Use Of Beta-blockers Research Articles

Safety of Beta-Blocker Administration in STEMI Patients With Risk Factors for Cardiogenic Shock

Beta-blockers are recommended in the first 24 hours after ST-segment elevation myocardial infarction (STEMI) except in those at risk of cardiogenic shock. This retrospective cohort study aimed to assess if early beta-blocker use was associated with cardiogenic shock development in STEMI patients. Cardiogenic shock was assessed in adult patients with STEMI undergoing percutaneous coronary intervention (PCI) with guideline defined risk factors for shock (age above 70 years, systolic blood pressure below 120 mmHg, and heart rate above 120 bpm or below 60 bpm) who did or did not receive a beta-blocker within 24 hours of PCI. Multivariable logistic regression was used to assess the association between cardiogenic shock development and early beta-blocker administration. A total of 216 patients were included, 85 with early beta-blocker administration and 131 without. Patients who received an early beta-blocker versus those who did not had a median (interquartile range) age of 63 (52-71) versus 66 (54-76; P = .2260) and peak troponin of 58.3 (15.0-132.4) ng/mL versus 51.6 (16.6-139.5; P = .9884). Cardiogenic shock occurred in 4.7% (n = 4) patients with early beta-blocker use versus 12.2% (n = 16; P = .0909) without. After backward stepwise logistic regression, early beta-blocker use was not associated with cardiogenic shock (adjusted odd ratio [aOR] 0.334, 95% confidence interval (CI) 0.106-1.047; P = .0599), but those with a peak troponin over 56 ng/mL had an over three-fold increased risk of developing cardiogenic shock (aOR 3.434, 95% CI 1.191-9.902; P = .0224) regardless of beta blocker administration. Early beta-blocker administration in STEMI patients may not be associated with shock development.

Iatrogenic cardiac arrest during thyroid storm

Introduction: Thyroid storm is a life-threatening condition with often severe cardiac implications. Correct treatment choices can vary depending on underlying cardiac systolic function. Case description: We present a case of a 47-year-old male with untreated Grave’s disease who presented with a thyroid storm. After propranolol administration, he experienced a cardiac arrest with the return of spontaneous circulation after cardiopulmonary resuscitation. Further evaluation revealed severe thyroid-induced cardiomyopathy with left ventricular ejection fraction of 15–20%, which had decreased from 60–65% over one year. The patient was discharged home on hospital day 8 after an unremarkable ischaemic work-up. He experienced a full cardiac systolic function recovery with an ejection fraction of 60–65% at the 90-day follow-up. Conclusion: Thyroid storm can present with overt or subclinical heart failure. Prompt evaluation of cardiac systolic function with a transthoracic echocardiogram before beta-blockade and the use of shorter-acting beta blockers can prevent devastating suppression of myocardial function.

The role of beta blockers in the treatment of cardiovascular diseases

Beta-blockers are used to treat various cardiovascular diseases, including hypertension and chronic heart failure. They act by suppressing the effects of catecholamines through various pathways and affect heart rate, strength, and renin release, providing antihypertensive and anti-ischemic effects. The individual effects of various drugs on clinical outcomes in this group were determined according to characteristics of the patient, underlying disease, and type of beta-blocker used. In recent years, beta-blockers have faced a serious obstacle when new guidelines on hypertension suggest their use as second-line therapy after angiotensin converting enzyme inhibitors, angiotensin receptor blockers and slow calcium channel blockers in the absence of clear indications. In fact, these recommendations were based on meta-analyses that showed that beta-blockers have fewer beneficial effects on overall mortality, cardiovascular events, and brain stroke. In addition, according to currently available data, the appointment of beta-blockers for diseases such as heart failure with preserved ejection fraction and stable coronary heart disease can cause more harm than good outcomes. Bisoprolol is a beta-blocker with the highest selectivity for beta1-adrenergic receptors, which determines the rare frequency of side effects that develop because of its use. This review presents current data on the use of beta-blockers for treating cardiovascular diseases, with an emphasis on the use of bisoprolol.

