BACKGROUND: Conduction system pacing (CSP) replaces right ventricular pacing (RVP) in bradycardia patients. OBJECTIVE: To compare CSP vs RVP in patients with pacemaker indication due to atrioventricular conduction disease. METHODS: This study randomized patients to CSP or RVP in 1:1 ratio and followed them for 12 months. CSP received either His bundle pacing or left bundle branch area pacing; The primary end point was a change in the left ventricular ejection fraction (LVEF). The combined composite clinical end point consisted of cardiovascular death, cardiac resynchronization therapy upgrade, or hospitalization for heart failure. RESULTS: Of 249 patients, 125 were randomized to RVP and 124 to CSP; there were no differences between clinical parameters. In CSP, 10 patients received His bundle pacing, 96 left bundle branch area pacing, 15 deep septal pacing, and 3 RVP. Procedural and fluoroscopy times were longer in CSP vs RVP (63 vs 40 and 7 vs 3 minutes; P < .001). In the intention-to-treat analysis, the LVEF decline in CSP was smaller than RVP (-2% vs -4%, P = .03), and a LVEF decrease ≥ 10% occurred more often in RVP 19 (16%) than CSP 6 (5%), P = .01. There was no difference in the composite clinical outcome between RVP and CSP (9 vs 4, P = .15). There was also no difference in procedural complications (9 in RVP vs 2 in CSP, P = .09). CONCLUSION: In patients with severe conduction disease, CSP led to a smaller LVEF decline than RVP after 1 year of pacing. Both pacing methods had similar rates of clinical end points and procedural complications.

• Keywords
• Conduction system pacing, His bundle pacing, Left bundle branch pacing, Randomized trial, Right ventricular pacing,
• MeSH
• Atrioventricular Block * therapy   physiopathology   MeSH
• Electrocardiography MeSH
• Ventricular Function, Left physiology   MeSH
• Bundle of His * physiopathology   MeSH
• Cardiac Pacing, Artificial * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Heart Conduction System * physiopathology   MeSH
• Prospective Studies MeSH
• Aged MeSH
• Heart Ventricles * physiopathology   MeSH
• Stroke Volume physiology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

Severe aortic stenosis (AS) is a recognized risk factor for sudden cardiac death (SCD). Although ventricular tachyarrhythmias are the most common immediate cause of SCD, the majority of cases of SCD in patients with severe AS exhibited bradyarrhythmia as the primary rhythm. Enhanced activation of left ventricular baroreceptors (Bezold-Jarisch reflex) has been implicated in the pathogenesis of syncope in patients with AS. However, the precise mechanism by which an otherwise benign circulatory syncope can progress to cardiac arrest in severe AS remains unclear. This study proposes a haemodynamic-energetic mechanism to explain this progression, and demonstrates its plausibility using a mathematical model of cardiac haemodynamics and energetics. The model identifies states of cardiac energy imbalance, in which the energy expenditure of the heart exceeds the energy delivered to it. In individuals with a normal aortic valve, compensatory mechanisms can restore energy balance following syncope. By contrast, in severe AS, all conditions involving low peripheral vascular resistance are energetically unstable, regardless of compensatory response. Because energy imbalance is incompatible with sustained cardiac function, such states inevitably result in cardiac arrest. Importantly, the proposed mechanism does not require an exaggerated Bezold-Jarisch reflex, although the reflex probably acts as a trigger of syncope by initiating peripheral vasodilatation. Additionally, the limited coronary vasodilatory reserve commonly observed in severe AS significantly contributes to the development of myocardial energy imbalance. KEY POINTS: The precise mechanism of sudden cardiac death in patients with severe aortic stenosis remains uncertain. In the present study, we propose a novel haemodynamic-energetic mechanism of sudden cardiac death explaining how otherwise benign circulatory syncope can progress to cardiac arrest in patients with severe aortic stenosis. The plausibility of the mechanism is verified using a mathematical model. The model identifies states of cardiac energy imbalance in patients with severe aortic stenosis, where the energy expenditure of the heart exceeds the energy delivered to it, which inevitably leads to cardiac arrest. Mathematical simulation of a circulatory syncope reveals significant differences in the effects of compensatory response in patients with and without severe aortic stenosis. The results provide a comprehensive understanding of the mechanism of sudden cardiac death in patients with severe aortic stenosis.

