Right Heart Research Articles

Reprint of: How He Did It – The James S. Tweddell Approach to Single Ventricle Palliation in Patients With Hypoplastic Left Heart Syndrome

This article will detail Dr. James Tweddell's operative technique and considerations for 26 all three stages of SVP in patients with HLHS. This will include the Norwood Procedure with 27 Right-Ventricle-to-Pulmonary-Artery Conduit (Sano Modification), Bidirectional Glenn 28 (Superior Cavopulmonary Connection), and Extracardiac, Fenestrated Fontan Completion (Total 29 Cavopulmonary Connection). These techniques are the culmination of over 20 years of experience 30 and represent the final techniques he employed at both Children's Hospital of Wisconsin and 31 Cincinnati Children's Hospital Medical Center.

Fetal single ventricle journey to first postnatal procedure: a multicentre UK cohort study

ObjectivesUK single ventricle (SV) palliation outcomes after first postnatal procedure (FPP) are well documented. However, survival determinants from fetal diagnosis to FPP are lacking. To better inform parental-fetal counselling, we...

Vago-splenic signal transduction of cardioprotection in humans.

The spleen serves as an important relay organ that releases cardioprotective factor(s) upon vagal activation during remote ischaemic conditioning (RIC) in rats and pigs. The translation of these findings to humans was attempted. Remote ischaemic conditioning or electrical auricular tragus stimulation (ATS) were performed in 10 healthy young volunteers, 10 volunteers with splenectomy, and 20 matched controls. Venous blood samples were taken before and after RIC/ATS or placebo, and a plasma dialysate was infused into isolated perfused rat hearts subjected to global ischaemia/reperfusion. Neither left nor right RIC or ATS altered heart rate and heart rate variability in the study cohorts. With the plasma dialysate prepared before RIC or ATS, respectively, infarct size (% ventricular mass) in the recipient rat heart was 36 ± 6% (left RIC), 34 ± 3% (right RIC) or 31 ± 5% (left ATS), 35 ± 5% (right ATS), and decreased with the plasma dialysate from healthy volunteers after RIC or ATS to 20 ± 4% (left RIC), 23 ± 6% (right RIC) or to 19 ± 4% (left ATS), 26 ± 9% (right ATS); infarct size was still reduced with plasma dialysate 4 days after ATS and 9 days after RIC. In a subgroup of six healthy volunteers, such infarct size reduction was abrogated by intravenous atropine. Infarct size reduction by RIC or ATS was also abrogated in 10 volunteers with splenectomy, but not in their 20 matched controls. In humans, vagal innervation and the spleen as a relay organ are decisive for the cardioprotective signal transduction of RIC and ATS.

Pulmonary hypertension across the spectrum of left heart and lung disease.

Patients with pulmonary hypertension (PH) are grouped based upon clinical and haemodynamic characteristics. Groups 2 (G2, left heart disease [LHD]) and 3 (G3, lung disease or hypoxaemia) are most common. Many patients display overlapping characteristics of heart and lung disease (G2-3), but this group is not well-characterized. Patients with PH enrolled in the prospective, NHLBI-sponsored PVDOMICS network underwent intensive clinical, biomarker, imaging, gas exchange and exercise phenotyping. Patients with pure G2, pure G3, or overlapping G2-3 PH were compared across multiple phenotypic domains. Of all patients with predominant G2 (n = 136), 66 (49%) were deemed to have secondary lung disease/hypoxaemia contributors (G2/3), and of all patients categorized as predominant G3 (n = 172), 41 (24%) were judged to have a component of secondary LHD (G3/2), such that 107 had G2-3 (combined G2/3 and G3/2). As compared with G3, patients with G2 and G2-3 were more obese and had greater prevalence of hypertension, atrial fibrillation, and coronary disease. Patients with G2 and G2-3 were more anaemic, with poorer kidney function, more cardiac dysfunction, and higher N-terminal pro-B-type natriuretic peptide than G3. Lung diffusion was more impaired in G3 and G2-3, but commonly abnormal even in G2. Exercise capacity was severely and similarly impaired across all groups, with no differences in 6-min walk distance or peak oxygen consumption, and pulmonary vasoreactivity to nitric oxide did not differ. In a multivariable Cox regression model, patients with G2 had lower risk of death or transplant compared with G3 (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.86), and patients with G2-3 also displayed lower risk compared with G3 (HR 0.57, 95% CI 0.38-0.86). Overlap is common in patients with a pulmonary or cardiac basis for PH. While lung structure/function is clearly more impaired in G3 and G2-3 than G2, pulmonary abnormalities are common in G2, even when clinically judged as isolated LHD. Further study is required to identify optimal systematic evaluations to guide therapeutic innovation for PH associated with combined heart and lung disease. ClinicalTrials.gov NCT02980887.