Exploring the Relationship Between NOD2 Risk Variants and First Decompensation Events in Cirrhotic Patients With Varices.

NOD2 mutations are associated with impaired gut mucosal barrier function. According to the systemic inflammation hypothesis, bacterial translocation is central in the development of decompensation. The aim was to evaluate whether the presence of NOD2 variants is associated with the development of first decompensation. Secondary analysis of prospectively collected consecutive patients with compensated cirrhosis, who were screened between 2014 and 2018. Patients with and without NOD2 variants were compared and stratified analysis according to the presence of varices was performed. 360 patients [239 (66%) men, median age 61 (53-69) years, 70 (19%) with NOD2 variants, 90 (25%) with varices] were followed for a median of 9 (4-16) months. Similar baseline characteristics were observed across NOD2 status groups, except for beta-blocker use (45% vs. 32% amongst variant carriers vs. non-carriers, p = 0.05). During follow-up, 34 patients (12%) developed their first decompensation, with no differences according to NOD2 status [HR 1.75 (95% CI 0.84-3.67)]. On multivariate analysis, only MELD remained an independent predictor of decompensation. Amongst patients with varices (n = 90), 18 (24.4%) carried a NOD2 variants, with a higher incidence of first decompensation [HR 3.00 (95% CI 1.08-8.32)], primarily due to ascites [HR 3.32 (95% CI 1.07-10.32)]. In this subgroup, MELD [HR 1.18 (95% CI 1.06-1.32)] and NOD2 variants [HR 2.91 (95% CI 0.95-8.89)] were determined to be independent predictors of decompensation. The presence of NOD2 risk variants leads to a greater incidence of first decompensation only in compensated patients with varices.

Effects of beta blockers on outcome in patients with PAH with and without comorbid conditions: a Multicenter Prospective Cohort Study (BNP-PL)

Abstract Background The current guidelines do not recommend the use of beta-blockers (BB) in patients with pulmonary arterial hypertension (PAH) unless necessitated by comorbidities. However, the evidence regarding the role of BB in PAH is contradictory. This study investigates the effects of BB on clinical outcomes in patients newly diagnosed with PAH, stratified by the presence of cardiovascular comorbidities that justify their use. Methods We analyzed data from 806 patients newly diagnosed with PAH, who were prospectively enrolled from March 1, 2018, to August 31, 2023, in the multicentre registry, Database of Pulmonary Hypertension in the Polish population (BNP-PL). The primary endpoints were all-cause mortality and a composite of hospitalization due to right heart exacerbation, syncope, or death. The follow-up period for these patients extended until August 31, 2023. Comorbidities in the study group that indicated the need for BB therapy included hypertension, significant arrhythmia, and coronary artery disease. In the Cox regression analysis, the association between BB use and the predefined endpoints was adjusted for age, baseline European Society of Cardiology risk score, and upfront therapy. Results Among the 806 patients, BBs were administered to 469 (58.2%) at the time of PAH diagnosis. In the entire cohort, BB therapy was linked to increased all-cause mortality (29.6% vs 21.4%; p=0.005, Fig 1.A) and a higher incidence of the composite endpoint (34.1% vs 22.6%; p<0.0001, Fig 1.B). The Number Needed to Harm (NNH) for BB treatment, regarding mortality and the composite endpoint, were 12.1 and 8.7, respectively. In patients without comorbidities, BB use significantly raised the risk of both all-cause mortality (Hazard Ratio [HR] 1.81, 95% Confidence Interval [CI]: 1.01-3.15) and the composite endpoint (HR 1.85, 95% CI 1.09-3.14), after adjustments for age, baseline three-strata PAH mortality risk, and upfront therapy. However, in patients with at least one comorbidity, BB therapy showed a neutral effect on both outcomes. Across the whole group, the use of nonselective BB was associated with a higher risk of the composite endpoint (HR 1.78, 95% CI 1.13-2.82, p=0.01) compared to selective β1 agents, although this did not extend to all-cause mortality (HR 1.34, 95% CI 0.79-2.25, p=0.28). Conclusion BBs, particularly nonselective, pose significant risks in patients with PAH who lack comorbidities that justify their use.

