Citations

This analysis provides a novel assessment of the relationship between the severity of right ventricular dysfunction (RVD) and blood volume expansion (BVE) on clinical outcomes in patients with chronic left-sided heart failure. Findings demonstrate that despite the high prevalence of moderate or greater RVD, persistent BVE was associated with better 1-year event-free survival relative to normal BV. Hypothesis-generating, this suggests that BVE may provide an adaptive response compensating in part for the impact of RVD in chronic HF.

Abstract Aims Tricuspid valve regurgitation (TR) is common and associated with increased mortality. The interaction between the pulmonary artery (PA) circulation and the right ventricle (RV) and association with outcomes is incompletely understood. The effective PA elastance (PA Ea) is a composite measure of RV afterload that refers to the pulmonary vascular load that the RV must overcome to eject blood. Whether PA Ea discriminates mortality risk in unselected patients with significant TR is unknown. Methods and results In consecutive patients with ≥moderate TR, we compared all-cause mortality at 5 years based on the PA Ea (defined as the RV systolic pressure/stroke volume as measured by transthoracic echocardiography). In a total of 12 682 patients, the median PA Ea was 0.7 mm Hg/mL (interquartile range 0.5, 0.9). Increasing levels of PA Ea were associated with heart failure, liver and kidney disease, and clinical markers of risk such as the Tricuspid Regurgitation Impact on Outcomes score. Increasing levels of PA Ea were associated with larger RVs, worse RV systolic function, higher N-terminal pro-brain natriuretic peptide levels, and greater degrees of right heart failure. After adjusting for age and sex, PA Ea was associated with higher risk of death (hazard ratio 1.55 per 0.5 mm Hg/mL change of PA Ea; 95% confidence intervals 1.51–1.60; P < 0.0001). In multivariable modelling incorporating available clinical variables, PA Ea was independently predictive of outcome compared with other indexes of RV–PA coupling. Conclusion In patients with significant TR, higher PA Ea is progressively associated with RV dysfunction, right heart failure, and worse survival. Incorporating PA Ea into the routine echo assessment may help stratify risk.

ABSTRACT Background Incident atrial functional mitral regurgitation (AFMR) is associated with mortality. Transcatheter edge‐to‐edge repair (TEER) has shown effectiveness in improving MR and symptoms in AFMR, but previous studies lacked comparison to conservative management. We aimed to study the association of AFMR severity and mitral TEER with symptoms, heart failure hospitalizations (HFH) and all‐cause mortality in moderate/severe AFMR. Methods Consecutive adults with moderate/severe AFMR managed conservatively or with TEER 2010−2023 were identified retrospectively. To ensure similar technique in evaluation in the two groups, variables were obtained from the closest transthoracic echocardiogram before TEER in the TEER group. In addition to multivariable analysis, the association of TEER (vs. conservative management) with HFH and mortality was assessed using propensity‐score matched analyses; the propensity score was based on age, sex, EuroSCORE II, effective regurgitant orifice area, integrative MR severity, and NYHA class III/IV (vs. I/II). Results Among 230 patients with moderate/severe AFMR [mean age 77; 56% females], 46 were managed with TEER. Severe (vs. moderate) AFMR was independently associated with baseline NYHA class III/IV (multivariable OR 2.18 [95% CI 1.13−4.26]) and HFH [multivariable HR 2.75 (95% CI 1.25−6.03)] but not mortality ( p = 0.26). TEER improved MR to ≤ moderate in 93% but was not associated with lower HFH or death rates versus conservative management on multivariable or matched analysis. However, 1‐year NYHA improved more with TEER versus conservative management in patients with baseline NYHA class III/IV (62% vs. 27%, p = 0.03). Rhythm control was associated with improved survival (HR 0.38 [0.15−0.98]). Conclusions AFMR severity was associated with symptoms and HFH but not mortality. MR severity and NYHA class improved with TEER, but the association of TEER with HF hospitalizations or death remains unproven. Randomized studies are needed to evaluate the potential role of TEER and rhythm control on outcomes in AFMR.