Mechanisms of myocardial reverse remodelling and its clinical significance: A scientific statement of the ESC Working Group on Myocardial Function.

Cardiovascular disease (CVD) is the leading cause of morbimortality in Europe and worldwide. CVD imposes a heterogeneous spectrum of cardiac remodelling, depending on the insult nature, that is, pressure or volume overload, ischaemia, arrhythmias, infection, pathogenic gene variant, or cardiotoxicity. Moreover, the progression of CVD-induced remodelling is influenced by sex, age, genetic background and comorbidities, impacting patients' outcomes and prognosis. Cardiac reverse remodelling (RR) is defined as any normative improvement in cardiac geometry and function, driven by therapeutic interventions and rarely occurring spontaneously. While RR is the outcome desired for most CVD treatments, they often only slow/halt its progression or modify risk factors, calling for novel and more timely RR approaches. Interventions triggering RR depend on the myocardial insult and include drugs (renin-angiotensin-aldosterone system inhibitors, beta-blockers, diuretics and sodium-glucose cotransporter 2 inhibitors), devices (cardiac resynchronization therapy, ventricular assist devices), surgeries (valve replacement, coronary artery bypass graft), or physiological responses (deconditioning, postpartum). Subsequently, cardiac RR is inferred from the degree of normalization of left ventricular mass, ejection fraction and end-diastolic/end-systolic volumes, whose extent often correlates with patients' prognosis. However, strategies aimed at achieving sustained cardiac improvement, predictive models assessing the extent of RR, or even clinical endpoints that allow for distinguishing complete from incomplete RR or adverse remodelling objectively, remain limited and controversial. This scientific statement aims to define RR, clarify its underlying (patho)physiologic mechanisms and address (non)pharmacological options and promising strategies to promote RR, focusing on the left heart. We highlight the predictors of the extent of RR and review the prognostic significance/impact of incomplete RR/adverse remodelling. Lastly, we present an overview of RR animal models and potential future strategies under pre-clinical evaluation.

The assessment of left ventricular diastolic function: guidance and recommendations from the British Society of Echocardiography.