Beta-blocker use and outcomes in patients with heart failure and mildly reduced and preserved ejection fraction

Abstract Background Concerns have been raised about the appropriateness of use and safety of beta-blockers (BBs) in patients with heart failure and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF). However, randomized trial evidence is still lacking. Purpose To perform an observational analysis of the association between BB use and clinical outcomes in a large dataset of patients with HFmrEF and HFpEF. Methods We pooled individual patient data from four large HFmrEF/HFpEF trials (I-Preserve, TOPCAT, PARAGON-HF, and DELIVER). The associations between baseline BB use and outcomes were analyzed. The primary outcome was the composite of cardiovascular death or HF hospitalization. Results Among the 16,951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13,400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12,812 patients (75.6%) received a BB. The median bisoprolol-equivalent dose of BB was 5.0 (Q1-Q3: 2.5-5.0) mg with BB continuation rates of 95.1% at 1 year and 93.1% at 2 years (in patients who survived more than 1 and 2 years, respectively). Overall, the hazard ratio (HR) for the primary outcome did not differ between BB users and non-users (HR: 0.98 [95% CI: 0.91-1.05]) but among patients with HFmrEF, BB users had a lower HR (0.84 [95% CI 0.71-0.98]), whereas in HFpEF the HR was similar BB users and non-users (0.99 [95% CI 0.92-1.08]). However, after comprehensive adjustment for known prognostic variables, including NT-proBNP, BB use was associated with a better outcome in the overall cohort (HR 0.81 [0.74-0.88]), and this association was maintained across the range of LVEF (Figure 1). In subgroup analyses, the risk of the primary outcome was similar in BB users and non-users with or without a history of myocardial infarction, with or without a history of hypertension, or with or without a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (Figure 2). Conclusions Although this is an observational analysis of non-randomized treatment, there was no suggestion that BB use was associated with worse HF outcomes even after extensive adjustment for other prognostic variables. Figure Legends Figure 1. Association between beta-blocker use and outcomes across the range of LVEF. Risk in beta-blocker users versus non-users is shown as an adjusted continuous hazard ratio Figure 2. Association between beta-blocker use and non-use in the overall population and clinically relevant patient subgroups, shown as an adjusted hazard ratio (HR). The outcome analyzed was the composite of CV death or HF hospitalization (primary outcome)Figure 1Figure 2

Clinical phenotyping and treatment response in patients with chronic heart failure: a latent class analysis from a Japanese multicentre registry

