Ventricular Abnormalities Research Articles

Effects of β-blockers on ventricular repolarization documented by 24-hour electrocardiography in long QT syndrome type 2

Long QT syndrome (LQTS) is an inherited arrhythmia disorder characterized by ventricular repolarization abnormalities and a risk of sudden cardiac death. The electrophysiological components generating the high risk of arrhythmias in LQTS are prolonged repolarization, increased dispersion of repolarization, and early afterdepolarizations, which are clinically estimated as QT interval, T-wave peak to T-wave end (TPE) interval, and T2/T1-wave amplitude ratio, respectively. In experimental LQTS type 2 (LQT2) models, β-blockers decrease dispersion of repolarization and prevent early afterdepolarizations. In clinical studies in patients with LQT2 , β-blockers are more effective against exercise-induced than arousal-induced cardiac events. The aim of the study was to investigate the effects of β-blocker therapy on repolarization properties in LQT2. QT and TPE intervals and maximal T2/T1-wave amplitude ratios recorded by 24-hour electrocardiograms before and during β-blocker therapy were evaluated in 25 patients with LQT2. β-Blocker therapy decreased the maximal T2/T1-wave amplitude ratio from 2.9 ± 1.1 to 1.8 ± 0.7 (P < .001), but did not change the pause-induced T2/T1-wave amplitude ratio. Under medication, abrupt maximal TPE intervals were shorter at heart rates of ≥75 beats/min and maximal QT intervals were shorter at a heart rate of 100 beats/min. β-Blockers stabilize ventricular repolarization in LQT2 by reducing electrocardiographic early afterdepolarizations and by reducing abrupt prolongation of electrocardiographic dispersion of repolarization and ventricular repolarization duration at elevated heart rates. The effect of β-blockers on pause-induced electrocardiographic early afterdepolarizations is weak. The findings provide electrocardiographic explanation for the protective effects of β-blockers against exercise-induced cardiac events in LQT2.

Significance of abnormal and late ventricular signals in ventricular tachycardia ablation of ischemic and nonischemic cardiomyopathies

Abnormal ventricular signals (AVS) are the cornerstone of substrate-based ventricular tachycardia (VT) ablation in sinus rhythm. Signal characterization of AVS in ischemic and nonischemic cardiomyopathies has never been performed. The purpose of this study was to describe ventricular signal abnormalities in 3 different pathologies and examine their association with the diastolic component of VT circuits. A total of 45 patients (15 ischemic cardiomyopathy [ICM], 15 arrhythmogenic cardiomyopathy [ACM], 15 dilated cardiomyopathy [DCM]) who had undergone VT ablation with >50% of the diastolic pathway of the VT circuit recorded were studied. AVS were classified into late potentials (LPs) and continuous fractionated ventricular signals (CFVS), and their characteristics and correlation with the diastolic pathway of VT circuits were analyzed. Seventy-five VT circuits were analyzed. Bipolar scars were greatest in ICM endocardially (53 cm2 ICM vs 36 cm2 ACM vs 25 cm2 DCM; P = .010) and in ACM epicardially (98 cm2 ACM vs 25 cm2 ICM vs 24 cm2 DCM; P = .005). Location of the VT diastolic interval coincided with AVS location in 54% of VTs in ICM, 89% in ACM, and 72% in DCM (P = .036). There was a trend toward a greater association of diastolic intervals coinciding with LPs than with CFVS (78% vs 57%; P = .052) (69% diastolic intervals in ICM coincided with LPs, 33% with CFVS; P = .063). All patients (100%) with CFVS in ACM hadVTdiastolic components arising from CFVS (33% ICM, 64% DCM; P = .049). Positive predictive value for LPs vs CFVS was 77.8% vs 56.7%, and sensitivity was 67.3% vs 32.7%, respectively. The nature of abnormal signals in different cardiomyopathies reflects underlying pathology. LPs rather than CFVS seem to be more linked to diastolic components of VT circuits, especially in ICM. LPs have greater sensitivity and specificity for VT; however, CFVS may be of more relevance in ACM.

