Cardio-ocular syndrome: Retinal microvascular changes in acutely decompensated heart failure.

AIMS: To investigate the changes in retinal microvasculature by contemporary imaging techniques during episodes of acute decompensated heart failure (ADHF) and following recompensation compared to age-matched controls without known cardiac or retinal disease. METHODS AND RESULTS: Adult patients hospitalized with a primary diagnosis of ADHF, regardless of left ventricular ejection fraction (LVEF) and treated with a minimum dose of 40 mg of intravenous furosemide or equivalent were included. Transthoracic echocardiography was conducted in all patients. Eye examinations were performed out within the initial 24 h after admission and after recompensation before discharge. All eyes underwent a general examination, including a best corrected visual acuity test, dilated fundoscopy, spectral-domain optical coherence tomography (OCT) as well as OCT angiography (OCT-A). In addition, 40 participants without documented cardiac or retinal diseases served as controls. Forty patients with ADHF (mean age 78.9 ± 8.8 years; 32% female) with a mean LVEF of 43 ± 12.8% were included. All patients were treated with intravenous diuretics for a median of 4.3 ± 2.8 days. There was a significant reduction in N-terminal pro-B-type natriuretic peptide from baseline up to discharge (10 396 [interquartile range 6410] vs. 6380 [interquartile range 3933] pg/ml, p ≤ 0.001) and inferior vena cava diameters (2.13 ± 0.4 vs. 1.63 ± 0.3 cm, p = 0.003). Compared to the control group, patients with ADHF showed on admission impaired visual acuity (0.15 ± 0.1 vs. 0.35 ± 0.1 logMAR, p < 0.001), reduced macular vessel density (18.0 ± 1.9 vs. 14.3 ± 3.6 mm/mm2, p < 0.001) and perfusion density (42.6 ± 3.2 vs. 35.2 ± 9.7%, p < 0.001). After recompensation, the mean overall vessel density and mean overall perfusion density were markedly increased at discharge (14.3 ± 3.6 vs. 19.7 ± 2.6 mm/mm2, p = 0.001, and 35.2 ± 9.7 vs. 39.2 ± 6.5%, p = 0.005, respectively). The mean diameter of the superior temporal retinal vein at admission was significantly larger compared to the control group (136 ± 19 vs. 124 ± 22 µm, p = 0.008) and decreased significantly to 122 ± 15 µm at discharge (p < 0.001). CONCLUSION: This analysis revealed a remarkable reversible change in retinal microvasculature after ADHF. This could provide a valuable evidence for use of OCT-A in the assessment of overall microperfusion and haemodynamic status in patients with acute heart failure.

Effects of dapagliflozin according to QRS duration across the spectrum of left ventricular ejection fraction: An analysis of DAPA-HF and DELIVER.

AIMS: The primary aim was to evaluate the effect of dapagliflozin according to QRS duration across the spectrum of left ventricular ejection fraction (LVEF), given that prolongation of QRS duration is associated with less favourable ventricular remodelling with pharmacological therapy and worse outcomes. METHODS AND RESULTS: A pooled analysis of the DAPA-HF and DELIVER trials, excluding patients with a paced rhythm and cardiac resynchronization therapy. Overall, 4008 patients had heart failure (HF) with reduced ejection fraction (HFrEF), and 5816 had HF with mildly reduced/preserved ejection fraction (HFmrEF/HFpEF). QRS duration was <120 ms in 7039 patients (71.7%), 120-149 ms in 1725 (17.6%), and ≥150 ms in 1060 patients (10.8%). The median follow-up time was 23 months. The rate of the primary composite outcome of cardiovascular death or worsening HF was 9.2 (95% confidence interval [CI] 8.7-9.7), 14.3 (13.0-15.7), and 15.9 (14.1-17.9) per 100 patient-years in the <120, 120-149, and ≥150 ms groups, respectively. This gradient in event rates was observed both in HFrEF and HFmrEF/HFpEF. Dapagliflozin, compared with placebo, reduced the risk of the primary outcome consistently across the QRS duration subgroups (hazard ratio [95% CI] 0.75 [0.67-0.85], 0.79 [0.65-0.96], and 0.89 [0.70-1.13] in the <120, 120-149, and ≥150 ms groups, respectively; p for interaction = 0.28). The effect of dapagliflozin on the primary outcome was consistent across the QRS duration regardless of HF phenotype that is, HFrEF or HFmrEF/HFpEF. CONCLUSIONS: Prolongation of QRS duration is associated with worse outcomes irrespective of HF phenotype. Dapagliflozin reduced the risk of the primary outcome, regardless of QRS duration, in DAPA-HF and DELIVER.

