Advanced Heart Failure Symptoms Research Articles

Left atrioventricular coupling index: association with diastolic dysfunction and prognostic implications in heart failure patients

Abstract Background Left atrioventricular coupling index (LACI), an index coupling left atrial (LA) to left ventricular (LV) volume at end-diastole (Figure 1), showed to be associated with prognosis in different clinical settings. However, the relation between LACI and LV diastolic dysfunction (DD) remains to be established. Purpose The present study aimed to investigate the association between LACI and LV DD and to assess its prognostic value in patients with heart failure (HF). Methods We retrospectively analyzed 1158 stable HF patients (mean age 66±12 years, 75% men) on optimal medical therapy (derivation cohort). Clinical and echocardiographic features were characterized across LACI tertiles. The independent prognostic value of LACI (endpoint: all-cause death/HF-hospitalization) was assessed by Cox regression and spline curve analyses. Results were validated in an external cohort of 242 HF patients. Results In the derivation cohort, the median LACI value was 0.29 (IQR:0.19-0.42). Patients in the third tertile (LACI>0.36) were older and presented with more advanced HF symptoms. While prevalence of grade-1 DD (ASE/EACVI classification) progressively decreased across LACI tertiles, the prevalence of grade-3 DD significantly increased (8%,23%, and 46% respectively, P<0.0001). A cut-off value ³0.26 identified moderate-to-severe DD with an area-under the-curve of 0.75. During follow-up (median 28 months, IQR:11-53), 407 (35%) patients reached the endpoint. On multivariable analysis, LACI was independently associated with outcomes (HR for 1-unit-increase 2.34; 95%CI 1.35-4.03; P=0.002 – Figure 2), showing incremental predictive value over the DD grading system (net reclassification improvement=0.150, P<0.0001). The prognostic value of LACI was consistent in the external validation cohort. Conclusions LACI is associated with DD severity and is an independent predictor of outcomes in HF patients.How to assess LACIPrognostic value of LACI in HF

Sex differences in left ventricular dilatation in patients with significant aortic regurgitation: prognostic implications

Abstract Background Left ventricular (LV) dilatation is a strong indicator of adverse outcome in patients with aortic regurgitation (AR). Accordingly, current guidelines recommend the use of LV end-systolic diameter index (LVESDi) as one of the criteria to trigger aortic valve surgery (AVS) in patients with severe AR, but with the same threshold regardless of gender. Purpose To assess sex differences in LV remodeling using both volumetric and linear measurements in a large cohort of patients with significant AR (moderate or greater) and to investigate their prognostic implications. Methods A total of 1070 patients (56 ± 18 years, 691 men) were included. The primary outcome was all-cause mortality. Results Women presented with older age (58 ± 19 vs. 55 ± 17, p=0.023) and more advanced heart failure (HF) symptoms than men (NYHA class III-IV 12% vs. 9%, p=0.017). Men showed significantly larger LVESDi (21 ± 5 vs. 20 ± 5 mm/m2, p=0.013) and LV end-systolic volume index (LVESVi 37 ± 28 vs. 26 ± 17 ml/m2 p<0.001). During a median follow-up of 89 (IQR, 54-132) months, 168 patients died. Women had lower survival rates at 3, 5, and 10 years of follow-up compared to men (92% vs. 94.3%; 85% vs. 89.7% and 75.3% vs. 84.1%, p=0.005) (Figure 1). Spline curve analysis revealed that the threshold of LVESDi associated with an increased risk of mortality was 20 mm/m2 for both sexes. In turn, the threshold for LVESVi was 40 ml/m2 for women and 45 ml/m2 for men. Univariable Cox regression models were constructed separately for men and women. The variables associated with all-cause mortality were age, NYHA class III-IV, and AVS as time-dependent covariate in women, and age, diabetes, AVS as time-dependent covariate, and LAVI (left atrial volume index) in men. These parameters were used as a basal multivariable Cox regression model on top of which LVESDi >20 mm/m2 (Model 1), LVESVi >40 ml/m2 for women and 45 ml/m2 for men (Model 2) were added (Table 1A). LVESVi >40 ml/m2 was not a significant univariate predictor in men. In women, LVESDi >20 mm/m2 (HR: 2.046, 95%CI 1.244-3.419; p=0.006) and LVESVi >40 ml/m2 (HR 1.758, CI 1.095-2.825; p=0.020) showed an independent association with all-cause mortality among other factors (Table 1A). In men, death was independently associated with LVESDi >20 mm/m2 (HR 1.979, 95%CI 1.255-3.121; p=0.003) and LVESVi >45 ml/m2 (HR 2.388, 1.522-3.746; p<0.001), among other factors (Table 1A). Moreover, when added to a basal model that included clinical and echocardiographic variables associated with prognosis, LV dilatation based on volumetric LV enlargement resulted in a greater discriminatory power for both genders (Table 1B). Conclusion Men and women have a similar LVESDi threshold of 20 mm/m2, which is associated with an increased risk of death. However, their respective cut-off values for LVESVi differ, with the optimal threshold for women being 40 ml/m2 and for men 45 ml/m2.

