Digoxin is Not Related to Mortality in Patients with Heart Failure: Results from the SELFIE-TR Registry.

AIMS: Digoxin has been used in the treatment for heart failure for centuries, but the role of this drug in the modern era is controversial. A particular concern is the recent observational findings suggesting an increase in all-cause mortality with digoxin, although such observations suffer from biased results since these studies usually do not provide adequate compensation for the severity of disease. Using a nationwide registry database, we aimed to investigate whether digoxin is associated with 1-year all-cause mortality in patients with heart failure irrespective of phenotype. METHODS: A total of 1014 out of 1054 patients in the registry, of whom 110 patients were on digoxin, were included in the study. Multivariable adjustments were done and propensity scores were calculated for various prognostic indicators, including signs and symptoms of heart failure and functional capacity. Crude mortality, mortality adjusted for covariates, mortality in the propensity score-matched cohort, and Bayesian factors (BFs) were analyzed. RESULTS: Crude 1-year mortality rate did not differ between patients on and off digoxin (17.3% vs 20.1%, log-rank p = 0.46), and digoxin was not related to mortality following multivariable adjustment (hazard ratio 0.87, 95% confidence interval 0.539-1.402, p = 0.57). Similarly, all-cause mortality was similar in 220 propensity-score adjusted patients (17.3% vs 20.0%, log-rank p = 0.55). On Bayesian analyses, there was moderate to strong evidence suggesting a lack of difference between in unmatched cohort (BF10 0.091) and weak-to-moderate evidence in the matched cohort (BF10 0.296). CONCLUSIONS: In this nationwide cohort, we did not find any evidence for an increased 1-year mortality in heart failure patients on digoxin.

Interatrial Block and Electrocardiographic Markers of Repolarization in Patients Hospitalized with COVID-19: Classical and Bayesian Analysis.

Objective: Coronavirus disease-2019 (COVID-19) is associated with atrial fibrillation (AF) and ventricular arrhythmias. Several electrophysiological abnormalities on surface electrocardiography (ECG) are associated with AF and ventricular arrhythmias, either as markers of abnormal interatrial conduction or abnormal repolarization. The present study sought to understand whether such ECG markers are more common in patients hospitalized with COVID-19 infection during the pandemic. Methods: A total of 87 COVID-19 patients formed the study group, whereas 64 patients who were hospitalized for any reason other than COVID-19 infection served as controls. The frequency of partial and advanced interatrial block (IAB), QT and corrected QT (QTc) durations, QT dispersion (QTd), and T peak-to-end duration (Tpe) were measured from ECGs at admission. Results: Both partial and advanced IAB were more common in patients with COVID-19, although statistical significance was only observed for advanced IAB (11.5% in COVID-19 patients vs. 0.0% in controls, p=0.005). There were no differences between the groups for QTc, QTd or Tpe. On Bayesian analyses, there was strong evidence favoring an association between COVID-19 and advanced IAB (BF10:16), whereas there was no evidence for an association for partial IAB, QTc, QTd, or Tpe (BF10<1 for all). Conclusions: Patients hospitalized with COVID-19 were more likely to have advanced IAB, which may explain why AF is more frequent in these patients.

Estimated plasma volume is not a robust indicator of the severity of congestion in patients with heart failure.

BACKGROUND: Congestion is the main cause of morbidity and a prime determinant of survival in patients with heart failure (HF). However, the assessment of congestion is subjective and estimation of plasma volume (ePV) has been suggested as a more objective measure of congestion. This study aimed to explore the relationships and interactions between ePV, the severity of congestion and survival using a nationwide registry. METHODS: Of the 1054 patients with HF enrolled in the registry, 769 had sufficient data to calculate ePV (using the Duarte, Kaplan, and Hakim equations) and relative plasma volume status (rPVS), and these patients were subsequently included in the present analysis. The severity of congestion was assessed using a 6-point congestion score (CS). Patients were divided into three groups according to the degree of congestion. RESULTS: Out of four equations tested, only ePVDuarte and rPVS were statistically higher in patients with severe congestion as compared to patients with no congestion (p<0.001 for both). Both ePVDuarte (r = 0.197, p<0.001) and rPVS (r = 0.153, p<0.001) showed statistically significant correlations with CS and both had a modest accuracy (70.4% for ePVDuarte and 69.4% for rPVS) to predict a CS ≥3. After a median follow up of 496 days, both ePVDuarte (OR:1.14,95%CI:1.03-1.26, p = 0.01) and rPVS (OR:1.02, 95%CI:1.00-1.03, p = 0.03) were associated with all-cause mortality after adjusting for demographic and clinical variables. However, none of the indices were associated with mortality following the introduction of CS to the models (p>0.05 for both). CONCLUSIONS: Elevated ePVDuarte and rPVS were indicators of congestion but with a limited robustness, and either parameter could be clinically useful when a comprehensive clinical evaluation of congestion is not feasible.

