Cardiac Modulation Research Articles

Cost-utility of cardiac contractility modulation in patients with heart failure with reduced ejection fraction in Italy.

Cardiac contractility modulation (CCM) is a device therapy for heart failure, based on the delivery of high-voltage biphasic impulses to the right ventricular septum during the myocardial absolute refractory period. This study evaluated the cost-effectiveness of CCM therapy plus optimal medical therapy (OMT) vs. OMT alone in patients with heart failure with reduced ejection fraction. A Markov model with a lifespan time horizon was developed to assess the cost-utility using the FIX trials as main data sources. A deterministic sensitivity analysis and a probabilistic sensitivity analysis were run to analyse the decision uncertainty in the model through cost-effectiveness acceptability curve (CEAC) and cost-effectiveness acceptability frontier (CEAF). Value of information analysis was also conducted computing the expected value of perfect information (EVPI) and the expected value of partial perfect information. The base case results showed that the CCM plus OMT option was highly cost-effective compared with OMT alone with an incremental cost-utility ratio of €7034/quality-adjusted life year (QALY). The CEAC and CEAF illustrated that for all willingness to pay levels above €5600/QALY, tested up to €50000/QALY, CCM plus OMT alternative had the highest probability of being cost-effective. The EVPI per patient was estimated to be €124412 on a willingness to pay threshold of €30000/QALY. For patients with heart failure with reduced ejection fraction, CCM therapy could be cost-effective when taking a lifetime horizon. Further long-term, post-approval clinical studies are needed to verify these results in a real-world context, particularly concerning the effect of CCM therapy on mortality.

Abstract 18085: Effect of Therapies on Quality of Life in Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis

Introduction: Minnesota Living with Heart Failure (MLWHF) questionnaire is a validated tool to assess quality of life in patients with heart failure with reduced ejection fraction (HFrEF) Hypothesis: We performed this systematic review and meta-analysis to evaluate the effect of therapies on improvement in MLWHF; analyzed across randomized controlled trials (RCTs) of drug based therapy, device based therapy, autonomic modulation, and exercise. Methods: We conducted a systematic search of MEDLINE and EMBASE for RCTs measuring MLWHF at baseline and follow-up in patients with HFrEF. Primary outcome was improvement in MLWHF. Meta-analysis was stratified in groups based on medical therapy, device based therapy (cardiac resynchronization therapy and cardiac contractility modulation), autonomic modulation (vagus nerve stimulation and baroreflex activation therapy), and exercise. Mean difference (MD) with 95% Confidence Interval (CI) were reported across multiple studies included in meta-analysis. Results: A total of 23 studies met the inclusion criteria. Analysis showed statistically significant improvement in MLWHF at follow-up for drug based therapy (MD: -2.77; 95% CI: -5.10, -0.44) (Panel A), device based therapy (MD: -6.86; 95% CI: -9.60, -4.12) (Panel B), autonomic modulation (MD: -15.21; 95% CI: - 19.25, -11.17) (Panel C), and exercise group (MD: -10.05; 95% CI: -16.66, -3.43) (Panel D). Sub-group analyses based on various treatment modalities showed statistically significant improvement in MLWHF at follow-up for cardiac resynchronization therapy (MD: -8.11; 95% CI: -11.88, -4.33), cardiac contractility modulation (MD: -5.47; 95% CI: -9.46, -1.49), and baroreflex activation therapy (MD: -19.79; 95% CI: -24.90, -14.67). Conclusions: Drug based therapy, device based therapy, autonomic modulation, and exercise are associated with improvement in quality of life in patients with HFrEF.