Impairment of left ventricular (LV) diastolic function is common amongst those with left heart disease and is associated with significant morbidity. Given that, in simple terms, the ventricle can only eject the volume with which it fills and that approximately one half of hospitalisations for heart failure (HF) are in those with normal/'preserved' left ventricular ejection fraction (HFpEF) (Bianco et al. in JACC Cardiovasc Imaging. 13:258-271, 2020. 10.1016/j.jcmg.2018.12.035), where abnormalities of ventricular filling are the cause of symptoms, it is clear that the assessment of left ventricular diastolic function (LVDF) is crucial for understanding global cardiac function and for identifying the wider effects of disease processes. Invasive methods of measuring LV relaxation and filling pressures are considered the gold-standard for investigating diastolic function. However, the high temporal resolution of trans-thoracic echocardiography (TTE) with widely validated and reproducible measures available at the patient's bedside and without the need for invasive procedures involving ionising radiation have established echocardiography as the primary imaging modality. The comprehensive assessment of LVDF is therefore a fundamental element of the standard TTE (Robinson et al. in Echo Res Pract7:G59-G93, 2020. 10.1530/ERP-20-0026). However, the echocardiographic assessment of diastolic function is complex. In the broadest and most basic terms, ventricular diastole comprises an early filling phase when blood is drawn, by suction, into the ventricle as it rapidly recoils and lengthens following the preceding systolic contraction and shortening. This is followed in late diastole by distension of the compliant LV when atrial contraction actively contributes to ventricular filling. When LVDF is normal, ventricular filling is achieved at low pressure both at rest and during exertion. However, this basic description merely summarises the complex physiology that enables the diastolic process and defines it according to the mechanical method by which the ventricles fill, overlooking the myocardial function, properties of chamber compliance and pressure differentials that determine the capacity for LV filling. Unlike ventricular systolic function where single parameters are utilised to define myocardial performance (LV ejection fraction (LVEF) and Global Longitudinal Strain (GLS)), the assessment of diastolic function relies on the interpretation of multiple myocardial and blood-flow velocity parameters, along with left atrial (LA) size and function, in order to diagnose the presence and degree of impairment. The echocardiographic assessment of diastolic function is therefore multifaceted and complex, requiring an algorithmic approach that incorporates parameters of myocardial relaxation/recoil, chamber compliance and function under variable loading conditions and the intra-cavity pressures under which these processes occur. This guideline outlines a structured approach to the assessment of diastolic function and includes recommendations for the assessment of LV relaxation and filling pressures. Non-routine echocardiographic measures are described alongside guidance for application in specific circumstances. Provocative methods for revealing increased filling pressure on exertion are described and novel and emerging modalities considered. For rapid access to the core recommendations of the diastolic guideline, a quick-reference guide (additional file 1) accompanies the main guideline document. This describes in very brief detail the diastolic investigation in each patient group and includes all algorithms and core reference tables.

Impact of veno-venous collaterals on outcome after the total cavopulmonary connection

ObjectiveTo evaluate the prevalence of veno-venous collaterals (VVCs) after total cavopulmonary connection (TCPC) and analyze their impact on outcomes. MethodsPatients undergoing TCPC between 1994 and 2022 were evaluated. VVCs were identified using angiograms of cardiac catheterizations and their impact on outcomes was analyzed. ResultsA total of 635 patients were included. Median age at TCPC was 2.3 (interquartile ranges (IQR): 1.8–3.3) years. The most frequent diagnosis was hypoplastic left heart syndrome in 173 (27.2%) patients. Prior bidirectional cavopulmonary shunt was performed in 586 (92.3%) patients at a median age of 5.3 (3.6–9.9) months. VVCs were found in 94 (14.8%) patients at a median of 2.8 (0.1–11.8) years postoperatively. The prevalence of VVCs was similar between the dominant right and left ventricle (14.7 vs. 14.9%, p = 0.967). Mean pulmonary artery pressure (16.2 vs. 16.0 mmHg, p = 0.902), left atrial pressure (5.5 vs. 5.7 mmHg, p = 0.480), transpulmonary gradient (4.0 vs. 3.8 mmHg, p = 0.554) and oxygen saturation (81.4 vs. 82.6%, p = 0.103) before TCPC were similar between patients with and without VVCs. The development of VVCs did not affect survival after TCPC (p = 0.161). Nevertheless, VVCs were a risk for the development of plastic bronchitis (PB, p < 0.001). Interventional closure of VVCs was performed in 60 (9.4%) patients at a median of 8.9 (0.6–15.1) years after TCPC, and improvement of oxygen saturation was observed in 66% of the patients. ConclusionsThe prevalence of VVCs after TCPC was 15%. VVCs had no impact on survival following TCPC but were associated with a high prevalence of PB.

Atrial septal interventions during and after hybrid stage I palliation of hypoplastic left heart syndrome.