European Society of Cardiology quality indicators update for the care and outcomes of adults with heart failure. The Heart Failure Association of the ESC.

AIMS: To update the European Society of Cardiology (ESC) quality indicators (QIs) for the evaluation of the care and outcomes of adults with heart failure. METHODS AND RESULTS: The Working Group comprised experts in heart failure including members of the ESC Clinical Practice Guidelines Task Force for heart failure, members of the Heart Failure Association, and a patient representative. We followed the ESC methodology for QI development. The 2023 focused guideline update was reviewed to assess the suitability of the recommendations with strongest association with benefit and harm against the ESC criteria for QIs. All the new proposed QIs were individually graded by each panellist via online questionnaires for both validity and feasibility. The existing heart failure QIs also underwent voting to 'keep', 'remove' or 'modify'. Five domains of care for the management of heart failure were identified: (1) structural QIs, (2) patient assessment, (3) initial treatment, (4) therapy optimization, and (5) patient health-related quality of life. In total, 14 'main' and 3 'secondary' QIs were selected across the five domains. CONCLUSION: This document provides an update of the previously published ESC QIs for heart failure to ensure that these measures are aligned with contemporary evidence. The QIs may be used to quantify adherence to clinical practice as recommended in guidelines to improve the care and outcomes of patients with heart failure.

Heart failure with preserved ejection fraction epidemiology, pathophysiology, diagnosis and treatment strategies.

The prevalence of HF with preserved ejection raction (HFpEF, with EF ≥50%) is increasing across all populations with high rates of hospitalization and mortality, reaching up to 80% and 50%, respectively, within a 5-year timeframe. Comorbidity-driven systemic inflammation is thought to cause coronary microvascular dysfunction and increased epicardial adipose tissue, leading to downstream friborsis and molecular changes in the cardiomyocyte, leading to increased stiffness and diastolic dynsfunction. HFpEF poses unique challenges in terms of diagnosis due to its complex and diverse nature. The diagnosis of HFpEF relies on a combination of clinical assessment, imaging studies, and biomarkers. An additional important step in diagnosing HFpEF involves excluding certain cardiac diagnoses that may be specific underlying causes of HFpEF or may be masquerading as HFpEF and require specific alternative treatment approaches. In addition to administering sodium-glucose cotransporter 2 inhibitors to all patients, the most effective approach to enhance clinical outcomes may involve tailored therapy based on each patient's unique clinical profile. Exercise should be recommended for all patients to improve the quality of life. Glucagon-like peptide-1 1 agonists are a promising treatment option in obese HFpEF patients. Novel approaches targeting inflammation are also in early phase trials.

[Therapy of heart failure with reduced pump function]. / Therapie der Herzinsuffizienz mit reduzierter Pumpfunktion.

HFrEF causes significant morbidity and mortality and represents a major public health burden. Recently, there have been significant scientific advances in the treatment of HFrEF, with ARNI, BB, MRA, and SGLT-2i forming the GDMT for HFrEF. Basic quadruple therapy has been shown to significantly reduce of HF hospitalizations, all-cause mortality, and cardiovascular mortality. In addition, new initiation and titration procedures have recently been introduced that may progressively improve the management and prognosis of HFrEF. Further efforts are also needed to improve the use of GDMT, which is currently underutilized.

Neuromodulation interventions in the management of heart failure.

Despite remarkable improvements in the management of heart failure (HF), HF remains one of the most rapidly growing cardiovascular condition resulting in a substantial burden on healthcare systems worldwide. In clinical practice, however, a relevant proportion of patients are treated with suboptimal combinations and doses lower than those recommended in the current guidelines. Against this background, it remains important to identify new targets and investigate additional therapeutic options to alleviate symptoms and potentially improve prognosis in HF. Therefore, non-pharmacological interventions targeting autonomic imbalance in HF have been evaluated. This paper aims to review the physiology, available clinical data, and potential therapeutic role of device-based neuromodulation in HF.

Chronic renal failure as predictive factor for acute elevation of systolic blood pressure after fluorescein angiography in patients with retinal diseases.