Abstract EC101: Premature Stop Mutations In Mybphl Share The Common Pathomechanism Of Preventing Protein Incorporation Into The Cardiac Myofilament

Cardiomyopathy and arrhythmia are diseases with significant genetic linkage. Cardiac myosin binding protein-C (cMyBP-C) is a myofilament associated protein with a C-terminal composed of repeating immunoglobulin (Ig) and fibronectin III (FnIII) domains that bind to the myosin thick filaments and titin. Truncating mutations in the C-terminal of MyBP-C result in improper myofilament incorporation and degradation of the truncated protein and is a major cause of hypertrophic cardiomyopathy. Myosin-binding protein-H like ( MyBP-HL ) is a protein that was recently identified that is structurally related to MyBP-C. Both cMyBP-C and MyBP-HL contain repeated C-terminal Ig and FnIII domains that bind to myosin. MyBP-HL is different in that it is primarily expressed in the atria where it interacts with the myofilament. MyBP-HL premature stop mutations are associated with improper myofilament incorporation, and has been linked to ventricular conduction system abnormalities, atria enlargement, and dilated cardiomyopathy (DCM) in humans. The gnomAD database reports 9 stop-gain mutations for MYBPHL in humans including: Gln29, Trp54, Arg113, Tyr123, Trp158, Trp192, Lys250, Arg255 and Tyr307. Prior investigation modeled the MyBP-HL Arg255X mutation and showed no MyBP-HL localization into the myofilament. A null mouse model showed that loss of MyBP-HL resulted in arrhythmia and cardiomyopathy, similar to that observed in humans. We hypothesize that all MyBP-HL truncation mutations will share a common mechanism by failing to produce MyBP-HL that integrates into the sarcomere. We test this hypothesis by transfecting neonatal rat cardiomyocytes with MyBP-HL constructs containing these mutations. We tested Trp54, Arg113, Tyr123, Trp158, Trp192, Lys250 and Arg255 MyBP-HL mutations. We measured co-localization events between MyBP-HL mutants and MyBP-C in atrial and ventricular overexpressed cells and observed that stop gained mutations disrupt normal localization as we expected. Moreover, we tested wild-type MyBP-HL overexpression, and both showed to be able to incorporate in a similar pattern to cMyBP-C C-zone doublets. These truncating mutations in MYBP-HL may increase risk for developing arrhythmias, atria enlargement and DCM.

Clinical profile and long-term follow-up of a cohort of patients with desmoplakin cardiomyopathy.

Desmoplakin (DSP) genetic variants have been reported in arrhythmogenic cardiomyopathy with particular regard to predominant left ventricular (LV) involvement. The purpose of this study was to improve our understanding of clinical phenotype and outcome of DSP variant carriers. The clinical picture and outcome of 73 patients (36% probands) harboring a pathogenic/likely pathogenic DSP variant were evaluated. The phenotype during follow-up (mean 11 years; range 1-39 years) changed in 25 patients (35%), arrhythmogenic LV cardiomyopathy (ALVC) forms being the most frequent (n = 26 [36%]), followed by biventricular (BIV; n = 20 [27%]) and arrhythmogenic right ventricular cardiomyopathy (ARVC; n = 16 [22%]) forms. Major ventricular arrhythmias were detected in 21 patients (29%), and they were more common in ARVC (n = 6, 56%) and BIV forms (n = 8, 40%) than in ALVC forms (n = 4, 15%). In patients with ALVC, major ventricular arrhythmias occurred in the setting of a normal/mildly reduced systolic function. Heart failure (HF) occurred in 6patients(8%); none affected with ALVC. Females showed more commonly LV involvement, while ARVC forms were more frequently detected in males (21 [61%] vs 15 [38%]; P = .147). Males showed a higher incidence of major ventricular arrhythmias (18 [52%] vs 9 [24%]; P = .036), HF (11 [31%] vs 1 [3%]; P = .004), and cardiac death (11 [31%] vs 0 [0%]; P < .001). The clinical phenotype in pathogenic/likely pathogenic DSP variant carriers is wide. Although most patients show LV involvement, 16 (22%) has right ventricular abnormalities in keeping with a "classical" arrhythmogenic cardiomyopathy form. In ALVC, HF and major ventricular arrhythmias seem less common than in right ventricular and BIV variants. Females show more frequently LV involvement and a better outcome.