Hybrid stage I palliation (HS1P) is an alternative approach for initial palliation in hypoplastic left heart syndrome (HLHS) patients. Unlike surgical stage I palliation where atrial septectomy is routinely performed, atrial septal intervention (ASI) during HS1P is variable. In this study, we described our experience with ASI in single ventricle (SV) patients who underwent HS1P and identified factors associated with need for ASI after HS1P. Data were retrospectively collected for all HLHS patients who underwent HS1P at our center over the past 12 years. We evaluated ASIs performed during the HS1P (intra-HS1P ASI) and ASIs performed during the period from HS1P to the subsequent surgical stage, either interval Norwood stage I or comprehensive stage II (post-HS1P ASI). Patient factors and procedural data were compared to identify factors associated with undergoing post-HS1P ASI and the impact of ASI on patient outcomes was evaluated. Of 50 SV patients included, 23 (46%) underwent intra-HS1P ASI and 26 (52%) underwent post-HS1P ASI. Need for post-HS1P ASI was lower among patients who had an intra-HS1P ASI as compared to those who did not (30% vs. 70%; p = 0.005). There were no significant differences in short or Midterm outcomes between patients who underwent intra-HS1P ASI or post-HS1P ASI and their counterparts. ASI is common both during and after HS1P but is generally well tolerated and type of ASI does not significantly impact overall patient outcomes. Our findings suggest that the current approach of individualizing management of ASI in the HS1P population is effective and safe.

The effect of garlic formulation on some hematological parameters and organ weight of male and female Wister albino rats

The study was conducted to investigate the impact of garlic formulation on certain haematological parameters and organ weights in both male and female rats. Haematological data, including the count of red blood corpuscles (RBC), the volume of packed cells (PCV), the count of white blood corpuscles (WBC), and the count of platelets, were evaluated using a fully automated haematology analyser. The liver, right kidney, left kidney, heart, and spleen of the rats were weighed to determine their respective organ weights. A total of thirty (30) albino Wister rats, consisting of both males and females, were randomly assigned to five groups, with six animals in each group. Group 1 acted as the positive control and was given 100% standard feed. Group II rats were given a mixture of 10% garlic and 90% feed. Group III animals were provided with a diet consisting of 20% garlic and 80% feed. Group IV received a diet containing 40% garlic and 60% feed. The final group, Group V, was fed a diet consisting of 80% garlic and 20% feed daily for a period of 21 days. The feed formulation was assessed at concentrations of 10, 20, 40, and 80 g/dl, based on the weight of the animal. The findings indicated a noteworthy (P&lt;0.05) reduction in white blood cell count (WBC) and lymphocyte count (LYM). There were no statistically significant changes (P&gt;0.05) observed in the levels of haemoglobin (HGB), haematocrit (HCT), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV), and mean corpuscular haemoglobin (MCH) when compared to the control group. Furthermore, there was a noteworthy (P&lt;0.05) reduction in HGB, MCV, and MCH when the rats reached a body weight of 80 g/100dl. The results indicated a statistically significant (P&lt;0.05) reduction in the weight of the left kidney, heart, and spleen, as well as in the liver and right kidney weights at 20, 40, and 80 g/dl body weight. There were no statistically significant differences (P&gt;0.05) in the body weight of the liver and right kidney, which were both 10g/dl. Ultimately, the use of garlic formulation in appropriate dosages can impact certain haematological markers and the weights of organs.

Cardioprotective effects of Empagliflozin in cardiac volume overload-induced by aortocaval fistula in rats

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Slovak Research and Development Agency under the contract no. 21-0410 VEGA grants no. 2/0006/23 Heart failure is characterized by reduction in cardiac output and the occurrence of malignant arrhythmias, thereby contributing significantly to high morbidity and mortality worldwide. Myocardial structural remodelling is a key factor contributing to the development of these life-threatening events and belongs to unsolved clinical issues challenging to investigate in animal models. The aim of our study was to explore the impact of cardiac volume overload (VO) on structural remodelling and electrical coupling protein, connexin43 (Cx43) in the left and right heart ventricles as well as the efficacy of treatment with SGLT2i, Empagliflozin. Aortocaval fistula (ACF) was surgically induced in 6-month-old Wistar rats, to develop VO during 4 weeks, followed by oral administration of Empagliflozin 10 mg/kg/b.w. daily for 5 weeks. At the end of the experiment, biometric parameters were registered and left and right heart tissue samples were snap-frozen and kept at -80°C for western blot analysis and microscopic examination. Findings revealed an increase of heart, left and right ventricular mass due to ACF-VO versus sham controls, which was associated, with eccentric myocardial hypertrophy. Noteworthy, Empagliflozin reduced heart, left and right ventricular mass. Levels of myocardial protein Cx43, that determine electrical coupling among cardiomyocytes, were reduced by ACF-VO, while normalized by treatment with Empagliflozin. Moreover, treatment attenuated ACF-VO-induced increase of interstitial collagen visualized by van Gieson staining. It was in line with the protein expression of MMP-2, which is involved in structural remodeling. The protein levels of PKCε, concerned/associated with modulation of Cx43 and extracellular matrix, were decreased due to ACV-VO but normalized after treatment with Empagliflozin. On the other hand, protein levels of PKCδ, involved in proapoptotic and prohypertrophic pathways, were increased and normalized by Empagliflozin. The changes were more pronounced in the right ventricle compared to the left heart ventricle. In summary, our pilot results point out the benefit of Empagliflozin due to the suppression of myocardial structural remodelling and preservation of Cx43 in the rat ACF-VO model. Furthermore, this Empagliflozin-induced cardioprotection was associated with the normalization of Cx43, MMP-2, and PKC levels independent of glucose control. However, further analyses are needed to reveal the molecular mechanisms of the cardioprotective effects of Empagliflozin.