Purpose: To investigate the influence of fluorescein angiography (FA) on blood pressure (BP) in patients with retinal diseases, and analyze the predictive factors for acute elevation of systolic BP after FA. Design: and Methods: A prospective study was conducted with 636 patients undergoing FA between April 2021 and October 2021. BP and pulse were measured in each patient before and 20 min after FA. The baseline characteristics of patients who developed an acute elevation in systolic BP (>10 mmHg) were compared with those of the remaining patients to detect factors that may predict this acute elevation. Results: Overall, mean systolic BP changed from 142 ± 17 mmHg to 140 ± 20 mmHg after 20 min (p = 0.1). Mean diastolic BP changed from 79 ± 15 mmHg to 78 ± 13 mmHg after 20 min (p = 0.45). Mean pulse rate changed from 73 ± 14 bpm to 70 ± 12 bpm after 20 min (p = 0.001). 103 patients (16 %) had acute elevation of systolic BP (>10 mmHg). Mean systolic BP changed from 143 ± 17 mmHg to 162 ± 19 mmHg after 20 min in this group (p = 0.001). Patients in this group were significantly older compared to the rest (73 ± 12 vs 67 ± 15, p = 0.001). The rate of chronic renal failure was significantly higher in this group compared to the rest of the patients (42/7.8 % vs 15/14.6 %, p = 0.01). Conclusions: This study demonstrated that fluorescein angiography is a relatively safe procedure with regards to blood pressure changes. However, chronic renal failure could be considered as predictive factor for acute elevation of systolic blood pressure after this procedure.

Impact of the COVID-19 pandemic on implementation of novel guideline-directed medical therapies for heart failure in Germany: a nationwide retrospective analysis.

Background: Guideline-directed medical therapy (GDMT) is the cornerstone in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) and novel substances such as sacubitril/valsartan (S/V) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated marked clinical benefits. We investigated their implementation into real-world HF care in Germany before, during, and after the COVID-19 pandemic period. Methods: The IQVIA LRx data set is based on ∼80% of 73 million people covered by the German statutory health insurance. Prescriptions of S/V were used as a proxy for HFrEF. Time trends were analysed between Q1/2016 and Q2/2023 for prescriptions for S/V alone and in combination therapy with SGLT2i. Findings: The number of patients treated with S/V increased from 5260 in Q1/2016 to 351,262 in Q2/2023. The share of patients with combination therapy grew from 0.6% (29 of 5260) to 14.2% (31,128 of 219,762) in Q2/2021, and then showed a steep surge up to 54.8% (192,429 of 351,262) in Q2/2023, coinciding with the release of the European Society of Cardiology (ESC) guidelines for HF in Q3/2021. Women and patients aged >80 years were treated less often with combined therapy than men and younger patients. With the start of the COVID-19 pandemic, the number of patients with new S/V prescriptions dropped by 17.5% within one quarter, i.e., from 26,855 in Q1/2020 to 22,145 in Q2/2020, and returned to pre-pandemic levels only in Q1/2021. Interpretation: The COVID-19 pandemic was associated with a 12-month deceleration of S/V uptake in Germany. Following the release of the ESC HF guidelines, the combined prescription of S/V and SGLT2i was readily adopted. Further efforts are needed to fully implement GDMT and strengthen the resilience of healthcare systems during public health crises. Funding: Supported by Novartis Pharma GmbH, Nuremberg, Germany.

Outcomes of left bundle branch area pacing compared to His bundle pacing as a primary pacing strategy: Systematic review and meta-analysis.

BACKGROUND: Novel pacing technologies, such as His bundle pacing (HBP) and left bundle branch area pacing (LBBaP), have emerged to maintain physiological ventricular activation. We investigated the outcomes of LBBP with HBP for patients requiring a de novo permanent pacing. METHODS AND RESULTS: Systematic review of randomized clinical trials and observational studies comparing LBBaP with HBP until March 01, 2023 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included pacing metrics, QRS duration, lead revision, procedure parameters, all-cause mortality and heart failure hospitalization (HFH). Overall, 10 studies with 1596 patients were included. Implant success rate was higher in LBBaP compared with HBP (RR 1.24, 95% CI: 1.08 to 1.42, p = .002). LBBaP was associated with lower capture threshold at implantation (mean difference (MD) -0.62 V, 95% CI: -0.74 to -0.51 V, p < .0001) and at follow-up (MD -0.74 V, 95% CI: -0.96 to -0.53, p < .0001), shorter procedure duration (MD -14.66 min, 95% CI: -23.54 to -5.78, p = .001) and shorter fluoroscopy time (MD -4.2 min, 95% CI: -8.4 to -0.0, p = .05). Compared with HBP, LBBaP was associated with a decreased risk of all-cause mortality (RR: 0.50, 95% CI: 0.33 to 0.77, p = .002) and HFH (RR: 0.57, 95% CI: 0.33 to 1.00, p = .05). No statistical differences were found in lead revisions and QRS duration before and after pacing. CONCLUSION: This meta-analysis found that LBBaP was superior to HBP regarding pacing metrics and implant success rate as an initial pacing strategy, although absence of head-to-head randomized comparison warrants caution in interpretation of the results.

