Phosphodiesterase inhibitor for heart failure with preserved ejection fraction: A systematic review and meta-analysis.

Background: Although heart failure with preserved ejection fraction (HFpEF) is a serious disease, only limited options are available for its treatment. Recent studies have analyzed the effects of phosphodiesterase (PDE) inhibitors, especially PDE5 and PDE3 inhibitors, in patients with HFpEF, with mixed outcomes. Methods: We searched PUBMED and EMBASE databases up to August 2021. Randomized controlled trials (RCTs) and clinical trials that tested the effects of PDE inhibitors on patients with HFpEF were included as eligible studies. Indicators of left ventricular (LV) function, pulmonary arterial pressure (PAP), right ventricular (RV) function, exercise capacity, and quality of life (QOL) were used to evaluate the efficacy of PDE inhibitors in HFpEF. Results: Six RCTs that reported in 7 studies were included to evaluate the efficiency of PDE inhibitors on HFpEF patients. In the pooled analysis, PDE inhibitors showed insignificant changes in the ratio of early diastolic mitral inflow to annular velocities, left atrial volume index, pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), peak oxygen uptake, 6-minute walking test distance, as well as Kansas City Cardiomyopathy Questionnaire score. However, substantial improvement was observed in the tricuspid annular plane systolic excursion (TAPSE). Additionally, the regression analysis showed that PDE inhibitor administration time is a critical factor for the decrease in PASP. Conclusions: PDE inhibitors did not effectively improve LV function, PAP, exercise capacity, and QOL in patients with HFpEF. However, they improved RV function with significant difference, suggesting that PDE inhibitors might be a promising option for HFpEF patients with RV dysfunction.

Prevalence of markers of atrial cardiomyopathy in embolic stroke of undetermined source: A systematic review.

BACKGROUND: Emerging evidence suggests the potential role of atrial cardiomyopathy (AC) as a direct thromboembolic determinant in embolic stroke of undetermined source (ESUS). OBJECTIVE: We aimed to quantify the prevalence of potential AC markers among ESUS, non-cardioembolic (NCE) and cardioembolic (CE) stroke patients. METHODS: PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for publications from inception to October 2021, with duplicate data extraction and risk of bias assessment. The Newcastle-Ottawa assessment scale was used to evaluate study quality. RESULTS: Among 398 screened studies, 11 observational studies with 2009 ESUS patients (mean age 66.5 years) fulfilled the inclusion criteria. Of electrocardiographic markers, increased P-wave terminal force in lead V1 was more prevalent in ESUS vs NCE (OR=2.26, 95%CI: 1.40-3.66). Of imaging markers, left atrial volume index (LAVI) and left atrial diameter (LAd) were higher in ESUS vs NCE (OR=1.04, 95%CI: 1.02-1.06 and OR=3.41, 95%CI: 1.35-8.61 respectively). Non-chicken wing morphology of the left atrial appendage was more frequent in ESUS compared to NCE patients in the majority of studies. Of serum biomarkers, the prevalence of NT-proBNP >250 pg/ml did not differ among ESUS vs NCE (OR=0.73, 95%CI: 0.39 -1.35). CONCLUSIONS: Electrocardiographic, echocardiographic markers and advanced imaging modalities able to assess the morphologic characteristics of left atrial appendage and left atrial function may be important tools to discriminate AC among ESUS vs NCE stroke patients. Prospective studies exploring the association of potential AC markers with ESUS occurrence are warranted to validate their clinical utility.

Serial changes of coronary flow reserve over one year after transcatheter aortic valve implantation in patients with severe aortic stenosis.