Catheter-Based Fetal Cardiac Interventions.

Fetal cardiac intervention (FCI) is an emerging and rapidly advancing group of interventions designed to improve outcomes for fetuses with cardiovascular disease. Currently, FCI is comprised of pharmacologic therapies (e.g., trans-placental antiarrhythmics for fetal arrhythmia), open surgical procedures (e.g., surgical resection of pericardial teratoma), and catheter-based procedures (e.g., fetal aortic valvuloplasty for aortic stenosis). This review focuses on the rationale, criteria for inclusion, technical details, and current outcomes of the three most frequently performed catheter-based FCI procedures: (1) aortic valvuloplasty for critical aortic stenosis (AS) associated with evolving hypoplastic left heart syndrome (HLHS), (2) atrial septal intervention for HLHS with severely restrictive or intact atrial septum (R/IAS), and (3) pulmonary valvuloplasty for pulmonary atresia with intact ventricular septum (PA/IVS).

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects

Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. ClinicalTrials.gov Identifier: NCT02133573.

Postextrasystolic repolarization changes of ventricular premature beats correlate with structural heart disease and suggest prognostic implications

Ventricular premature beats (VPBs) can potentially lead to life-threatening arrhythmias, especially in patients with structural heart disease (SHD). However, identifying dangerous VPBs has always been a topic and challenge in clinical research. This study aimed to evaluate the relationship of postextrasystolic repolarization changes of VPBs with SHD and its possible additional prognostic value. 125 cases of frequent VPBs with SHD and 156 cases without SHD were included. VPBs were stratified selected from 24 h Holter recording according to the scale of heart rate. Average QTDV (difference value of QT interval between the first beat follow VPB with beats preceding VPB) and max QTDV were significantly longer in SHD group than that in the non-SHD group. For identifying patients with SHD, the best cutoff value were 19 ms for average QTDV (AUC = 0.931) and 29 ms for max QTDV (AUC = 0.910) respectively. For Tu morphology analysis, PT2 (postextrasystolic T wave amplitude change ≥2 mV), reversed T wave, and Pu (postextrasystolic u wave) change were all highly specific, but low sensitive as identification of SHD. Compared with average QTDV < 19 ms patients, average QTDV ≥ 19 ms patients had significantly larger left heart size and wores left cardiac function. The presence of non-persistent ventricular tachycardia runs was higher in average QTDV ≥ 19 ms group and positive Pu change group than that in control groups. The findings indicated that postextrasystolic repolarization changes of VPBs correlated with SHD and suggested potential value in prognosis asssessment.