Cellular and extracellular proteomic profiling of paradoxical low-flow low-gradient aortic stenosis myocardium.

Patients with severe aortic stenosis (AS), low transvalvular flow (LF) and low gradient (LG) with normal ejection fraction (EF)-are referred to as paradoxical LF-LG AS (PLF-LG). PLF-LG patients develop more advanced heart failure symptoms and have a worse prognosis than patients with normal EF and high-gradient AS (NEF-HG). Despite its clinical relevance, the mechanisms underlying PLF-LG are still poorly understood. Left ventricular (LV) myocardial biopsies of PLF-LG (n = 5) and NEF-HG patients (n = 6), obtained during transcatheter aortic valve implantation, were analyzed by LC-MS/MS after sequential extraction of cellular and extracellular matrix (ECM) proteins using a three-step extraction method. Proteomic data are available via ProteomeXchange with identifier PXD055391. 73 cellular proteins were differentially abundant between the 2 groups. Among these, a network of proteins related to muscle contraction and arrhythmogenic cardiomyopathy (e.g., cTnI, FKBP1A and CACNA2D1) was found in PLF-LG. Extracellularly, upregulated proteins in PLF-LG were related to ATP synthesis and oxidative phosphorylation (e.g., ATP5PF, COX5B and UQCRB). Interestingly, we observed a 1.3-fold increase in cyclophilin A (CyPA), proinflammatory cytokine, in the extracellular extracts of PLF-LG AS patients (p < 0.05). Consistently, immunohistochemical analysis confirmed its extracellular localization in PLF-LG AS LV sections along with an increase in its receptor, CD147, compared to the NEF-HG AS patients. Levels of core ECM proteins, namely collagens and proteoglycans, were comparable between groups. Our study pinpointed novel candidates and processes with potential relevance in the pathophysiology of PLF-LG. The role of CyPA in particular warrants further investigation.

Left Atrioventricular Coupling Index: A Novel Diastolic Parameter to Refine Prognosis in Heart Failure

Left atrioventricular coupling index (LACI), an index coupling left atrial to left ventricular (LV) volume at end-diastole, has been shown to be associated with prognosis in different clinical settings. However, the relation between LACI and LV diastolic dysfunction (DD) remains to be established. The aims of the present study were to investigate the association between LACI and LV DD and to assess its prognostic value in patients with heart failure (HF). A total of 1,158 patients with HF in stable condition, on optimal medical therapy, were retrospectively analyzed (derivation cohort). Clinical and echocardiographic features were characterized across LACI tertiles. The independent prognostic value of LACI (end point: all-cause death or HF hospitalization) was assessed using Cox regression. Results were validated in an external cohort of 242 patients with HF. In the derivation cohort, the median LACI value was 0.29 (interquartile range, 0.19-0.42). Patients in the third tertile (LACI>0.36) were older and presented with more advanced HF symptoms. Although the prevalence of grade 1 DD (American Society of Echocardiography/European Association of Cardiovascular Imaging classification) progressively decreased across LACI tertiles, the prevalence of grade 3 DD significantly increased (8%, 23%, and 46%, respectively; P<.0001). A cutoff value of ≥0.26 identified moderate to severe DD with an area under the curve of 0.75. During follow-up (median, 28months; interquartile range, 11-53 months), 407 patients (35%) reached the end point. On multivariable analysis, LACI was independently associated with outcomes (hazard ratio for a 1-SD increase, 1.16; 95% CI, 1.06-1.28; P=.002), showing incremental predictive value over the DD grading system (net reclassification improvement=0.150, P<.0001). The prognostic value of LACI was consistent in the external validation cohort. LACI is associated with DD severity and is an independent predictor of outcomes in patients with HF.

Retrograde Conduction in Left Bundle Branch Block: Insights From Left Bundle Branch Pacing.

Biventricular pacing is a well-established therapy for patients with heart failure (HF), left bundle branch block (LBBB) and left ventricular (LV) dysfunction. Left bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing. The aim of this study was to assess the retrograde conduction properties of the left bundle branch in patients with nonischemic cardiomyopathy and LBBB during LBBP and its clinical implications. Patients undergoing successful LBBP for nonischemic cardiomyopathy with LV ejection fraction (LVEF)≤35% and LBBB were included. Continuous recording of His potential was performed using a quadripolar catheter. Unidirectional block was defined as retrograde His bundle activation during LBBP with stimulus to His potential (SH) duration less than or equal to antegrade HV interval and bidirectional block as VH dissociation or SH duration greater than HV interval. HF hospitalization, ventricular arrhythmias, and mortality were documented. A total of 165 patients were included. The mean follow-up duration was 21.8 ± 13.1months. Bidirectional block (group I) was observed in 82% (n=136), and these patients were noted to have advanced HF stage and prolonged baseline QRS duration. Unidirectional block (group II) with intact retrograde conduction was observed in 18% (n=29) and was associated with narrow paced QRS duration and higher LVEF during follow-up. Super-response (LVEF≥50%) was observed in 54.4% (n=74) in group I compared with 73.3% (n=22) in group II (P=0.03). The OR for LVEF normalization was 4.1 (95%CI: 1.26-13.97; P=0.02), with unidirectional block compared with bidirectional block in patients with LBBB and LV dysfunction. Adverse clinical outcomes as measured by a composite of HF hospitalization, ventricular arrhythmias, and mortality were significantly higher in group I compared with group II (12.5% vs 0%; P=0.04). Bidirectional block in LBBB was characterized by advanced HF symptoms, while unidirectional block was associated with better clinical outcomes after cardiac resynchronization therapy by LBBP.

