Severe Heart Failure Symptoms Research Articles

Psychosocial predictors of health behavior adherence in heart-failure patients with comorbid depression: a secondary analysis of the Hopeful Heart trial

BackgroundDepression affects 20–30% of individuals with heart failure (HF), and it is associated with worse health outcomes independent of disease severity. One potential explanation is the adverse impact of depression on HF patients’ adherence to the health behaviors needed to self-manage their condition. The aim of this study is to identify characteristics associated with lower adherence in this population, which could help to recognize individuals at higher risk and eventually tailor health behavior interventions to their needs.MethodsUsing data from a randomized, controlled, collaborative care treatment trial in 629 patients with HF and comorbid depression, we performed mixed effects logistic regression analyses to examine the cross-sectional and prospective relationships between medical and psychosocial variables and health behavior adherence, including adherence to medications, a low-sodium diet, and physician appointments.ResultsIn cross-sectional analyses, married marital status and higher physical health-related quality of life (HRQoL) were associated with greater overall adherence (compared to married, single Odds Ratio [OR] = 0.46, 95% Confidence Interval [CI] = 0.26–0.80; other OR = 0.60, CI = 0.38–0.94; p = .012. Physical HRQoL OR = 1.02, CI = 1.00-1.04, p = .047). Prospectively, greater levels of social support were associated with improved overall adherence one year later (OR = 1.04, 95% CI = 1.00-1.08, p = .037). Social support, HF symptom severity, race and ethnicity, and age were predictors of specific types of adherence. Neither depression nor optimism was significantly associated with adherence outcomes.ConclusionsThese results provide important preliminary information about risk factors for poor adherence in patients with both HF and depression, which could, in turn, contribute to the development of interventions to promote adherence in this high-risk population.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT02044211; registered 1/21/2014.

The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association.

Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often present late in their disease course with severe right-sided heart failure, pulmonary hypertension, and life-limiting symptoms that have few durable treatment options. Traditionally, the only treatment for tricuspid valve disease has been medical therapy or surgery; however, there have been increasing interest and success with the use of transcatheter tricuspid valve therapies over the past several years to treat patients with previously limited therapeutic options. The tricuspid valve is complex anatomically, lying adjacent to important anatomic structures such as the right coronary artery and the atrioventricular node, and is the passageway for permanent pacemaker leads into the right ventricle. In addition, the mechanism of tricuspid pathology varies widely between patients, which can be due to primary, secondary, or a combination of causes, meaning that it is not possible for 1 type of device to be suitable for treatment of all cases of tricuspid valve disease. To best visualize the pathology, several modalities of advanced cardiac imaging are often required, including transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, to best visualize the pathology. This detailed imaging provides important information for choosing the ideal transcatheter treatment options for patients with tricuspid valve disease, taking into account the need for the lifetime management of the patient. This review highlights the important background, anatomic considerations, therapeutic options, and future directions with regard to treatment of tricuspid valve disease.

Resection of hypertrophic papillary muscles and mitral valve replacement in a patient with midventricular hypertrophic obstructive cardiomyopathy – a new approach

Midventricular hypertrophic obstructive cardiomyopathy (HOCM) is characterized by hypertrophy of the interventricular septum (IVS) and - in rare cases - of the papillary muscles (PM), which subsequently can cause dynamic left ventricular outflow tract obstruction (LVOTO) and severe heart failure symptoms. We report on a rare case of a 44-year-old patient suffering from midventricular HOCM with hypertrophic anterolateral PM and an additional chorda between the PM and the IVS.We describe a new surgical approach via right anterolateral thoracotomy in 3-dimensional (3D) video-assisted minimal-invasive technique with resection of hypertrophic PMs as well as the entire mitral valve-apparatus and valve replacement avoiding septal myectomy and potentially associated complications. After an uneventful procedure clinical symptoms improved from NYHA III-IV at baseline to NYHA 0-I postoperatively and remained stable over a follow-up period of 24 months. Therefore, the presented technique may be considered as a new and alternative approach in patients with hypertrophic PMs and hypertrophic IVS as subtype of midventricular HOCM.

Vutrisiran (Amvuttra)


 CADTH recommends that Amvuttra be reimbursed by public drug plans for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin-mediated (hATTR) amyloidosis if certain conditions are met.
 Amvuttra should only be covered to treat adults with stage 1 or stage 2 genetically confirmed hATTR amyloidosis with polyneuropathy (hATTR-PN) who are symptomatic with early-stage neuropathy, do not have severe heart failure symptoms, and have not had a liver transplant. A patient’s response to treatment with Amvuttra should be assessed at least every 6 months to determine whether they would benefit from continued treatment. Treatment with Amvuttra should not be continued in patients who are permanently bedridden and dependent on assistance for basic activities of daily living or who are receiving end-of-life care.
 Amvuttra should only be reimbursed if the patient is under the care of a specialist with experience in the diagnosis and management of hATTR-PN and should not be reimbursed if it is used in combination with interfering ribonucleic acid drugs or transthyretin stabilizers. The cost of Amvuttra should be reduced so that it does not cost more than other drugs for hATTR amyloidosis.