Bridging the gap in the symptomatic heart failure patient journey: insights from the Italian scenario

ABSTRACT Background The prognosis for heart failure (HF) patients remains poor, with a high mortality rate, and a marked reduction in quality of life (QOL) and functional status. This study aims to explore the ongoing needs of HF management and the epidemiology of patients followed by Italian HF clinics, with a specific focus on cardiac contractility modulation (CCM). Research design and methods Data from patients admitted to 14 HF outpatients clinics over 4 weeks were collected and compared to the results of a survey open to physicians involved in HF management operating in Italian centers. Results One hundred and five physicians took part in the survey. Despite 94% of patients receive a regular follow-up every 3–6 months, available therapies are considered insufficient in 30% of cases. Physicians reported a lack of treatment options for 23% of symptomatic patients with reduced ejection fraction (EF) and for 66% of those without reduced EF. Approximately 3% of HF population (two patients per month per HF clinic) meets the criteria for immediate CCM treatment, which is considered a useful option by 15% of survey respondents. Conclusions Despite this relatively small percentage, considering total HF population, CCM could potentially benefit numerous HF patients, particularly the elderly, by reducing hospitalizations, improving functional capacity and QOL.

Established and Emerging Device Therapy in Heart Failure: Cardiac Contractility Modulation.

Established and Emerging Device Therapy in Heart Failure: Cardiac Contractility Modulation.

Influence of Fluid Ingestion on Heart Rate, Cardiac Autonomic Modulation and Blood Pressure in Response to Physical Exercise: A Systematic Review with Meta-Analysis and Meta-Regression.

A systematic review was undertaken to investigate the involvement of hydration in heart rate (HR), HR variability (HRV) and diastolic (DBP) and systolic (SBP) blood pressure in response to exercise. Data synthesis: The EMBASE, MEDLINE, Cochrane Library, CINAHL, LILACS and Web of Science databases were searched. In total, 977 studies were recognized, but only 36 were included after final screening (33 studies in meta-analysis). This study includes randomized controlled trials (RCTs) and non-RCTs with subjects > 18 years old. The hydration group consumed water or isotonic drinks, while the control group did not ingest liquids. For the hydration protocol (before, during and after exercise), the HR values during the exercise were lower compared to the controls (-6.20 bpm, 95%CI: -8.69; -3.71). In the subgroup analysis, "water ingested before and during exercise" showed lower increases in HR during exercise (-6.20, 95%CI: 11.70 to -0.71), as did "water was ingested only during exercise" (-6.12, 95%CI: -9.35 to -2.89). Water intake during exercise only revealed a trend of avoiding greater increases in HR during exercise (-4,60, 95%CI: -9.41 to 0.22), although these values were not significantly different (p = 0.06) from those of the control. "Isotonic intake during exercise" showed lower HRs than the control (-7.23 bpm, 95% CI: -11.68 to -2.79). The HRV values following the exercise were higher in the hydration protocol (SMD = 0.48, 95%CI: 0.30 to 0.67). The values of the SBP were higher than those of the controls (2.25 mmHg, 95%CI: 0.08 to 4.42). Conclusions: Hydration-attenuated exercise-induced increases in HR during exercise, improved autonomic recovery via the acceleration of cardiac vagal modulation in response to exercise and caused a modest increase in SBP values, but did not exert effects on DBP following exercise.

Electrical therapies in heart failure: Evolving technologies and indications

Device therapy for heart failure has rapidly evolved over 2 decades. The knowledge of indications, assessment lead and device technology has expanded to include CRT, leadless pacing and conduction system pacing such as His bundle and left bundle branch area pacing. But there is still a lack of evidence for these new technologies as well as for common indications such as atrial fibrillation and upgrading from a previous device. The role of personalized medicine will become increasingly important when selecting candidates for CRT, primary preventive ICD ablation procedures and emerging new devices such as cardiac contractility modulation (CCM). Rapidity of therapy is associated with outcome which will be a challenge. If properly implemented devices and drugs will have a large positive affect of HF outcomes.