Contemporary pharmacological treatment and management of heart failure.

The prevention and treatment strategies for heart failure (HF) have evolved in the past two decades. The stages of HF have been redefined, with recognition of the pre-HF state, which encompasses asymptomatic patients who have developed either structural or functional cardiac abnormalities or have elevated plasma levels of natriuretic peptides or cardiac troponin. The first-line treatment of patients with HF with reduced ejection fraction includes foundational therapies with angiotensin receptor-neprilysin inhibitors, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors and diuretics. The first-line treatment of patients with HF with mildly reduced ejection fraction or with HF with preserved ejection fraction includes SGLT2 inhibitors and diuretics. The timely initiation of these disease-modifying therapies and the optimization of treatment are crucial in all patients with HF. Reassessment after initiation of these therapies is recommended to evaluate patient symptoms, health status and left ventricular function, and timely referral to a HF specialist is necessary if a patient has persistent advanced HF symptoms or worsening HF. Lifestyle modification and treatment of comorbidities such as diabetes mellitus, ischaemic heart disease and atrial fibrillation are crucial through each stage of HF. This Review provides an overview of the management strategies for HF according to disease stages that are derived from the recommendations in the latest US and European HF guidelines.

Multifactorial risk factors for hospital readmissions among patients with symptoms of advanced heart failure.

Economic burden of heart failure is attributed to hospital readmissions. Previous studies assessing risk factors for readmissions have focused on single group of risk factors, were limited to 30-day readmissions, or did not account for competing risk of mortality. This study investigates the biological, socio-economic, and behavioural risk factors predicting hospital readmissions while accounting for the competing risk of mortality. In this prospective cohort study, we recruited 250 patients hospitalized with symptoms of advanced heart failure [New York Heart Association (NYHA) Class III and IV] between July 2017 and April 2019. We analysed their baseline survey data and their hospitalization records over the next 4.5years (July 2017 to January 2022). We used a joint-frailty model to determine the multifactorial risk factors for all-cause and unplanned hospital readmissions and mortality. At the time of recruitment, patients' mean (SD) age was 66 (12) years, majority being male (72%) and NYHA class IV (68%) with reduced ejection fraction (72%). 87% of the patients had poor self-care behaviours, 51% had diabetes and 56% had weak grip strength. Within 2years of a hospital admission, 74% of the patients had at least one readmission. Among all readmissions during follow-up, 68% were unplanned. Results from the multivariable regression analysis shows that the independent risk factors for hospital readmissions were biologic-weak grip strength [hazard ratio (95% CI): 1.59 (1.06, 2.13)], poor functional status [1.79 (0.98, 2.61)], diabetes [1.42 (0.97, 1.86)]; behavioural-poor self-care [1.66 (0.84, 2.49)], and socio-economic-preference for maximal life extension at high cost for those with high education [1.98 (1.17, 2.80)]. Risk factors for unplanned hospital readmissions were similar. A higher hospital readmission rate increased the risk of mortality [1.86 (1.23, 2.50)]. Other risk factors for mortality were biologic-weak grip strength [3.65 (0.57, 6.73)], diabetes [2.52 (0.62, 4.42)], socio-economic-lower education [2.45 (0.37, 4.53)], and being married [2.53 (0.37, 4.69)]. Having a private health insurance [0.40 (0.08, 0.73)] lowered the risk for mortality. Risk factors for hospital readmissions and mortality are multifactorial. Many of these factors, such as weak grip strength, diabetes, poor self-care behaviours, are potentially modifiable and should be routinely assessed and managed in cardiac clinics and hospital admissions.

Prognostic impact of chronic obstructive pulmonary disease in patients with heart failure with mildly reduced ejection fraction

BackgroundThe aging population has led to a significant increase in heart failure (HF) patients. Related to demographic changes, the burden with comorbidities was shown to increase in patients with HF. Whereas chronic obstructive pulmonary disease (COPD) was yet demonstrated to be associated with adverse outcomes in patients with HF, the prognostic impact of COPD in HF with mildly reduced ejection fraction (HFmrEF) has not yet been clarified. ObjectiveThe study investigates the prognostic impact of COPD in patients hospitalized with HFmrEF. MethodsConsecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Patients with COPD were compared to patients without with regard to the primary endpoint all-cause mortality at 30 months (median follow-up). Secondary endpoints comprised in-hospital mortality, HF-related re-hospitalization, cardiac re-hospitalization and major adverse cardiac and cerebrovascular events (MACCE) at 30 months. ResultsA total of 2184 patients with HFmrEF were included with a prevalence of COPD of 12.0 %. Patients with COPD were older (median 77 vs. 75 years; p = 0.025), had increased burden of cardiovascular comorbidities and more advanced HF symptoms. At 30 months, patients with COPD had an increased risk of all-cause mortality compared to patients without (45 % vs. 30 %; HR = 1.667; 95 % CI 1.366–2.034; p = 0.001), alongside with a higher risk of re-hospitalization for worsening HF (20 % vs. 12 %; HR = 1.658; 95 % CI 1.218–2.257; p = 0.001). ConclusionCOPD is independently associated with adverse outcomes in patients hospitalized with HFmrEF.

