Lin, Grace

ABSTRACT Aims Mild to moderate functional mitral regurgitation (MR) is common in patients with heart failure and preserved ejection fraction (HFpEF) where it is usually considered as an innocent bystander. We hypothesized that MR in HFpEF reflects greater left atrial (LA) myopathy, leading to more adverse haemodynamics and poorer exercise reserve. Methods and results Patients with HFpEF (n = 280) with and without MR underwent echocardiography, invasive haemodynamic exercise testing, and expired gas analysis. As compared to non-MR-HFpEF (n = 163), patients with MR-HFpEF (n = 117; 78 mild and 39 moderate, central jet in 90%) were older, more likely female, with lower body mass and higher prevalence of atrial fibrillation (AF). HFpEF patients with MR displayed greater LA volume, reduced LA strain and compliance, and greater mitral annular dilatation, which was strongly correlated with LA dilatation (r = 0.63, P < 0.0001) but was only weakly related to left ventricular remodelling (r = 0.37). Patients with MR-HFpEF displayed worse biventricular function, more adverse pulmonary haemodynamics, impaired pulmonary vasodilatation, blunted right ventricular reserve, and reduced cardiac output with exercise as compared to non-MR-HFpEF. Importantly, these findings were maintained after excluding patients with HFpEF and AF, suggesting a role for LA myopathy in contributing to MR in HFpEF, independent of rhythm. Conclusions Functional MR in patients with HFpEF reflects LA myopathy, even in the absence of AF, and is associated with greater haemodynamic severity of disease and poorer functional capacity. Further study is required to better define causal mechanisms and potential treatments for MR and LA dysfunction in patients with HFpEF.

AbstractBackgroundThe accurate separation of undifferentiated wide complex tachycardias (WCTs) into ventricular tachycardia (VT) or supraventricular wide complex tachycardia (SWCT) using conventional, manually‐applied 12‐lead electrocardiogram (ECG) interpretation methods is difficult.PurposeWe sought to devise a new WCT differentiation method that operates solely on automated measurements routinely provided by computerized ECG interpretation software.MethodsIn a two‐part analysis, we developed and validated a logistic regression model (ie, VT Prediction Model) that utilizes routinely available computerized measurements derived from patients' paired WCT and baseline ECGs.ResultsThe derivation cohort consisted of 601 paired WCT (273 VT, 328 SWCT) and baseline ECGs from 421 patients. The VT Prediction Model, composed of WCT QRS duration (ms) (P < .0001), QRS duration change (ms) (P < .0001), QRS axis change (°) (P < .0001) and T axis change (°) (P < .0001), yielded effective VT and SWCT differentiation (area under the curve [AUC]: 0.924; confidence interval [CI]: 0.903‐0.944) for the derivation cohort. The validation cohort comprised 241 paired WCT (97 VT, 144 SWCT) and baseline ECGs from 177 patients. The VT Prediction Model's implementation on the validation cohort yielded effective WCT differentiation (AUC: 0.900; CI: 0.862‐0.939) with overall accuracy, sensitivity, and specificity of 85.0%, 80.4%, and 88.2%, respectively.ConclusionThe VT Prediction Model is an example of how readily available ECG measurements may be used to distinguish VT and SWCT effectively. Further study is needed to develop and refine newer WCT differentiation approaches that utilize computerized measurements provided by ECG interpretation software.

Abstract Background Secondary mitral regurgitation (SMR) impacts outcomes in heart failure with reduced ejection fraction (HFrEF) but whether it is a specific therapeutic target in heart failure patients with preserved ejection fraction (HFpEF) is less clear. Purpose The aims of this study were to investigate whether surgical or trans-catheter intervention reduces SMR and improves outcomes compared to optimal medical therapy in HFpEF patients. Methods We retrospectively identified 120 HFpEF patients with moderate-to-severe or greater SMR from January 1, 2007, until December 31, 2017. Moderate-to-severe SMR was defined as an effective regurgitant orifice area of >0.3cm2, and/or a regurgitation volume of >45ml per beat. Those with primary mitral regurgitation, endocarditis, HFrEF, hypertrophic cardiomyopathy, congenital heart disease, and history of valve intervention were excluded. All-cause mortality was analyzed and correlated to clinical and echocardiographic characteristics. Amongst the 120 patients, 36 received surgical or trans-catheter procedure in addition to medical therapy (procedure group) and 84 patients received optimal medical therapy only (conservative treatment group). The median follow-up period was 864 (15–3553) days. Results Patients in the procedure group were younger (75±8 vs 81±10, P=0.0002) and with fewer comorbidities (Charlson Comorbidity Index 7.0±2.4 vs 8.0±2.0, P=0.022) compared to the conservative treatment group. In addition, the procedure group had larger left ventricular end-diastolic diameters and higher SMR volume at baseline. During follow-up, SMR decreased by ≥2 grades in 75% of patients (27/36) in the procedure group compared to 20% of patients (12/60) in the conservative treatment group. After adjusting for age and comorbidities, the procedure group showed better overall survival compared to the conservative treatment group (HR 0.37; 95% CI 0.17–0.80; P=0.011). On multivariate analysis for the different groups (procedure group vs. conservative treatment group) (HR 0.40; 95% CI 0.17–0.91; P=0.019), increasing Charlson Comorbidity Index (HR 1.16; 95% CI 1.02–1.32; P=0.028) and average mitral E/e' ratio (HR 1.06; 95% CI 1.01–1.11; P=0.031) were independent predictors of increased all-cause mortality. Kaplan-Meier Survival Curve Conclusion Among heart failure patients with preserved ejection fraction and moderate-to-severe or severe SMR, surgical or trans-catheter mitral-valve repair or replacement resulted in lower all-cause mortality compared to conservative treatment after 9 years of follow-up.