Predictive value of incidental right ventricular abnormalities identified on SPECT for mortality and pulmonary hypertension

BackgroundThe clinical significance of incidentally found RV abnormalities on low-risk SPECT studies is not well-defined. The objective of this study was to determine the predictive value of incidental right ventricular (RV) abnormalities identified on single photon emission computed tomography (SPECT) scans for mortality and pulmonary hypertension (PH). MethodsWe retrospectively analyzed all low-risk SPECT studies in patients without known coronary artery or pulmonary vascular disease, performed at our institution, from 2007-2020. Adjusted Cox proportional hazards models were used to evaluate the association between incidental RV abnormalities on low-risk SPECT studies and outcomes. ResultsOf the 4761 patients included in the analysis, mortality events were present in 494, and echocardiographic PH was present in 619. Incidental RV abnormalities on low-risk SPECT studies were significantly and independently associated with all-cause mortality (HR = 1.41, CI [1.07-1.86], P = 0.0152) and echocardiographic PH (HR = 2.06, CI [1.64-2.60], P < 0.0001). ConclusionsThese data suggest incidental RV abnormalities found on low-risk SPECT imaging studies are significantly and independently associated with increased mortality and risk of developing echocardiographic PH, and could identify high-risk patients for closer monitoring and additional diagnostic testing.

Genetic Background and Clinical Features in Arrhythmogenic Left Ventricular Cardiomyopathy: A Systematic Review.

In recent years a phenotypic variant of Arrhythmogenic cardiomyopathy has been described, characterized by predominant left ventricular (LV) involvement with no or minor right ventricular abnormalities, referred to as Arrhythmogenic left ventricular cardiomyopathy (ALVC). Different disease-genes have been identified in this form, such as Desmoplakin (DSP), Filamin C (FLNC), Phospholamban (PLN) and Desmin (DES). The main purpose of this critical systematic review was to assess the level of knowledge on genetic background and clinical features of ALVC. A search (updated to April 2022) was run in the PubMed, Scopus, and Web of Science electronic databases. The search terms used were “arrhythmogenic left ventricular cardiomyopathy” OR “arrhythmogenic cardiomyopathy” and “gene” OR “arrhythmogenic dysplasia” and “gene”. The most represented disease-gene turned out to be DSP, accounting for half of published cases, followed by FLNC. Overall, ECG abnormalities were reported in 58% of patients. Major ventricular arrhythmias were recorded in 26% of cases; an ICD was implanted in 29% of patients. A total of 6% of patients showed heart failure symptoms, and 15% had myocarditis-like episodes. DSP is confirmed to be the most represented disease-gene in ALVC patients. An analysis of reported clinical features of ALVC patients show an important degree of electrical instability, which frequently required an ICD implant. Moreover, myocarditis-like episodes are common.

Differences in Regulation of Cortisol Secretion Contribute to Left Ventricular Abnormalities in Patients With Essential Hypertension.

Left ventricular (LV) abnormalities were reported in patients with overt and subclinical Cushing syndrome. The aim of this study was to investigate the relationships of daily plasma cortisol profile and cortisol response to an overnight suppression test with cardiac changes in patients with hypertension. In a cross-sectional study, we included 136 nondiabetic, patients with essential hypertension who were free of cardiovascular and renal complications. Plasma cortisol was measured at 8 am, 3 pm, and 12 am and at 8 am after overnight suppression with 1 mg dexamethasone (dexamethasone suppression test [DST]). Echocardiography was performed with standard B-mode and tissue-Doppler imaging. LV hypertrophy was present in 30% and LV diastolic dysfunction in 51% of patients who were older and had significantly higher body mass index, systolic blood pressure, duration of hypertension, and 12 am and DST cortisol. LV mass index and relative wall thickness increased progressively across tertiles of DST cortisol, together with progressive worsening of diastolic function. LV mass index was directly related to age, systolic blood pressure, duration of hypertension, and 12 am and DST cortisol, and inversely to creatinine clearance. Multivariate regression analysis showed independent correlation of LV mass index with body mass index, systolic blood pressure, and 12 am and DST cortisol. Logistic regression showed that DST cortisol independently predicted LV hypertrophy. Midnight and DST plasma cortisol levels are independent determinants of LV mass and geometry in patients with essential hypertension suggesting that even minor changes in regulation of cortisol secretion could contribute to cardiac abnormalities in these patients.

Prognostic Value of T-wave Positivity in Lead aVR in COVID-19 Pneumonia.