Abstract Background There are diversities of pathophysiology and co-morbidities in patients with chronic heart failure (HF), irrespective of left ventricular ejection fraction (LVEF). Therefore, the identification of subgroups with different outcomes and treatment response patterns may help to tailor strategies to each individual HF patient. Purpose We sought to identify phenogroups of patients with different prognosis and response to medical therapies in patients with chronic HF. Methods A total of 1565 patients with a broad spectrum of LVEF in a prospective multicentre registry of patients with chronic HF were enrolled between January 2020 and December 2023. Latent class analysis was performed in each subgroup using 80 features including patients’ demographics, laboratory, and echocardiographic data. The optimal number of phenogroups was determined using the first minimum of the Bayesian information criterion. The primary outcome was a composite of all-cause death and hospitalisation due to worsening HF. Results The analysis subclassified patients into six phenogroups. Patients in phenogroup A (young non-ischaemic cardiomyopathy, n = 242, 15.5%) were the youngest and had lower LVEF and lowest prevalence of coronary artery disease (CAD) and other comorbidities. Phenogroup B (atrial fibrillation [AF] and small left atrium, n = 282, 18.0%) had higher proportion of AF but smaller left atrium volume. Phenogroup C (ischaemic cardiomyopathy, n = 204, 13.0%) had the highest proportion of CAD and lower LVEF. Phenogroup D (classical HF with preserved ejection fraction [HFpEF], n =308, 19.7%) had the highest age, proportion of female, LVEF and thickness of LV wall. Phenogroup E (elderly and AF , n = 235, 15.0%) had higher age, the highest proportion of AF and largest left atrium volume. Phenogroup F (biventricular failure and multiple comorbidities, n = 294, 18.8%) had the highest proportion of co-morbidities and the lowest LVEF, right ventricular systolic function and renal function. During a median follow-up period of 538 (interquartile range 286-701) days, the incidence of the primary outcome significantly differed among the phenogroups (P < 0.001, Figure 1). Regarding treatment response for renin-angiotensin system blockers and beta blockers, there were no significant associations between the use of renin-angiotensin system blockers and the risk of the primary outcome among the phenogroups whereas the use of beta-blockers was significantly associated with increased risk of the primary outcome in patients classified to phenogroup D (classical HFpEF) (hazard ratio 1.83 95% confidence interval 1.05-3.19) among the phenogroups (Figure 2). Conclusion We identified six phenogroups with distinct clinical outcomes in patients with chronic HF, and the use of beta-blockers might have unfavorable effect in the classical HFpEF phenogroup. This phenotyping provides novel risk stratification and may aid in clinical decision making.Clinical outcomes among the phenogroupsTreatment effect among the phenogroups

Heart failure treatment in the last years of life - a nationwide study of 364,000 individuals

Abstract Background Heart failure treatment patterns towards the end of life have rarely been studied at large scale. Yet, this is important to assess, since heart failure is a chronic condition with patients on treatment for potentially many years. Purpose To investigate treatment patterns in the last years of life in patients with heart failure. Methods In a register-based study covering the whole Swedish population between 2007 and 2020, we investigated treatment patterns in the last years of life in 364,480 individuals who died with heart failure. We combined binomial models (to estimate proportion on treatment at death) and Poisson models (to estimate discontinuation rate), to estimate the proportion on each heart failure treatment up to 5 years prior to death, using penalized splines to allow for non-linearities. We also assessed comorbidity patterns over time. Results All heart failure treatments saw a gradual discontinuation closer to death, but the discontinuation rate of beta blockers decreased over time, resulting in an increasing proportion of patients on treatment at the time of death (Fig). Also, the pattern of comorbidities changed over time, with an increase in e.g., hypertension and atrial fibrillation, but a decline in ischemic heart disease (63% in 2007 gradually declining to 54% in 2020). Conclusions In this nationwide study, we observed a changing pattern of medical treatment of heart failure during the last years of life, most notably with an increasing use of beta blockers. Comorbidities and the shares of heart failure etiologies also changed over time, with an increase in several conditions but a decline in ischemic heart disease. Taken together, this may have important implications for planning and optimizing care for these patients.

Mortality effects of beta-blockers on myocardial infarction in patients without reduced ejection fraction or heart failure in the contemporary reperfusion era : a systematic review and meta-analysis