Weak grip strength predicts higher unplanned healthcare utilization among patients with heart failure.

Frailty increases healthcare utilization and costs for patients with heart failure but is challenging to assess in clinical settings. Hand grip strength (GS) is a single-item measure of frailty yet lacks evidence as a potential screening tool to identify patients at risk of higher unplanned events and related healthcare costs. We examined the association of baseline and longitudinal GS measurements with healthcare utilization and costs among patients with advanced heart failure. Between July 2017 and April 2019, we enrolled 251 patients with symptoms of advanced heart failure (New York Heart Association class III or IV) in a prospective cohort study in Singapore. We measured GS at baseline and every 4months for 2years and linked patients' survey data with their medical and billing records. We categorized patients as having weak GS if their GS measurement was below the 5th percentile of the age- and gender-specific normative GS values in Singapore. We assessed the association between baseline GS and healthcare utilization (unplanned and planned events and healthcare costs, total costs, and length of inpatient stay) over the next 2years using regression models. We investigated the association between longitudinal 4-monthly GS assessments and the ensuing 4months of healthcare utilization and costs using mixed-effects logistic and two-part regression models. At baseline, 22.5% of patients had weak GS. Baseline and longitudinal GS measurements were significantly associated with longer length of inpatient stay, greater likelihood of unplanned events, and higher related costs. Patients with weak GS had higher odds of an unplanned event occurring by 8 percentage points [95% confidence interval (CI) (0.01, 0.14), P=0.026], incurred longer inpatient stays by 4days [95% CI (1.97, 6.79), P=0.003], and additional SG$ 4792 [US$~3594, 95% CI (1894, 7689), P=0.014] in unplanned healthcare costs over the next 4months. GS is a simple tool to identify and monitor heart failure patients at risk of unplanned events, longer inpatient stays, and higher related healthcare costs. Findings support its routine use in clinical settings.

The prognostic value of low-flow in severe aortic stenosis patients undergoing TAVI - should we follow the flow?

Abstract Funding Acknowledgements Type of funding sources: None. Background Low-flow conditions are associated with higher mortality after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (SAS). Two parameters have been described to determine low-flow status – although the most currently used is stroke volume index, transaortic flow rate (FR – stroke volume divided by left ventricle ejection time) was recently suggested as being superior, as it more closely reflects valvular resistance. Purpose Determine the prognostic impact of low-flow conditions in survival of patients undergoing TAVI for SAS, using low-FR and low-SVi definitions. Methods A database comprising all patients treated with TAVI between 2011 and 2019 in a single-centre was retrospectively analyzed, and cases with echocardiograms performed before intervention in our centre were included. Low-flow patients were defined according to a basal FR&amp;lt;200mL/s or SVi&amp;lt;35mL/m2, and compared with normal counterparts. The prognostic impact of flow was tested using Kaplan-Meier curves, log-rank test and Cox proportional hazard model adjusted for EuroSCORE II, using FR or SVi both as categorical and continuous variables. A subsequent analysis compared patients with preserved and reduced ejection fraction (EF, &amp;lt;52%). Primary endpoint was defined as time to all-cause mortality or last follow-up over the five years after TAVI. Results Of 657 TAVI performed, 490 (74.6%) patients were included in the present analysis, over a median follow-up of 56 months. Of these, 59.6% presented low-FR, and 43.3% had low-SVI. Low-flow patients, using each definition, were of higher estimated surgical risk (EuroSCORE and STS), presented a more advanced NYHA class, had a worse estimated creatinine clearance, and more frequently had coronary disease. Additionally, low-FR patients were older and more frequently female. Atrial fibrillation was more common in low-SVi cases. Echocardiographic studies revealed a lower functional aortic valve area in low-flow cases, and low-SVi was associated with lower transaortic gradients, and lower EF before and after TAVI. Low-FR before TAVI was associated with higher mortality over follow-up [Hazard Ratio (HR) 1.43 (1.06–1.92), p = 0.019)], even after adjusting for EuroSCORE II [HR 1.39 (1.03–1.90), p = 0.034], which was not observed for low-SVi (p = 0.06 and p = 0.2 for uni- and multivariable analysis, respectively). When analyzing FR and SVi as continuous variables, a higher SVi, but not FR, was associated with improved survival [HR 0.98 (0.97–1.00), p = 0.018; HR 0.99 (0.97–1.00), p = 0.044 for uni- and multivariable analysis, respectively). When stratifying by preserved or reduced EF, both FR and SVi did not predict mortality. Conclusions About half of SAS patients undergoing TAVI present with a low-flow condition, which is frequently associated with more advanced heart failure symptoms and higher estimated surgical risk. Low-FR negatively impacts survival after intervention. SVi is also prognostic, but not at a &amp;lt;35ml/s cut-off.