SUMMARYOBJECTIVE:T-wave positivity in the lead aVR is a marker of ventricular repolarization abnormality and provides information on short- and long-term cardiovascular mortality in heart failure patients, those with anterior myocardial infarction, and patients who underwent hemodialysis for various reasons. The aim of this study was to investigate the relationship between T-wave positivity in the lead aVR on superficial electrocardiogram and mortality from COVID-19 pneumonia.METHODS:This study retrospectively included 130 patients who were diagnosed with COVID-19 and treated as an outpatient or in the thoracic diseases ward in a single center between January 2021 and June 2021. All patients included in the study had clinical and radiological features and signs of COVID-19 pneumonia. The COVID-19 diagnosis of all patients was confirmed by polymerase chain reaction detected from an oropharyngeal swab.RESULTS:A total of 130 patients were included in this study. Patients were divided into two groups: survived and deceased. There were 55 patients (mean age: 64.76–14.93 years, 58.18 male, 41.12% female) in the survived group and 75 patients (mean age: 65–15 years, 58.67 male, 41.33% female) in the deceased group. The univariate and multivariate regression analyses showed that positive transcatheter aortic valve replacement (OR 5.151; 95%CI 1.001–26.504; p=0.0012), lactate dehydrogenase (OR 1.006; 95%CI 1.001–1.010; p=0.012), and d-dimer (OR 1.436; 95%CI 1.115–1.848; p=0.005) were independent risk factors for mortality.CONCLUSION:A positive transcatheter aortic valve replacement is useful in risk stratification for mortality from COVID-19 pneumonia.

Observational study on detection of atrial and ventricular arrhythmias with smartphone-based ECG

The Interpretation provided by the smartphone-based Portable ECG devices is still questioned for its reliability and are a subject of study for the detection of arrhythmia and abnormal cases. The heart abnormality is the marker of the uncertain change in the electrical activity of the heart. Hence, its early and true detection can prevent sudden cardiac death and, in some cases even Myocardial Infarction. This study provides insights into such kind of smartphone-based ECG device in comparison to the 12-lead gold standard ECG. Arrhythmia Detection for both atrial and ventricular abnormalities is done by 12- lead ECG machines. Here, we have compared and observed the performance of one such kind of portable device with clinical interpretation and 12 lead gold standard generated computer interpretations. Among the 153 number of enrolled participants 110 subjects were taken into the consideration as per the study protocols. The trials were validated according to the specificity and sensitivity of the smartphone-based ECG which was evaluated at 97.2% specific and 98.63% sensitive in detecting the ventricular and atrial abnormalities in the subjects. Whereas, NPV and PPV were evaluated at 97.2 % and 98.6% respectively.

Left Ventricular diastolic dysfunction among hypertensive patients.

Objectives: To assess the occurrence of left ventricular diastolic dysfunction among hypertensive patients on echocardiography. Study Design: Cross Sectional study. Setting: South East Hospital and Research Center, Islamabad. Period: August 2021 to January 2022. Material &amp; Methods: By using non probability convenient sampling method technique through pre-structured Performa. We enrolled a two hundred (n=200) patients in our study. Ethical consideration was taken from hospital ethical review board committee. Result: Thirty Six percent respondents were at the age of &lt; 60 years and 64% were at the of &gt; 60 years. Detection of left ventricular diastolic dysfunction shows, 44% had grade I, 40% grade II and 16% grade III. Association of variables towards detection of diastolic dysfunction, Systolic BP, duration of hypertension, EF%, Left ventricular hypertrophy and co-morbidities shows good association towards the detection of diastolic dysfunction at (p-value≤0.01). Conclusion: It is concluded that, Diastolic dysfunction is most common left ventricular functional abnormality in hypertensive patients. Doppler echocardiography is the most important investigational method for the detection of LV diastolic dysfunction. Not only more than 60 years old patients detect left ventricular diastolic dysfunction but less than 60 years old can also develop diastolic dysfunction.

Insulin Resistance and Other Comorbidities of Obesity as Independent Variables on Ventricular Repolarization in Children and Adolescents