Abstract Aims To develop a deep learning model that: (i) utilizes transthoracic echocardiography (TTE) clips to detect left ventricular (LV) enlargement without being provided information regarding a patient’s sex and body size; and (ii) can be accurately applied to clips acquired using either standard comprehensive TTE or handheld cardiac ultrasound (HCU). Methods and results Using retrospective TTE data (training: 8722 patients; internal validation: 468 patients), we developed a deep learning model that estimates a patient’s end-diastolic LV volume (indexed to body surface area and normalized across the sexes), and then thresholds this estimate to perform the following classifications: (1) normally sized LV vs. ≥ mild LV enlargement; (2) normal/mildly enlarged LV vs. ≥ moderate LV enlargement. For retrospective datasets, the model showed strong performance in TTE across three geographically distinct locations (Minnesota and Wisconsin: 1082 patients, AUC = 0.925 and 0.953 for classifications 1 and 2, respectively; Arizona: 1475 patients, AUC = 0.935 and 0.969; and Florida: 1481 patients, AUC = 0.934 and 0.970). Additionally, performance was strong for both TTE and HCU clips collected from a prospective cohort of 410 patients who underwent HCU immediately following TTE (TTE: AUC = 0.925 and 0.971; HCU: AUC = 0.874 and 0.902, for classifications 1 and 2, respectively). Conclusion An automated deep learning model applied to TTE or HCU images accurately categorizes LV volumes. These results lay a foundation for future work aimed at optimizing clinical outcomes for heart failure patients by enabling early detection of LV enlargement across various point-of-care settings.

BACKGROUND: Pharmacological treatments for fibrocalcific aortic valve stenosis (FCAVS) have been elusive for >50 years. Here, we tested the hypothesis that reactivation of oxidized sGC (soluble guanylate cyclase), the primary receptor for nitric oxide, with ataciguat is a safe and efficacious strategy to slow progression of FCAVS. METHODS: We used quantitative real-time reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry to characterize sGC signaling and the biological effects of ataciguat on signaling cascades related to nitric oxide, calcification, and fibrosis in excised human aortic valve tissue, aortic valve interstitial cells, and mouse aortic valves. We then conducted randomized, placebo-controlled phase I (14-day safety/tolerance) and phase II (6-month efficacy) trials in patients with moderate aortic valve stenosis. RESULTS: In excised human tissue, we found robust losses in sGC signaling despite upregulation of sGC subunits. In vitro, ataciguat increased sGC signaling and reduced BMP2 (bone morphogenetic protein 2) signaling in aortic valve interstitial cells. In mice with established FCAVS, treatment with ataciguat attenuated BMP signaling and slowed progression of valve calcification and dysfunction. In a phase I, randomized, placebo-controlled trial, treatment with ataciguat for 2 weeks was safe and well tolerated in patients with moderate FCAVS ( https://www.clinicaltrials.gov ; Unique identifier: NCT02049203). In a separate phase II, randomized, placebo-controlled trial, treatment with ataciguat for 6 months slowed the progression of aortic valve calcification and tended to slow the progression of valvular and ventricular dysfunction in patients with moderate FCAVS ( https://www.clinicaltrials.gov ; Unique identifier: NCT02481258). CONCLUSIONS: Collectively, this study highlights the therapeutic potential of the targeted restoration of the diseased/inactive form of sGC for treatment of FCAVS. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02049203. URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02481258.