Background: Impaired coronary flow reserve (CFR) portends a poor prognosis in patients with aortic stenosis. The present study aims to investigate how CFR changes over one year after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis, and to explore factors related to the changes. Methods: Consecutive patients undergoing TAVI were registered. CFR in the left anterior descending artery was measured by transthoracic echocardiography on three occasions pre-TAVI, one-day post-TAVI, and one-year post-TAVI. Results: A total of 59 patients were enrolled, 46 of whom completed one-year follow-up. CFR was impaired in 35 (59.3%) patients pre-TAVI, but the impairment was only seen in 2 patients (4%) one-year post-TAVI. CFR value improved from 1.75 (1.50-2.10) cm/s pre-TAVI, to 2.00 (1.70-2.30) one-day post-TAVI, and further to 2.60 (2.30-3.10) one-year post-TAVI (P < 0.001). The median difference in CFR between pre-TAVI and one-year post-TAVI was 0.90 (0.53-1.20). Patients with significant improvement of CFR (more than the median value of 0.9) had larger aortic valve area (1.55 [1.38-1.92] vs. 1.36 cm2 [1.26-1.69], P = 0.042) and greater improvement in left ventricular ejection fraction (3.10 [-1.67-4.24] vs. -1.46 [-3.42-1.48] percentage points, P = 0.019) than those without. Conclusions: CFR is impaired in a considerable proportion of patients with severe aortic stenosis, but improvement is seen immediately after TAVI, and one year later. Patients with significant improvement of CFR had larger aortic valve area and greater increase in left ventricular ejection fraction after TAVI.

Comparison Between Bicuspid and Tricuspid Aortic Regurgitation: Presentation, Survival, and Aorta Complications.

Background: Although the Asian population is growing globally, data in Asian subjects regarding differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in aortic regurgitation (AR) remain unexplored. Objectives: The aim of this study was to examine differences between Asian BAV-AR and TAV-AR in significant AR, including aorta complications. Methods: The study included 711 consecutive patients with chronic moderate to severe and severe AR from 2008 to 2020. Outcomes included all-cause death, aortic valve surgery (AVS), and incidence of aortic dissection (AD). Results: There were 149 BAV-AR (mean age: 48 ± 16 years) and 562 TAV-AR (mean age: 68 ± 15 years; P < 0.0001) patients; baseline indexed left ventricle and indexed aorta size were larger in TAV-AR. Total follow-up was 4.8 years (IQR: 2.0-8.4 years), 252 underwent AVS, and 185 died during follow-up; 18 cases (only 1 BAV) of AD occurred, with a mean maximal aorta size of 60 ± 9 mm. The 10-year AVS incidence was higher in TAV-AR (51% ± 4%) vs BAV-AR (40% ± 5%) even after adjustment for covariates (P < 0.0001). The 10-year survival was higher in BAV-AR (86% ± 4%) vs TAV-AR (57% ± 3%; P < 0.0001) and became insignificant after age adjustment (P = 0.33). Post-AVS 10-year survival was 93% ± 5% in BAV-AR and 78% ± 5% in TAV-AR, respectively (P = 0.08). The 10-year incidence of AD was higher in TAV-AR (4.8% ± 1.5%) than in BAV-AR (0.9% ± 0.9%) and was determined by aorta size ≥45 mm (P ≤ 0.015). Compared with an age- and sex-matched population in Taiwan, TAV-AR (HR: 3.1) had reduced survival (P < 0.0001). Conclusions: Our findings suggest that TAV-AR patients were at a later stage of AR course and had a high AD rate as opposed to BAV-AR patients in Taiwan, emphasizing the importance of early referral for timely management. Surgery on the aorta with a lower threshold in TAV-AR should be considered.

Left ventricular filling pressure in Tetralogy of Fallot: Correlation between invasive and noninvasive indices.