The burden of ischemic heart disease and the epidemiologic transition in the Eastern Mediterranean Region: 1990-2019.

It has been estimated that in the next decade, IHD prevalence, DALYs and deaths will increase more significantly in EMR than in any other region of the world. This study aims to provide a comprehensive description of the trends in the burden of ischemic heart disease (IHD) across the countries of the Eastern Mediterranean Region (EMR) from 1990 to 2019. Data on IHD prevalence, disability-adjusted life years (DALYs), mortality, DALYs attributable to risk factors, healthcare access and quality index (HAQ), and universal health coverage (UHC) were extracted from the Global Burden of Disease (GBD) database for EMR countries. The data were stratified based on the social demographic index (SDI). Information on cardiac rehabilitation was obtained from publications by the International Council of Cardiovascular Prevention and Rehabilitation (ICCPR), and additional country-specific data were obtained through advanced search methods. Age standardization was performed using the direct method, applying the estimated age structure of the global population from 2019. Uncertainty intervals were calculated through 1000 iterations, and the 2.5th and 97.5th percentiles were derived from these calculations. The age-standardized prevalence of IHD in the EMR increased from 5.0% to 5.5% between 1990 and 2019, while it decreased at the global level. In the EMR, the age-standardized rates of IHD mortality and DALYs decreased by 11.4% and 15.4%, respectively, during the study period, although both rates remained higher than the global rates. The burden of IHD was found to be higher in males compared to females. Bahrain exhibited the highest decrease in age-standardized prevalence (-3.7%), mortality (-65.0%), and DALYs (-69.1%) rates among the EMR countries. Conversely, Oman experienced the highest increase in prevalence (14.5%), while Pakistan had the greatest increase in mortality (30.0%) and DALYs (32.0%) rates. The top three risk factors contributing to IHD DALYs in the EMR in 2019 were high systolic blood pressure, high low-density lipoprotein cholesterol, and particulate matter pollution. The trend analysis over the 29-year period (1990-2019) revealed that high fasting plasma glucose (64.0%) and high body mass index (23.4%) exhibited increasing trends as attributed risk factors for IHD DALYs in the EMR. Our findings indicate an increasing trend in the prevalence of IHD and a decrease in mortality and DALYs in the EMR. These results emphasize the need for well-planned prevention and treatment strategies to address the risk factors associated with IHD. It is crucial for the countries in this region to prioritize the development and implementation of programs focused on health promotion, education, prevention, and medical care.

Associations between baseline heart rate and blood pressure and time to events in heart failure with reduced ejection fraction patients: Data from the QUALIFY international registry.

AIMS: A high resting heart rate (RHR) and low systolic blood pressure (SBP) are a risk factor and a risk indicator, respectively, for poor heart failure (HF) outcomes. This analysis evaluated the associations between baseline RHR and SBP with outcomes and treatment patterns in patients with HF and reduced ejection fraction (HFrEF) in the QUALIFY (QUality of Adherence to guideline recommendations for LIFe-saving treatment in heart failure surveY) international registry. METHODS AND RESULTS: Between September 2013 and December 2014, 7317 HFrEF patients with a previous HF hospitalization within 1-15 months were enrolled in the QUALIFY registry. Complete follow-up data were available for 5138 patients. The relationships between RHR and SBP and outcomes were assessed using a Cox proportional hazards model and were analysed according to baseline values as high RHR (H-RHR) ≥75 bpm versus low RHR (L-RHR) <75 bpm and high SBP (H-SBP) ≥110 mmHg versus low SBP (L-SBP) <110 mmHg and analysed according to each of the following four phenotypes: H-RHR/L-SBP, L-RHR/L-SBP, H-RHR/H-SBP and L-RHR/H-SBP (reference group). Compared to the reference group, H-RHR/L-SBP was associated with the worst outcomes for the combined primary endpoint of cardiovascular death and HF hospitalization (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.51-2.21, p < 0.001), cardiovascular death (HR 2.70, 95% CI 1.69-4.33, p < 0.001), and HF hospitalization (HR 1.62, 95% CI 1.30-2.01, p < 0.001). Low-risk patients with L-RHR/H-SBP achieved more frequently ≥50% of target doses of angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers (BBs) than the other groups. However, 48% and 46% of low-risk patients were not well treated with ACEIs and BBs, respectively (≤50% of target dose or no treatment). CONCLUSION: In patients with HFrEF and recent hospitalization, elevated RHR and lower SBP identify patients at increased risk for cardiovascular endpoints. While SBP and RHR are often recognized as barriers that deter physicians from treating with high doses of recommended drugs, they are not the only reason leaving many patients suboptimally treated.