Clinical characteristics, etiological profile, treatment and long term outcomes in patients with non ischemic systolic heart failure; Himachal Pradesh heart failure registry (HP–HF registry)

BackgroundThe data on clinical characteristics, treatment practices and out comes in patients with Non- ischemic Systolic Heart Failure (NISHF) is limited. We report clinical characteristics, treatment and outcomes in patients with NISHF. Methods1004 patients with NISHF were prospectively enrolled and their demographics, clinical characteristics, and treatment were recorded systematically. Patients were followed annually for a median of 3 years (1 year to 8 years) for allcause death, major adverse cardiovascular events (MACE); composite of all-cause death, hospitalization of heart failure, and or for stroke. ResultsPatients of NISHF were middle-aged (58.8±16.2 years) population with severely depressed left ventricular ejection fraction (29.3±7.02%) and 31.1% had symptoms of advanced Heart failure. Hypertension (43.6%), obesity and or overweight (28.0%), Diabetes (15.0%), and valvular heart disease (11.8%) were the common risk factors. The guideline directed medical treatment was prescribed in more than 80% of the study cohort. Incidence of all cause death and MACE was 7 (6.8, 8.8) per 100 person years and 11(10, 13) per 100 person years respectively. The cumulative incidence of deaths and MACE was 35% (30%, 40%) and 49% (44%, 53%) at 8 years of follow-up. ConclusionsPatients of NISHF were middle-aged population with severely depressed LV systolic function with significant incident morbidity and mortality. Early detection of risk factors and their risk management and enhancing the use of guideline directed treatment may improve the outcomes. Keywords: Non-ischemic systolic heart failure, risk factors, outcomes, guideline directed treatment.

635 AMYLOIDOSIS AND THE ILE68LEU MUTATION OF THE TTR GENE: A RARE DISEASE YOU CAN TREAT.

Abstract Case presentation During the last year, a 66-year-old man was repetitively hospitalized for anasarcatic heart failure in an infiltrative heart disease with an impaired left ventricular function. In March 2022 the patient first presented to our emergency department with clinical signs of decompensated heart failure. An accurate diagnosis was made during the inpatient care. The electrocardiogram documented sinus bradycardia, degree I atrioventricular block, and right bundle branch block. Echocardiography showed a slight reduction in biventricular function, concentric hypertrophy and a significant reduction in longitudinal systolic function (GLS -11.8%) with an apical-sparing pattern. At the same time, the presence of mild to moderate circumferential pericardial effusion was documented. According to the clinical suspicion, a cardiac MRI was performed, revealing consistent amyloid infiltrative disease. A 99-mTc-HDP myocardial scintigraphy confirmed pathological accumulation of trans-thyretine with a Perugini Score 2. Serum and urinary immunofixation were negative. A genetic test was subsequently performed whereby a heterozygous Ile68Leu (p.Ile88Leu) pathogenic mutation in the TTR gene was documented. Follow-up neurologic evaluation ruled out the indication to start Patisiran therapy due to the absence of significant neurologic involvement. In the meantime, the patient was put on Torasemide therapy with moderate clinical benefit. Few months ago, shortly after the diagnosis, the patient was hospitalized again for anasarcatic heart failure complicated by a severe ascites, underwent a paracentesis. During this hospitalization, therapy with Tafamidis was started. The patient is currently in good cardiovascular clinical compensation. Discussion This clinical case offers the chance to investigate the characteristics and phenotype of cardiac amyloidosis caused by the Ile68Leu mutation. The typical Ile68Leu ATTRm patient is caucasian, tipically a 70 years’man (slightly younger than ATTRwt fenotipe), seeks medical attention with heart failure symptoms, and receives the correct diagnosis of cardiac amyloidosis almost 1 year after the onset of these symptoms. Usually, the mutation leads to predominantly cardiac manifestations, instead of a combined form (cardiac and/or neurological manifestations). The Ile68Leu TTR mutation is a cause of cardiac amyloidosis that leads to a phenotype similar to ATTRwt. The electrocardiogram and echocardiogram features described in the clinical case are typical and often indistinguishable from that of ATTRwt. The age at diagnosis and advanced heart failure symptoms at presentation were the only factors independently associated with mortality. The subject patient is younger than the average affected ones and suffers from an aggressive form of the disease. The take home message could be that we should definitely learn and remember the importance of etiologic screening in infiltrative diseases, especially in young people, now that there are effective therapies capable to reduce mortality and improve quality of life.