Effect of renal function on the prognostic importance of chloride in patients with heart failure.

Hypochloremia has recently gained interest as a potential marker of outcomes in patients with heart failure (HF). The exact pathophysiologic mechanism linking hypochloremia to HF is unclear but is thought to be mediated by chloride-sensitive proteins and channels located in kidneys. This analysis aimed to understand whether renal dysfunction (RD) affects the association of hypochloremia with mortality in patients with HF. Using data from a nationwide registry, 438 cases with complete data on serum chloride concentration and 1-year survival were included in the analysis. Patients with an estimated glomerular filtration rate of <60 mL/min/m2 at baseline were accepted as having RD. Hypochloremia was defined as a chloride concentration <96 mEq/L at baseline. For HF patients without RD at baseline, patients with hypochloremia had a significantly higher 1-year all-cause mortality than those without hypochloremia (41.6% vs 13.0%, log-rank p < 0.001) and the association remained significant after multivariate adjustment (odds ratio (OR): 2.55, 95% confidence interval (CI): 1.25-5.21). The evidence supporting the association was very strong in this subgroup (Bayesian Factor (BF)10: 48.25, log OR: 1.56, 95% CI: 0.69-2.43). For patients with RD at baseline, there was no statistically significant difference for 1-year mortality for patients with or without hypochloremia (36.3% vs 29.7, log-rank p = 0.35) and there was no evidence to support an association between hypochloremia and mortality (BF10: 1.18, log OR :0.66, 95% CI: -0.02 to 1.35). In patients with HF, the association between low chloride concentration and mortality is limited to those without RD at baseline.

Alterations in right ventricular mechanics in patients with Behcet's disease.

Manifest myocardial involvement is somewhat rare in patients with Behcet's disease (BD), although echocardiographic studies suggest that subclinical alterations in left ventricular (LV) contractility is rather common. Data on right ventricular (RV) involvement in BD is rather scarce. This study aims to determine whether RV systolic performance is affected in BD patients, and to understand the clinical and echocardiographic correlates of RV contractility in these patients. Forty-five patients who fulfilled criteria for BD and 45 age and gender matched controls were enrolled. All participants underwent a comprehensive echocardiographic examination, including deformation imaging, to characterize RV mechanics. Conventional morphologic and echocardiographic indicators of RV morphology and function were not different between groups, but RV apical strain and RV free wall strain (FWS) were significantly lower in BD patients as compared to the controls (P < 0.001 and P = 0.02, respectively). The only significant correlates of FWS were tricuspid regurgitation velocity and related indices in healthy controls, while FWS correlated with LV global longitudinal strain (GLS), morphologic measures of left and right atria and ventricles, and with conventional measures of right ventricular contractility. The relationship between FWS and GLS remained statistically significant after adjusting for other clinical and echocardiographic parameters (ß = 0.379, P = 0.01). In patients with BD, there is a subclinical alteration in RV contractility and the degree of alteration in the RV systolic performance paralleled that of LV. Thus, present results support the presence of RV involvement in these patients.

Lack of right ventricular hypertrophy is associated with right heart failure in patients with left ventricular failure.