BACKGROUND: Left heart filling pressures, as measured by pulmonary artery wedge pressure (PAWP), is associated with heart failure related mortality. Because of the prognostic importance of PAWP, several echocardiographic indices have been proposed for noninvasive assessment of PAWP. However, these indices have not been validated in the congenital heart disease population. The purpose of this study was to determine the correlation between echocardiographic indices of PAWP, and the effect of high PAWP on transplant-free survival in adults with tetralogy of Fallot (TOF). METHODS: Retrospective study of adult TOF patients that underwent cardiac catheterization at Mayo Clinic, 1990-2017. We selected these pre-defined set of echocardiographic indices of LV diastolic function: mitral valve early velocity (E), mitral valve early and late velocity ratio (E/A), mitral valve deceleration time (DT), mitral annular tissue Doppler early velocity (e'), and left atrial volume index (LAVI). RESULTS: Of the echocardiographic indices analyzed among 213 patients (age 37 ± 14 years), only E velocity (ß = 5.83, standard error = 1.52, p < 0.001) and LAVI (ß = 0.14, standard error = 0.05, p = 0.007) correlated with PAWP. LAVI > 28 ml/m2 had sensitivity of 79% and specificity of 63% (AUC 0.712), and E velocity > 1.0 m/s had sensitivity of 66% and specificity of 89% (AUC 0.692), for detecting PAWP > 15 mmHg. LAVI > 28 ml/m2 was associated with reduced 10-year transplant-free survival (49% vs 90%, p < 0.001). CONCLUSION: This study supports the use of LAVI for noninvasive assessment of PAWP and for prognostication. Further studies are required to validate these results in a different population.

Cardiac Versus Renal Response to Volume Expansion in Preclinical Systolic Dysfunction With PDEV Inhibition and BNP.

Impaired cardiorenal response to acute saline volume expansion in preclinical systolic dysfunction (PSD) may lead to symptomatic heart failure. The objective was to determine if combination phosphodiesterase-V inhibition and exogenous B-type natriuretic peptide (BNP) administration may enhance cardiorenal response. A randomized double-blinded, placebo-controlled study was conducted in 21 subjects with PSD and renal dysfunction. Pre-treatment with tadalafil and subcutaneous BNP resulted in improved cardiac function, as evidenced by improvement in ejection fraction, left atrial volume index, and left ventricular end-diastolic volume. However, there was reduced renal response with reduction in renal plasma flow, glomerular filtration rate, and urine flow. (Tadalafil and Nesiritide as Therapy in Pre-clinical Heart Failure; NCT01544998).

Association of Cardiac Structure and Function With Neurocognition in Hispanics/Latinos: The Echocardiographic Study of Latinos.

OBJECTIVE: To study the associations of comprehensive measures of cardiac structure and function with multidimensional neurocognitive measures. PATIENTS AND METHODS: The Echocardiographic Study of Latinos is a population-based cohort of Hispanic/Latino adults older than 45 years enrolled from October 1, 2011, through June 30, 2014. Neurocognitive measures included Word Fluency (WF), Brief-Spanish English Verbal Learning Test (B-SEVLT), and Digit Symbol Substitution Test. The B-SEVLT included B-SEVLT-recall and B-SEVLT-sum. Echocardiographic measures included cardiac structure, systolic and diastolic function, and myocardial strain. Multivariable regression models were fit using survey statistics and sampling probabilities. RESULTS: A total of 1794 participants (mean age, 56±0.5 years; 56% women) were included in the analysis. In the adjusted model, higher left ventricular mass index was associated with lower B-SEVLT-sum and Digit Symbol Substitution Test scores. Left ventricular systolic dysfunction was associated with lower WF scores. Abnormal left ventricular geometry was associated with lower B-SEVLT-sum scores. Higher relative wall thickness was associated with B-SEVLT-recall and B-SEVLT-sum scores. Mitral annular relaxation velocities were associated with lower B-SEVLT-recall, B-SEVLT-sum, and WF scores. Higher mitral inflow to annular early diastolic velocity ratio was associated with lower B-SEVLT-recall and B-SEVLT-sum scores. Diastolic dysfunction was associated with lower B-SEVLT-sum scores. Finally, lower global longitudinal strain was associated with lower WF scores. CONCLUSION: Alterations in cardiac structure, systolic and diastolic function, and myocardial strain were associated with worse neurocognitive function. Further study is needed to determine the mechanisms (ie, impairment of cerebral flow and silent brain infarctions) mediating these heart-brain associations.