900 PREDICTORS OF OUTCAMES IN PATIENTS WITH MITRAL REGURGITATION UNDERGOING PERCUTANEOUS VALVE REPAIR

Abstract Aims Mitral regurgitation is the second-most frequent VHD in Europe. According to the latest ESC Guidelines, transcatheter edge-to-edge repair (TEER) was included as a treatment option in patients with severe symptomatic MR at high risk for surgery (Class IIb recommendation) for primary MR and a Class IIa recommendation for secondary MR. We sought to investigate predictors of clinical outcome in patients with mitral regurgitation undergoing percutaneous valve repair. Methods and Results The MITRA-UMG study, a single-center registry, retrospectively collected consecutive patients with symptomatic moderate-to-severe or severe MR undergoing MitraClip therapy between March 2012 to October 2021 at Magna Graecia University. Clinical, echocardiographic and procedural data were collected and compared with post procedural outcomes. Procedural success was defined as successful implantation of one or more clip(s) with a post-procedure reduction of MR of 2 + or less at discharge. The primary endpoint was the composite of cardiovascular death or rehospitalization for heart failure. The median follow-up was 456 days (IQR 372–1130 days) with a complete 1-year follow- up in 188 of 200 (97%) patients. A functional aetiology was classified in 75% of patients. Procedural success was obtained in 98% of patients. The composite primary endpoint of cardiovascular death or rehospitalization for HF was met in 77 patients (36%) with cumulative incidences of 7% at 30 days and 25% at 1 year. In the Cox multivariate model, NYHA functional class and left ventricular end-diastolic volume index (LVEDVi), independently increased the risk of the primary endpoint at long-term follow-up. At Kaplan–Meier analysis, a LVEDVi &amp;gt; 92 ml/m2 was associated with an increased incidence of the primary endpoint (HR 3.55, 95%CI [2.03, 6.18], P&amp;lt;0.0001) (Figure). Conclusions In this study, patients presenting with dilatated ventricles (LVEDVi &amp;gt; 92 ml/m2) and advanced heart failure symptoms (NYHA IV) carried the worst prognosis after TEER.

Is Maintenance of Sinus Rhythm of Value in Patients with Atrial Fibrillation and Heart Failure?

Heart failure (HF) and atrial fibrillation (AF) frequently co-exist, with the prevalence of AF increasing in patients with more advanced HF symptoms. When present, AF increases morbidity and mortality in patients with HF. The purpose of this review is to examine emerging evidence addressing the value of restoration and maintenance of sinus rhythm in patients with HF. Earlier trials comparing a rhythm control strategy with antiarrhythmic drugs have failed to demonstrate benefit in patients with HF and reduced ejection fraction. More recent trials, including the recently published RAFT-AF, utilizing catheter ablation for rhythm control, have shown greater promise, possibly due to reduced medication-related side effects and higher efficacy in maintaining sinus rhythm. A strategy of sinus rhythm maintenance with catheter ablation appears to improve mortality, reduce HF events and improve quality of life in patients with AF and HF.

Transcatheter Mitral Valve Repair in Patients With Atrial Functional Mitral Regurgitation

BackgroundAmong patients with severe functional mitral regurgitation (FMR), atrial functional mitral regurgitation (aFMR) represents an underrecognized entity. Data regarding outcomes after mitral valve transcatheter edge-to-edge repair (M-TEER) in aFMR remain scarce. ObjectivesThe objective of this study was to analyze the outcome of aFMR patients undergoing M-TEER. MethodsUsing patients from the international EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry undergoing M-TEER for FMR, the authors analyzed baseline characteristics and 2-year outcomes in aFMR in comparison to non-aFMR and ventricular FMR. Additionally, the impact of right ventricular dysfunction (RVD) (defined as right ventricular to pulmonary artery uncoupling) on outcome after M-TEER was assessed. ResultsAmong 1,608 FMR patients treated by M-TEER, 126 (7.8%) were categorized as aFMR. All 126 aFMR patients had preserved left ventricular function without regional wall motion abnormalities, left arterial dilatation and Carpentier leaflet motion type I. Procedural success (defined as mitral regurgitation ≤2+ at discharge) was 87.2% (P < 0.001) and New York Heart Association (NYHA) functional class significantly improved during follow-up (NYHA functional class III/IV: 86.5% at baseline to 36.6% at follow-up; P < 0.001). The estimated 2-year survival rate in aFMR patients was 70.4%. Two-year survival did not differ significantly between aFMR, non-aFMR, and ventricular FMR. Besides NYHA functional class IV, RVD was identified as a strong independent predictor for 2-year survival (HR: 2.82 [95% CI: 1.24-6.45]; P = 0.014). ConclusionsaFMR is a frequent cause of FMR and can be effectively treated with M-TEER to improve symptoms at follow-up. Advanced heart failure symptoms and RVD were identified as important risk factors for survival in aFMR patients.