Presence of right heart failure (RHF) is associated with a worse prognosis in patients with left ventricular failure (LVF). While the cause of RHF secondary to LVF is multifactorial, an increased right ventricular (RV) afterload is believed as the major cause of RHF. However, data are scarce on the adaptive responses of the RV in patients with LVF. Our aim was to understand the relationship of right ventricular hypertrophy (RVH) with RHF and RV systolic and diastolic properties in patients with LVF. 55 patients with a left ventricular ejection fraction of 40% or less were included in the present study. A comprehensive two-dimensional transthoracic echocardiographic examination was done to all participants. 12 patients (21.8%) had RHF, and patients with RHF had a significantly lower right ventricular free wall thickness (RVFWT) as compared to patients without RHF (5.3 ± 1.7 mm vs. 6.6 ± 0.9 mm, p = 0.02) and the difference remained statistically significant after adjusting for confounders (Δx̅:1.34 mm, p = 0.002). RVFWT had a statistically significant correlation with tricuspid annular plane systolic excursion (r = 0.479, p < 0.001) and tricuspid annular lateral systolic velocity (r = 0.360, p = 0.007), but not with the indices of the RV diastolic function. None of the patients with concentric RVH had RHF, while 22.2% of patients with eccentric RVH and 66.7% of patients without RVH had RHF (p < 0.01 as compared to patients with concentric RVH). In patients with left ventricular systolic dysfunction, absence of RVH was associated with worse RV systolic performance and a significantly higher incidence of RHF.

Pressure-dimension index: A novel "morphologic-functional" index of right ventricle that predicts short-term survival after left ventricular assist device implantation.

BACKGROUND: Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is a major cause of postoperative morbidity and mortality. Despite the availability of multiple imaging parameters, none of these parameters had adequate predictive accuracy for post-LVAD RVF. AIM: To study whether right ventricular pressure-dimension index (PDI), which is a novel echocardiographic index that combines both morphologic and functional aspects of the right ventricle, is predictive of post-LVAD RVF and survival. METHODS: 49 cases that underwent elective LVAD implantation were retrospectively analyzed using data from an institutional registry. PDI was calculated by dividing systolic pulmonary artery pressure to the square of the right ventricular minor diameter. Cases were categorized according to tertiles. RESULTS: Patients within the highest PDI tertile (PDI>3.62 mmHg/cm2 ) had significantly higher short-term mortality (42.8%) and combined short-term mortality and severe RVF (50%) compared to other tertiles (P < .05 for both, log-rank p for survival to 15th day 0.014), but mortality was similar across tertiles in the long-term follow-up. PDI was an independent predictor of short-term mortality (HR:1.05-26.49, P = .031) and short-term composite of mortality and severe RVF (HR:1.37-38.87, P = .027). CONCLUSIONS: Increased PDI is a marker of an overburdened right ventricle. Heart failure patients with a high PDI are at risk for short-term mortality following LVAD implantation.

Combined past preeclampsia and gestational diabetes is associated with a very high frequency of coronary microvascular dysfunction.

BACKGROUND: A history of preeclampsia (pPE) and gestational diabetes (pGDM) are female-specific risk markers for atherosclerosis and future cardiovascular risk. In addition to increasing the risk of established risk factors for atherosclerosis, such as hypertension or diabetes, evidence suggests that pregnancy-related complications can also directly accelerate atherosclerosis by inducing endothelial dysfunction. A combination of both conditions is seen in a subset of patients with pregnancy, though it is not known whether this combination increases the overall risk for cardiovascular events. AIMS: Present study aimed to find the impact of combined pPE/pGDM on the prevalence of coronary microvascular dysfunction (CMD). METHODS: A total of 24 patients with combined pPE/pGDM, 19 patients with isolated pPE and 63 patients with pGDM were included to the present study and a further 36 healthy women with no previous pregnancy-related complications served as controls. Coronary flow reserve was measured using echocardiography and CMD was defined as a coronary flow reserve ≤2.5. RESULTS: Patients with combined pPE/pGDM had a high prevalence of CMD (91%), which was significantly higher than controls (5.6%, p < 0.001) and patients with pGDM (55%, p = 0.01). A history of pPE on top of pGDM was associated with an increased risk of CMD (HR:6.28, 95%CI:1.69-23.37, p = 0.006) after multivariate adjustment, but pGDM did not increase the odds for CMD in those with pPE. CONCLUSIONS: Combined pPE/pDM is associated with a very high prevalence of CMD, which may indicate an increased risk for future cardiovascular events.