An Insidious Comorbidity: Depression and Chronic Heart Failure

Depression and heart failure (HF) are in a close bilateral relationship: the appearance of one is potentiated by the other entity and the effects on the outcome are amplified within this ”dangerous liaison”. Depression is present in about one in five HF patients and is severe in almost half of them. The risk factors for depression in HF are female gender, elderly, the severity of HF symptoms, a history of isolated systolic hypertension or coronary heart disease (CHD), previous hospitalization and previous depressive episodes. Depression in HF patients increases medication non-adherence, is associated with poor outcomes after heart transplantation and is predictive of events and mortality in cardiac resynchronization therapy (CRT). The current assumptions related to the physiopathological mechanisms include a common genetic polymorphisms, inflammation, generalized immune system disturbance, disturbances of platelet function, increased catecholamine levels, deamination of monoamines linked with monoamine oxidase activity, a dysregulation of the autonomic nervous system, increased serotonin levels, ischemia, life-style and medication non-compliance, a poor familial support and social isolation. Assessment of cognitive functioning should be part of routine clinical examination in HF, the diagnosis of depression is based on questionnaires (e.g. Patient Health Questionnaire-2 - PHQ-2) and on clinical interview. There is still no consensus on the best therapy for HF patients with depression (non-pharmacological and pharmacological therapies) but, for sure, depression in HF is harder to treat.

Human Genetics of Ebstein Anomaly.

Ebstein anomaly (EA) is a rare, congenital cardiac defect of the tricuspid valve with a birth prevalence between 0.5 and 1 in 20,000 [1]. It is characterized by displacement of the tricuspid valve toward the apex of the right ventricle (RV) and "atrialization" of the RV (Fig. 57.1) [2]. EA accounts for about 0.5% of all congenital heart diseases (CHD) [2]. Depending on severity of the defect and due to heterogeneity of the disease, patient's presentation varies from severe heart failure symptoms and arrhythmia in neonatal life to asymptomatic adults.

Depression and heart failure - the incidence of depressive symptoms assessed by the PHQ9 and their association with HF outcomes

Abstract Background Depression is a prevalent, debilitating, and potentially modifiable comorbidity that affects heart failure (HF) patients and is associated with increased mortality and morbidity. Current HF guidelines recommend addressing depression using questionnaires, including the Patient Health Questionnaire-9 (PHQ-9), which is a 9-item questionnaire that can be self-administered in less than 3 minutes. Objectives To evaluate the performance of PHQ-9 in a Portuguese cohort of HF patients and present a practical approach for the screening and management of depression in patients with HF. Methods We conducted a prospective study enrolling consecutive patients observed in the HF clinic from June 2022 to August 2022. Patients answered the PHQ-9 before the beginning of the appointment, during which the physician evaluated the results and managed them according to the suggested protocol. – figure 1. We then evaluated the severity of depression by PHQ-9 at baseline and its association with the levels of serum NT-proBNP, the severity of HF symptoms, and the incidence of a composite of all-cause mortality and HF exacerbation at 90-days follow-up. Results A total of 124 patients were observed in the HF consultation and answered PHQ-9: mean age of 74±12,1years, 68% (n=84) male, 82% (n=102) with NYHA I-II, 48% (n=60) with preserved ejection fraction, 23% (n=29) with a previous diagnosis of depression and on antidepressant therapy. After the evaluation of PHQ-9, 52% (n=65), 27% (n=33), 10% (n=12), 8% (n=10) and 3% (n=4) had minimal, mild, moderate, moderately severe, and severe depression symptoms, respectively. In the no previous depression diagnosis group, 49% (n=46) had at least mild depressive symptoms. The presence of depressive symptoms was associated with higher levels of serum NT-proBNP (r=0.31; p<0.001) and worse HF symptoms assessed by the NYHA classification (p<0,001). Patients who met the composite outcomes (death or HF exacerbation) during follow-up had a significantly higher PHQ-9 score (10±7 vs. 5±5; p<0,001). Conclusions This study confirmed the high prevalence of depressive symptoms in this real-world cohort of HF patients and demonstrated that screening for depressive symptoms can be efficiently integrated in the HF consultation. A higher burden of depressive symptoms was associated with higher serum NT-proBNP, more severe symptoms and higher incidence of death or HF admissions.