Abstract Aims Transcatheter mitral valve replacement (TMVR) has become a feasible alternative to surgical mitral valve replacement (SMVR) in selected patients at high surgical risk. The risk of valve thrombosis following SMVR and TMVR, and the optimal antithrombotic therapy following these procedures, remains uncertain. We aimed to compare the incidence of bioprosthetic mitral valve thrombosis (bMVT) after SMVR and TMVR, and the incidence of bMVT between patients on different antithrombotic regimens. Methods and results A literature search of Medline, Embase, and Cochrane Library was performed between January 2000 and August 2024. Random-effects models were used to derive pooled estimates of the incidence of bMVT in the absence of prior or active endocarditis and valve thrombosis. A total of 47 studies (6170 patients, total follow-up 9541.8 patient-years) were eligible for inclusion. The overall incidence of bMVT was 5.05 [95% confidence interval (CI) 3.18–8.01, I2 = 82%] per 100-patient-years. Subclinical bMVT was more common than clinically significant bMVT: incidence 19.11 vs. 7.91 per 100-patient-years, adjusted incidence rate ratio (aIRR) 4.62 (95% CI 1.39–15.36), P = 0.012. bMVT was numerically more common after TMVR than SMVR, but the comparison was not statistically significant: incidence 7.03 vs. 0.58 per 100-patient-years, aIRR 2.19 (95% CI 0.72–6.72), P = 0.170. Patients on vitamin-K antagonists (VKA) had a lower incidence of bMVT than patients on direct oral anticoagulants (DOAC; incidence 5.72 vs. 17.08, aIRR 0.31, 95% CI 0.13–0.73, P = 0.007). Conclusions bMVT is not uncommon, with numerically higher incidence in transcatheter compared to surgical valves, but the comparison was not statistically significant. VKAs are associated with a lower incidence of bMVT compared to DOACs.

Abstract Introduction Echocardiography is the recommended modality for non-invasive assessment of pulmonary pressures. However, in patients with severe tricuspid regurgitation (TR), the reliability of echocardiographically derived systolic pulmonary artery pressure (sPAP) is questioned. Limited data exists on the correlation between echocardiography and right heart catheterization (RHC) in selected group of patients with severe TR. Purpose To evaluate the correlation between echocardiographic and RHC measurements for sPAP in patients with varying TR severity. Method Patients who underwent echocardiography and RHC within three days at a large single referral center were retrospectively included. Exclusion criteria included incomplete echocardiographic and RHC data, ≥moderate pulmonary stenosis, low-quality images, and pregnancy. Echocardiographic sPAP was calculated using simplified Bernoulli equation. Echocardiographic right atrial pressure (RAP) was assessed by evaluating inferior vena cava (IVC) dimension and collapsibility. A difference of ≥10 mmHg between the two modalities for sPAP was considered clinically significant. Results Of 3696 patients included, mean age was 64±14 years, 1689 (46%) were females, 1659 (45%) had systemic hypertension, and 582 (16%) had atrial fibrillation. TR was <moderate in 2475 (67%) patients, moderate in 499 (14%), moderate-severe in 277 (7%), and severe in 445 (12%). Pulmonary hypertension (PH) was diagnosed in 3079 subjects (83%). A good correlation was found between sPAP derived by echocardiographic and RHC in the whole cohort (correlation coefficient (LCC) 0.79, CI 0.78-0.80), in severe TR subgroup (LCC 0.78, CI 0.75-0.82), and in severe TR with PH subgroup (LCC 0.76, CI 0.71-0.79). The mean echocardiographic misestimation for sPAP in severe TR was 3.97 mmHg (CI -5.24 to -2.71). The correlation between the two modalities for RAP was moderate in the whole cohort (LCC 0.59, CI 0.57-0.61) and fair in severe TR (LCC 0.35, CI 0.27-0.42). A clinically significant difference between the two modalities for sPAP was found in 1504 patients (41%), predominantly due to the right ventricle-right atrium gradient misestimation, rather than RAP misestimation, in patients with no PH (67% vs 33%), patients with mild-moderate PH (mean Pulmonary Artery Pressure (mPAP) 21-34 mmHg) (67% vs 33%) and severe PH (mPAP ≥35 mmHg) (76% vs 24%). Conclusion The correlation between echocardiographic and RHC measurements is good for sPAP, even in severe TR patients, while it is only fair to moderate for RAP. A clinically significant difference between echocardiographic and RHC sPAP is more commonly observed in patients with PH, with right ventricle-right atrium gradient misestimation being the most common cause.