Background: Obesity, a rapidly increasing global health problem in all age groups, is accepted as the basis for many chronic diseases through insulin resistance mechanism. This study aimed to examine whether insulin resistance and other comorbidities of obesity have an effect on the cardiac conduction system.&#x0D; Methods: The study included 50 obese and 47 healthy individuals aged 6–18 years. ECGs of all cases were taken; ECG waves and intervals were measured manually.&#x0D; Results: Of the obese group, 19 were boys (38%) and 31 were girls (62%), 27 were children (54%) and 23 were adolescents (46%), their ages were 11.3 ± 3.5 years. These particular characteristics were similar compared to the control group. However, in the obese group, the ECG parameters QTc (p = 0.001), QTd (p &lt; 0.001), QTdc (p &lt; 0.001), JTc (p &lt; 0.001), Tp-e (p &lt; 0.001), Tp-e/QT (p &lt; 0.001), Tp-e/QTc (p &lt; 0.001), Tp-e/JT (p &lt; 0.001), and Tp-e/JTc (p &lt; 0.001) were significantly longer. Twenty-five obese subjects (50%) had insulin resistance, when ECG parameters are compared to those without it, only JTc was significantly longer (332.3 ± 16.5 vs 321.7 ± 17.7 ms, p = 0.033). JTc duration mostly affected JT (p &lt; 0.001) and QTc (p &lt; 0.001). The 327 ms cut-off value of JTc indicated insulin resistance in the obese patients (p = 0.044) (sensitivity 60%, specificity 60%).&#x0D; Conclusion: Insulin resistance and other comorbidities of obesity may cause ventricular repolarization abnormalities at an early age. JTc, an ECG parameter, can be a guide in assessing ventricular repolarization abnormality and the risk of arrhythmia in these patients.&#x0D; Keywords: obesity, insulin resistance, comorbidities, ventricular repolarization, child, adolescence

Commentary on the enigma of small vessel disease in hypertrophic cardiomyopathy: is invasive assessment of microvascular resistance a novel independent predictor of prognosis?

The key pathophysiological features in hypertrophic cardiomyopathy are ventricular hypertrophy, diastolic dysfunction, and abnormalities in the mitral valve apparatus, but coronary microvascular dysfunction and ischemia have also been described. The small vessel disease changes could be reflected in the invasive measurement of the index of microvascular resistance, with prognostic potential.

Risk Stratification and Outcomes in Patients With Pulmonary Hypertension: Insights into Right Ventricular Strain by MRI Feature tracking.

Despite a recommended multidimensional approach for pulmonary hypertension (PH) risk stratification and guidance of treatment decisions, this may not always be achievable in patients with advanced disease. One issue is the lack of an imaging modality to assess right ventricular (RV) structure and function abnormalities. To explore the risk stratification and prognostic value of cardiac MR feature tracking (MR-FT)-derived RV strain. Retrospective. A total of 80 patients with idiopathic pulmonary artery hypertension (N=52) or chronic thromboembolic PH (N=28). A 1.5 T or 3.0 T, balanced steady-state free precession sequence. All patients underwent laboratory testing, right heart catheterization, and MR imaging (and in 37 cases, a cardiopulmonary exercise test was also performed) within a 1-month period. Cardiac functional parameters and both global longitudinal strain (GLS) and global circumferential strain (GCS) were analyzed. Patients were stratified into low, intermediate, and high-risk groups by guideline suggested stratified values of risk factors. The combined endpoint was death or hospitalization for congestive heart failure assessed during follow-up since the date of MR examination. Kolmogorov-Smirnov's test, independent-sample t-tests, Wilcoxon's rank-sum tests, one-way analysis of variance, χ2 tests or Fisher's exact test, receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression analysis. A P value < 0.05 was considered statistically significant. The median follow-up duration was 3.4 years. Thirty-five patients presented with combined endpoint including 10 cardiac deaths. RV structural and deformation impairments were significantly associated with combined endpoint (ejection fraction: 31.3% ± 13.2% vs. 38.0% ± 14.8%, hazard ratio [HR: 0.974; GLS: -14.5 [-18.6, -10.9] % vs. -20.4 [-26.0, -13.2] %, HR: 1.071; GCS: -9.8 [-14.5, -7.3] % vs. -12.3 [-19.9, -8.4] %, HR: 1.059). There were significant differences in RVGLS among low, intermediate, and high-risk groups (-19.3% ± 7.2% vs. -17.3% ± 9.4% vs. -11.5% ± 4.4% by cardiac functional class, -21.8% ± 7.3% vs. -19.4% ± 8.2% vs. -12.7 ± 5.3% by NT-proBNP, -19.7% ± 7.7 vs. -15.8% ± 6.5% vs. -12.6% ± 8.2% by cardiac index). RV deformation may aid risk stratification in patients with PH, providing crucial information for RV remodeling, pulmonary hemodynamic condition and exercise capacity. 3 TECHNICAL EFFICACY: Stage 2.

Status and Update on Cardiac Resynchronization Therapy Trials.

After decades of clinical use, cardiac resynchronization therapy (CRT) can be considered an established therapy. However, there are multiple open questions to be addressed that shall further improve the proportion of patients responding to CRT. Progress in better understanding the relationship between electrical and mechanical disorder in patients with heart failure with ventricular conduction abnormalities is important. This article presents and discusses ongoing studies in different areas of CRT research, including patient selection by novel diagnostic tools, extension of clinical criteria, left ventricular lead positioning and pacing site selection, optimization of CRT delivery and programming, and selection of device type.