Choice of cardiac implantable electronic device and age-stratified clinical outcome in patients with known heart failure prior to implant

Abstract Background Patients with heart failure (HF) and bradycardia may be eligible for different types of cardiac implantable devices, depending on presence of AV conduction disease, left ventricular ejection fraction, severity of heart failure symptoms, other comorbidities, and age. Once a pacing device is in place, there is a risk that ensuing heart failure progression or worsening of symptoms do not always prompt a device upgrade to resynchronization or conduction system pacing therapy, even if this should be warranted. We therefore aimed to compare prognosis in a national cohort of patients with prior HF diagnosis, who received a pacemaker or defibrillator with or without resynchronization therapy. Methods All patients with preexisting HF diagnosis who received a pacemaker with a right ventricular lead during the period 2005-2018 in Sweden were identified via the Pacemaker Registry. Data was crossmatched with the population registry and national disease registries. Primary outcome was 5-year mortality, and secondary was mode of death and hospitalization for heart failure. Cox regression and Kaplan Meier curves with log rank test were used for time dependent outcome analyses. Demography variables were compared with Chi2 test or Mann Whitney U test, as appropriate. Adjustment was done for history of atrial fibrillation, diabetes, hypertension, malignancy, age, gender, ischemic heart disease, renal disease, lung disease and cerebrovascular disease. Separate analyses were made for patients with complete AV block, based on the assumption of 100% ventricular pacing in this group, regardless of choice of implanted device. Results 37745 patients were included in the study (see figure 1). Demographic data was similar for the different device groups, except that patients with single chamber pacemaker were older, and all those with single chamber devices (pacemaker, ICD) were more likely to have a history of atrial fibrillation. All listed comorbidities, male sex and higher age were associated with lower 5-year survival in multivariable Cox regression analyses. Unadjusted 5-year mortality was 40% (highest for single chamber pacemakers (61%), and lowest for dual chamber ICDs (17%), p=0.001). When stratified by age group, and adjusted for relevant covariables, patients with single-chamber pacemakers still had higher mortality in all age decile groups (ranging from <60 to >90 years old, all p<0.001). Proportion of device upgrades to CRT was very low; 2.9% for dual- and 0.8% for single-chamber pacemakers. 17% of patients with traditional pacemakers died from HF, and 31% were hospitalized for HF. Conclusions Survival for patients with prior HF diagnosis who receive traditional pacemakers is poor, risk of HF hospitalization is high, whereas upgrades to CRT are scarce. This highlights the need for choosing correct device type at the primary implant, if ventricular pacing is anticipated.Flowchart of included patientsAge stratified survival per device group

Female gender is an independent predictor of clinical benefit from cardiac resynchronisation therapy - results from the BIOWOMEN study

Abstract Background Presently, only indirect evidence indicates that women may benefit more from CRT than men. Since some gender-specific baseline variables are related to CRT benefit, it is unclear whether gender by itself is predictive of CRT benefit after correction for all these differences. We aimed to examine the impact of gender-specific differences on CRT response. Methods The BIOWOMEN study is a prospective, multicenter, international study, that enrolled 206 women and 214 men with a standard indication for CRT. The change in left-ventricular ejection fraction (LVEF) at 12 months follow-up after CRT was used as a primary endpoint to measure CRT benefit. The LVEF was quantified by a core lab blinded to gender and other patient characteristics. We used a median split to dichotomize continuous variables, if required. Uni- and multivariate analyses were used to identify baseline variables that are connected to an increase in LVEF. The latter model allows to estimate the change in LVEF that can be attributed to gender and other baseline variables. Results At baseline, women and men had similar LVEF, age and QRS duration, but there was a significant difference in the presence of left bundle branch block (88.3% vs. 79.9%, P=0.023). Women had less often ischemic heart disease (18.4% vs. 51.4%, P<0.001) and previous history of myocardial infarction (MI, 6.8% vs. 32.2%, P<0.001), but more severe heart failure symptoms (NYHA I/II/III 7%/51%/42% vs. 10%/63%/27%, P=0.019) and a shorter 6 minute walk test (345±117 vs. 409±148 m, P<0.001). In univariate analysis, women presented a significantly larger gain of 3.1 points in LVEF (+14.6±12.4% vs. +11.5±11.6%, P=0.004) compared to men. Additionally, the rate of CRT responders (defined as an improvement in LVEF >5%) was higher in women (82.0% vs. 70.6%, p=0.008). Other variables predictive of larger improvement in LVEF were LBBB (13.9±11.9% vs. 8.4±12.2%, P<0.001), NYHA I compared to NYHA II or III (I: 18.4±11.8%; II: 12.2±12.0%; III: 13.1±12.0%), no history of MI (14.0±11.6% vs. 8.9±13.0%, P<0.001), and an LVEF <32% at baseline (16.9±11.8% vs. 9.7±11.3%, P< 0.001). In multivariate analysis, female gender remained a significant predictor of a better improvement in LVEF (+2.6% absolute, P=0.036). Other significant predictors were LBBB (+5.2%, P<0.001), NYHA I (+6.9%, P<0.001 vs. NYHA II and +6.3%, P=0.004 vs. NYHA III), no history of MI (+4.1%, P=0.007), baseline LVEF <32% (+7.5%, P<0.001). Conclusion Gender has an important impact on the relevant baseline clinical differences that determine CRT response. Whereas women more often have LBBB and no prior-MI, suggesting more benefit from CRT, the BIOWOMEN study shows for the first time that female gender itself is linked to a larger clinical benefit from CRT. These gender-based baseline parameters need to be considered in daily clinical practice when screening patients for CRT, with particular attention to females.