Contemporary usefulness of pulmonary venous flow parameters to estimate left ventricular end-diastolic pressure on transthoracic echocardiography.

Measurement of pulmonary venous flow (PVF) parameters can be used to estimate left ventricular end-diastolic pressure (LVEDP) on transthoracic echocardiography. Despite that, 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) algorithm gave a secondary role to PVF to assess left ventricular filling pressure. We aimed to test correlations between several PVF parameters, including novel measurements, with LVEDP and to analyze whether PVF parameters have an incremental usefulness over ASE/EACVI algorithm to estimate LVEDP. Seventy-two patients that underwent left and right cardiac catheterization for assessment of heart failure or pulmonary hypertension were enrolled. All patients had a detailed echocardiographic study immediately before catheterization. Patients were categorized into those with an LVEDP < 15 mmHg vs. LVEDP ≥ 15 mmHg to analyze data. Patients with an elevated LVEDP had significantly lower peak S/D velocity ratio, S wave deceleration time, D wave acceleration time and D wave deceleration time (DWDT), as well as higher D wave acceleration rate (DWAR), but only peak S/D velocity ratio (ß = - 0.28, p = 0.01), DWDT (ß = - 0.33, p = 0.001) and DWAR (ß = 0.23, p = 0.03) were independent predictors for an elevated LVEDP. ASE/EACVI algorithm had a sensitivity of 71% and specificity of 74% to predict an elevated LVEDP. When PVF parameters were adjusted for ASE/EACVI algorithm; DWDT and DWAR remained as independent predictors. Sensitivity and specificity of ASE/EACVI algorithm increased to 79% and 96%, respectively, if either DWDT or DWAR was also suggestive of an elevated LVEDP. DWDT and DWAR have incremental usefulness over existing algorithm to determine LVEDP.

Snapshot evaluation of acute and chronic heart failure in real-life in Turkey: A follow-up data for mortality.

OBJECTIVE: Heart failure (HF) is a progressive clinical syndrome. SELFIE-TR is a registry illustrating the overall HF patient profile of Turkey. Herein, all-cause mortality (ACM) data during follow-up were provided. METHODS: This is a prospective outcome analysis of SELFIE-TR. Patients were classified as acute HF (AHF) versus chronic HF (CHF) and HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction, and HF with preserved ejection fraction and were followed up for ACM. RESULTS: There were 1054 patients with a mean age of 63.3±13.3 years and with a median follow-up period of 16 (7-17) months. Survival data within 1 year were available in 1022 patients. Crude ACM was 19.9% for 1 year in the whole group. ACM within 1 year was 13.7% versus 32.6% in patients with CHF and AHF, respectively (p<0.001). Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta blocker, and mineralocorticoid receptor antagonist were present in 70.6%, 88.2%, and 50.7%, respectively. In the whole cohort, survival curves were graded according to guideline-directed medical therapy (GDMT) scores ≤1 versus 2 versus 3 as 28% versus 20.2% versus 12.2%, respectively (p<0.001). Multivariate analysis of the whole cohort yielded age (p=0.009) and AHF (p=0.028) as independent predictors of mortality in 1 year. CONCLUSION: One-year mortality is high in Turkish patients with HF compared with contemporary cohorts with AHF and CHF. Of note, GDMT score is influential on 1-year mortality being the most striking one on chronic HFrEF. On the other hand, in the whole cohort, age and AHF were the only independent predictors of death in 1 year.

Correlation and agreement between 2D and 3D speckle-tracking echocardiography for left ventricular volumetric, strain, and rotational parameters in healthy volunteers and in patients with mild mitral stenosis.