LONGITUDINAL LEFT VENTRICULAR FUNCTION IN HYPERTENSIVE SUBJECTS WITH NORMAL EJECTION FRACTION: NEW INSIGHT BY SPECKLE TRACKING ECHOCARDIOGRAPHY

Objective: The aim of the current case-control study was to use speckle tracking imaging to identify subclinical longitudinal left ventricular systolic function abnormalities in hypertensive subjects with normal ejection fraction (EF). Design and method: Standard 2D Doppler echocardiography, tissue Doppler imaging, and 2D speckle strain imaging were performed in 50 hypertensive subjects with normal ejection fraction and 50 control subjects. Peak systolic (S) and diastolic (E’) annular velocities were obtained by tissue Doppler imaging, whereas longitudinal myocardial strain was obtained by speckle tracking. Results: The two groups were comparable by age (56,4 ± 8,87 years in the hypertensives versus 55,7 ± 8,24 years in the controls, p = 0,66) and gender distribution (42% males in hypertensives vs 46% in the controls; p = 0,68). Other baseline characteristics, except for blood pressure parameters, which were predictably higher in the hypertensive subjects, were comparable between the two groups. Among the hypertensive subjects, 28 had diastolic dysfunction. 27 hypertensives (54%) had normal geometry, 7 (14%) had excentric hypertrophy and 11(22%) had concentric hypertrophy. LV systolic longitudinal function as assessed by systolic myocardial velocity (S) was not significantly reduced in the hypertensive group compared with controls(8,92 ± 1,46 cm/s vs. 9,15 ± 0,79 cm/s; p = 0,33). However, global longitudinal strain (GLS) was significantly reduced compared with controls (-20,39 % ± 2,65 vs. -22,52% ± 2,3; p = 0,000). Longitudinal strain appears to be correlated with LV mass index (r = 0,293; p = 0,039), age, E/E’ ratio (R = 0,303 (IC = 0, 95 [0,023–0,506]) p = 0,032), left atrium size and duration of hypertension. No correlation was found between GLS and systolic or diastolic blood pressure. Conclusions: Patients with hypertension and normal EF were demonstrated to have reduced LV systolic longitudinal function. Longitudinal strain is more sensitive than tissue Doppler imaging to assess this dysfunction.There is a significant association between age, obesity, LV mass index, impaired diastolic function and reduced LV longitudinal contractility. Thus, LV systolic strain is early reduced during systemic hypertension and seems to be an index of global LV remodelage.

Left ventricular dysfunction with preserved ejection fraction: the most common left ventricular disorder in chronic kidney disease patients.

Chronic kidney disease (CKD) is a risk factor for premature cardiovascular disease. As kidney function declines, the presence of left ventricular abnormalities increases such that by the time kidney replacement therapy is required with dialysis or kidney transplantation, more than two-thirds of patients have left ventricular hypertrophy. Historically, much research in nephrology has focussed on the structural and functional aspects of cardiac disease in CKD, particularly using echocardiography to describe these abnormalities. There is a need to translate knowledge around these imaging findings to clinical outcomes such as unplanned hospital admission with heart failure and premature cardiovascular death. Left ventricular hypertrophy and cardiac fibrosis, which are common in CKD, predispose to the clinical syndrome of heart failure with preserved left ventricular ejection fraction (HFpEF). There is a bidirectional relationship between CKD and HFpEF, whereby CKD is a risk factor for HFpEF and CKD impacts outcomes for patients with HFpEF. There have been major improvements in outcomes for patients with heart failure and reduced left ventricular ejection fraction as a result of several large randomized controlled trials. Finding therapy for HFpEF has been more elusive, although recent data suggest that sodium-glucose cotransporter 2 inhibition offers a novel evidence-based class of therapy that improves outcomes in HFpEF. These observations have emerged as this class of drugs has also become the standard of care for many patients with proteinuric CKD, suggesting that there is now hope for addressing the combination of HFpEF and CKD in parallel. In this review we summarize the epidemiology, pathophysiology, diagnostic strategies and treatment of HFpEF with a focus on patients with CKD.