Temporal trends in characteristics and outcomes in patients undergoing percutaneous mitral valve repair for secondary mitral regurgitation

Abstract Background and purpose Several studies have investigated the procedural and clinical outcomes of patients with secondary mitral regurgitation (MR) who underwent percutaneous mitral valve repair. However, temporal trend of patients’ characteristics and outcomes has not been studied in comparison with landmark studies. Thus, this systematic review investigated the temporal trend in patient characteristics and outcomes from observational studies over years in comparison with landmark studies in secondary MR. Methods The identified observational studies were grouped into two 5-year periods. The first 5-year period included 36 studies that started recruiting patients at any year between 2008 and 2012, whereas 25 studies in the second 5-year period started recruitment between 2012 and 2018. Pooled data of two every 5-year period were compared with the landmark studies. Multicenter studies with potential overlap in term of recruitment periods were excluded. Variables from observational studies were compared with those of landmark trials using a random-effects model for each variable. R software was used for non-comparative pooling of variables, and the RevMan software was used for the comparative meta-analysis. Results EVEREST versus observational studies: In first 5-year period, patients in EVERST program were more likely to have non-ischemic MR aetiology and less likely to be symptomatic at presentation (i.e., NYHA III/IV) or getting implanted cardiac device. They were less likely to have MR grade ≤2+ (OR 0.58, 95% CI:0.44-0.78) post procedure but maintained NYHA class I/II at 12-month follow-up (OR 1.74, 95% CI: 1.38-2.19) with no difference in mortality. In the subsequent 5-year period, there was no change from the former comparisons. COAPT versus observational studies: In the first period, COAPT patients were more likely to have renal insufficiency and receive beta-blockers and implanted device. They were less likely to present with severe heart failure symptoms or severe MR. There was no difference in post procedure outcomes, but they were more likely to maintain MR grade ≤2+ at follow-up (OR 3.98, 95% CI: 2.15-7.37). In the following period, COAPT patients were more likely to present with MR grade 3+ without a difference in procedural or clinical outcomes except for more chance to maintain procedural success at 12-mont follow-up (i.e., MR grade ≤2+; OR 2.41, 95% CI: 1.27-4.58). MITRA-FR versus observational studies: In the first period, MITRA-FR patients were less likely to have atrial fibrillation, renal insufficiency, or NYHA class III/IV. They were more likely receive beta-blockers and implanted device. However, there was no difference in post procedure and clinical outcomes. In the second period, there was no major change from the previous comparisons. Conclusion Although patients from landmark studies, namely COAPT and MITRA-FR, may have favourable characteristics, this did not translate into better outcome over time.

CA-125 concentrations are associated with renal function decline but not congestion or prognosis in patients with chronic heart failure: results from EMPEROR-POOLED

