Vincent Algalarrondo

Early, structured ambulatory follow-up after hospitalization for acute cardiac events remains a key unmet need in cardiovascular care. This clinical consensus statement of the Association for Acute CardioVascular Care of the ESC provides pragmatic, condition-specific guidance on post discharge management and (early) ambulatory re-evaluation for patients admitted to an acute cardiac care unit. It complements existing disease-oriented guidelines by focusing on the vulnerable transition from hospital to home rather than on acute in-hospital treatment. The document first defines key concepts and outlines general principles regarding timing, content, and organization of the first post-discharge contacts, including risk stratification, medication reconciliation, symptom assessment, evaluation of psychosocial status and comorbidities, patient and family education, and integration of cardiac rehabilitation. In practice, the consensus statement discusses the patient’s path after discharge: how should the follow-up team look like, when should the first and subsequent visits be planned, what should be done at each contact, and how can multidisciplinary teams and hybrid (in-person plus remote) models be implemented according to local resources. Supplementary material highlights major evidence gaps, including the optimal timing and intensity of follow-up, the composition of ambulatory teams, the role of telemonitoring and digital health, and the needs of vulnerable populations. Overall, this consensus aims to support clinicians in designing structured, individualized, and scalable ambulatory pathways after acute cardiac care.

BACKGROUND: In HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy), vutrisiran reduced the risk of all-cause mortality (ACM) and recurrent cardiovascular events and slowed disease progression measures versus placebo in patients with TTR (transthyretin) amyloidosis with cardiomyopathy after 33 to 36 months. We report the long-term efficacy and safety of vutrisiran from an ongoing open-label extension of HELIOS-B. METHODS: Patients who completed HELIOS-B could enroll in the open-label extension, continuing with vutrisiran 25 mg every 3 months (continuous vutrisiran) or, if previously receiving placebo, initiating vutrisiran 25 mg every 3 months (placebo/vutrisiran). Prespecified end points assessed in the open-label extension are the composite of ACM and cardiovascular events, ACM, Kansas City Cardiomyopathy Questionnaire–Overall Summary score, New York Heart Association class, and NT-proBNP (N-terminal pro–B-type natriuretic peptide) and troponin I levels. Outcomes were assessed through month 48 in this analysis. RESULTS: Of 654 participants in HELIOS-B (vutrisiran, n=326; placebo, n=328), 478 completed double-blind treatment and 466 (vutrisiran, n=243; placebo, n=223) entered the open-label extension. In the continuous vutrisiran group, the risk of first cardiovascular event or ACM was reduced by 37% (hazard ratio, 0.63 [95% CI, 0.51, 0.79]; P =0.0001) and ACM by 37% (hazard ratio, 0.63 [95% CI, 0.46, 0.84]; P =0.0023) versus the placebo/vutrisiran group. Through month 48, patients in the continuous vutrisiran group had preserved health status and quality of life per Kansas City Cardiomyopathy Questionnaire–Overall Summary score (least squares mean difference, 9.0 [95% CI, 5.3, 12.6]; P P =0.0084) versus the placebo/vutrisiran group. Benefits in the continuous vutrisiran group were maintained for NT-proBNP and troponin I levels (adjusted geometric mean fold change ratios, 0.66 [95% CI, 0.58, 0.74]; P P <0.0001, respectively) versus the placebo/vutrisiran group. Similar benefits were observed in the vutrisiran monotherapy population. No new safety signals were observed. CONCLUSIONS: Long-term vutrisiran resulted in clinically meaningful benefits across mortality, cardiovascular events, cardiac biomarkers, functional status, and quality of life in patients with TTR amyloidosis with cardiomyopathy through month 48. Patients initially treated with vutrisiran had better outcomes than those first receiving placebo, highlighting the importance of early diagnosis and treatment in TTR amyloidosis with cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04153149.

