp allele, suggesting MYBPC3 Δ25bp as a risk allele with sub-clinical pathology prior to late onset LV dysfunction in South Asians .

Urine Albumin to Creatinine Ratio and Echocardiographic Left Ventricular Structure and Function in Patients with Essential Hypertension

2011 ◽  
Vol 9 (2) ◽  
pp. 90 ◽  
Author(s):  
Rohola Hemmati ◽  
Mojgan Gharipour ◽  
Hasan Shemirani ◽  
Alireza Khosravi ◽  
Elham Khosravi ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Peak Velocity ◽  
Left Ventricular ◽  
Lv Function ◽  
Creatinine Ratio ◽  
Uncomplicated Hypertension ◽  
Urine Albumin ◽  
Lv Dysfunction ◽  
Mitral Annulus Velocity ◽  
Lv Mass

Background:Appearance of microalbuminuria, particularly in patients with hypertension, might be associated with a higher prevalence of left ventricular (LV) dysfunction and geometric abnormalities. This study was undertaken to determine whether high urine albumin to creatinine ratio (UACR) as a sensitive marker for microalbuminuria can be associated with LV hypertrophy (LVH) and systolic and diastolic LV dysfunction.Methods:The study population consisted of 125 consecutive patients with essential uncomplicated hypertension. Urine albumin and creatinine concentration was determined by standard methods. LVH was defined as a LV mass index >100 g/m2 of body surface area in women and >130 g/m2 in men. Echocardiographic LV systolic and diastolic parameters were measured.Results:The prevalence of microalbuminuria in patients with essential hypertension was 5.6 %. UACR was significantly no different in patients with LVH than in patients with normal LV geometry (21.26 ± 31.55 versus 17.80 ± 24.52 mg/mmol). No significant correlation was found between UACR measurement and systolic and diastolic function parameters, including early to late diastolic peak velocity (E/A) ratio (R=-0.192, p=0.038), early diastolic peak velocity to early mitral annulus velocity (E/E') ratio (R=-0.025, p=0.794), LV ejection fraction (R=0.008, p=0.929), and LV mass (R=-0.132, p=0.154). According to the receiver operator characteristic (ROC) curve analysis, UACR measurement was not an acceptable indicator of LVH with areas under the ROC curves 0.514 (95 % confidence interval 0.394–0.634). The optimal cut-off value for UACR for predicting LVH was identified at 9.4, yielding a sensitivity of 51.6 % and a specificity of 48.3 %.Conclusion:In patients with uncomplicated essential hypertension, abnormal systolic and diastolic LV function and geometry cannot be effectively predicted by the appearance of microalbuminuria.

Applanation Tonometry for Assessment of Left Ventricular Systolic Load

2019 ◽  
Vol 12 (2) ◽  
pp. 94-99
Author(s):  
Rene D. Mileva-Popova ◽  
Nina Y. Belova
Keyword(s):  
Arterial Stiffness ◽  
Augmentation Index ◽  
Age Groups ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Applanation Tonometry ◽  
Non Invasive ◽  
Pressure Area ◽  
Older Subjects ◽  
And Gender

Summary Vascular-ventricular coupling is a major determinant of left ventricular load. The aim of our study was to assess non- invasively left ventricular load and its dependency on central hemodynamics. Sixty-five healthy and gender-matched individuals were divided in two groups according to their age: 20y/o and 50y/o. Applanation tonometry was performed using the Sphygmocor device. Central pressures and pulse wave analysis indices were computed. Central systolic (120±3 vs. 98±2 mm Hg) and pulse pressures (43±3 vs. 29±1 mm Hg) as well as the augmentation index (AIx75) (23±3 vs. 6±2%) were significantly higher in the 50y/o group (p<0.01). These parameters are relevant markers of arterial stiffness and evidenced the development of central arterial morphological and functional alterations in the older subjects. The time-tension index (TTI) computed from the systolic pressure area was significantly higher in the 50y/o subjects as compared to the 20y/o group (2378±66 vs. 1954±73 mmHg×s, p<0.01). Moreover, we have shown the presence of significant correlation between TTI and AIx75 (p<0.01) in both age groups. This finding confirmed the contribution of arterial stiffness for the impaired vascular-ventricular coupling. In conclusion, applanation tonometry might be utilized for non-invasive evaluation of the left ventricular load, which is an important parameter of cardiovascular risk.