Transcriptome, network analysis, and molecular docking approaches to elucidate the modes of action of Astragaloside IV against myocardial infarction with mitochondrial energy metabolism network-targeted regulation

BackgroundMitochondria play central role in cardiac energy metabolism modulations. Cardiac energy metabolism could be potential therapeutic target for the treatment of ischemic heart disease (IHD). We proposed strategy to analyze the regulation modes of astragaloside IV (AST) by targeting mitochondrial-energy-metabolism (MEM) in IHD based on transcriptome, network analysis, molecular docking (MD) and western blot (WB). MethodIHD-associated genes and AST potential targets were collected from databases and references. MEM-related genes were obtained from MitoProteome. Cytoscape was applied to construct networks, present visualization, and conduct KEGG pathway enrichment. AST regulated energy-metabolism-associated-IHD-network (AEIN) was created, and reverse rates calculated from network analysis of transcriptome from rat myocardial infarction experiments were assigned to AEIN. Binding affinities and modes were evaluated by MD with further WB validation of targets expression. ResultsThe study identified 1713 IHD-related genes, 528 MEM-related genes, and 169 potential AST target genes. 21 AST targets were obtained from AEIN, while the top three targets Akt1, ERK1/2 and RPS6KB1 showed good binding affinities with AST (-10, -9.8, -8.6 and -8.8 kcal/mol for Akt1, Erk1, Erk2 and RPS6KB1 respectively). AST reversed the decreased expressions of three targets against OGD injury of H9c2. 13 MEM-associated signaling pathways, including HIF-1, and PI3K-Akt signaling pathways, were retrieved showing certain inter-relationships both in compositions and functions. ConclusionsAST may have coordinated roles among multi-pathways in regulating MEM homeostasis in IHD. While further deep investigations should be designed and conducted to decipher and pinpoint the multi-target, multi-pathway modes of action of AST in the future.

Paediatric quality of life in toddlers and children who underwent arterial switch operation beyond early neonatal period.

The aim of this study was to evaluate the quality of life (QOL) of children who underwent the arterial switch operation (ASO) for Transposition of Great Arteries in our population and, specifically, to explore early modifiable factors and the influence of parental and socioeconomic factors on the QOL of these children. Cross-sectional study using Paediatric Quality of Life Inventory™ 3.0 Cardiac Module was carried out on 3- to 12-year-old children who had undergone ASO between the years 2012-2018. Socioeconomic status was calculated using the modified Kuppuswamy scale (2019). Other clinical factors with possible bearing on the outcome were also analysed. Immediate survival after surgery was 196 out of 208 (94.2%) with an attrition of 19 patients (9.6%) over the follow-up period. Most surviving children (98.9%) had started formal schooling in age-appropriate classes. Two children had severe neuromotor impairment. The median cumulative health-related QOL score of the children was 97.9 (interquartile range 4.2) at 5.6 ± 1.27 years of life. The median scores each of the health-related QOL parameters, viz, heart problem symptoms, treatment compliance, perceived physical appearance, treatment-related anxiety, cognitive problems, and communication was 100 with negative skewing. Excellent QOL was observed in most children after ASO with the median total paediatric QOL scores in all domains of 97.9. Social factors did not show a statistically significant influence on the QOL parameters in the current cohort. The gradually declining trend across the age groups emphasizes the need for continued follow-up for early identification of possible correctable factors and initiating intervention to ensure good QOL into teenage and adulthood.

Impaired cardiac modulation in patients with functional seizures: Results from a face intensity judgment task.

Although interoceptive abnormality in patients with functional seizure (FSs) has been demonstrated using explicit tasks, implicit measurements of interoception such as the effect of interoception on perceptual brain processes have not been investigated. It has been shown that perception is normally modulated by interoceptive signals related to the different phases (systole vs diastole) of the cardiac cycle (cardiac modulation effect). Given our previous findings using explicit measures of interoception, we hypothesized that cardiac modulation would be impaired in FSs. Thirty-two patients with FSs and 30 age- and sex-matched non-clinical individuals conducted a face intensity judgment task, in which their intensity rating when fearful or neutral faces was presented was compared between systolic and diastolic phases. They also conducted the heartbeat discrimination task as a measure of their capacity to integrate both interoceptive and exteroceptive information. Patients with FSs had impaired cardiac modulation of the perception of neutral faces (corrected p = .044). Individual differences in the heartbeat discrimination task predicted the degree to which cardiac modulation occurred across the whole group (p = .028). This cardiac modulation effect was significantly associated with seizure severity (p = .021). Regardless of cardiac phase, patients rated fearful facial expressions as less intense compared to control participants (p = .006). These findings highlight impaired implicit cardiac modulation effects in patients with FSs. This reflects interoceptive dysfunction in patients with FSs, and an inability of the brain to integrate interoceptive signaling with perceptual processing. This may have implications for our understanding of the pathophysiology in FSs and inform novel diagnostic approaches.

Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives.

Sarcomeric hypertrophic cardiomyopathy (HCM) is a prevalent genetic disorder characterised by left ventricular hypertrophy, myocardial disarray, and an increased risk of heart failure and sudden cardiac death. Despite advances in understanding its pathophysiology, treatment options for HCM remain limited. This narrative review aims to provide a comprehensive overview of current clinical practice and explore emerging therapeutic strategies for sarcomeric HCM, with a focus on cardiac myosin inhibitors. We first discuss the conventional management of HCM, including lifestyle modifications, pharmacological therapies, and invasive interventions, emphasizing their limitations and challenges. Next, we highlight recent advances in molecular genetics and their potential applications in refining HCM diagnosis, risk stratification, and treatment. We delve into emerging therapies, such as gene editing, RNA-based therapies, targeted small molecules, and cardiac myosin modulators like mavacamten and aficamten, which hold promise in modulating the underlying molecular mechanisms of HCM. Mavacamten and aficamten, selective modulators of cardiac myosin, have demonstrated encouraging results in clinical trials by reducing left ventricular outflow tract obstruction and improving symptoms in patients with obstructive HCM. We discuss their mechanisms of action, clinical trial outcomes, and potential implications for the future of HCM management. Furthermore, we examine the role of precision medicine in HCM management, exploring how individualised treatment strategies, including exercise prescription as part of the management plan, may optimise patient outcomes. Finally, we underscore the importance of multidisciplinary care and patient-centred approaches to address the complex needs of HCM patients. This review also aims to encourage further research and collaboration in the field of HCM, promoting the development of novel and more effective therapeutic strategies, such as cardiac myosin modulators, to hopefully improve the quality of life and outcome of patients with sarcomeric HCM.

Soluble interleukin-1 receptor type 2 plasma levels in Parkinson's disease: relationship with cardiac autonomic profile before and after peripheral mechanical somatosensory stimulation.

Introduction: Systemic inflammation promotes neurodegeneration in Parkinson's disease (PD). Interleukin-1 receptor type 2 (sIL-1R2) plasma levels increase during inflammation. Data on sIL-1R2 in PD patients and its relationship with PD cardiac autonomic profile are limited, given the possible anti-inflammatory effect of vagal activation. Previously, automated mechanical peripheral somatosensory stimulation (AMPSS) enhanced cardiac vagal modulation. Objectives were to 1) evaluate sIL-1R2 plasma concentrations in PD patients and healthy controls and 2) investigate the correlations between sIL-1R2 and cardiac autonomic indices obtained by spectrum analysis of heart rate variability before and after AMPSS. Methods: sIL-1R2 plasma levels were assessed in 48 PD patients and 50 healthy controls. Electrocardiogram and beat-by-beat arterial pressure were recorded at baseline and after 5 AMPSS sessions in 16 PD patients. Results: PD patients had higher sIL-1R2 levels than controls. In the PD subgroup, an inverse correlation between sIL-1R2 and HFnu was found. There was a negative correlation between changes induced by AMPSS on HFnu and sIL-1R2. Discussion: Higher sIL-1R2 levels in PD patients reflect the inflammatory dysregulation associated with the disease. In PD patients, higher sIL-1R2 was associated with reduced cardiovagal tone. Increased cardiovagal modulation following AMPSS was associated with lower sIL-1R2 levels in Parkinson's disease patients, suggesting inflammatory state improvement.

