Raffaele Scorza

Premature ventricular contractions (PVCs) arise from an early depolarization originating in either of the cardiac ventricles. They are common in individuals both with and without structural heart disease, although their true prevalence remains uncertain. Several electrophysiological mechanisms can initiate the PVC, with re-entry being the most frequent. The detection of PVCs should prompt a thorough clinical evaluation to identify potential underlying cardiac disease, yet many PVCs ultimately prove to be idiopathic. In individuals with established structural heart disease, PVCs have been associated with a poorer prognosis; however, clinical trials aimed at suppressing PVCs in this population have not demonstrated improved outcomes. In contrast, the prognostic significance of PVCs in patients without structural heart disease remains unclear. Factors such as PVC burden, PVC morphology, and cardiac magnetic resonance findings have been proposed as prognostic markers, although the evidence is still debated. In general, patients without structural heart disease and with a low PVC burden can be reassured regarding their prognosis. Treatment is primarily guided by symptoms, although reducing PVC burden may be considered even in asymptomatic individuals to mitigate the risk of complications such as PVC-induced cardiomyopathy or PVC-triggered sustained ventricular arrhythmias. Antiarrhythmic drugs are commonly used as first-line therapy, and the choice of medication should take into account patient characteristics, suspected pathophysiology, and PVC features. Catheter ablation (CA) is more effective than pharmacologic therapy in reducing or eliminating PVCs and may be considered as a first-line option in specific situations where rapid PVC suppression is desired. As an invasive procedure, CA carries potential risks that must be weighed carefully. Operator experience, PVC origin, anatomical considerations, and patient preference all play important roles in decision-making. Further research is needed to better identify patients at risk and to target specific pathophysiological mechanisms. Advances in device-based, patient-driven arrhythmia monitoring and the integration of artificial intelligence are likely to influence future PVC diagnostics and risk stratification.

Background and Aims: Heart failure (HF) and chronic kidney disease (CKD) are prevalent and often co-exist. Whether CKD is preferentially associated with a specific HF ejection fraction (EF) phenotype remains unclear. We aimed to investigate the association between CKD and new-onset HF across the EF spectrum and according to CKD severity. Methods: Patients with a first HF diagnosis from the Swedish HF Registry (2005–2021) were matched 1:1 by sex, year of birth, and county to controls without HF. In separate analyses, CKD was defined according to (i) ICD-10 codes in both HF patients and controls; (ii) an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 in HF patients. Renal function was further stratified into the KDIGO categories G2−G5, i.e. G2:60–89;G3a:45–59; G3b:30–44; G4:15–29; G5 < 15 ml/min/1.73 m2 in eGFR-defined CKD analyses. Results: 51 848 HF patients (20% HF with preserved EF [HFpEF], 23% HF with mildly reduced EF [HFmrEF], 57% HF with reduced EF [HFrEF]) and 51 848 controls were considered. CKD was associated with ∼two-fold higher odds of HF, particularly HFpEF, compared with HFmrEF and HFrEF vs non-HF (ICD-10 definition: odds ratio [OR]2.46, 1.30, and 1.52, respectively; P-interaction=0.001) and with 8% higher odds of HFpEF vs HFrEF when defined by eGFR in the HF population. Across KDIGO stages, with G2 as reference, G3b–G5 were more likely associated with HFpEF vs HFrEF, G3a had similar associations with HFpEF and HFrEF, and G3a–G3b were less likely associated with HFmrEF vs. HFrEF. Conclusions: CKD was independently associated with new-onset HF, especially HFpEF in moderate to advanced CKD, and both HFpEF and HFrEF in mild CKD. Targeting CKD may be crucial to prevent HF.

Aims: Advanced heart failure (AdvHF) remains a major clinical challenge, yet contemporary epidemiological real-world data on AdvHF patients are limited. The aim was to assess 20-year trends in clinical characteristics, outcomes, and use of left ventricular assist devices (LVAD) and heart transplantation (HTx) in patients with AdvHF and reduced ejection fraction (AdvHFrEF) in Sweden. Methods and results: Between 2003 and 2022, 5323 patients (median age 76 [IQR 68–82], 23% females) included in the Swedish HF Registry met adapted ESC-HFA criteria for AdvHF (NYHA III–IV, EF <30%, ≥1 HF hospitalization ≤6 months). Of these, 29% were eligible for AdvHF therapies (median age 63 [IQR 57–67] years, 18% females) according to the following additional criteria: ≤70 years old, no dialysis within ≤5 years, no active cancer within ≤3 years. Unadjusted temporal trends in 1-year outcomes (all-cause, CV and non-CV death, HTx, and LVAD implantation) were presented as estimated annual percent change (eAPC). 1-year all-cause mortality declined significantly in the overall cohort (eAPC −3.8; 95%CI −5.3 to −2.2) as well as in patients eligible for AdvHF therapies (eAPC −3.2; 95%CI −6.3 to −0.1) over the study period. These improvements were largely driven by reductions in CV mortality (overall cohort: eAPC −4.3; 95%CI −6.0 to −2.6; eligible cohort: eAPC −5.6, 95%CI −9.4 to −1.7). Use of LVAD significantly increased over the study period, while HTx showed a modest but non-significant rise. Conclusion: In a large nationwide cohort, all-cause and CV-mortality among AdvHFrEF patients markedly declined over the past 20 years, potentially reflecting improvements in treatments. Despite progress, significant opportunities remain to improve access to and adoption of advanced therapies.