Ventricular Morphology and Outcomes in Fontan Circulation without Hypoplastic Left Heart Syndrome: A Single-Center's Experience

Ventricular Morphology and Outcomes in Fontan Circulation without Hypoplastic Left Heart Syndrome: A Single-Center's Experience

Defining the cardiovascular phenotype of adults with Alström syndrome

Background>40% of infants with Alström Syndrome (AS) present with a transient, severe cardiomyopathy in the first months of life, with apparent recovery in survivors. One in five individuals then develop a later-onset cardiomyopathy but wide clinical variability is observed, even within the same family. The rationale for this study is to provide a comprehensive evaluation of the cardiovascular phenotype in adults with AS. MethodsAdults attending the National Centre for AS in England were studied. All patients underwent biochemical, 12- lead electrocardiography, echocardiography, and cardiovascular magnetic resonance imaging. Results47 adults with AS (64% male; mean age 33 years; 66% white British) were studied. Seven (15%) survived infantile cardiomyopathy and 23 (49%) developed adult-onset cardiomyopathy. Conventional risk factors for cardiovascular disease were present in 39 (83%). Abnormalities were present on biomarkers in 16 (34%), ECG 30 (64%), echocardiography 19 (40%) and CMR 31 (66%). Coronary artery imaging was performed in six (13%), with abnormalities in two. Cardiac, renal, and liver markers were more often impaired in older patients, with impaired left ventricular ejection fraction, reduced global longitudinal strain and late enhancement. 6 (13%) had severe pulmonary hypertension (mean pulmonary artery pressure 46 mmHg) due to left heart disease on invasive testing. ConclusionCardiomyopathy is common in adults with AS, complicated in a significant proportion by atherosclerotic coronary artery disease and restrictive cardiomyopathy, confirmed on CMR and invasive testing. With advancing age, cardiovascular complications are compounded by contemporaneous renal and liver disease.

Comparison of long-term risk of device-related complications between left bundle branch area pacing and biventricular pacing in candidates for resynchronization therapy

Abstract Introduction Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS. Left bundle branch area pacing (LBBAP) has recently been shown to be a feasible and effective alternative to BVP. Comparative data on the risk of complications between LBBAP and BVP among CRT candidates are lacking. Purpose The aim of this study was to compare the long-term risk of device-related complications between LBBAP and BVP in a cohort of patients undergoing CRT. Methods Prospective, multicenter, observational study enrolling 668 consecutive patients (71.2±10.0 years, 52.2% male, 59.4% NYHA class &amp;gt;II), with LVEF ≤35% (mean 33.4±4.3%) who underwent BVP (n=560) or LBBAP (n=108) for the first time for Class I or II indications for CRT from January 2020 to June 2023 at 6 Italian centers. Propensity matching for baseline characteristics yielded 90 matched pairs. Rate and nature of device-related complications occurring during follow-up were prospectively collected and compared between the two groups. Results During a mean follow-up of 18 months, device-related complications were observed in 14 patients: 11 in BVP (12.2%), and in 3 in LBBAP (3.3%) (p=0.026). Compared to BVP patients, LBBAP patients showed a higher cumulative survival free from first device–related complication (Figure). Complications related to coronary sinus lead were most frequently observed in BVP patients (36.4% of all complications). The rate of overall lead-related complications was 6.7 and 2.2% in BVP and LBBAP patients, respectively (p=0.149). Conclusion LBBAP was associated with a lower long-term risk of device-related complications compared with BVP in patients with CRT indications.

Permanent pacemaker at the time of coronary artery bypass grafting and long-term outcome: a nationwide study from the SWEDEHEART registry