• Keywords
• Bezold–Jarisch reflex, aortic stenosis, cardiac energetics, mathematical model, sudden death,
• Publication type
• Journal Article MeSH

BACKGROUND: Ultra-high-frequency electrocardiography (UHF-ECG) is a noninvasive tool visualizing the ventricular activation sequence. It was never compared with other methods of dyssynchrony assessment in patients with bradycardia. OBJECTIVE: We aimed to compare UHF-ECG interventricular electrical dyssynchrony (e-DYS) with interventricular mechanical delay (IVMD) measured by echocardiography in patients receiving right ventricular pacing (RVP) or conduction system pacing (CSP). METHODS: Fifty-three patients with advanced atrioventricular conduction disease and preserved ventricular systolic function were prospectively assigned to RVP (n=32 [60 %]) or CSP (n=21 [40 %]). IVMD was measured as the time difference between left ventricular and right ventricular preejection periods. Interventricular e-DYS was calculated by software as the time difference between activation in V1 and V7 chest electrodes using UHF-ECG. RESULTS: The median age of patients was 75 (interquartile range 72-80) years, and both groups had similar clinical characteristics. Baseline IVMD and interventricular e-DYS were similar in the entire population (-2 [-8 to 5] ms vs-1 [-6 to 5] ms, respectively; P=.52). Both methods showed the same dyssynchrony trends after pacemaker implantation; that is, while both IVMD and interventricular e-DYS increased in the RVP group (IVMD 28 [23-33] ms vs interventricular e-DYS 26 [19-33] ms; P=.99), they remained low in the CSP group (IVMD -7 [-16 to 2] ms vs interventricular e-DYS -5 [-12 to 2] ms; P=.91). There was a moderate overall correlation between IVMD and interventricular e-DYS for all studied ventricular rhythms (R=0.74). CONCLUSION: UHF-ECG noninvasively expresses interventricular dyssynchrony from V7-V1 chest leads with similar results to echocardiography. RVP increases interventricular dyssynchrony, while CSP preserves synchronous ventricular activation.

• Keywords
• Bradycardia, Conduction system pacing, Echocardiography, RV pacing, UHF-ECG, Ventricular dyssynchrony,
• MeSH
• Bradycardia * physiopathology   therapy   diagnosis   MeSH
• Echocardiography MeSH
• Electrocardiography * methods   MeSH
• Cardiac Pacing, Artificial * methods   MeSH
• Humans MeSH
• Heart Conduction System * physiopathology   MeSH
• Prospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Heart Ventricles * physiopathology   diagnostic imaging   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH

BACKGROUND: The role of heart failure-specific therapies in left ventricular assist device (LVAD) recipients is unclear, and observational data suggest improved outcomes with neurohormonal blockers. OBJECTIVES: ENVAD-HF (Multicenter, Randomized, Open-Label, Parallel Group, Study to Evaluate the Use of Sacubitril/Valsartan in HeartMate 3 LVAD Recipients) sought to evaluate the safety and tolerability of the angiotensin-neprilysin inhibitor sacubitril/valsartan vs standard of care (SOC) for managing blood pressure (BP) in HeartMate 3 LVAD recipients. METHODS: ENVAD-HF was a prospective multicenter, randomized, open-label study of sacubitril/valsartan vs SOC for managing BP (mean arterial pressure goal: 75-90 mm Hg) in stable LVAD recipients with 12-month follow-up. The composite primary endpoint was time to death, deterioration in renal function, hyperkalemia, or symptomatic hypotension leading to drug withdrawal. Exploratory endpoints included clinical and biomarker assessments and patient-reported outcomes. RESULTS: In 60 randomized patients (30 in each arm), sacubitril/valsartan compared with SOC demonstrated an HR of 0.42 (95% CI: 0.08-2.18; P = 0.30) for the primary endpoint at 12 months. Two primary endpoints were reached in the sacubitril/valsartan group (1 death and 1 symptomatic hypotension event) compared with 5 in the SOC group (2 deaths, 2 worsening renal function events, and 1 symptomatic hypotension event). Numerical trends in favor of sacubitril/valsartan were noted for other exploratory endpoints, including a reduced number of BP medications (difference: -1.09 [95% CI: -1.52 to -0.66]; P < 0.0001) and a significantly better Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (improvement: +10.6 [95% CI: 2.6-18.7]; P = 0.011). CONCLUSIONS: ENVAD-HF, a prospective randomized controlled trial of angiotensin-neprilysin inhibition in stable HeartMate 3 LVAD recipients, demonstrated the safety and tolerability of this therapy in this unique population. The trial forms the basis for a pivotal trial to investigate the usefulness of HF-specific therapies in the LVAD population. (Sacubitril/Valsartan in Left Ventricular Assist Device Recipients [ENVAD-HF], NCT04103554; A multicENter, randomized, open-label, parallel group, pilot study to evaluate the use of sacubitril/valsartan in HeartMate 3 LVAD recipients, 2019-003888-22).