Aims: To assess the cost-effectiveness of guideline-directed medical treatments for heart failure with reduced ejection fraction (HFrEF) by performing a network meta-analysis (NMA) of randomized controlled trials (RCTs) feeding a subsequent cost-effectiveness analysis. Methods: A random-effects NMA of RCTs was conducted. The primary analysis included only RCTs evaluating drugs in clinical settings as recommended in the 2021 European Society of Cardiology HF guidelines. Main efficacy outcomes included all-cause mortality (ACM) and total HF hospitalizations (HFH). A decision tree-Markov model was populated with NMA-derived efficacy estimates, quality-of-life data, and costs from United Kingdom (UK, main analysis), as well as Sweden and United States (US) (scenario analyses) healthcare perspectives. Results: A total of 47 RCTs (75 978 patients) were included. The risk of ACM and total HFH decreased with increasing number of pharmacological treatments. In the main (UK) analysis, the greatest benefit was observed with a quadruple therapy including angiotensin receptor–neprilysin inhibitor (ARNI) + β-blocker (BB) + mineralocorticoid receptor antagonist (MRA) + sodium–glucose cotransporter 2 inhibitors (SGLT2i), which resulted as the most cost-effective strategy (12.31 quality-adjusted life-years; net monetary benefit of £338 460; UK perspective). Findings were consistent in Sweden and USA. Conclusion: Quadruple therapy with ARNI + BB + MRA + SGLT2i had the highest probability of being the most cost-effective strategy. Our findings might inform future health economic policies and reimbursement decisions, while also considering affordability, budget impact, and implementation feasibility.

Aims: Patients with heart failure and reduced ejection fraction (HFrEF) are frequently exposed to polypharmacy, placing them at risk of potentially inappropriate prescribing (PIP)—defined as use of drugs that may worsen HF prognosis, counteract guideline-directed medical therapies (GDMTs), or increase harmful interactions. The prevalence, predictors, and prognostic impact of PIP in HFrEF remain unclear. Therefore, the aim was to investigate the prevalence, predictors, and outcomes of PIP in a large, real-world HFrEF population. Methods: Patients with HFrEF enrolled in the Swedish HF Registry (2005–2020) were included. The ESC position statement of PIP-HFrEF was used to retrieve PIP from the National Prescribed Drugs Register. Associations between PIP and outcomes were assessed using Cox proportional hazards and negative binomial regression for recurrent events. Results: Among 50,348 patients (median age 75 years, 29% female), 23,583 (47%) were prescribed ≥1 PIP. The most frequent agents were neuroleptics (29%), systemic steroids (10%), and NSAIDs (6%). Independent predictors included rheumatoid arthritis (OR 3.39; 95%CI 2.92–3.94), depression (OR 3.06; 95%CI 2.74–3.42), chronic obstructive pulmonary disease (OR 1.86; 95%CI 1.76–1.98), and gout (OR 1.48; 95%CI 1.35–1.62). Patients on PIP were less likely to receive GDMT. Presence of ≥1 PIP was independently associated with increased 3-year risk of HF death (HR 1.13; 95%CI 1.04–1.23), all-cause and cardiovascular death, first and recurrent HF hospitalisations. Conclusions: Nearly half of HFrEF patients received PIP medications, particularly those with multimorbidity, which was independently associated with worse outcomes and less GDMT use. Our data underscore the need for targeted strategies to reduce inappropriate prescribing in HFrEF.

Background: Premature ventricular complexes (PVCs) are common and can cause concerns in both patients and their caregivers. In patients with structural heart disease, PVCs are associated with worse clinical outcomes. However, in patients without such disease, the prognostic implications of PVCs are more uncertain. Methods: In this observational cohort study, we included patients who were diagnosed with PVCs at three major hospitals in Stockholm between 2010 and 2016. All included patients had normal results on echocardiography and stress test, and no history of structural heart disease. The expected survival from the age-matched, sex-matched and calendar year-matched Swedish population was obtained from the Human Mortality Database. Relative survival was estimated using the Ederer II method. Results: A total of 803 PVC patients were included. Median age was 59 years, and 57% were women. In all, 185 (23%) patients had more than 10 000 PVCs per day and 86 (11%) had more than 20 000 PVCs per day. The observed survival was greater than the expected survival at 1, 5, 10 and 12 years (100% vs 99%, 97% vs 94%, 93% vs 86% and 90% vs 82%, respectively). The relative survival at 1, 5, 10 and 12 years was 100%, 104%, 109% and 111%, respectively. The median follow-up time was 10 years (maximum 14 years). Conclusions: PVC patients without structural heart disease had a favourable long-term survival, exceeding the expected survival of the general population. These results suggest that most PVC patients without structural heart disease may be given a reassuring message.