Abstract Introduction A permanent pacemaker is not rare in patients who undergo coronary artery bypass grafting (CABG). It is unknown if the presence of a pacemaker influences the long-term prognosis after surgery. Purpose To investigate if patients with permanent pacemaker have a higher risk for severe complications after CABG. Methods All patients who underwent CABG in Sweden 2006-2020 were included in a nationwide observational study based on prospectively collected data. Exclusion criteria were implantation of a cardioverter defibrillator at any time (prior to or after surgery) and death within 30 days. Individual patient data was merged from SWEDEHEART, The Swedish ICD- and pacemaker registry, the Cause of Death Register and the National Patient Register. Multivariable Cox regressions models were used to obtain hazard ratios (HR) with 95% confidence intervals (95%CI). The model was adjusted for age at operation, sex, left ventricular ejection fraction, heart failure, previous myocardial infarction, diabetes, peripheral artery disease, chronic respiratory disease, hypertension and atrial fibrillation. Results In total 41,722 patients underwent CABG during the study period, 555 (1.3%) of these had a previously implanted permanent pacemaker. Patients with a previous pacemaker were older, more often male, and had more often reduced left ventricular ejection fraction heart failure, atrial fibrillation, diabetes, hypertension and peripheral artery disease. Permanent pacemaker was not associated with higher risk for all-cause mortality (adjusted HR (aHR) 1.09 (95%CI=0.96-1.26), p=0.30, Figure 1), myocardial infarction (aHR: 1.01 (95%CI=0.73-1.41), p=0.94), or cardiovascular mortality (HR: 1.19 (95%CI=0.98-1.44), p=0.082). However, permanent pacemaker implantation was associated with increased risk for heart failure hospitalization (HR: 2.16 (95%CI=1.84-2.53), p&amp;lt;0.001). Conclusions A permanent pacemaker before CABG is not associated with increased mortality, cardiovascular mortality nor new myocardial infarction, but an increased risk for heart failure hospitalization after CABG. These patients could benefit from increased surveillance for heart failure symptoms after surgery to prevent hospitalizations.

Accelerated pacing reduces left heart filling pressures: a novel therapy for heart failure with preserved ejection fraction?

Abstract Background The recent MyPACE trial demonstrated significant improvement of quality-of-life, physical activity, and atrial fibrillation (AF) burden with accelerated pacing as compared to the standard 60bpm back-up rate setting in patients with heart failure with preserved ejection fraction (HFpEF) and indication for pacemaker therapy. We hypothesized that a potential working mechanism underlying these improved outcomes lies in the reduction of left heart filling pressures during accelerated pacing, reducing congestion and atrial stretch. Aim To assess the acute effects of accelerated atrial pacing on left heart filling pressures in consecutive AF patients undergoing catheter ablation. Methods Fifty AF patients undergoing catheter ablation were prospectively enrolled for accelerated atrial pacing. As illustrated in Figure 1, pacing was performed proximally in coronary sinus (CS). Pacing rate was increased incrementally from resting heart rate by 10-bpm increments up to Wenckebach rhythm, with 30-sec intervals of pacing on and off for hemodynamic stabilization. Left atrial pressure (LAP) was continuously monitored via a fluid-filled transseptal sheath (SL0 sheath, Abbott). Acute pacing-induced changes in mean LAP and PR-interval were evaluated at each pacing rate and compared between resting heart rate, the patient-specific optimal heart rate (i.e., the rate resulting in the lowest mean LAP), and the maximum pacing rate. Results Atrial pacing acutely decreased mean LAP from 14.8[9.8; 18.4] to 12.8[8.5; 15.8]mmHg (median[IQR], p&amp;lt;0.001) as heart rate increased from 51[47; 61] to 90[70; 100]bpm (p&amp;lt;0.001) (Figure 2, resting versus optimal category). Among the 50 patients included, only 4 did not exhibit a decrease in LAP. Further increasing pacing rate to a maximum of 130[100; 140]bpm resulted in an acute LAP increase to 16.2[12.7; 19.9]mmHg (p&amp;lt;0.001) to values above resting mean LAP. Accelerated pacing induced negative AV dromotropy, i.e., lengthening of the PR-interval from 169[150; 185] to 186[164; 209]ms (p=0.003) and 270[217; 310]ms (p&amp;lt;0.001). Conclusion Our study demonstrated that moderately accelerated atrial pacing reduced mean LAP in AF patients undergoing catheter ablation. While our primary focus was on acute response in AF patients, the reduction in mean LAP during moderate pacing rates may suggest a promising therapeutic approach for managing HFpEF patients. However, caution is warranted as pacing rates beyond the optimal range led to a marked increase in LAP. Additionally, increasing pacing rates were observed to induce varying degrees of AV-node dromotropy, which potentially modulates therapy response.Fig 1. Overview of clinical protocolFig 2. Response to accelerated pacing

Predictors of quality of life improvement in patients undergoing catheter ablation for atrial fibrillation: a cluster-based analysis