• Keywords
• advanced heart failure, blood pressure, left ventricular assist device, neurohormonal blocking therapy, outcomes, sacubitril/valsartan,
• Publication type
• Journal Article MeSH

From previous studies, the right heart is considered less critical than the left heart in maintaining normal global hemodynamic performance. However, there is now substantial evidence underscoring the importance of comprehensive right ventricular (RV) function. Acute hypoxia is associated with an increase in pulmonary artery pressure (PAP), leading to changes in RV hemodynamics. Moreover, hypoxia may directly affect the RV. The current literature assessing the impact of acute hypoxia on RV hemodynamics remains insufficiently elucidated. This paper aims to delineate the effects of acute hypoxia exposure on the RV in healthy individuals.

• MeSH
• Ventricular Function, Right * physiology   MeSH
• Adaptation, Physiological * physiology   MeSH
• Hemodynamics * physiology   MeSH
• Hypoxia * physiopathology   pathology   MeSH
• Humans MeSH
• Ventricular Remodeling * physiology   MeSH
• Heart Ventricles * physiopathology   pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Serum canrenone concentrations have so far only been measured in patients with acute heart failure or heart failure with preserved ejection fraction. The results of these studies showed that low or undetectable canrenone concentrations could contribute to the lack of pharmacological effect of spironolactone, while patients with detectable canrenone concentrations had significantly higher potassium concentrations. However, no detailed information on serum canrenone concentrations in patients with heart failure with reduced ejection fraction (HFrEF) has been published to date. The aim of the study was to determine serum canrenone concentrations in samples collected from patients with HFrEF during routine medical care and correlate them with selected clinical parameters such as left ventricular ejection fraction (LVEF), systolic and diastolic blood pressure, and the levels of N-terminal pro-B-type natriuretic peptide, serum potassium, liver enzymes, and renal function markers. METHODS: This cross-sectional study analyzed data from 64 patients treated for HFrEF with oral spironolactone. Patients were recruited from the Cardiology Outpatient Clinic of the University Hospital, Ostrava, Czech Republic. Blood samples were collected in an outpatient setting from each patient between November 2022 and October 2023 as part of a routine examination to determine steady-state serum canrenone concentrations. RESULTS: Serum canrenone concentrations ranged from 5.0 to 336.2 µg/L. A correlation was observed between canrenone concentration and both the daily spironolactone dose and dose per kilogram of body weight. However, wide inter-individual variability was observed in canrenone concentrations achieved after administering the same dose of spironolactone and in the concentration-to-dose ratio. Patients with LVEF < 30% used the same dose per day and kilogram of body weight as patients with LVEF ≥ 30% but achieved significantly higher canrenone concentrations. A correlation was observed between canrenone and serum urea, creatinine, and potassium concentrations. An inverse correlation was observed between diastolic blood pressure and dose per kilogram of body weight. CONCLUSIONS: Wide inter-individual variability in the minimum serum concentrations of canrenone was observed after the same dose of spironolactone was administered. Patients with impaired renal and/or myocardial function were found to be at a higher risk of canrenone accumulation, leading to increased serum potassium concentrations.

• Keywords
• Canrenone, Concentrations, Heart failure, Monitoring, Spironolactone,
• Publication type
• Journal Article MeSH