Abstract P3142: Engineering A Genetically Encoded Enhancer Of L-type Ca 2+ Currents

L-type calcium channels (LTCC) play a crucial role as they serve as vital portals for Ca 2+ entry into cardiac myocytes, neurons, and other physiological systems. Altered LTCC function is linked to various pathologies including cardiac arrhythmias and neurodevelopmental disorders. In particular, genetic studies have identified loss-of-function mutations in Ca V 1.2 channels in patients with shortened QT interval and Brugada Syndrome, as well as neuropsychiatric disorders. Given the broad physiological importance of LTCC in various tissues, conventional pharmacological agonists of LTCC may yield off-target effects and toxicity. Therefore, new approaches to upregulate LTCC function in a cell-type dependent manner is sought after. To do so, we here develop a genetically encoded enhancer of calcium channels (GeeCC, “geek”) by leveraging both a cardiac specific L-type channel modulator, leucine rich repeat containing protein 10 (Lrrc10), and selective nanobodies that target the LTCC complex. Specifically, Lrrc10 co-expression markedly upregulates LTCC currents. Furthermore, mutations in Lrrc10 are linked to cardiac diseases, including cardiomyopathies. Through extensive structure-function analysis, we identified a minimal action domain within Lrrc10 that is critical for functional modulation of LTCC. However, as this segment alone has a low affinity for the channel complex, its expression alone yielded minimal changes in Ca 2+ current amplitude. However, fusion of this Lrrc10 domain to a nanobody (nb.F3) that targets the Ca 2+ channel beta subunit resulted in a significant increase in the LTCC current amplitude. In depth analysis revealed exquisite selectivity of GeeCC for Ca V 1.2/Ca V 1.3 channels. In mouse cardiomyocytes, deployment of GeeCC via adenovirus enhances endogenous L-type currents when compared to uninfected controls or cardiomyocytes infected with nanobodies alone. Additionally, in neurons, co-expression of GeeCC enhanced excitation-transcription coupling. In all, we have developed a genetically-encoded approach to selectively enhance L-type currents. This strategy may enable new insights into cardiovascular and neuronal physiology and pathophysiology, and may have potential therapeutic applications.

Cardiac contractility modulation therapy in patients with implanted cardiac resynchronization therapy: results of the 2 year follow-up

Aim. Cardiac contractility modulation (CCM) is a device therapy for patients with heart failure with reduced ejection fraction (HFrEF), most of the data on its programming are concerned patients with narrow QRS and of limited follow up. Our aim was to propose programming approach for Optimizer device in setting of wide QRS complex and fragmented ventricular local activation.Methods. We enrolled 11 patients with HFrEF (median age, 8 males, median NYHA class 3) and LBBB-related wide QRS complex, who underwent Optimizer™ device implantation. Three patients got Optimizer™ IV system and eight patients were implanted Optimizer™ Smart. Ten patients were previously implanted with CRT-D due to HFrEF and LBBB; one patient received CRT-D after Optimizer™ implantation.Results. During the implantation procedure ventricular local sense (LS) channel signal fragmentation was detected in all patients. In five patients signal detection was optimized by lead relocation. In six patients LS signal sensitivity limitations were resolved by programming. At two-year follow-up survival 4 patients died of noncardiac causes (1 intracranial hemorrhage, 1 gastrointestinal bleeding and 2 - terminal kidney failure). At 12-month follow-up we observed a non-significant improvement in 6-minute walking distance (300 vs 305, p=0.093), NYHA class (2.75 vs 2, p=0.085), MLHF score (53 vs 42, p=0.109) and left ventricular ejection fraction (LVEF) (30 vs 33.5, p=0.212).Conclusion. CCM system implantation is feasible and safe in patients with HFrEF and LBBB-related wide QRS complex. Device programming maneuvers can resolve the challenges of ventricular local signal detection in these patients.