Abstract Background Carbohydrate antigen 125 (CA-125, also described as cancer antigen 125), has emerged as a candidate biomarker of congestion in heart failure (HF). Effects of sodium/glucose cotransporter-2 inhibitor therapy on CA-125 and its role as a prognostic measure in HF remains uncertain. Purpose In study participants from the EMPEROR-Preserved and EMPEROR-Reduced trials, across a wide spectrum of ejection fraction (EF) and renal function, we sought to investigate associations between CA-125 and congestion, the effect of empagliflozin on CA-125 concentrations, and the ability of the biomarker to predict cardio-renal outcomes. Methods 1111 patients with HF and available biomarker data were included into this analysis. Serum CA-125 was measured at baseline, 12 and 52 weeks using an Electroluminescence assay. The measurements were performed within a biomarker research agreement of Boehringer Ingelheim, the sponsor of these trials and Roche Diagnostics International Ltd. Congestion signs or symptoms were evaluated across CA-125 tertiles. A mixed model for repeated measurements was used to compare the treatment effects on CA-125. Multivariable analyses adjusted for the prespecified EMPEROR baseline variables plus N-terminal pro-B type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were used to examine the association of CA-125 with HF hospitalization or cardiovascular (CV) death and estimated glomerular filtration rate (eGFR) slope. Results Across CA-125 tertiles at baseline, no significant association was present with HF symptom severity, jugular vein distention, pulmonary rales, S3 gallop or peripheral oedema (all p-values >0.10). Treatment with empagliflozin was associated with 7% greater reduction of CA-125 level versus placebo to week 12 (adjusted geometric mean ratio: 0.93; 95% confidence interval [CI], 0.87-0.99, p = 0.03) but not to week 52 (adjusted geometric mean ratio: 0.97, 95% CI 0.90-1.06; p = 0.50). No significant association was found for tertiles of CA-125 at baseline with the risk of CV death/HF hospitalization; with a hazard ratio (HR) for higher vs lower CA-125 tertiles of 1.34 (95% CI 0.91–1.96). In the same model NT-proBNP and hs-cTnT were strongly prognostic (both p-values <0.0001). Compared to lower tertiles, study participants in the third CA-125 tertile had higher rate of kidney function decline with a more negative eGFR slope (p for trend = 0.03). Conclusion In chronic HF, across a wide range of EF and of renal function, CA-125 levels were not strongly associated with clinical signs or symptoms of congestion. Empagliflozin lowered CA-125 levels more than placebo at week 12 but not at week 52. Among individuals with HF, CA-125 concentrations did not provide additional prognostic information for CV death/HF hospitalization beyond conventional cardiac biomarkers but may predict subsequent kidney function decline.

Eight year follow-up data on a leadless pacing system real life experience in comparison to data of the prospective trial

Abstract Introduction The Micra™ leadless intracardiac pacing system has been introduced and implemented into clinical routine in 2015, with its next generation MICRA AV ™ in 2020. Feasibility, implantation safety, and acute success have been proven in the setting of controlled studies. Even apart from controlled studies, this new technology was beneficial for the individual patient. We aimed to report our single center follow-up (FU) data with a follow-up of up to six years. Methods In 272 patients (136 men; age: 81±5,7 y), Micra™ implantation was performed. Pacemaker interrogation was performed one to seven days after implantation and during FU (1; 3; 6, then every 6 month) up to 84 months. Data were assessed in a real-life setting and compared with existing data of a controlled prospective trial. Results The implantation was successful in all 272 attempts with only one pericardial effusion as major complication. During follow up there were two patients developing severe heart failure symptoms resulting in an implantation of a CRT-device and switching of the leadless pacemaker system. The average acute thresholds, sensing and impedance after system release were: 0.57±0.34V@0.24ms; 10,02±3,96mV and 752±1201Ohm. During follow up of up to 7 years neither, pacemaker failure, nor infections were reported. Measurements were reevaluated for long-term thresholds, sensing and impedance: 0.75 ± 0.38V @ 0.24 ms; 18,38 ±2,75 mV and 525 ± 102 Ohm. During seven years, no significant changes from acute to long-term measurements were detectable. In comparison to the controlled trial, our measurements of this real-life cohort were very similar. Conclusion In a real-life setting, the implantation of the leadless Micra™ system demonstrates a high rate of implantation success without major complications. We were also able to show stable long-term system parameters in the clinical setting of up to seven years of follow up with a very good battery longevity of about 12,3 years.

Abstract 14717: Gene Therapy Mediated Rescue of Chronic Non-Ischemic Cardiomyopathy in Minipigs

Heart failure (HF) is a major cause of morbidity and mortality worldwide, yet with limited therapeutic options. Recent evidence indicates that the cardiac bridging integrator 1 (cBIN1)-organizes transverse tubule microdomains which organize the calcium handling machinery important for cardiac function. In rodent models, adeno-associated virus 9 (AAV9)-cBIN1 effectively reconstitutes microdomains and rescues HF. Here we explored the therapeutic efficacy of AAV9-cBIN1 in a minipig model of non-ischemic HF. 6-7 months old Yucatan minipigs were subjected to continuous right ventricular rapid pacing (RVP) at 170 bpm. After continuous RVP for 5.7 ± 1.0 weeks (N=10), minipigs developed dilated cardiomyopathy with increased left ventricular (LV) end diastolic volume (EDV, 70.7 ± 4.5 vs. baseline 45.5 ± 1.6 mL) and reduced ejection fraction (EF, 36.5 ± 1.2 vs. baseline 71.3 ± 1.5 %). Once EF ≤ 40% over a week, pigs were randomized to receive intravenous AAV9-cBIN1 or control (AAV9-GFP or PBS). Pacing was continued throughout the study period. In control animals (N=5 with 4 PBS and 1 AAV9-GFP treatment), LV further dilated (78.0 ± 8.7 mL) with EF declining to 27.6 ± 6.7 % by four weeks post injection. The first three control animals already died of severe HF symptoms by 7 weeks post injection (Figure 1A) and the other two animals are currently at 4 weeks post injection with EF reduced to 27 and 33 %, respectively. Despite of continuous RVP, AAV9-cBIN1 rescued HF with EF recovered to 52.6 ± 4.0 % and EDV at 67.3 ± 6.6 mL at 4 weeks post injection. Three cBIN1-treated animals survived the full protocol of 6-month monitoring with EF maintained at 57.5 ± 15.5 % (Figure 1B-C), with two ongoing pigs currently surviving at 4 weeks post-injection with normal EF. Figure contains data of the animals who died or have already completed the 6-month protocol (N=3 per group). No toxicity was observed. In conclusion, intravenous cBIN1 gene therapy rescues non-ischemic HF and improves mortality in pigs.

