Advanced Heart Failure Symptoms Research Articles

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.

Successful aortic arch cannulation and perfusion of a heart donated after circulatory death: A case report.

We describe successful aortic arch cannulation and perfusion of a heart donated after circulatory death using the Transmedics Organ Care System™. A 47-year old man developed advanced heart failure symptoms after prior mustard operation for transposition of the great arteries. He matched a DCD-donor and required an elongated aorta for implantation due to his altered anatomy. The donor heart was retrieved and successfully perfused via aortic arch cannulation for 4.5h with satisfactory perfusion parameters. Although Transmedics advises against aortic arch cannulation due to concerns regarding malperfusion, satisfactory and safe perfusion can be achieved by careful positioning of the heart. Awareness and attention to the occurrence of malperfusion is mandatory, especially during transport, to achieve satisfactory outcome. Aortic arch cannulation is feasible without compromising quality of perfusion. This is relevant for patient that require an elongated aorta after surgically corrected congenital heart disease.

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<200mL/s or SVi<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, <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 <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 > 92 ml/m2 was associated with an increased incidence of the primary endpoint (HR 3.55, 95%CI [2.03, 6.18], P<0.0001) (Figure). Conclusions In this study, patients presenting with dilatated ventricles (LVEDVi > 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.

The first 200 septal myectomies: Ensuring gold standard outcomes.

Septal myectomy remains the gold standard treatment for symptomatic left ventricular outflow tract obstruction refractory to medical treatment. It is recommended that this operation be performed in dedicated hypertrophic obstructive cardiomyopathy centres by experienced surgeons. The septal myectomy option remains unavailable to many patients based solely on geography, including those who would clearly benefit more substantially from surgery than other therapeutic options. Here, we share our experience in starting new hypertrophic cardiomyopathy programmes. We retrospectively reviewed initial septal myectomy experiences at two hypertrophic cardiomyopathy programmes starting in 2014. Two-hundred septal myectomies were performed. Mean age was 58.8 years and 51% were females. Advanced heart failure symptoms were present in 95.5% of patients and 23.5% had experienced syncope. Mean maximal intraventricular gradient was 89 mmHg and 48.5% underwent concomitant procedures at the time of septal myectomy. There was no perioperative (in-hospital or 30 days) mortality. Ninety-two per cent had provoked left ventricular gradients of ≤ 15 mmHg and 97% had none/mild mitral regurgitation at post-operative assessment. In our contemporary cohort, there were 2 (1%) intraoperative ventricular septal defects and 5% required a permanent pacemaker. Our early septal myectomy experience targeted a complex population, frequently in need of concomitant procedures. Abolition of left ventricular obstruction and resolution of systolic anterior motion mediated mitral regurgitation can be expected. The safety and efficacy of septal myectomy carried at hypertrophic cardiomyopathy centres by properly trained surgeons achieved the desired outcomes established by recent hypertrophic cardiomyopathy guidelines.

Surgical management of diastolic heart failure after septal myectomy for obstructive hypertrophic cardiomyopathy.

ObjectiveSome patients with obstructive hypertrophic cardiomyopathy may remain limited after surgical relief of the subaortic obstruction. In this report, we describe experience in surgical management of patients with advanced diastolic heart failure symptoms after adequate transaortic septal myectomy for obstructive hypertrophic cardiomyopathy.MethodsWe identified adult patients who presented with heart failure symptoms after previous transaortic septal myectomy for obstructive hypertrophic cardiomyopathy and underwent repeat sternotomy for transapical myectomy to enlarge a small left ventricular cavity. Functional recovery after hospital dismissal was assessed through a questionnaire-based survey.ResultsSix patients with previous septal myectomy presented with New York Heart Association functional class III symptoms. Preoperative transthoracic Doppler echocardiography confirmed adequate relief of subaortic outflow tract obstruction with only trivial or mild mitral valve regurgitation; left atrial volume index was increased at 46 mL/m2 (range, 44-47 mL/m2). Following transapical myectomy, the left ventricular diameter was enlarged from 23 mm (range, 21-27 mm) to 29 mm (range, 27-31 mm) at end-systole and from 40 mm (range, 38-42 mm) to 43 mm (range, 42-50 mm) at end-diastole. All the patients were alive after a median follow-up of 0.6 years (range, 0.4-3.5 years), and 5 patients responded to a postoperative survey and indicated improvement in their heart condition compared with functional status before the repeat myectomy.ConclusionsPatients with diastolic heart failure after septal myectomy for obstructive hypertrophic cardiomyopathy may present with systolic cavity obliteration due to excessive myocardial hypertrophy. Repeat transapical myectomy can enlarge the left ventricular chamber and augment the diastolic volume, which results in improved physical capacity and patient-perceived functional status.