Turkish validity and reliability study of Pediatric Quality of Life Inventory (PedsQL) 3.0 cardiac module for 8–18 years old children and parents

BackgroundThis study aimed to evaluate the Turkish validity and reliability of the 8–12- and 13–18-years child and parent forms of the Pediatric Quality of Life Inventory (PedSQL) 3.0 Cardiac Module. MethodsThis methodological study was conducted in children (8–18 years old) with cardiac disease and their parents. The PedsQL 4.0 were also used to collect data for the parallel form method. Pearson correlation coefficients between the scale and its sub-dimensions were evaluated for construct validity. For construct validity, mean scores of children with cardiac disease and healthy children and their parents were compared. Cronbach's alpha coefficient was calculated to evaluate the internal consistency of the items. ResultsIn this study, 136 children aged 8–12 years and 135 adolescents aged 13–18 years with cardiac diagnosis and their parents participated. The Cronbach alpha coefficients were found to be above 0.80 for all sub-dimensions and the total scale. Correlations between PedsQL 3.0 Cardiac module and PedsQL 4.0 scores were moderate to highly significant. A significant difference was found between the mean scores of the children with cardiac disease and healthy child and parent forms (p < .001). ConclusionPedsQL 3.0 Cardiac Module's 8–12- and 13–18-year child and parent forms are valid and reliable for the Turkish language. Application to practiceIt is important to evaluate the PedsQL cardiac module, which is a very comprehensive scale, with accurate measurements to increase the general health level and life satisfaction of these patient groups.

Influence of physical fitness and weight status on autonomic cardiac modulation in children.

This study provides reference values for cardiovascular modulation at rest, during maximal exercise test and recovery after exercise in Caucasian children according to weight status and cardiorespiratory fitness (CRF)level. Additionally, the current study analyzed several correlations between autonomic cardiovascular modulation, cardiorespiratory performance and cardiometabolic risk. The principal goal of this study was to analyze cardiac function at rest, during maximum exercise, and during the recovery phase in children grouped according to weight status and CRFlevel. One hundred and fifty-two healthy children (78 girls) 10-16 years of age were divided into three groups: soccer and basketball players (SBG), endurance group (EG), and sedentary people with overweight and obesity (OOG). A cardiac RR interval monitor recorded the cardiac data and specific software analyzed the cardiac autonomic response through heart rate (HR) and HR variability. The study analyzed resting HR (RHR), HRpeak, and HR recovery (HRR). OOG showed significant poorer performance in the Léger test lower V̇O2 max and higher values of blood pressure at rest and post-exercise than sport groups. The EG presented the best results in CRF and cardiometabolic risk (CMR) in relation to SBG and OOG. The OOG showed higher percentage of HR values, compatible with an unhealthy cardiovascular autonomic modulation than the sport groups, with significant differences in bradycardia, HR reserve, and HRR 5 min. Aerobic performance, vagal activity, blood pressure, chronotropic competence, and HRR have significant associations with CMR parameters. The current study presents reference values of autonomic cardiac function in Caucasian children according to weight status and cardiorespiratory fitness level. Aerobic performance, vagal activity, blood pressure, chronotropic competence, and heart rate during the recovery period after exercise have significant associations with cardiometabolic risk parameters. Children with overweight and obesity show signs of autonomic dysfunction reflected as low cardiac vagal activity and poor chronotropic competence.

Rejuvenating a failing heart: A case report

Heart Failure (HF) is a complicated, fatal medical condition that poses a severe threat to human life. It is a complex ailment that can lead to death and is associated with high healthcare costs, significant morbidity and mortality rates, and a reduction in functional capacity and quality of life. Recent data analysis reveals that approximately 64million people worldwide are affected by HF.1 Patients with HFrEF can benefit from cardiac contractility modulation (CCM), a revolutionary device-based treatment. In patients with HFrEF, CCM treatment has been associated with an improvement in exercise tolerance, an improvement in quality of life, a decrease in HF hospitalizations, and a reversal remodeling of the left ventricle. In this instance, we describe the therapeutic benefit of CCM in an elderly individual with advanced HFrEF triggered by ischemic dilated cardiomyopathy who frequently required hospitalization for heart failure-related issues and had a low quality of life despite receiving the best possible guideline-directed medical therapy (GDMT).