High-sensitivity Cardiac Troponin T Is a Useful Biomarker for Predicting the Prognosis of Patients with Systemic Sarcoidosis Regardless of Cardiac Involvement.

Objective Cardiac involvement defines the prognosis for patients with systemic sarcoidosis. Despite advancements in techniques for diagnosing cardiac lesions, there remains significant room for improvement in cardiac screening and prognostic prediction. The present study therefore assessed the prognostic factors associated with cardiovascular events in patients with sarcoidosis. Methods We retrospectively studied 132 patients with systemic sarcoidosis and evaluated the clinical data obtained between 2009 and 2022. A Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the associations between cardiovascular events and prognostic factors. Results The median age of the patients at the diagnosis was 64.0 (55.0-71.0) years old. During a mean follow-up period of 6.3±3.2 years, 28 patients suffered from cardiovascular events. Patients in the event group had more severe heart failure symptoms, more frequent ventricular tachycardia, higher serum high-sensitivity cardiac troponin T (hs-cTnT) values [0.025 (0.017-0.044) vs. 0.011 (0.007-0.019) ng/mL, p<0.001], and lower left ventricular ejection fraction values than those in the non-event group. These trends were observed even if the patients were not diagnosed with cardiac involvement at the time of enrollment. A multivariate analysis revealed that hs-cTnT was an independent biomarker for the prediction of cardiac events (hs-cTnT >0.014 ng/mL: HR: 7.31, 95% confidence interval: 2.20 to 24.28, p<0.001). Conclusion Hs-cTnT is a useful biomarker for predicting cardiovascular events in patients with sarcoidosis, even if cardiac involvement is not detected at the initial evaluation.

Predictors of therapeutic response to specific therapy in distal chronic thromboembolic pulmonary hypertension

Aim. To assess therapeutic response to specific therapy in patients with distal CTEPH who are ineligible for surgical management as pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA).Materials and methods. The study included inoperable patients with CTEPH (n=53) who are ineligible for surgical management as pulmonary endarterectomy or balloon pulmonary angioplasty. The effectiveness of specific therapy were assessed after dividing the patients into improvement or nonimprovement groups based on the following indicators: functional class I-II (WHO), mean pulmonary artery pressure according to right heart catheterization ≤40 mm Hg, pulmonary vascular resistance ≤400 dyn×s×cm-5, cardiac index ≥2,5 L/min/m2 , decrease in N-terminal brain natriuretic peptide &gt;30%, and increase in 6-minute test distance &gt;30 m at 12th-month follow-up compared to baseline parameters.Results. There were no differences in groups by gender, age, and received specific therapy. Multiple logistic regression was performed, resulting in a model for predicting clinical improvement with sensitivity (57,1%) and specificity (87,1%), p=0,002. It was revealed, that the absence of the loss of pulmonary vascularity by X-ray at the time of verification of the diagnosis in patients with CTEPH by 5,91 times increases the chance of achieving clinical improvement after 12 months of the specific therapy, while the absence of signs of heart failure by 5,79 times, and degree of pulmonary valve insufficiency 0-1 according to echocardiography by 9,2 times, respectively.Conclusion. Early initiation of specific therapy in inoperable CTEPH patients due to distal lesions with the absence of severe vascular remodeling and heart failure symptoms leads to the better therapeutic response after 12 months of treatment.