Abstract Background The 2023 ESC and AHA/ACC guidelines note that contemporary data are heterogenous regarding the use of beta-blockers (BB) post-myocardial infarction (MI) in patients without reduced ejection fraction (EF) or heart failure (HF). Purpose We performed a systematic review and meta-analysis to address the heterogeneity in existing literature around BB post-MI in patients without HF. Methods We searched 6 databases from Jan 1, 2000 to Jan 12, 2024 to identify modern randomized controlled trials (RCTs) or observational studies enrolling MI patients without reduced EF or history of HF who received BB at index MI, and comparing outcomes between BB users and non-users. Reduced EF was defined as EF ≤40%. The primary outcome was all-cause death. Subgroup analyses and meta-regression were conducted to explore heterogeneity. Meta-analysis was conducted using the restricted maximum likelihood method. Results There were 22 studies, including 1 RCT, involving 281,631 patients enrolled between 1997 and 2020. BB did not confer a significant reduction in all-cause death in patients with a 1-year event-free period (HR, 0.99; 95% CI, 0.94 to 1.06; I2 = 0%; Figure 1A), defined as no death, recurrent MI, or HF while on BB following index MI. In patients with a 3-year event-free period, a non-significant trend towards increased all-cause mortality was observed in BB users (HR, 1.39; 95% CI, 0.81 to 2.40; I2 = 0%; Figure 1A). For patients without a stable period, meta-regression showed BB morality benefits were modified by study inclusion period (P = 0.01; R2 = 51%; Figure 1B), indicating a temporal trend of decreasing mortality benefits of BB over time. Of note, BB exhibited no mortality benefits in patients enrolled after 2010 (HR, 0.97; 95% CI, 0.90 to 1.04; I2 = 0%; Figure 1C). Subgroup analysis showed BB led to a significantly lower all-cause death in patients with mildly-reduced EF (HR, 0.79; 95% CI, 0.68 to 0.91; I2 = 0%; Figure 2A). No mortality benefit of BB was observed in patients with preserved EF (HR, 0.83; 95% CI, 0.68 to 1.02; I2 = 66%; Figure 2A), however, with high statistical heterogeneity. Further exploration of this heterogeneity via meta-regression revealed a pronounced temporal trend of decreasing BB mortality benefits in patients with preserved EF (P <.0001; R2 = 100%; Figure 2B). The R2 value rising from 51% to 100% suggests that unexplained 49% heterogeneity is attributed to mildly-reduced EF patients. Similarly, BB's mortality benefit was not significant in patients enrolled after 2010 (HR, 1.02; 95% CI, 0.95 to 1.09; I2 = 0%; Figure 2C). Conclusion In the contemporary reperfusion era, BB do not confer additional mortality benefits beyond a 1-year event-free period post-MI in patients without reduced EF. Moreover, given the temporal decreases in observed mortality benefits, especially in studies post-2010, BB may not remain an essential medication in post-MI care for patients with preserved EF in modern practice.Patients with/without a stable periodMildly-reduced and preserved EF patients

Continuation of beta-blockers at discharge is associated with improved outcome in patients with HFpEF and concomitant moderate aortic stenosis

Abstract Background In patients with severe aortic stenosis or decompensated heart failure with preserved ejection fraction (HFpEF), beta-blockers are usually discontinued despite the absence of unequivocal evidence. The data on the effect of beta-blockers in patients with moderate aortic stenosis (MAS) are scarce. Aim To investigate the relationship between beta-blocker use and outcome in patients with MAS, who were hospitalized for decompensated HFpEF. Methods The current study includes 61 patients admitted for decompensated HFpEF with concomitant MAS. The mean age of the population was 82.7±7.59 years old and 41% were females. The diagnosis MAS was established on criteria including aortic valve area between 1-1.5 cm², mean gradient - 20-39 mmHg, and max velocity between 3-3.9 m/s. For those with borderline measurements, the Doppler Velocity Index (DVI) was calculated (DVI < 0.25 indicates severe aortic stenosis). All echocardiographic data were assessed by an experienced echocardiographer. Patients with previous aortic valve replacement and a severe mixed of multivalvular disease were excluded. Result The median follow-up was 52 months (interquartile range 34-63 months). During this period 38 patients (62.3%) died from any cause while 42 (68.9%) individuals experienced a composite endpoint, of all-cause death or hospitalization due to worsening HFpEF. In survivors, we observed higher prescription of beta-blockers at hospital discharge (66% vs. 34%, p<0,05) and better diastolic function than in patients with endpoints. In multivariate Cox regression analysis the use of beta-blockers (HR = 0,27; 95% CI 0,13-0,57; p<0.01) and better diastolic function, defined as higher septal e` (HR=0,76; 95% CI 0,61-0,94; p=0.01) were identified as independent predictors for both - survival and composite endpoint (Figure 1). Advanced age was recognized as an associated factor for outcomes. Conclusion In the present study, continuation of beta-blockers at discharge was independently associated with better survival in patients with decompensated HFpEF and concomitant MAS. It remains to be addressed in future studies, whether or not beta-blockers should be started in these patients or if there is any prognostic interaction between beta-blockers and aortic valve intervention for MAS.Figure 1.Kaplan-Meier survival curve