Cardiovascular autonomic regulation correlates with cognitive performance in patients with a history of traumatic brain injury

Background and objectiveTraumatic brain injury (TBI) may afflict brain areas contributing to both cardiovascular autonomic regulation and cognitive performance. To evaluate possible associations between both functions in patients with a history of TBI (post-TBI-patients), we determined correlations between cardiovascular autonomic regulation and cognitive function in post-TBI-patients.MethodsIn 86 post-TBI-patients (33.1 ± 10.8 years old, 22 women, 36.8 ± 28.9 months after injury), we monitored RR intervals (RRI), systolic and diastolic blood pressures (BPsys, BPdia), and respiration (RESP) at rest. We calculated parameters of total cardiovascular autonomic modulation (RRI-standard-deviation (RRI-SD), RRI-coefficient-of-variation (RRI-CV), RRI-total-powers), sympathetic (RRI-low-frequency-powers (RRI-LF), normalized (nu) RRI-LF-powers, BPsys-LF-powers) and parasympathetic modulation (root-mean-square-of-successive-RRI-differences (RMSSD), RRI-high-frequency-powers (RRI-HF), RRI-HFnu-powers), sympathetic-parasympathetic balance (RRI-LF/HF-ratios), and baroreflex sensitivity (BRS). We used the Mini-Mental State Examination and Clock Drawing Test (CDT) to screen the general global and visuospatial cognitive function, and applied the standardized Trail Making Test (TMT)-A assessing visuospatial abilities and TMT-B assessing executive function. We calculated correlations between autonomic and cognitive parameters (Spearman’s rank correlation test; significance: P < 0.05).ResultsCDT values positively correlated with age (P = 0.013). TMT-A values inversely correlated with RRI-HF-powers (P = 0.033) and BRS (P = 0.043), TMT-B values positively correlated with RRI-LFnu-powers (P = 0.015), RRI-LF/HF-ratios (P = 0.036), and BPsys-LF-powers (P = 0.030), but negatively with RRI-HFnu-powers (P = 0.015).ConclusionsIn patients with a history of TBI, there is an association between decreased visuospatial and executive cognitive performance and reduced parasympathetic cardiac modulation and baroreflex sensitivity with relatively increased sympathetic activity. Altered autonomic control bears an increased cardiovascular risk; cognitive impairment compromises quality of life and living conditions. Thus, both functions should be monitored in post-TBI-patients.

How to fill the gap in the symptomatic HF patient journey between optimal medical therapy and advanced heart failure treatment: two Italian surveys

Abstract Funding Acknowledgements Type of funding sources: None. Background Heart failure (HF) is the pandemic of our century and an estimated 64.3 million people are living with HF worldwide. New therapies alongside the old ones have been recently introduced in clinical practice with good results but the prognosis for a high percentage of patients remains poor with a high mortality rate and markedly reduced functional status. Purpose This study aims to investigate through two surveys what physicians think are the current needs in HF management to gain insight into the epidemiology and characteristics of patients followed by Italian HF outpatient clinics. In particular, we evaluated the gap that Cardiac Contractility Modulation (CCM) could fill in HF management in a real-world scenario. Methods a 20-question survey on HF management in different scenarios addressed to all physicians operating in Italian centers involved in HF care was published on the website Cardioinfo. A second survey was sent to Italian high-volume referral outpatient HF clinics. The participating centers were asked to collect the number of patients admitted during 4 weeks and to fill out a 19 items survey regarding some characteristics of these patients. Results A total of 105 physicians (77% cardiologists) and 14 high-volume referral outpatient HF clinics took part in the surveys. Despite regular clinical follow-up at 3-6 months in 94% of cases, the currently available medical therapy is considered insufficient in stabilizing HF patients in 30% of cases. 23% of physicians perceive to have a lack of treatment options in symptomatic patients with reduced ejection fraction and this percentage rises to 66% in patients without reduced ejection fraction (Figure 1). Cardiac contractility modulation is considered a valid option by 15% of physicians. According to Food and Drug Administration criteria, in the cohort of patients referred to HF clinics around 3% of patients are suitable for CCM implantation (2 patients a month per heart failure outpatient clinic), but considering additional selection criteria the percentage of patients eligible may increase to 5-6%. Conclusions The surveys confirm the significant attention paid to HF in Italian hospitals, however the lack of therapeutic options for a non-negligible number of patients, who are clinically evaluated regularly, but without associated substantial changes in therapy, leads to frustration for the patient and the physician, and an increase in costs for the health care system. A relatively small percentage of the total HF population fulfills the indication for immediate CCM treatment. Nevertheless, considering the size of the HF population, CCM, reducing hospitalizations, improving functional capacity and QoL may be of key importance for many HF patients, especially the elderly.