Safety Indicators in Patients Receiving High-intensity Care After Hospital Admission for Acute Heart Failure: The STRONG-HF Trial

BackgroundSafety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies (STRONG-HF) demonstrated the safety and efficacy of rapid up-titration of guideline-directed medical therapy (GDMT) with high-intensity care (HIC) compared with usual care in patients hospitalized for acute heart failure (HF). In the HIC group, the following safety indicators were used to guide up-titration: estimated glomerular filtration rate of <30 mL/min/1.73 m2, serum potassium of >5.0 mmol/L, systolic blood pressure (SBP) of <95 mmHg, heart rate of <55 bpm, and N-terminal pro-B-type natriuretic peptide concentration of >10% higher than predischarge values. Methods and ResultsWe examined the impact of protocol-specified safety indicators on achieved dose of GDMT and clinical outcomes. Three hundred thirteen of the 542 patients in the HIC arm (57.7%) met ≥1 safety indicator at any follow-up visit 1–6 weeks after discharge. As compared with those without, patients meeting ≥1 safety indicator had more severe HF symptoms, lower SBP, and higher heart rate at baseline and achieved a lower average percentage of GDMT optimal doses (mean difference vs the HIC arm patients not reaching any safety indicator, –11.0% [95% confidence interval [CI] –13.6 to –8.4%], P < .001). The primary end point of 180-day all-cause death or HF readmission occurred in 15.0% of patients with any safety indicator vs 14.2% of those without (adjusted hazard ratio 0.84, 95% CI 0.48–1.46, P = .540). None of each of the safety indicators, considered alone, was significantly associated with the primary end point, but an SBP of <95 mm Hg was associated with a trend toward increased 180-day all-cause mortality (adjusted hazard ratio 2.68, 95% CI 0.94–7.64, P = .065) and estimated glomerular filtration rate decreased to <30 mL/min/1.73 m2 with more HF readmissions (adjusted hazard ratio 3.60, 95% CI 1.22–10.60, P = .0203). The occurrence of a safety indicator was associated with a smaller 90-day improvement in the EURO-QoL 5-Dimension visual analog scale (adjusted mean difference –3.32 points, 95% CI –5.97 to –0.66, P = .015). ConclusionsAmong patients with acute HF enrolled in STRONG-HF in the HIC arm, the occurrence of any safety indicator was associated with the administration of slightly lower GDMT doses and less improvement in quality of life, but with no significant increase in the primary outcome of 180-day HF readmission or death when appropriately addressed according to the study protocol.

Abstract GS.07: Cardiac Bridging Integrator 1 Gene Therapy Rescues Heart Failure In Swine.

Heart failure (HF) is a major cause of morbidity and mortality worldwide, yet with limited therapeutic options. Recent evidence indicates that the cardiac bridging integrator 1 (cBIN1)-organized transverse tubule microdomain is key to calcium handling and cardiac function. In rodent models, adeno-associated virus 9 (AAV9)-cBIN1 effectively reconstitutes microdomains to rescue HF. Here we explored the therapeutic efficacy of AAV9-cBIN1 in a minipig model of non-ischemic HF. 6-7 months old Yucatan minipigs were subjected to continuous right ventricular rapid pacing (RVP) at 170 bpm. After 8-11 weeks of RVP, minipigs developed dilated cardiomyopathy with increased left ventricular (LV) end diastolic volume (EDV, 69.0 ± 5.3 vs. baseline 50.0 ± 3.8 mL) and reduced ejection fraction (EF, 36.3 ± 2.9 vs. baseline 68.7 ± 0.8 %). Once EF ≤ 40% over a week, pigs were randomized to receive AAV9-cBIN1 (6 x 10 11 vg/kg, intravenous, n = 3) or control (AAV9-GFP or PBS, n = 3). Weekly echocardiography, bloodwork, clinical assessment, and pacing interrogation were performed. In control animals, LV further dilated with EF declining and all three animals died of severe HF symptoms by 7 weeks post injection (terminal EF 18.3 ± 1.7, EDV 107.4 ± 25.0). Despite of continuous RVP, AAV9-cBIN1 limited LV dilation and rescued EF (58.0 ± 4.2, 59.0 ± 4.4 % at 4, 13 weeks post injection). Two cBIN1-treated animals survived to the end of protocol at 6 months post treatment (EF, 57.5 ± 15.5 %), with the third pig currently surviving at 13 weeks post treatment with a 60% EF. No significant toxicity was observed. In conclusion, low dose intravenous cBIN1 gene therapy rescues non-ischemic HF and improves mortality in pigs.

Impact of pregnancy on the natural history of women with hypertrophic cardiomyopathy.