Aims: The cAMP-specific phosphodiesterases 4B and 4D (PDE4B and PDE4D) are critical regulators of cardiac excitation-contraction coupling, but their role in controlling heart rate (HR) remains poorly defined. This study aimed to evaluate their respective contributions to cardiac automaticity. Methods and results: PDE4 activity, measured by a radioenzymatic assay, accounted for ∼60% of the total cAMP-hydrolytic activity in the mouse sinoatrial node (SAN). Western blot and in situ RNA fluorescence hybridization (RNAscopeTM) showed that both PDE4B and PDE4D are expressed in the SAN and in isolated pacemaker cardiomyocytes. HR, measured by electrocardiogram (ECG) telemetry, was increased in Pde4b knockout (Pde4b−/−) and Pde4d knockout (Pde4d−/−) mice compared with wild-type (WT) littermates, during both day and night. Upon autonomic nervous system blockade, elevated HR persisted in Pde4b−/− but not in Pde4d−/− mice. Consistently, isolated perfused hearts from Pde4b−/− mice beat faster than WT littermates, whereas Pde4d−/− did not. Increased automaticity in Pde4b−/− hearts was not accompanied by modified Ca2+ homeostasis in Fluo-4-loaded isolated SAN tissue, either at baseline or during β-adrenergic (β-AR) stimulation with 10 nM isoprenaline (ISO). In contrast, Pde4d−/− SAN challenged with ISO exhibited an increased total sarcoplasmic reticulum Ca2+ leak and prolonged Ca2+ transients. Patch-clamp recordings revealed an increased action potential firing rate in Pde4b−/− but not in Pde4d−/− pacemaker cardiomyocytes. In Pde4b−/− cells, basal and ISO-stimulated L-type calcium current (ICa,L) densities were not significantly altered, whereas funny current (If) density was increased. Conversely, Pde4d ablation did not alter basal ICa,L nor If. Conclusion: These results show that PDE4B controls intrinsic SAN automaticity by regulating the voltage clock through the pacemaker current If, whereas PDE4D regulates the calcium clock via β-AR-induced calcium release through RyR2.

Background and Aims: Subcutaneous implantable cardioverter defibrillator (S-ICD) therapy is well-established therapy for the prevention of sudden cardiac death. Although general anesthesia (GA) was initially advocated for implantation, non-GA has emerged as a feasible alternative in clinical practice. This study evaluated the early and long-term outcomes associated with anesthetic modality during S-ICD implantation procedures. Methods: The HONEST study nationwide, single-arm, observational cohort included all patients implanted with an S-ICD (EMBLEM™, Boston Scientific) in France between 2012 and 2019. GA was characterized by controlled unconsciousness with airway management, while non-GA included all alternative techniques. Results: Among 4,924 patients, 1,041 (21.1%) underwent non-GA. The proportion of non-GA use increased from 2.5% to 26.9% between 2012 and 2019 (p<0.001). Patients implanted with non-GA modality tended to be older (51 ± 14 vs. 50 ± 15 years), had lower left ventricular ejection fraction (41±16 vs. 43±17%), and fewer secondary prevention indications (33 vs. 38%) (all p0.1). Conclusion: Anesthesia strategy used for S-ICD implantation was not associated with poorer short- or long-term clinical outcomes, supporting non–general anesthesia as a feasible alternative in appropriately selected patients.