Prognostic value of peak stress cardiac power in patients with normal ejection fraction undergoing exercise stress echocardiography

2020 ◽  
Author(s):  
Vidhu Anand ◽  
Garvan C Kane ◽  
Christopher G Scott ◽  
Sorin V Pislaru ◽  
Rosalyn O Adigun ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Stress Echocardiography ◽  
Stress Test ◽  
Peak Stress ◽  
Left Ventricular ◽  
Exercise Stress ◽  
Cardiac Power ◽  
Exercise Stress Echocardiography ◽  
Lv Mass

Abstract Aims  Cardiac power is a measure of cardiac performance that incorporates both pressure and flow components. Prior studies have shown that cardiac power predicts outcomes in patients with reduced left ventricular (LV) ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise cardiac power and power reserve in patients with normal EF. Methods and results  We performed a retrospective analysis in 24 885 patients (age 59 ± 13 years, 45% females) with EF ≥50% and no significant valve disease or right ventricular dysfunction, undergoing exercise stress echocardiography between 2004 and 2018. Cardiac power and power reserve (developed power with stress) were normalized to LV mass and expressed in W/100 g of LV myocardium. Endpoints at follow-up were all-cause mortality and diagnosis of heart failure (HF). Patients in the higher quartiles of power/mass (rest, peak stress, and power reserve) were younger and had higher peak blood pressure and heart rate, lower LV mass, and lower prevalence of comorbidities. During follow-up [median 3.9 (0.6–8.3) years], 929 patients died. After adjusting for age, sex, metabolic equivalents (METs) achieved, ischaemia/infarction on stress test results, medication, and comorbidities, peak stress power/mass was independently associated with mortality [adjusted hazard ratio (HR), highest vs. lowest quartile, 0.5, 95% confidence interval (CI) 0.4–0.6, P &lt; 0.001] and HF at follow-up [adjusted HR, highest vs. lowest quartile, 0.4, 95% CI (0.3, 0.5), P &lt; 0.001]. Power reserve showed similar results. Conclusion  The assessment of cardiac power during exercise stress echocardiography in patients with normal EF provides valuable prognostic information, in addition to stress test findings on inducible myocardial ischaemia and exercise capacity.

Cardiac tissue characterization with t1 and t2 mapping in anderson fabry patients: new pathophysiological concepts and early cardiac involvement

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Zanoni ◽  
V Ferrara ◽  
G Lanati ◽  
G Vitale ◽  
F Di Nicola ◽  
...  
Keyword(s):  
Cardiac Disease ◽  
Tissue Characterization ◽  
Cardiac Involvement ◽  
Late Onset ◽  
T2 Mapping ◽  
Serum Levels ◽  
Left Ventricular ◽  
Control Group ◽  
Funding Source ◽  
T1 And T2

Abstract Background Anderson Fabry (AF) disease is a X-linked lysosomal storage disorder with multiorgan involvement. Cardiac disease, mainly represented by left ventricular hypertrophy (LVH) and arrhythmias, is the most frequent cause of premature death. It is well know that specific therapy is less effective after the development of LVH and myocardial fibrosis, therefore early cardiac detection (before LVH) is important. New cardiac magnetic resonance (CMR) parametric imaging techniques (T1 and T2 maps) enable myocardial tissue changes associated with AF disease. Purpose To evaluate the relationship between CMR tissue characterization and clinical and instrumental manifestations of AF disease to find early markers of cardiac involvement. Methods 31 AF patients (9 males, mean age 49±16 years) underwent ECG, echocardiogram and contrast CMR. TnI, BNP, pro-BNP and serum lyso-Gb3 were dosed. T1 mapping was performed in a pre-contrast acquisition with the modified Look-Locker inversion recovery (MOLLI) sequences. CMR results were compared with those of 43 healthy age and gender-matched controls. Results In AF patients native septal T1 values were significantly lower compared to healthy controls (median 949 vs 991 msec, p=0.0137) and were inversely related to Lyso-Gb3 serum levels (p=0.003). Patients with LVH had lower T1 septal values in comparison with patients without LVH (892 vs 981 msec; p=0.0012). Patients with classic form had abnormal low T1 values more frequently than pts with late onset variant (78 vs 23%; p=0.038). In AF patients native septal T2 values were significantly higher compared to the control group (53 vs 49 msec; p=0.0004) and correlated with troponin I (p=0.008) and NT-pro BNP (p=0.006) serum levels. No difference was found between pts with and without LVH (53.5 vs 52.5 ms; p=0.797) and the prevalence of abnormal high T2 values was similar between patients with late onset AF and pts with classical form (53% vs 50%; p=1.000). All patients with late onset AF and high T2 values were females. Conclusions CMR T1 (low values) and T2 (high values) mapping are useful tools to detect early cardiac involvement before LVH and to better understand the pathophysiology of cardiac disease in AF patients. Subclinical tissue inflammation, detectable through T2 maps, seems to be an additional pathogenetic mechanism related to the Gb3 storage that contributes to organ damage and precedes LVH, particularly in females patients with late onset phenotype. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Sant'Orsola-Malpighi Hospital

scholarly journals The role of neurohormonal blockers in the primary prevention of acute-, early-, and late-onset anthracycline-induced cardiotoxicity