Changing Demographics in Hypertrophic Cardiomyopathy and Implications for Management: Clinical Research

PurposeThis study aimed to determine whether clinicians are encountering a phenotype of hypertrophic cardiomyopathy that is evolving from the disease recognized several years ago. MethodsA total of 3161 consecutive patients with established hypertrophic cardiomyopathy were encountered (2003-2020) and studied clinically with imaging. ResultsPatients were identified as progressively older now (average 56 ± 15 years) compared with previously (44 ± 17 years; P < .001), and with an increasing frequency of outflow obstruction (from 46% to 61% of patients; P < .001), albeit without more advanced heart failure symptoms. Notably, maximum left ventricular wall thickness (usually ventricular septum) decreased progressively over the same period (20.4 ± 5.7 to 17.5 ± 3.4 mm). ConclusionsThese novel observations are counter-intuitive to practitioners (expecting hypertrophic cardiomyopathy to be associated with particularly substantial hypertrophy), and potentially impact disease recognition, while also highlighting emergence of symptomatic obstructive patients with mild septal thickness < 15 mm, requiring modification of the traditional myectomy operation. While a primary change in the phenotypic expression of hypertrophic cardiomyopathy cannot be excluded by our data, these observations most likely reflect evolving referral practice patterns including greater diagnostic suspicion for the disease in the community particularly at advanced ages, and/or with less substantial left ventricular hypertrophy.

Right Ventricular Function Improves Early After Percutaneous Mitral Valve Repair in Patients Suffering From Severe Mitral Regurgitation.

BackgroundPercutaneous mitral valve edge-to-edge procedure (PMVR) using the MitraClip® system (Abbot Vascular, CA) is an established therapy for severe mitral regurgitation (MR) in patients judged inoperable or at high surgical risk. Besides determining exercise capacity, right ventricular (RV) function has prognostic value in heart failure and after cardiac surgery. We therefore investigated the impact of PMVR on RV function in patients with severe MR.Methods and ResultsSixty-three patients undergoing PMVR at our department were prospectively enrolled. Transthoracic echocardiography was performed before, early (2–12d) after PMVR and after 3 months, including advanced echocardiographic analyses such as 3D imaging and strain analyses. At baseline, all patients presented with advanced heart failure symptoms. Etiology of MR was more often secondary and, if present, left ventricular (LV) dysfunction was predominantly caused by ischemic cardiomyopathy. PMVR substantially reduced MR to a grade ≤ 2 in most patients. Echocardiographic assessment revealed a largely unchanged LV systolic function early after PMVR, while in contrast RV function substantially improved after PMVR [3D RV EF (%): pre 33.7% [27.4; 39.6], post 40.0% [34.5; 46.0] (p < 0.01 vs. pre), 3 months 42.8% [38.3; 48.1] (p < 0.01 vs. pre); 2D RV GLS (%): pre −12.9% [−14.5; −10.5], post −16.0% [−17.9; −12.6] (p < 0.01 vs. pre), 3 months −17.2% [−21.7; −14.9] (p < 0.01 vs. pre)]. Factors that attenuated RV improvement were larger ventricular volumes, lower LV function, secondary MR, and a higher STS score (all p < 0.05).ConclusionBy using advanced echocardiographic parameters, we discovered an early improvement of RV function after PMVR that is preserved for months, independent from changes in LV function. Improvement of RV function was less pronounced in patients presenting with an advanced stage of heart failure and a higher burden of comorbidities reflected by the STS score.

Current and Future Challenges in Mechanical Circulatory Support

The field of left ventricular assist devices (LVADs) has transitioned from older, bulkier devices which provided short-term life prolongation in severe heart failure, to newer generation continuous-flow devices which are small in profile, with fewer moving parts and greater durability. These devices have provided meaningful life prolongation in a manner similar to heart transplantation even for those deemed ineligible for such an approach, a paradigm referred to as destination therapy. a) Clinical confidence in the therapy: Most practitioners do not recognize that the latest generation HeartMate 3 LVAD, provides 80% 2-year survival, dramatically improves quality of life and is now cost-effective even as destination therapy. Thus, we need to ensure that clinicians are provided the knowledge to communicate effectively with their peers and patients. In this regard, development of individualized risk scores may be necessary. b) Timely referral for LVAD therapy: Late referral of patients with symptoms of advanced heart failure remains a critical challenge. A simple rule of 3 should be used and this includes a) repetitive hospitalizations for heart failure, b) staircase diuretic requirements over time (e.g., an increase of oral loop diuretic therapy by 50% in the preceding 6 months), and c) intolerance to neurohormonal therapy with onset of cardio-renal perturbation. Those with moderate-severe secondary mitral regurgitation ineligible for a percutaneous mitral valve transcatheter edge to edge repair (or those implanted with a MitraClip who remain ill without improvement in heart failure) and non-responders to cardiac resynchronization therapy should also be referred for management at centers specializing in advanced heart failure therapeutics. c) Need for continued innovation in LVAD therapy: Newer technology that can promote recovery, provide freedom from external cables, use biocompatible surfaces to reduce need for anticoagulation, and physiologically responsive to demands of an active lifestyle is needed. In summary, the future of LVAD therapy is bright but we must not only pursue innovative engineering but also focus on clinical implementation to provide such therapy to advanced heart failure patients in a timely manner. The field of left ventricular assist devices (LVADs) has transitioned from older, bulkier devices which provided short-term life prolongation in severe heart failure, to newer generation continuous-flow devices which are small in profile, with fewer moving parts and greater durability. These devices have provided meaningful life prolongation in a manner similar to heart transplantation even for those deemed ineligible for such an approach, a paradigm referred to as destination therapy. a) Clinical confidence in the therapy: Most practitioners do not recognize that the latest generation HeartMate 3 LVAD, provides 80% 2-year survival, dramatically improves quality of life and is now cost-effective even as destination therapy. Thus, we need to ensure that clinicians are provided the knowledge to communicate effectively with their peers and patients. In this regard, development of individualized risk scores may be necessary. b) Timely referral for LVAD therapy: Late referral of patients with symptoms of advanced heart failure remains a critical challenge. A simple rule of 3 should be used and this includes a) repetitive hospitalizations for heart failure, b) staircase diuretic requirements over time (e.g., an increase of oral loop diuretic therapy by 50% in the preceding 6 months), and c) intolerance to neurohormonal therapy with onset of cardio-renal perturbation. Those with moderate-severe secondary mitral regurgitation ineligible for a percutaneous mitral valve transcatheter edge to edge repair (or those implanted with a MitraClip who remain ill without improvement in heart failure) and non-responders to cardiac resynchronization therapy should also be referred for management at centers specializing in advanced heart failure therapeutics. c) Need for continued innovation in LVAD therapy: Newer technology that can promote recovery, provide freedom from external cables, use biocompatible surfaces to reduce need for anticoagulation, and physiologically responsive to demands of an active lifestyle is needed. In summary, the future of LVAD therapy is bright but we must not only pursue innovative engineering but also focus on clinical implementation to provide such therapy to advanced heart failure patients in a timely manner.