BACKGROUND: With notable improvements in long-term survival and hemocompatibility-related events, heart failure (HF) is emerging as a leading cause of death in the contemporary left ventricular assist device (LVAD) population. Although prospective randomized controlled trials have not investigated the use of HF therapies in recipients of LVAD, observational data suggest benefits of neurohormonal blockers, especially in achieving blood pressure (BP) targets associated with improved outcomes. METHODS: The study "multicENter, randomized, open-label, parallel group, pilot study to evaluate the use of sacubitril/valsartan in HeartMate 3 LVAD recipients" (ENVAD-HF) is an investigator-initiated prospective multicenter, randomized, open-label, parallel group, pilot study of recipients of HeartMate 3 (HM3) LVADs to evaluate the safety and tolerability and insights on efficacy of sacubitril/valsartan compared to standard of care (SOC) for managing BP. Medically stable recipients of LVADs after a recent HM3 implantation or in ambulatory follow-up were eligible for participation and randomized 1:1 to receive sacubitril/valsartan or SOC used for treating BP, both titrated aiming for a mean arterial pressure goal 75-90 mm Hg over a 12-month follow-up. The primary endpoint, designed to assess the safety and efficacy of sacubitril/valsartan compared with SOC, is a composite of freedom from all-cause death, deterioration in renal function, hyperkalemia, or symptomatic hypotension. The occurrence of the primary endpoint will be assessed in the first three months and during the overall duration of the trial (12 months). Other endpoints include clinical and patient-reported outcomes, biomarker, and echocardiography assessments during follow-up. RESULTS: ENVAD-HF enrolled 60 patients between February 2021 and March 2024: 17% were female, mean age was 57 ± 12 years, 67% were in ambulatory follow-up, 55% had ischemic etiology, and 25% were receiving an LVAD as destination therapy, with mean baseline mean arterial pressure 87 ± 7 mm Hg and median N-terminal pro B-type natriuretic peptide 2552 (1595-3543) pg/mL. CONCLUSION: ENVAD-HF is the first prospective randomized controlled trial of pharmacologic therapy for the management of BP in stable recipients with HM3 LVADs achieving target enrollment. It will provide data on safety, tolerability, and insights on efficacy of sacubitril/valsartan versus SOC used for treating BP.

• Keywords
• Left ventricular assist device, blood pressure, outcomes, sacubitril/valsartan,
• Publication type
• Journal Article MeSH

BACKGROUND: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is an established treatment of heart failure with reduced ejection fraction and wide QRS. Left bundle branch area pacing (LBBAP) has emerged as a physiologic alternative by directly engaging the His-Purkinje system, potentially improving electrical resynchronization and clinical outcomes. OBJECTIVE: The aim of the study was to compare the clinical outcomes between BVP and LBBAP in patients with left ventricular ejection fraction (LVEF) ≤50% undergoing CRT. METHODS: This multicenter observational study included patients with LVEF ≤50% receiving CRT with either LBBAP or BVP at 18 centers from January 2018 to June 2023. The primary outcome was a composite of all-cause mortality or first heart failure hospitalization (HFH). Secondary outcomes included separate analyses of HFH and all-cause mortality. Propensity score matching was used to balance baseline characteristics. Kaplan-Meier curves, Cox proportional hazards models, and competing risk analyses were performed. RESULTS: A total of 2579 patients were included (BVP, 1118; LBBAP, 1461). In the propensity score-matched cohort (BVP, 780; LBBAP, 780), LBBAP demonstrated shorter paced QRS duration (129 ± 19 ms vs 143 ± 22 ms; P < .001). LBBAP was associated with a significantly lower risk of the composite primary outcome (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.66-0.98; P = .048) and reduced HFH (HR, 0.63; 95% CI, 0.49-0.82; P < .001). No significant difference in all-cause mortality was observed (HR, 0.82; 95% CI, 0.63-1.07; P = .156). Procedural complications were lower with LBBAP (3.5% vs 6.5%, P = .004). CONCLUSION: LBBAP was associated with superior electrical resynchronization, fewer HFHs, and lower procedural complications compared with BVP in patients with LVEF <50% requiring CRT. Randomized trials are needed to confirm long-term benefits.

• Keywords
• Biventricular pacing, Cardiac resynchronization therapy, Heart failure hospitalization, Left bundle branch area pacing, Mortality,
• MeSH
• Ventricular Function, Left * physiology   MeSH
• Bundle of His * physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Cardiac Resynchronization Therapy * methods   MeSH
• Heart Failure * therapy   physiopathology   mortality   MeSH
• Stroke Volume * physiology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Comparative Study MeSH