Whether pregnancy is a modifier of the long-term course and outcome of women with hypertrophic cardiomyopathy (HCM) is unknown. We assessed the association of pregnancy with long-term outcomes in HCM women. Retrospective evaluation of women with HCM from 1970 to 2021. Only women with pregnancy-related information (pregnancy present or absent) and a follow-up period lasting ≥1 year were included. The peri-partum period was defined as -1 to 6 months after delivery. The primary endpoint was a composite for major adverse cardiovascular events [MACE: cardiovascular death, sudden cardiac death, appropriate defibrillator shock and heart failure (HF) progression]. Overall, 379 (58%) women were included. There were 432 pregnancies in 242 (63%) patients. In 29 (7.6%) cases, pregnancies (n = 39) occurred after HCM diagnosis. Among these, three carrying likely pathogenic sarcomeric variants suffered MACEs in the peri-partum period. At 10 ± 9 years of follow-up, age at diagnosis [hazard ratio (HR) 1.034, 95% confidence interval (CI) 1.018-1.050, P < 0.001] and New York Heart Association (NYHA) class (II vs. I: HR 1.944, 95% CI 0.896-4.218; III vs. I: HR 5.291, 95% CI 2.392-11.705, P < 0.001) were associated with MACE. Conversely, pregnancy was associated with reduced risk (HR 0.605; 95% CI 0.380-0.963, P = 0.034). Among women with pregnancy, multiple occurrences did not modify risk. Pregnancy is not a modifier of long-term outcome in women with HCM and mostly occurs before a cardiac diagnosis. Most patients tolerate pregnancy well and do not show a survival disadvantage compared to women without. Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features.

Improved long-term survival with tafamidis treatment in patients with transthyretin amyloid cardiomyopathy and severe heart failure symptoms.

The value of disease-modifying therapies (such as tafamidis) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and severe heart failure symptoms has been debated. This study assessed long-term all-cause survival in patients with New York Heart Association (NYHA) class III symptoms in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) long-term extension (LTE) study. At the baseline of ATTR-ACT, 55/176 (31.3%) patients receiving tafamidis 80 mg and 63/177 (35.6%) receiving placebo had NYHA class III symptoms. After 30 months of treatment, patients could join an ongoing LTE study to receive open-label tafamidis. In an interim analysis of the LTE study (August 2021), all-cause mortality was lower among patients with NYHA class III symptoms who received continuous tafamidis in ATTR-ACT and the LTE study (hazard ratio 0.64; 95% confidence interval 0.41-0.99; median follow-up: 60 months), as compared with those who received placebo in ATTR-ACT and tafamidis in the LTE study (median follow-up: 56 months). Similar findings were observed in patients with NYHA class I/II symptoms at baseline (0.50; 0.35-0.73; tafamidis 80 mg n = 121; placebo n = 114; median follow-up of 61 and 60 months, respectively). We observed reduced all-cause mortality with continuous tafamidis treatment compared with delayed tafamidis treatment (placebo then tafamidis) in patients with NYHA class III symptoms at baseline over a median follow-up of ∼5 years. These findings demonstrate the value of tafamidis treatment in patients with ATTR-CM and severe heart failure symptoms, and emphasize the importance of early treatment. ClinicalTrials.gov NCT01994889 and NCT02791230.

Cardio-hepatic syndrome in patients undergoing transcatheter aortic valve replacement

BackgroundCardiohepatic syndrome (CHS) has been identified as an important but underrecognized survival predictor in multiple cardiovascular disease entities. The objectives of this study were to evaluate the prevalence and prognostic value of CHS in patients undergoing TAVR for severe aortic stenosis (AS).MethodsThe study included patients with available laboratory parameters of hepatic function who underwent TAVR from July 2013 until December 2019 at our center. CHS was defined as an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal (bilirubin, alkaline phosphatase, and gamma glutamyl transferase). Study endpoints were three-year survival, technical and device failure (VARC 3), as well as New York Heart Association (NYHA) functional class at follow-up.ResultsAmong a total of 953 analyzed patients (47.6% females, median age 80.0 [76.0–85.0] years) CHS was present in 212 patients (22.4%). In patients with vs. without CHS, rates of technical (6.1% vs. 8.4%, p = 0.29) and device failure (18.9% vs. 17.3%, p = 0.59) were comparable. NYHA functional class at baseline and follow-up was more severe in patients with CHS. Nevertheless, heart failure symptoms improved from baseline to follow-up irrespective of hepatic function. Three-year survival rates were significantly lower in patients with CHS (49.4 vs. 65.4%, p < 0.001). The predictive value of CHS persisted after adjustment in a multivariable analysis (hazard ratio 1.58, p < 0.01).ConclusionIn patients undergoing TAVR, CHS is prevalent in 22% of patients and is associated with increased postinterventional mortality. Thus, CHS should be included in the decision-making process within the TAVR heart team.Graphical abstractCardiohepatic syndrome (CHS) as defined by an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal was prevalent in 22% of patients undergoing TAVR for severe AS. The presence of CHS was associated with more severe heart failure symptoms and worse three-year survival.