Rare and potential pathogenic mutations of LMNA and LAMA4 associated with familial arrhythmogenic right ventricular cardiomyopathy/dysplasia with right ventricular heart failure, cerebral thromboembolism and hereditary electrocardiogram abnormality

BackgroundArrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with ventricular arrhythmia, heart failure (HF), and sudden death. Thromboembolism is also an important and serious complication of ARVC/D. However, the etiology of ARVC/D and thromboembolism and their association with genetic mutations are unclear.MethodsGenomic DNA samples of peripheral blood were conducted for whole-exome sequencing (WES) and Sanger sequencing in the ARVC/D family. Then, we performed bioinformatics analysis for genes susceptible to cardiomyopathies and arrhythmias. Further, we analyzed how the potential pathogenic mutations were affecting the hydrophobicity and phosphorylation of amino acids and their joint pathogenicity by ProtScale, NetPhos and ORVAL algorisms.ResultsWe discovered a Chinese Han family of ARVC/D with right ventricular HF (RVHF), cerebral thromboembolism, arrhythmias (atrial fibrillation, atrial standstill, multifocal ventricular premature, complete right bundle block and third-degree atrioventricular block) and sudden death. Based on the WES data, the variants of LMNA p.A242V, LAMA4 p.A225P and RYR2 p.T858M are highly conserved and predicated as “deleterious” by SIFT and MetaSVM algorithms. Their CADD predicting scores are 33, 27.4 and 25.8, respectively. These variants increase the hydrophobicity of their corresponding amino acid residues and their nearby sequences by 0.378, 0.266 and 0.289, respectively. The LAMA4 and RYR2 variants lead to changes in protein phosphorylation at or near their corresponding amino acid sites. There were high risks of joint pathogenicity for cardiomyopathy among these three variants. Cosegregation analysis indicated that LMNA p.A242V might be an important risk factor for ARVC/D, electrocardiogram abnormality and cerebral thromboembolism, while LAMA4 p.A225P may be a pathogenic etiology of ARVC/D and hereditary electrocardiogram abnormality.ConclusionsThe LMNA p.A242V may participate in the pathogenesis of familial ARVC/D with RVHF and cerebral thromboembolism, while LAMA4 p.A225P may be associated with ARVC/D and hereditary electrocardiogram abnormality.

Abstract 53: Body Mass Index Is A Predictor Of Mortality And Adverse Cardiorespiratory Outcomes In Patients Hospitalized For SARS-COV-2 Infection

Objectives: We aimed to evaluate the association of body mass index (BMI) with in-hospital mortality and cardiorespiratory outcomes in patients admitted with COVID-19 infection. Methods: This data was collected from an academic tertiary referral center in upstate New York. Retrospective cohort analysis was conducted on patients admitted with COVID-19 infection (n=194). BMI was calculated and patients were stratified into two categories: ‘healthy’ (BMI=18.5-24.5) and ‘overweight’ (BMI&gt;25). Cardiorespiratory outcomes were classified as in-hospital mortality, need for vasopressors, mechanical ventilation, and hemodialysis. Transthoracic echocardiography was performed to evaluate for left ventricular (LV) ejection fraction, right ventricular (RV) systolic function and RV dilation. Cardiovascular (CV) risk factors such as history of COPD, Diabetes, HTN, CAD and cigarette smoking were analyzed. LDH, troponin, CRP and ferritin levels were also noted. Results: Out of 194 patients, 68% were overweight with a mean BMI of 29.8 +/- 9.5 kg/m2 and a mean age of 66 +/- 16, 75% of females and 63% of males were overweight. Mortality rate was 31% in overweight patients compared to 17% in healthy subset (p&lt;0.04). The rate of need for mechanical ventilation was higher in overweight group as well (34% vs. 17%, p&lt;0.02). There was no significant difference between the cohorts in terms of vasopressor and hemodialysis requirement (p=0.09 and 0.2 respectively). RV systolic function was depressed in 21% of overweight cohort vs. 8% of healthy patients (p&lt;0.02) while RV dilatation was seen in 15% of overweight patients compared with 5% of healthy patients (p&lt;0.03). There was no significant difference in LV ejection fraction between the groups. LDH was more frequently elevated in overweight cohort with a mean level of 346 +/- 185 IU/L (p&lt;0.01). No significant difference in rest of the laboratory analysis or CV risk factors were found. Conclusion: Elevated BMI (&gt;25) is associated with a statistically significant increase in in-hospital mortality, need for mechanical ventilation, right ventricular abnormalities, and LDH levels in patients hospitalized with COVID-19 infection.