Trends in the burden and determinants of hypertensive heart disease in the Eastern Mediterranean region, 1990-2019: an analysis of the Global Burden of Disease Study 2019.

Background: Hypertensive heart disease (HHD), one of the end-organ damage consequences of hypertension, is an important public health issue worldwide. Data on the HHD burden in the Eastern Mediterranean region (EMR) are scarce. We aimed to investigate the burden of HHD in the EMR, its member countries, and globally from 1990 to 2019. Methods: We used 2019 Global Burden of Disease (GBD) data to report the HHD age-standardised prevalence, disability adjusted life years (DALYs), years of life lost (YLLs), and mortality, as well as HHD risk factors attribution percent with their 95% uncertainty interval (UI). Global data are reported alongside EMR data, and its 22 respective countries. We compared the burden of HHD by socio-demographic index (SDI), sex, age groups, and countries. Findings: The age-standardised prevalence rate (per 100,000 population) of HHD was higher in the EMR (281.7; 95% UI: 204.5-383.4) in 2019, compared with the global prevalence (233.8; 95% UI: 170.5-312.9). The EMR age-standardised DALYs (per 100,000 population) for HHD in 2019 was 561.9 (361.0-704.1), compared with 268.2 (204.6-298.1) at the global level. There was an increase in HHD prevalence, reduction in mortality, and DALYs between 1990 and 2019 (4.01%, -7.6%, and -6.5%, respectively) in EMR. Among EMR countries, the highest versus lowest rates of age-standardised prevalence, mortality, and DALYs in 2019 [estimate (95% UI)] were in Jordan [561.62 (417.9-747.6)] versus Saudi Arabia [94.9 (69.5-129.0)]; Afghanistan [74.5 (23.7-112.3)] versus Saudi Arabia [4.3 (3.3-5.9)]; and Afghanistan [1374.1 (467.2-2020.7)] versus Qatar [87.11 (64.40-114.29)], respectively. Interpretation: HHD remains a significant problem in the EMR, with a higher burden than global levels. Serious efforts toward high-quality management and prevention are strongly recommended. Based on this study, our recommendation for the EMR is to adopt effective preventive strategies. For example, promoting healthy dietary patterns and prompt screening for undiagnosed HTN in public places, promoting regular blood pressure measurements at home, and creating community awareness about early detection of HTN. Funding: None.

Efficacy of ivabradine in heart failure patients with a high-risk profile (analysis from the SHIFT trial).

AIMS: Early start and patient profile-oriented heart failure (HF) management has been recommended. In this post hoc analysis from the SHIFT trial, we analysed the treatment effects of ivabradine in HF patients with systolic blood pressure (SBP) < 110 mmHg, resting heart rate (RHR) ≥ 75 b.p.m., left ventricular ejection fraction (LVEF) ≤ 25%, New York Heart Association (NYHA) Class III/IV, and their combination. METHODS AND RESULTS: The SHIFT trial enrolled 6505 patients (LVEF ≤ 35% and RHR ≥ 70 b.p.m.), randomized to ivabradine or placebo on the background of guideline-defined standard care. Compared with placebo, ivabradine was associated with a similar relative risk reduction of the primary endpoint (cardiovascular death or HF hospitalization) in patients with SBP < 110 and ≥110 mmHg [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.74-1.08 vs. HR 0.80, 95% CI 0.72-0.89, P interaction = 0.34], LVEF ≤ 25% and >25% (HR 0.85, 95% CI 0.72-1.01 vs. HR 0.80, 95% CI 0.71-0.90, P interaction = 0.53), and NYHA III-IV and II (HR 0.83, 95% CI 0.74-0.94 vs. HR 0.81, 95% CI 0.69-0.94, P interaction = 0.79). The effect was more pronounced in patients with RHR ≥ 75 compared with <75 (HR 0.76, 95% CI 0.68-0.85 vs. HR 0.97, 95% CI 0.81-0.1.16, P interaction = 0.02). When combining these profiling parameters, treatment with ivabradine was also associated with risk reductions comparable with patients with low-risk profiles for the primary endpoint (relative risk reduction 29%), cardiovascular death (11%), HF death (49%), and HF hospitalization (38%; all P values for interaction: 0.40). No safety concerns were observed between study groups. CONCLUSIONS: Our analysis shows that RHR reduction with ivabradine is effective and improves clinical outcomes in HF patients across various risk indicators such as low SBP, high RHR, low LVEF, and high NYHA class to a similar extent and without safety concern.