Aims: To evaluate in patients with heart failure with reduced ejection fraction (HFrEF) the association between patient characteristics and likelihood of receiving cardiac resynchronization therapy (CRT), as well as between CRT and clinical outcomes, according to comorbid atrial fibrillation (AF). Methods and results: Patients in the Swedish Heart Failure (HF) Registry who met the guidelines’ recommendation for CRT between 2014 and 2022 were included. The primary endpoint was the composite of time to first HF hospitalization or cardiovascular (CV) death. Secondary endpoints were its individual components, all-cause death, and the total number of HF hospitalizations. Out of 3530 patients with HFrEF and an indication for CRT, 24.7% received a CRT. A history of or concomitant AF were observed in 51.6% of patients. AF was not associated with the likelihood of receiving a CRT, and the patient characteristics independently associated with CRT were consistent regardless of AF, except for CRT being less likely implanted in patients with valvular disease without AF, and more likely among those with AF and university (vs. compulsory) education. Regardless of AF, CRT use was associated with a lower adjusted risk of CV death/first HF hospitalization [hazard ratio (HR): 0.71, 95% confidence interval (CI) 0.64–0.79], of its individual components, and of all-cause death (HR: 0.72, 95% CI 0.64–0.81), but not with total number of HF hospitalizations. Conclusion: A diagnosis of AF was not associated with the likelihood of receiving CRT in real-world HF care, nor did it affect the association between CRT and lower risk of clinical outcomes.

Aims: This study aims to assess pharmacological treatment patterns and outcomes according to the coexistence of heart failure (HF) and Type 2 diabetes (T2DM). Methods and results: Two cohorts were derived: HF patients with/without T2DM and T2DM patients with/without HF, by linking the Swedish HF Registry, the National Diabetes Registry, and other national registries in 2017–2021. In 37 903 patients with HF (35% females, median age 74), T2DM was independently associated with a 10-fold higher use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and less likely use of mineralocorticoid receptor antagonists (MRAs) irrespective of ejection fraction (EF), and of renin–angiotensin inhibitors (RASis)/angiotensin receptor–neprilysin inhibitors (ARNis) in HF with reduced and mildly reduced EF. Over a median follow-up of 1.8 years, T2DM was independently associated with higher risk of first HF hospitalization (HHF)/cardiovascular (CV) death, first HHF, and all-cause death, but not with CV death alone. In 16 266 patients with T2DM (29% females, median age 76), HF was independently associated with more likely use of SGLT2i but less likely use of metformin. Over a median follow-up of 2.2 years, HF was independently associated with higher risk of CV death, all-cause death, and myocardial infarction. Conclusion: In HF, T2DM was associated with higher use of SGLT2i and lower use of MRA and RASi/ARNI despite being linked with a higher risk of death and HHF. In T2DM, presence of HF was linked with higher SGLT2i use and an independent higher risk of death and myocardial infarction. Heart failure was associated with comparatively greater risk increase than T2DM.

Background and objective: Prior studies have suggested that patients with premature ventricular complexes (PVCs) may have an increased risk for atrial fibrillation (AF) and stroke. It is unclear whether frequent PVCs are linked to an increased risk of AF and stroke in patients where structural heart disease (SHD) has been excluded. We aimed to study if PVCs increase the risk of AF or stroke in patients without SHD. Methods: In this retrospective observational cohort study, we included patients who received a PVC diagnosis at three major hospitals in Stockholm, Sweden. The patients had no history of heart disease, normal results at stress test and echocardiography, and no previous diagnosis of AF or stroke. For each case, four matched controls were obtained from the general population. We used inverse probability weighting (IPW) to control for differences in baseline characteristics. Results: A total of 751 PVC patients and 3041 controls were included. The median age was 59 years, and 2239 (59%) were women. The median follow-up time was 5.2 years. There was a higher risk of AF among patients in the PVC group compared with the control group in the unadjusted analysis (HR 2.08, 95% CI 1.35 to 3.20, p=0.0009). After IPW, there was no significant difference in the risk of AF (HR 1.44, 95% CI 0.88 to 2.37) or stroke (HR 1.32, 95% CI 0.81 to 2.14) between the PVC group and the control group. Conclusion: In patients with PVCs but without SHD, there was no increased risk of AF or stroke compared with controls from the general population after adjusting for known confounders. However, PVCs were associated with AF in the crude cohort, suggesting that PVCs may be a clinical marker for AF.