PO-714-02 RIGHT VENTRICULAR EPICARDIAL ACTIVATION DELAY IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY PATIENTS AND GENE CARRIERS UNMASKED BY BODY SURFACE MAPPING SYSTEM

ARVC is afflicted by life-threatening ventricular arrhythmias even before the manifestations of right ventricular (RV) structural abnormalities. Therefore, an early diagnosis is crucial albeit still challenging. To investigate whether a 252-leads noninvasive Body Surface Mapping (BSM) system could detect epicardial conduction delays in ARVC patients and unaffected gene-carrying family members (GC). Twelve ARVC patients, 20 GC and 8 gene-negative family members serving as controls (C) underwent 12-lead ECG, signal-averaged-electrocardiogram (SAECG), echocardiography, 252-lead BSM recordings and thoracic CT scan. Reconstructed epicardial signals were analysed using the Activation Time Editing tool of the activation map. Local depolarisation was defined as the steepest negative dV/dt of the unipolar local epicardial signal. The time from the earliest start of RV epicardial activation to the earliest local depolarisation (ELD) and to the latest local depolarisation (LLD), respectively, were measured separately for the RV free wall (RFW), inferior wall (RIW) and the whole RV. The activation duration, defined as LLD-ELD, was calculated for RFW, RIW and the whole RV. The ELD was similar in all study groups whereas the LLD in the RFW and whole RV was significantly longer among ARVC patients compared to C, but similar in the RIW. Similarly, the activation durations in the RFW and whole RV were significantly longer in ARVC patients but did not differ in the RIW among the groups. A 43ms LLD cut off in the RV and 20 msec activation duration cut off in the RV discriminated ARVC patients from C with highest sensitivity and specificity. Based on these cut-offs, 40% of GC group had longer LLD times and 20 % had also longer activation duration (figure 1). ARVC patients demonstrated prolonged LLD and activation duration times in the RFW and whole RV compared to C. The finding that prolonged conductions could be demonstrated in the GC group as well suggest that the 252-leads noninvasive BSM system may be used as screening tool for the detection of early delays of the RV epicardial activation. Larger studies are required to confirm our results.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Glycemic status, non-traditional risk and left ventricular structure and function in the Jackson Heart Study

BackgroundLeft ventricular structure and function abnormalities may be an early marker of cardiomyopathy among African Americans with diabetes (DM) even in the absence of coronary artery disease (CAD), arrhythmia, valvular heart disease and end-stage renal disease (ESRD). This study examined the association of prediabetes (PDM), DM and HbA1c with left ventricular structure and function among Jackson Heart Study (JHS) participants without traditional risk factors.MethodsRetrospective cross-sectional analyses of the association of PDM, DM and HbA1c with, left ventricular ejection fraction (LV EF), fractional shortening (LV FS), stroke volume index (SVI), cardiac index (CI), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume index (LVESVI), relative wall thickness (RWT), myocardial contraction fraction (MCF) and left ventricular mass index (LVMI). The study was conducted in 2234 adult JHS participants without preexisting CAD, arrhythmia, valvular heart disease or ESRD. Statistical analyses included descriptive, univariate and covariate adjusted linear regression analyses. Sensitivity analyses to explore the impact of hypertension on study outcomes were also carried out.ResultsDM compared with no DM was associated with lower, SVI (− 0.96 ml/m2, p = 0.029), LVEDVI (− 1.44 ml/m2p = 0.015), and MCF (− 1.90% p = 0.007) but higher CI (0.14 L/min/m2, p < 0.001), RWT (0.01 cm, p = 0.002) and LVMI (2.29 g/m2, p = 0.009). After further control for DM duration, only CI remaining significantly higher for DM compared with no DM participants (0.12 L/min/m2, p = 0.009). PDM compared with no PDM was associated with lower, SVI (− 0.87 ml/m2, P = 0.024), LVEDVI (− 1.15 ml/m2p = 0.003) and LVESVI (− 0.62 ml/m2p = 0.025). HbA1c ≥ 8.0% compared with HbA1c < 5.7% was associated with lower SVI (− 2.09 ml/m2, p = 0.004), LVEDVI (− 2.11 ml/m2p = 0.032) and MCF (− 2.94% p = 0.011) but higher CI (0.11 L/min/m2, p = 0.043) and RWT (0.01 cm, p = 0.035).ConclusionsGlycemic status is associated with important left ventricular structure and function changes among African Americans without prior CAD, arrhythmia, valvular heart disease and ESRD. Longitudinal studies may further elucidate these relationships.