AIMS: Patients with acute decompensated advanced heart failure requiring left ventricular assist device (LVAD) implantation often experience progressive cardiac function deterioration, negatively impacting surgical outcomes. This study aimed to assess the efficacy of different microaxial flow pump (mAFP) support devices (Impella®) in achieving optimal left ventricular unloading for preconditioning and facilitating definitive treatment in this high-risk patient cohort. METHODS AND RESULTS: A retrospective analysis was conducted across 19 high-volume European centres. The study population included patients transitioning from temporary to durable circulatory support over a 7.5-year period, with a median follow-up of 1 year. Patients were categorized based on mAFP support capacity: those receiving high-flow support (>5 L/min, '5+') and those with lower-flow support (3.5 L/min, 'CP'). Patients who were initially treated with CP but subsequently upgraded to 5+ support were classified in the 5+ group. Demographic and clinical characteristics, mobilization, right heart function, and organ dysfunction outcomes were analysed. A total of 339 patients received preoperative mAFP support prior to LVAD implantation. The 5+ group comprised 247 patients (73%), including 38 patients who were upgraded from CP, while the CP group included 92 patients (27%). Baseline demographic and clinical characteristics were comparable between groups, except for mobilization status, which showed significant differences (P < 0.001). Patients in the 5+ group achieved higher rates of full and partial mobilization compared to the CP group. Extracorporeal life support (ECLS) was more frequently required in the CP group than in the 5+ group (40.5% vs. 33.8%; P < 0.001). Additionally, right ventricular assist device (RVAD) implantation was significantly more common in the CP group (29.2% vs. 18.2%; P = 0.026). Patients in the 5+ group demonstrated greater reductions in both vasoactive inotropic scores (P = 0.006) and inotropic scores (P = 0.008). Furthermore, liver dysfunction (P = 0.016), renal failure (P = 0.041), and the need for dialysis (P = 0.013) were significantly more prevalent in the CP group. There were no significant differences between the two groups in terms of LVAD operative duration (P = 0.637) or cardiopulmonary bypass time (P = 0.408). CONCLUSIONS: High-flow mAFP devices (+5) provided superior haemodynamic support, enhanced left ventricular unloading, and reduced dependence on catecholamines compared to lower-flow CP devices. These improvements were associated with lower rates of right ventricular failure, renal dysfunction, and liver injury. However, no statistically significant difference was observed between mAFP groups regarding 30-day mortality rates.

• Keywords
• Cardiogenic shock, Durable mechanical circulatory support, Impella, Left heart failure, Microaxial flow pump,
• MeSH
• Equipment Design MeSH
• Ventricular Function, Left * physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Heart-Assist Devices * MeSH
• Prosthesis Design MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Heart Failure * surgery   physiopathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Comparative Study MeSH

BACKGROUND: Untreated thyroid disorders may precipitate heart failure (HF) decompensation. Assessment of cardiac filling pressures may aid in the early detection and prevention of clinical decompensation. Therapy guided by monitoring of cardiac filling pressures has been shown to improve quality of life and survival and reduce hospitalizations of individuals with HF. We have developed a non-invasive method to assess left ventricular filling pressures (LVFP) by analysing the photoplethysmography signal with Seeling HeartCore technology (Seerlinq, Bratislava, Slovakia). CASE DESCRIPTION: A 99-year-old female visited the clinic for a routine cardiac check-up. Laboratory investigations showed elevated NTproBNP and moderately elevated high sensitive troponin T. HeartCore algorithm indicated elevated LVFP. As part of the evaluation of worsening of sub-clinical HF, extended laboratory tests revealed low thyroid-stimulating hormone with high free thyroxine levels indicating increased thyroid function. The endocrinologist diagnosed hyperthyroidism with multinodular goitre and prescribed thiamazole. To prevent progression to clinical HF decompensation, the dose of furosemide was increased. At 4 months, during scheduled cardiac follow-up, the patient was clinically doing well, without any signs or symptoms of HF. DISCUSSION: Remote monitoring devices that track pressures in the pulmonary artery require invasive implantation and are associated to potential complications. The high cost of these devices presents a significant barrier to widespread use. SEERLINQ is a novel system for remote haemodynamic monitoring based on non-invasive assessment of LVFP, presenting a promising alternative to current invasive methods. CONCLUSION: This case underscores the potential benefits of this technology in the early recognition of pre-clinical deterioration and its implementation for remote home monitoring in patients with HF. LEARNING POINTS: Untreated thyroid disorders in patients with heart failure (HF) can exacerbate signs and symptoms of HF.Left ventricular filling pressure (LVFP) rises 3-4 weeks before HF symptoms. Echocardiographic assessment of LVFP can be challenging in patients with atrial fibrillation or paced rhythms.Photoplethysmography-based analysis could be utilized to assess LVFP, enabling remote monitoring of HF patients and potentially preventing HF decompensation and hospitalization.

• Keywords
• Heart failure, artificial intelligence, hyperthyroidism, photoplethysmography, telemonitoring,
• Publication type
• Journal Article MeSH