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Ahmed Ayuna ◽  
Nik Abidin
Keyword(s):  
Primary Prevention ◽  
Myocardial Injury ◽  
Troponin I ◽  
Late Onset ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Main Body ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

Abstract Background Anthracycline-induced cardiotoxicity has been classified based on its onset into acute, early, and late. It may have a significant burden on the quality and quantity of life of those exposed to this class of medication. Currently, there are several ongoing debates on the role of different measures in the primary prevention of cardiotoxicity in cancer survivors. Our article aims to focus on the role of neurohormonal blockers in the primary prevention of anthracycline-induced cardiotoxicity, whether it is acute, early, or late onset. Main body of the abstract PubMed and Google Scholar database were searched for the relevant articles; we reviewed and appraised 15 RCTs, and we found that angiotensin-converting enzyme inhibitors (ACEI) and B-blockers were the most commonly used agents. Angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs) were used in a few other trials. The follow-up period was on the range of 1–156 weeks (mode 26 weeks). Left ventricular ejection fraction (LVEF), left ventricular diameters, and diastolic function were assessed by either echocardiogram or occasionally by cardiac magnetic resonance imaging (MRI). The occurrence of myocardial injury was assessed by troponin I. It was obvious that neurohormonal blockers reduced the occurrence of LVEF and myocardial injury in 14/15 RCTs. Short conclusion Beta-blockers, especially carvedilol and ACEI, especially enalapril, should be considered for the primary prevention of acute- and early-onset cardiotoxicity. ARB and MRA are suitable alternatives when patients are intolerant to ACE-I and B-blockers. We recommend further studies to explore and establish the role of neurohormonal blockers in the primary prevention of the acute-, early-, and late-onset cardiotoxicity.

scholarly journals An Adult Mouse Model of Dilated Cardiomyopathy Caused by Inducible Cardiac-Specific Bis Deletion

2021 ◽  
Vol 22 (3) ◽  
pp. 1343
Author(s):  
Hye Hyeon Yun ◽  
Soon Young Jung ◽  
Bong Woo Park ◽  
Ji Seung Ko ◽  
Kyunghyun Yoo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Late Onset ◽  
Small Heat Shock Protein ◽  
Left Ventricular ◽  
Therapeutic Interventions ◽  
Ventricular Contractility ◽  
Knock Out ◽  
Multifunctional Protein ◽  
Cell Death Suppressor

BCL-2 interacting cell death suppressor (BIS) is a multifunctional protein that has been implicated in cancer and myopathy. Various mutations of the BIS gene have been identified as causative of cardiac dysfunction in some dilated cardiomyopathy (DCM) patients. This was recently verified in cardiac-specific knock-out (KO) mice. In this study, we developed tamoxifen-inducible cardiomyocyte-specific BIS-KO (Bis-iCKO) mice to assess the role of BIS in the adult heart using the Cre-loxP strategy. The disruption of the Bis gene led to impaired ventricular function and subsequent heart failure due to DCM, characterized by reduced left ventricular contractility and dilatation that were observed using serial echocardiography and histology. The development of DCM was confirmed by alterations in Z-disk integrity and increased expression of several mRNAs associated with heart failure and remodeling. Furthermore, aggregation of desmin was correlated with loss of small heat shock protein in the Bis-iCKO mice, indicating that BIS plays an essential role in the quality control of cardiac proteins, as has been suggested in constitutive cardiac-specific KO mice. Our cardiac-specific BIS-KO mice may be a useful model for developing therapeutic interventions for DCM, especially late-onset DCM, based on the distinct phenotypes and rapid progressions.