Cirrhotic cardiomyopathy (CCM) is cardiac dysfunction in patients with end‐stage liver disease in the absence of prior heart disease. First defined in 2005 during the World Congress of Gastroenterology, CCM criteria consisted of echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Significant advancements in cardiovascular imaging over the past 14 years, including the integration of myocardial deformation imaging into routine clinical practice to identify subclinical cardiovascular dysfunction, have rendered the 2005 CCM criteria obsolete. Therefore, new criteria based on contemporary cardiovascular imaging parameters are needed. In this guidance document, assembled by a group of multidisciplinary experts in the field, new core criteria based on contemporary cardiovascular imaging parameters are proposed for the assessment of CCM. This document provides a critical assessment of the diagnosis of CCM and ongoing assessment aimed at improving clinical outcomes, particularly surrounding liver transplantation. Key points and practice‐based recommendations for the diagnosis of CCM are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

Abstract Aims Left atrial (LA) function is impaired in heart failure with preserved ejection fraction (HFpEF) and predicts disease severity and risk of adverse outcome. We sought to evaluate whether LA strain could enhance diagnosis of HFpEF. Methods and results Consecutive patients with unexplained exertional dyspnoea and image quality suitable for measuring LA strain underwent invasive cardiopulmonary exercise testing to ascertain the presence of HFpEF or non-cardiac causes of dyspnoea (NCD). LA reservoir strain was measured in all patients, while LA conduit and booster strain were measured in patients with sinus rhythm. LA strain was measurable in 363 of 378 examinations (96.5%; HFpEF: 238, NCD: 125). LA reservoir strain (29 ± 16% vs. 40 ± 13%, P &lt; 0.0001) and conduit strain (18 ± 10% vs. 22 ± 10%, P = 0.0001) were significantly impaired in HFpEF compared to NCD. Of all echocardiographic indices, LA reservoir strain best discriminated HFpEF from NCD [area under the curve (AUC) 0.719, P &lt; 0.0001], outperforming E/e' (AUC difference +0.117, P &lt; 0.0001), LA enlargement (+0.090, P = 0.001), tricuspid regurgitation velocity &gt; 2.8 m/s (+0.082, P = 0.0085), left ventricular hypertrophy (+0.0159, P &lt; 0.0001) and left ventricular global longitudinal strain (+0.0198, P &lt; 0.0001). Indexing LA reservoir strain to estimated LA pressure (E/e') as a surrogate for LA compliance further improved diagnostic performance (AUC 0.772, P &lt; 0.0001; +0.053 compared to LA reservoir strain alone, P = 0.003). Conclusion Left atrial reservoir strain may provide enhanced diagnostic accuracy beyond conventional echocardiographic measures to discriminate HFpEF from NCD. Further study is required to verify the diagnostic utility of LA strain.

The tyrosine kinase inhibitor sorafenib improves hepatopulmonary syndrome (HPS) in an experimental model. However, the efficacy and adverse effect profile in patients with HPS are unknown. We aimed to determine the effect of sorafenib on the alveolar‐arterial oxygen gradient (AaPO2) at 3 months in patients with HPS. We performed a randomized, double‐blind, placebo‐controlled parallel trial of sorafenib in patients with HPS at 7 centers. A total of 28 patients with HPS were randomized to sorafenib 400 mg by mouth daily or a matching placebo in a 1:1 ratio. We found no statistically significant difference in the median change in AaPO2 from baseline to 12 weeks between the patients allocated to sorafenib (4.5 mm Hg; IQR, –3.8 to 7.0 mm Hg) and those allocated to placebo (–2.4 mm Hg; IQR, –4.8 to 8.2 mm Hg; P = 0.70). There was also no difference between the groups in terms of degree of intrapulmonary shunting by contrast echocardiography. Sorafenib significantly reduced circulating levels of angiogenic markers, including vascular endothelial growth factor receptors (P < 0.01) and TIE2‐expressing M2 monocytes (P = 0.03), but it reduced the mental component scores of the Short Form 36 (P = 0.04), indicating a worse quality of life. In conclusion, sorafenib did not change the AaPO2 or other disease markers at 3 months in patients with HPS. Alternative antiangiogenic therapies or treatments targeting other pathways should be investigated.