Cardiac contractility modulation: an effective treatment strategy for heart failure beyond reduced left ventricular ejection fraction?

Heart failure (HF) with preserved ejection fraction (HFpEF) causes a progressive limitation of functional capacity, poor quality of life (QoL) and increased mortality, yet unlike HF with reduced ejection fraction (HFrEF) there are no effective device-based therapies. Both HFrEF and HFpEF are associated with dysregulations in myocardial cellular calcium homeostasis and modifications in calcium-handling proteins, leading to abnormal myocardial contractility and pathological remodelling. Cardiac contractility modulation (CCM) therapy, based on a pacemaker-like implanted device, applies extracellular electrical stimulation to myocytes during the absolute refractory period of the action potential, which leads to an increase in cytosolic peak calcium concentrations and thereby the force of isometric contraction promoting positive inotropism. Subgroup analysis of CCM trials in HFrEF has demonstrated particular benefits in patients with LVEF between 35% and 45%, suggesting its potential effectiveness also in patients with higher LVEF values. Available evidence on CCM in HFpEF is still preliminary, but improvements in terms of symptoms and QoL have been observed. Future large, dedicated, prospective studies are needed to evaluate the safety and efficacy of this therapy in patients with HFpEF.

P259 S–ICD OFFERS A POTENTIAL SYNERGISTIC THERAPY FOR HEART FAILURE PATIENTS WITH AN INDICATION FOR ICD IMPLANTATION AND CANDIDATES FOR CCM IMPLANTATION

Abstract CCM (cardiac contractility modulation) is a very promising therapy in heart failure patients as it allows, by increasing intracellular calcium handling, an improvement in cardiac contractility, ejection fraction, and patient quality of life. It delivers high–energy (7.5 V) and long–duration (about 20 milliseconds) pulses in absolute refractory period through the use of two leads on the right ventricular septum. It is indicated in patients with narrow QRS (&amp;lt; 130 msec) and ejection fraction between 25 and 45%. Therefore, a large proportion of patients suitable for CCM therapy also have an indication for ICD implantation. The coexistence of an ICD (single–chamber or dual–chamber) and CCM presupposes the presence of 3 leads in the right ventricle and possibly a catheter in the right atrium if a dual–chamber ICD is used. The presence of numerous leads increases the risk of infection, mechanical complications, and damage on the leads. In view of the above, the strategy we propose in patients with concomitant indication for ICD and CCM is the use of the subcutaneous defibrillator (S–ICD) in patients with potential indication for CCM, narrow QRS, no pacing indication, and ejection fraction &amp;lt;35%, thus limiting the number of leads and the risk of complications. In our center, we have started using this strategy with excellent clinical results and in the absence of complications. One of the cases treated with this strategy is a 60–year–old patient with nonischemic dilated myocardiopathy, ejection fraction 34%, QRS &amp;lt; 130 msec, NYHA class III, despite therapy with beta blockers, ARNI, SGLT2–i, MRA at the maximum dose. The patient, also considering the potential future need for CCM implantation, underwent S–ICD implantation. After 3 months, NYHA class III with reduced quality of life persisted (MLHFQ 82). Therefore, the patient successfully underwent CCM implantation, with marked improvement in symptoms (MLHFQ 71) and ejection fraction (43%) 3 months later. This strategy avoided the placement of additional leads in the right ventricle while ensuring protection from potentially fatal arrhythmias and improvement in contractile function and symptoms. We suggest the use of the subcutaneous defibrillator (S–ICD) in all patients in whom there might be an indication for the use of CCM and no need for pacing, ensuring maximum efficacy and reducing the risk of infection and leads related complications.