Development and validation of a predicting model for risk of mortality in heart failure patients with mildly reduced ejection fraction post discharge

Abstract Background Prognostic prediction for heart failure with mildly reduced ejection fraction (HFmrEF) patients remains challenging. We aimed to create and validate a mortality risk prediction model for HFmrEF patients at 6-month, 1-year, and 3-year post discharge. Methods Clinical data of 1691 HFmrEF patients registered in the heart failure registry from 2015 to 2020 at the Heart Center of our hospital were analyzed. Patients were assigned into a training (1183 patients) and validation cohort (508 patients) at 7:3 ratio. Predictive variables for mortality at various period post discharge were identified by the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. The predicting model was then established based on these variables. Model performance was evaluated with ROC curve and Decision Curve Analysis (DCA). Results Eight predictors were identified including age, NT-proBNP, hemoglobin levels, use of beta-blockers, ACEI/ARB, invasive ventilation, PCI procedures, and pulmonary artery systolic pressure values. The model achieved a C-index of 0.748 (training set) and 0.755 (validation set). Area Under the Curve (AUC) for training set at 6 months, 1 year, and 3 years were 0.813, 0.784, and 0.774, and AUC for validation set were 0.775, 0.744, and 0.770, respectively. The DCA analysis confirmed the favorable net benefit of the established nomogram model. Conclusion This predicting model might be used for post-discharge risk stratification and individual decision-making of post-discharge management in HFmrEF patients.

Effect of renin-angiotensin system inhibitors in elderly patients with heart failure and reduced ejection fraction

Abstract Background More than half of the patients admitted for acute decompensated heart failure (ADHF) in Japan are over 80 years of age. Both Japanese and European heart failure guidelines recommend the use of renin-angiotensin system inhibitors (RASIs) in patients with heart failure with reduced ejection fraction (HFrEF). However, there is a paucity of data on the effect of RASIs in elderly patients with HFrEF, because elderly patients have been excluded from large clinical trials. Purpose The purpose of the current study was to clarify the effect of RASIs in elderly patients with HFrEF. Methods This was a post-hoc analysis of a prospective, observational, multicentre cohort study that enrolled consecutive patients admitted with ADHF to 19 secondary and tertiary hospitals in Japan between October 2014 and March 2016. Patients who were ≥ 80 years old, with left ventricular ejection fraction (LVEF) < 40% and discharged alive were included in the present study. RASIs were defined as either ACE inhibitors or angiotensin II receptor blockers. The primary endpoint was a composite of all-cause death and heart failure (HF) hospitalisation. Results Among 518 patients enrolled, 288 patients received RASIs at discharge and 230 patients did not. The median follow-up period was 335 days (interquartile range; 124 – 499 days). Patients receiving RASIs were younger (85.7 ± 4.4 vs. 86.5 ± 4.4 years of age, p=0.03), had a higher body mass index (BMI; 21.4 ± 3.3 vs. 20.6 ± 3.7 kg/m², p=0.01) and better renal function (eGFR; 45.4 ± 21.5 vs. 38.2 ± 19.2 ml/min/1.73m², p<0.001). Patients receiving RASIs had a higher LVEF (30.9 ± 6.3 vs. 28.5 ± 7.1%, p<0.001). The use of beta-blockers at discharge was more prevalent in patients receiving RASIs (77.8% vs. 60.4%, p<0.001), but the use of mineralocorticoid receptor antagonists was not (50.0% vs. 42.2%, p=0.08). The cumulative incidence of all-cause death or HF hospitalisation one year after discharge was significantly lower in patients receiving RASIs (40.1% vs. 59.5%, p<0.001). Even after adjusting for confounders, the risk of a composite of all-cause death and HF hospitalisation was significantly lower in patients receiving RASIs (adjusted hazard ratio 0.59, 95% confidence interval 0.45-0.77, p<0.001). There was no interaction between the effect of RASIs and subgroup factors such as age, BMI, dementia, malignancy, frailty, and renal function. Conclusion Use of RASIs at discharge was associated with lower incidence of all-cause death or HF hospitalisation in elderly patients with HFrEF.