Cathodic-anodal left ventricular stimulation during cardiac resynchronization therapy: haemodynamic evaluation and electrocardiographic analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Gravellone ◽  
G Dell' Era ◽  
F De Vecchi ◽  
E Boggio ◽  
E Prenna ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Arterial Pressure ◽  
Cardiac Resynchronization Therapy ◽  
Right Ventricle ◽  
Single Point ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Resynchronization Therapy ◽  
Biventricular Stimulation ◽  
Qrs Duration

Abstract Background Cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction (HFrEF). However, one third of patients are “non responders”. Cathodic-anodal (CA) left ventricle (LV) capture is a multisite pacing occurring during CRT using both bipolar and quadripolar LV lead. It allows depolarization to arise simultaneously from the cathode and the anode of the bipole located on the LV epicardium, activating a larger volume of myocardium than cathodal pacing alone, thus potentially improving electromechanical synchrony (figure 1). We have previously proven that CA-LV stimulation is feasible and similar to bicathodic multipoint pacing (MPP) in terms of QRS wavefront activation. Purpose We aimed to evaluate both the acute intraprocedural haemodynamic and electrical effects of CA biventricular stimulation (CA-BS), comparing it with right-ventricle only pacing (Right Ventricle-Stimulation: RV-S), single-point CRT (Single Point-Biventricular Stimulation: SP-BS) and multipoint bicathodic biventricular stimulation (Multi Point-Biventricular Stimulation:MP-BS) in de novo CRT implants. Methods Ten patients candidates to CRT (LV ejection fraction ≤35% and left bundle branch block) received a quadripolar LV lead. Four pacing configurations were tested: RV-S, SP-BS, MP-BS and CA-BS, where cathode and the anode were the same electrodes used as cathodes in MP-BS. QRS duration by 12-lead ECG was defined as the time from the earliest ventricular deflection until the return to the isoelectric line. Haemodynamic assessment by radial artery catheterization using Pressure Recording Analytical Method processed the following parameters: dP/dT max (mmHg/msec), systolic arterial pressure (aPsys, mmHg), diastolic arterial pressure (aPdia, mmHg), mean arterial pressure (aPmean, mmHg), Cardiac Index (CI, l/min/m2), Stroke Volume Index (SVI, ml/min/m2). Results dP/dT max and aPmean increased significantly from RV-S to SP-BS (mean dP/dT max 0,82±0,28 versus 0,87±0,29 mmHg/msec, p=0,02; mean aPmean 89±19 versus 93±20 mmHg, p=0,01), but not from RV-S to MP-BS. Comparing RV-S to CA-BS, only aPmean exhibited a significant increase (mean aPmean 89±19 versus 92±20 mmHg, p=0,01). There were no haemodynamic differences between SP-BS, MP-BS and CA-BS. QRS duration reduced significantly from RV-S (167±10 msec) to each biventricular stimulation (135±14 msec, p=0,0002 for SP-BS; 130±17 msec, p=0,0001 for MP-BS; 129±18 msec, p=0,0002 for CA-BS) and from SP-BS to MP-BS and CA-BS (p=0,03 for both), whereas there were no difference comparing MP-BS and CA-BS. Conclusions CA-LV stimulation is not superior to single-point CRT in terms of acute haemodynamic performance, whereas it reduces the duration of ventricular electrical activation, showing an electrohaemodynamic mismatch. Long-term studies are needed to evaluate if acute electrical benefits of CA stimulation can predict chronic benefits, in terms of reverse cardiac remodelling. Cathodic-anodal left ventricular capture Funding Acknowledgement Type of funding source: None

scholarly journals The ‘Inextricabilis Syndrome’: a case with no solution

2014 ◽  
Vol 1 (2) ◽  
pp. K13-K16
Author(s):  
Tigran Khachatryan ◽  
Roy Beigel ◽  
Reza Arsanjani ◽  
Robert J Siegel
Keyword(s):  
Cardiogenic Shock ◽  
Artery Bypass ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Cardiac Monitoring ◽  
List Type ◽  
Ventricular Assist ◽  
Surgical Interventions ◽  
Left Ventricular Assist ◽  
Bridge To Decision

Summary We describe a case of a 58-year-old man with cardiogenic shock who underwent triple vessel coronary artery bypass and a left ventricular assist device (LVAD) implantation. His course was complicated by stroke, worsening mitral regurgitation, aortic regurgitation, and multiple cardiac thrombi while on the device. We provide the details of the patient's hospital course, management, and echocardiographic findings. We also discuss the utility of echocardiography before LVAD insertion and its role for continued monitoring after insertion. Learning points Ventricular assist devices (VADs) are used as bridge to decision, transplant, recovery, or destination therapy in patients with advanced heart failure and cardiogenic shock. VADs improve survival and the quality of life but have significant associated complications. Echocardiography plays an essential role before VAD insertion and for postoperative cardiac monitoring. Information provided by echocardiography is used in device selection, consideration for corrective surgical interventions, and device explantation.

Sign in / Sign up

Export Citation Format

Share Document