BACKGROUND: Recent advances had allowed measurement of myocardial deformation parameters using 3D speckle-tracking echocardiography (STE). Agreement between these two modalities and interchangeability of findings remain as an issue since 2DSTE is more widely available than 3DSTE. The aim of this study was to investigate the correlation and agreement between 2DSTE and 3DSTE in healthy volunteers and in patients with mild mitral stenosis (MS). METHODS: Data from 31 patients with mild MS and 27 healthy volunteers were included in this study. Data were analyzed for the correlation and agreement between 2DSTE and 3DSTE for volumetric, strain, and rotational parameters. RESULTS: There were no significant differences between 2DSTE and 3DSTE in both control and MS groups for left ventricular volumetric and rotational parameters. 3D global longitudinal strain (GLS) and global circumferential strain (GCS) were significantly higher in healthy volunteers (P < 0.001 for both), while only 3DGCS was significantly higher than 2DGCS in MS group (P < 0.001). The correlation between 3DSTE and 2DSTE was weak-to-moderate in both groups for strain and rotational parameters, and overall, correlation coefficients were higher in MS group. An exception was GLS in MS group, where coefficient of correlation was excellent (r = 0.907). Agreement between two modalities was poor for strain and rotational parameters, and the average bias was high. CONCLUSIONS: Overall, the agreement between 2DSTE and 3DSTE for strain and rotational measures was poor with a high average bias. The agreement between 2DSTE and 3DSTE is affected by the presence of underlying MS and the direction of strain.

Right Ventricular Hypertrophy and Dilation in Patients With Human Immunodeficiency Virus in the Absence of Clinical or Echocardiographic Pulmonary Hypertension.

BACKGROUND: Involvement of right-sided heart chambers (RSHCs) in patients infected with human immunodeficiency virus (HIV) is common and is usually attributed to pulmonary arterial or venous hypertension (PH). However, myocardial involvement in patients with HIV is also common and might affect RSHCs even in the absence of overt PH. Our aim was to define morphologic and functional alterations in RSHC in patients with HIV and without PH. METHODS AND RESULTS: A total of 50 asymptomatic patients with HIV and 25 control subjects without clinical or echocardiographic signs for PH were included in the study. Transthoracic echocardiography was used to obtain measurements. Patients with HIV had significantly increased right ventricular end-diastolic diameter (RVEDD) and right ventricular free wall thickness (RVFWT), as well as increased right atrial area and pulmonary arterial diameter, compared with control subjects. After adjustment for age, sex, and body surface area, RVFWT (average 1.81 mm, 95% confidence interval [CI] 0.35-3.26 mm) and RVEDD (average 6.82 mm, 95% CI 2.40-11.24 mm) were significantly higher in subjects infected with HIV. More patients with right ventricular hypertrophy were on antiretroviral treatment, and RVFWT was on average 1.3 mm higher (95% CI 0.24-2.37 mm) in patients on antiretroviral treatment after adjustment for confounders. CONCLUSIONS: These findings suggest that alterations in RSHCs were present in patients with HIV without PH.

An unusual "mass" within the left atrium: Localized aneurysm of a patent foramen ovale tunnel.

Masses on the interatrial septum are usually caused by myxomas or thrombi within a patent foramen ovale. We report a 53-year-old male patient with a hollow mass within the left atrium that was incidentally found during a routine transthoracic echocardiography. Further investigation of the mass with transesophageal two- and three-dimensional echocardiography has revealed that the mass was a localized aneurysm of a patent foramen ovale tunnel. While aneurysms of interatrial septum are relatively common in normal population, to the best of our knowledge, present case is the first report of a localized aneursym of a patent foramen ovale tunnel.

A "congenitally corrected" variant of Ebstein's anomaly.

Ebstein's anomaly is a rare CHD that is characterised by caudal displacement of the functional tricuspid annulus and a dysfunctional tricuspid valve owing to a failure of proper leaflet coaptation. We present a balanced variant of Ebstein's anomaly, in which the overgrowth of the septal leaflet had allowed proper coaptation of the tricuspid leaflets, thus preserving the valve function.

Reverberation and multiple shadow artifacts recorded from patients with intra-pericardial centrifugal continuous-flow left ventricular assist devices.

Artifacts are by-products of ultrasound imaging that may cause confusion or misdiagnosis if not interpreted correctly. There are, however, several disorders where a specific pattern of artifacts can aid in diagnosis, especially when the object in question cannot be visualized directly. In this manuscript, we report two patients with reverberation and shadow artifacts originating from the housing and the propeller of a continuous-flow intra-pericardial left ventricular assist device. Visualization of the artifacts required modified transthoracic views, so these artifacts should not pose a diagnostic challenge during a routine echocardiographic evaluation. However, we consider that shadow artifacts might be used to evaluate pump thrombosis in patients with intra-pericardial assist devices.