Abstract Introduction Traditional classification of Atrial Fibrillation (AF) based on temporal patterns doesn't fully encompass the condition's complexity. Unsupervised cluster analyses have been used for classifying patients into groups with similar comorbid profiles. However, inconsistent comorbidity patterns have been found across different cohorts. Bayesian profile regression, a semi-supervised machine learning technique, may improve the precision of clustering by integrating outcome data, diminishing the variability observed with previous methods. Since quality of life (QoL) primarily drives the indication for AF ablation, we utilized the AF Effect on QualiTy-of-Life (AFEQT) questionnaire to cluster patients. Purpose Our aim is to use patient-reported outcome measures to identify clinically relevant phenotypes of AF that benefit the most from catheter ablation. Methods We implemented a single center follow-up (FUP) program for patients with AF referred for ablation since august 2020, including scheduled visits and remote monitoring through a digital health platform. AFEQT score reported by patients was analyzed using a non-linear mixed model and change in AFEQT by month 12 was used as outcome. Comorbidities, echocardiographic data, and biomarkers were collected. Profile regression mixture modelling guided by QoL improvement was performed to create clinically relevant patient groupings. Penalized multinomial logistic regression model was used for validation. Results From the 466 ablations performed, 354 patients were enrolled until July 2023. 211 patients had FUP &amp;gt; 12 months (age 59±10 years, 31% female, 80% paroxysmal). The overall AFEQT questionnaire completeness rate was 72%. Patients were classified into 3 clusters: 1) patients with long duration AF, left heart cavities enlargement and diastolic dysfunction (n=57); 2) patients with self-reported anxiety/depression (n=50); and 3) patients with low rates of comorbidities (n=104). For clinical application, 8 variables (dyslipidemia, AF type and duration since diagnosis, mitral E/A ratio, systolic pulmonary arterial pressure, left ventricle ejection fraction, and PROMIS T-score for anxiety and depression) were sufficient for classifying patients (85% accuracy in internal cross-validation). Patients with higher depressive and anxiety burden (cluster 2) had worse baseline AFEQT score (median: 46, IQR: 39-60) and derived less benefit (median improvement: 21, IQR: 12-32), while patients with low comorbid burden (cluster 3) displayed higher baseline (median: 58, IQR: 48-62) and final QoL (median improvement: 28, IQR: 21-36, p&amp;lt;0.01). Conclusion Our analysis identified 3 reproducible clinically relevant phenotypes of AF using widely available clinical data. These clusters have distinct associations with QoL, underscoring the heterogeneity of AF and importance of comorbidities and substrates. This approach may allow for the prediction of which patients are most likely to benefit from treatment.

Maternal-fetal comorbidities and obstetrical outcomes of fetal single ventricle cardiac defects: 10years' experience with a multidisciplinary management protocol at a single center.

To describe and compare maternal and fetal comorbidities and obstetrical outcomes in pregnancies with hypoplastic left and right heart (HLHS and HRH) single ventricle cardiac defects (SVCD) from a single center under a multidisciplinary protocol. A single center retrospective review of fetal SVCD from 2013 to 2022. Maternal-fetal comorbidities, delivery, and postnatal outcomes were compared between HLHS and HRH using descriptive statistics and univariate and multivariate analyses. Of 181 SVCD pregnancies (131 HLHS; 50 HRH), 9% underwent termination, 4% elected comfort care, 5 died in utero and 147/152 liveborns survived to the first cardiac intervention. Cesarean delivery occurred in 57 cases (37%), planned in 36 and unplanned in 21. Comorbidities, which did not differ between HLHS and HRH, included fetal growth restriction (FGR, 17%), prematurity (14%), maternal hypertension (9%), maternal obesity (50%), fetal extracardiac anomalies and chromosome anomalies (12%, 13%). In multivariate analysis, only earlier gestational age at delivery and oligohydramnios predicted decreased odds of survival at one year. Maternal-fetal comorbidities are common in both HLHS and HRH. Earlier gestational age at delivery and oligohydramnios predict lower postnatal survival. FGR, even with severe early onset, did not significantly impact short- or long-term neonatal survival in single ventricle conditions.