Contemporary use of beta-blockers in the outpatient treatment of heart failure with atrial fibrillation

Abstract Background Evidence of the effectiveness of β-blockers in heart failure (HF) and atrial fibrillation (AF) in a contemporary cohort is controversial. This study investigated the association between the use of β-blockers and prognosis in outpatients across a broad spectrum of HF with AF. Methods Patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between 2014 and 2021. Associations of β-blocker use at discharge and prognosis were compared by propensity score matching among the AF or non-AF group. A multilevel mixed-effects survival model was used with hazard ratio (HR) and 95% confidence interval (CI). Results Among 428,650 patients discharged with HF in 4,433 hospitals, 175,174 (40.9%) were ≥85 years old, 151,873 (35.4%) had complicated AF, and 236,457 (55.2%) were β-blocker users. In a matched AF group, β-blocker use was associated with a lower composite outcome of all-cause mortality or HF rehospitalization (HR [95% CI], 0.95 [0.93–0.97]). A similar result was obtained in a matched non-AF group (0.95 [0.94–0.96]). In addition, the HRs in patients aged ≥85 years and female patients were 1.00 [0.98–1.02] and 1.01 [0.98–1.03] in the AF group and 1.03 [1.01–1.05] and 0.98 [0.97–1.00] in the non-AF group, respectively (Figure). Conclusions The favorable prognostic associations of β-blocker use were observed regardless of AF in outpatients across a broad spectrum of HF in a superaged society. However, β-blocker use may not be effective in older or female patients.

A flattening systolic blood pressure response at the end of ramp exercise testing is not associated with all-cause mortality

Abstract Purpose Systolic blood pressure (SBP) is expected to rise linearly during ramp exercise, but sometimes plateaus before the end of exercise. We aimed to examine the predictive value of a plateauing SBP response at the end of a cycle exercise test. Methods We analyzed 9,001 consecutive patients aged ≥18 years with maximal cycle ergometer ramp tests, after excluding subjects with valvulopathy, pacemaker, arrhythmia during the test, or body mass index (BMI) >40kg/m², as well as tests with resting SBP <80mmHg or >200mmHg, exercise SBP <100 mmHg, <2 SBP measurements during the second half of the test or a test duration <4 minutes. The data were cross-linked with nationwide registries for mortality and in- and outpatient hospital diagnoses. The difference in SBP between the two last SBP measurements was standardized to the difference in Watts between the same time points, categorized as i) an SBP decrease (drop), ii) an SBP increase of <2.5 mmHg per 10 Watts increase (flat), iii) an SBP increase of 2.5-15 mmHg/10 Watts (intermediate), and iv) an SBP increase >15 mmHg/10 Watts representing the 97.5th percentile (steep). Hazards ratios (HR, [95% confidence interval, CI]) for all-cause mortality were calculated, stratified for exercise capacity (peak Watt % of predicted) with the intermediate SBP response as reference. Adjustments were made for age, sex, BMI, resting SBP, baseline diagnosis of ischemic heart disease, heart failure, chronic obstructive pulmonary disease, and the use of beta-blockers or anti-hypertensive medication. Results Decreasing, flat, intermediate, and steep SBP responses at the end of exercise were present in 1.1%, 25.6%, 70.8% and 2.5% of patients respectively (Table 1). During median follow-up 8.6 years (interquartile range 5.9–11.6 years) there were 844 deaths. When compared to an intermediate SBP response, a flat SBP response was not associated with all-cause mortality in any of the exercise capacity strata: lowest tertile of Wmax%pred unadjusted HR 0.88 (95% CI 0.69–1.11), middle tertile HR 0.91 (95% CI 0.66–1.24), and highest tertile HR 0.95 (95% CI 0.64–1.41), with HRs remaining non-significant after adjustment for covariates (Table 2). Conclusion In patients referred for exercise testing, a flattening SBP response at the end of exercise was not associated with increased all-cause mortality risk compared to an intermediate SBP response, consistent across the different exercise capacity strata.