Background and Objective We assessed the consistency of serum transthyretin (TTR) knockdown with the RNA interference therapeutic vutrisiran across subpopulations of patients with hereditary TTR amyloidosis (ATTR) with polyneuropathy (ATTRv-PN) in HELIOS-A (NCT03759379) and ATTR with cardiomyopathy (ATTR-CM) in HELIOS-B (NCT04153149). Methods Patients received vutrisiran 25 mg subcutaneously every 3 months (Q3M). Serum TTR was measured during randomized treatment through Month 18 in HELIOS-A (post-dose/peak and pre-dose/trough sampling) and Month 30 in HELIOS-B (trough only, except Week 6). The effects of intrinsic/extrinsic factors on serum TTR knockdown from baseline were assessed. Pharmacokinetic/pharmacodynamic modeling was used to support consistency in TTR knockdown between studies. Results Observed median (95% confidence interval [CI]) serum TTR knockdown with vutrisiran was 64.2% (61.6–67.8) at Week 3 (n = 114), with steady-state trough knockdown 86.2% (84.1–92.6) (n = 118) in HELIOS-A, and 69.0% (66.0–72.0) at Week 6 (n = 294), with steady-state trough knockdown 82.5% (80.5–84.9) (n = 307) in HELIOS-B. There were no meaningful differences in serum TTR percent knockdown across subgroups defined by baseline characteristics, including age, sex, ethnicity/race, weight, TTR genotype, N-terminal pro-B-type natriuretic peptide, and serum TTR concentration (both studies), and ATTRwt/ATTRv, disease stage/severity, troponin I, and tafamidis use (HELIOS-B), or anti-drug antibodies. Model-predicted peak serum TTR knockdown in HELIOS-B was sustained and consistent with observed knockdown in HELIOS-A; predicted median (95% CI) reduction at Month 30 was 87.1% (84.8–89.4). Conclusions Vutrisiran led to rapid, sustained, and consistent TTR knockdown in HELIOS-A and HELIOS-B, supporting fixed-dose vutrisiran 25 mg Q3M across patients with ATTRv-PN and ATTR-CM. Graphical abstract The alternative text for this image may have been generated using AI.

Background/Objectives: Transthyretin cardiomyopathy (ATTR-CM) is frequently associated with conduction disease requiring pacing. Conventional right ventricular pacing may worsen cardiac function, whereas left bundle branch area pacing (LBBAP) aims to preserve physiological activation. Evidence for LBBAP in ATTR-CM remains limited. Methods: A structured narrative review of PubMed and Google Scholar was performed through November 2025 using predefined terms related to LBBAP and ATTR-CM. Peer-reviewed articles, case reports, case series, and relevant abstracts were included. Studies exclusively on light-chain cardiac amyloidosis were excluded. Results: Ten publications met inclusion criteria, comprising three case reports, five case series, one retrospective cohort without a comparator, and one cohort comparing LBBAP with cardiac resynchronization therapy (CRT). In total, 56 patients with ATTR-CM underwent LBBAP. Implantation success was high, with stable acute and mid-term electrical parameters. Follow-up (typically 3–12 months) showed stable electrical parameters with narrow paced QRS complexes and preserved or improved left ventricular ejection fraction in most reports. Symptomatic improvement and reductions in natriuretic peptides were variably described. No major lead-related complications were reported. Comparative data remain sparse and inconclusive. Conclusions: This review suggests that LBBAP is a feasible and safe pacing approach in patients with ATTR-CM and may help to stabilize or improve heart failure symptoms. Further prospective studies are needed to confirm its clinical effectiveness.

Background: Transthyretin cardiac amyloidosis (ATTR-CM) is frequently associated with conduction disease requiring pacing. Conventional right ventricular pacing may worsen cardiac function, whereas left bundle branch area pacing (LBBAP) aims to preserve physiological activation. Evidence for LBBAP in ATTR-CM remains limited. Methods: A structured narrative review of PubMed and Google Scholar was performed through November 2025 using predefined terms related to LBBAP and ATTR-CM. Peer-reviewed articles, case reports, case series, and relevant abstracts were included. Studies exclusively on light-chain cardiac amyloidosis were excluded. Results: Ten publications met inclusion criteria, comprising three case reports, five case series, one retrospective cohort without a comparator, and one cohort comparing LBBAP with cardiac resynchronization therapy (CRT). In total, 56 patients with ATTR-CM underwent LBBAP. Implantation success was high, with stable acute and mid-term electrical parameters. Follow-up (typically 3–12 months) showed stable electrical parameters with narrow paced QRS complexes and preserved or improved left ventricular ejection fraction in most reports. Symptomatic improvement and reductions in natriuretic peptides were variably described. No major lead-related complications were reported. Comparative data remain sparse and inconclusive. Conclusions: This review suggests that LBBAP is a feasible and safe pacing approach in patients with ATTR-CM and may help stabilize or improve heart failure symptoms. Further prospective studies are needed to confirm its clinical effectiveness.