Left Atrial Strain is an Independent Determinant of Exercise Capacity in Hypertrophic Cardiomyopathy

Aims: The objective was to evaluate the potential contribution of left atrial (LA) function to reduced exercise capacity in patients with hypertrophic cardiomyopathy (HCM).Methods and results: Using a case-control design we randomly selected 95 patients with confirmed HCM based on guidelines criteria and without permanent atrial arrhythmia who underwent a treadmill exercise test. We measured echo-based left ventricular (LV) and LA morphology and function including mechanics using 2D speckle tracking. Preserved exercise capacity was defined as the 25 th percentile of metabolic equivalents (METs) or > 7 METs. Of 95 HCM patients, 36 had reduced exercise capacity (£7 METs) and 59 had preserved exercise capacity (>7 METs). Reduced exercise capacity patients were more likely to be older, female, had higher BMI, and more advanced heart failure symptoms. They also had a higher E/e’ ratio and lower LA reservoir and conduit strain but similar left ventricular outflow tract (LVOT) pressure gradients. By univariate analysis, LA reservoir and conduit strain, age, gender, BMI, NYHA class, and E/e’ correlated with METs. In multivariate analysis, LA conduit strain independently determined METs after adjusting for age, gender, BMI, NYHA and E/e’ (standardized coefficients 0.17, P=0.04). This relationship was primarily noted in non- and labile-obstructive but not in obstructive HCM. History of atrial fibrillation did not impact the association of LA strain with exercise capacity.Conclusion : Even after adjusting for LVOT gradients and diastolic function, reduced LA conduit strain is an independent determinant of exercise tolerance in HCM.

Abstract 12535: The Hemodynamic Response to Exercise in Patients With Obstructive Hypertrophic Cardiomyopathy and the Effect of Metoprolol

Introduction: Patients with obstructive hypertrophic cardiomyopathy (HCM) frequently experience advanced heart failure symptoms at low levels of physical activity. The relationship between symptoms and loading conditions during exercise is incompletely understood. Whether standard treatment with beta-blockers affects exercise hemodynamics is unknown. Objectives: The aim of this study was to investigate the invasive hemodynamic response to exercise in moderately symptomatic patients with obstructive HCM, and how treatment with metoprolol affects this response. Method: This double-blinded, placebo-controlled, randomized crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥ II from May 2018 to September 2020. Patients received metoprolol or placebo for two consecutive two-week periods in random order. During each treatment period, patients underwent right-heart catheterization at rest and during exercise. The primary outcome was the difference in pulmonary capillary wedge pressure (ΔPCWP) between peak exercise and rest. Results: There was no treatment effect on Δ PCWP between metoprolol and placebo treatment (21(9) mmHg versus 23(9) mmHg; p = 0.12). When comparing metoprolol to placebo treatment, there was no significant difference in PCWP at rest (15 (6) mmHg versus 13 (5) mmHg; p = 0.06) or at peak exercise (35 (12) mmHg versus 37 (10) mmHg; p = 0.38). At peak exercise, metoprolol treatment was associated with a higher stroke volume (101 (24) ml versus 92 (21) ml; p &lt; 0.01), a 25% lower heart rate (107 (19) beats/min versus 139 (23) beats/min; p &lt; 0.0001), and subsequently a lower cardiac output (10.8 (3.3) L/min versus 12.8 (3.2) L/min; p &lt; 0.0001). Conclusion: Exercise in patients with obstructive HCM is associated with a severe increase in left-sided filling pressures which are not affected by metoprolol treatment. Despite increased stroke volume during metoprolol treatment, cardiac output is reduced at peak exercise.