Abstract Introduction Secondary tricuspid regurgitation (STR) is a highly prevalent valve disease. STR and Heart Failure with preserved Ejection Fraction (HFpEF) share common features including exertional intolerance and high burden of atrial fibrillation (AF) and pulmonary hypertension (PH), making it challenging to disentangle HFpEF from TR. The incidence of clinically-recognized HFpEF in STR and its impact on mortality are not well established. Purposes To define the incidence of newly diagnosed HFpEF and its impact on mortality in a cohort of patients with significant STR and to evaluate the likelihood of a larger hidden burden of HFpEF. Methods Patients with a first diagnosis of ≥moderate-severe STR between 2004-2019 at our institution were retrospectively included. Patients with left ventricle ejection fraction <50%, left-sided valve diseases, and intracardiac device leads were excluded. HFpEF was identified by manual chart review as well as by use of ICD codes. The estimated prevalence of HFpEF was evaluated using an H2FPEF score ≥6, which corresponds to a ≥90% probability of having HFpEF. Results Of 2118 patients (mean age 70 ± 14, 36% females), 1057 (50%) had systemic hypertension (HTN) and 1091 (51%) had AF, with median 2.3 years of follow-up. From this cohort, 536 (25%) patients were diagnosed with HFpEF based upon chart review during the follow up period, while ICD diagnosis was only present in fewer than 50% of these patients (254). High H2FPEF score was present in 880 patients (41.5%), of whom 383 received a chart diagnosis of HFpEF, while 153 patients with H2FPEF score <6 received a chart HFpEF diagnosis. The cumulative incidence of chart-based diagnosis of HFpEF was 20.8% (N=158) at 1-year and 38.6% (N=273) at 5-years in patients with an H2FPEF score ≥6 and 5.5%(N=60) at 1-year and 11.1%(N=111) at 5-years in those with a score <6 (Figure). In Cox regression analyses, the diagnosis of HFpEF during follow-up was associated with increased mortality (HR 2.14, CI 1.86-2.46, p < 0.001) after adjusting for age, sex, body mass index, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, diuretics, HTN, pulmonary hypertension, chronic kidney disease and AF. Conclusions The incidence of clinically documented HFpEF in a cohort of patients with significant STR at index evaluation is high (25%). Use of ICD code underestimates clinical recognition, with the actual burden of HFpEF probably being even greater, as indicated by an H2FPEF score ≥ 6. Among those with significant STR, HFpEF diagnosis is an independent risk factor for mortality.

Abstract Background/Introduction Close monitoring of aortic stenosis (AS) by follow-up echocardiography is recommended by all Cardiology and Imaging Societies’ guidelines. Whether these guidelines are strictly followed is unknown. Purpose We aimed to describe our institution’s practice patterns for echocardiographic monitoring in patients with aortic sclerosis (AScl) and AS of any severity. Methods Adult patients residing in our institution’s county with an echocardiographic diagnosis of AScl or AS between 01/2005-01/2022 were identified and classified into 4 groups: AScl, mild AS, moderate AS, or severe AS, at each echocardiogram during the study timeframe. Kaplan Meier analyses were used to evaluate the composite outcome, the occurrence of follow-up echocardiogram or death. Patients were censored at the time of aortic valve replacement/repair, heart transplant, or last clinical follow-up. Guideline follow-up was considered appropriate when the primary outcome occurred by 5 years (AScl/mild AS), 2 years (moderate AS), and 1 year (severe AS). Results A total of 23,726 echocardiograms from 9,578 unique patients were included. At index echocardiogram, median patient age was 74 years (IQR 65-82) and 4,806 (50.2%) were women. AScl was observed in 7,358 (76.8%) cases, mild AS in 1,442 (15.1%) cases, moderate AS in 479 (5%), and severe AS in 301 (3.1%) cases. Rates of composite outcome achievement by the end of the guideline-recommended interval were 81%, 90%, 80%, and 72% in AScl, mild, moderate, and severe AS, respectively. Rates for men were 83%, 92%, 82%, and 75% in these groups, while rates for women were 78%, 88%, 78%, and 68%, respectively (Figure 1). Follow-up rates were similar before and after 2012 (when transcatheter aortic valve replacement was approved for treatment of severe AS in high-risk surgical patients in the USA). Follow-up rates were higher in patients managed by cardiovascular providers compared to non-cardiovascular providers (Figure 2). Conclusion Depending on disease severity, between one fourth and one tenth of patients remained alive and unfollowed at the end of their guideline-recommended surveillance interval. There is significant variability in echocardiogram monitoring based on sex and referring provider specialty. Figure 1 Figure 2