Paediatric mitral valve disease - from presentation to management

Mitral valve diseases are relatively rare in the paediatric population; however, they can cause considerable mortality and morbidity worldwide. Acquired causes are a major contributor to cardiovascular disease burden in the paediatric population. Diseases can be detected before birth, at birth, or when the child is older and presents with symptoms of advanced heart failure. Definitive management consists of surgical intervention, with mitral valve replacement being the gold standard.Conclusion: Repair has been gaining popularity; however, its outcomes require further study. Percutaneous mitral balloon valvuloplasty is an emerging technique which holds promise as a bridge to surgical treatment. The effect of these interventions on quality of life must be emphasised and requires further study. What is Known: • The epidemiology of mitral valve disease in the paediatric population- predominant causes include rheumatic disease and congenital defects. • Mitral valve repair and replacement are the standard treatment methods for paediatric mitral valve disease. What is New: • Emergence of percutaneous mitral valve interventions and their potential as bridge-to-surgery or definitive treatment in high-risk surgical candidates. • Recent evidence comparing mitral valve repair and replacement in the paediatric population demonstrates increasing popularity of repair techniques.

Clinical performance and exercise hemodynamics in patients with severe secondary tricuspid regurgitation and chronic atrial fibrillation

ObjectiveThe study aimed to investigate the functional capacity and hemodynamics at rest and during exercise in patients with chronic atrial fibrillation and severe functional symptomatic tricuspid regurgitation (AF-FTR).BackgroundSymptoms and clinical performance of severe AF-FTR mimic the population of patients with heart failure with preserved ejection fraction (HFpEF). Severe AF-FTR is known to be associated with an adverse prognosis whereas less is reported about the clinical performance including exercise capacity and hemodynamics in patients symptomatic AF-FTR.MethodsRight heart catheterization (RHC) at rest and during exercise was conducted in a group of patients with stable chronic AF-TR and compared with a group of patients with HFpEF diagnosed with cardiac amyloid cardiomyopathy (CA). All patients had preserved ejection fraction and no significant left-sided disease.ResultsPatients with AF-FTR demonstrated a low exercise capacity that was comparable to CA patients (TR 4.9 ± 1.2 METS vs. CA 4. 7 ± 1.5 METS; P = 0.78) with an average peak maximal oxygen consumption of 15 mL/min/kg. Right atrium pressure increased significantly more in the AF-FTR patients as compared to CA patients at peak exercise (25 ± 8 vs 19 ± 9, p < 0.01) whereas PCWP increased significantly to a similar extent in both groups (31 ± 4 vs 31 ± 8 mmHg, p = 0.88). Cardiac output (CO) was significantly lower among AF-FTR at rest as compared to CA patients (3.6 ± 0.9 vs 4.4 ± 1.3 l/min; p < 0.05) whereas both groups demonstrated a poor but comparable CO reserve at peak exercise (7.3 ± 2.9 vs 7.9 ± 3.8 l/min, p = 0.59).ConclusionsAF-FTR contributes to the development of advanced heart failure symptoms and poor exercise capacity reflected in increased atrial filling pressures, reduced cardiac output at rest and during exercise sharing common features seen in HFpEF patients with other etiologies.