Differential impact of clinic BP target on the prevalence and predictors of the masked uncontrolled hypertension and white-coat uncontrolled hypertension

Abstract Background Although intensive blood pressure (BP) control have been advocated, major clinical practices guidelines still recommend clinic BP (cBP) < 149/90 mmHg as the target for antihypertensive therapy. But, cBP targets could influence the prevalence and predictors of any hypertension phenotype. We investigated how different cBP targets impacted on the prevalence and predictors of masked uncontrolled hypertension (MUCH) and white-coat uncontrolled hypertension (WUCH) using the Korean Ambulatory Blood Pressure (KorABP) registry. Methods A multicenter prospective longitudinal cohort study was performed in outpatients with hypertension. Among 5,965 patients enrolled in the KorABP registry, 1,601 patients on antihypertensive medications with a valid ambulatory BP monitoring record were included in this study. Two different cBP targets, <130/80mmHg (intensive) and <140/90 mmHg (conventional) were investigated. Results Controlled ambulatory BP (aBP; <130/80 mmHg) was observed in 472 patients (29.5%). Controlled cBP was shown in 348 patients (21.7%) with the intensive cBP target and in 697 patients (43.5%) with the conventional cBP target. Controlled hypertension, WUCH, MUCH and uncontrolled hypertension were found in 294, 174, 54, and 1,075 patients with the intensive target and in 378, 94, 319 and 810 patients with the conventional target, respectively. Among the patients with controlled cBP, the prevalence of MUCH markedly decreased with the intensive target (15.5%), compared to the conventional target (45.8%). In contrast, among the patients with uncontrolled cBP, the prevalence of WUCH had only 3.8% increase with the intensive target (10.4%), compared to the conventional target (14.2%) (Figure 1). With the conventional target, 75.9% of patients with MUCH had cBP between 130/80 mmHg and 139/89 mmHg. The concordance between the controlled aBP and controlled cBP was higher with the intensive target than with the conventional target (Cohen’s κ 0.62 [0.58-0.67] vs. 0.46 [0.41-0.50]). The logistic models for MUCH included the left ventricular mass index and underuse of antihypertensive drugs (<2 types of drugs) as the common predictors of the both targets. With the conventional target, clinic systolic BP and diastolic BP were the strongest predictors of MUCH, but the cBP was not a predictor of MUCH with the intensive target. The logistic models for WUCH included beta-blocker use, increased heart rate and lower waist circumference and clinic systolic BP as the common predictors of WUCH with the both target. The logistic model for MUCH performed better with the conventional target, whereas the logistic model for WUCH performed better with the intensive target (Figure 2). Conclusion The use of the intensive cBP target (<130/80 mmHg) could reduce the prevalence of MUCH with minimal increase in the prevalence of WUCH and would provide the better assessment for the BP control status than the use of the conventional cBP target (<140/90 mmHg).Figure 1Figure 2

Integrating artificial intelligence into a real-world clinical pathway to facilitate clinician treatment optimisation in patients with HFrEF on suboptimal medical therapy

Abstract Background Despite evidence-based pharmacological recommendations, many patients with HFrEF remain undertreated. (1) These patients remain at risk of decompensation and might benefit treatment optimisation. Many patients may also have been diagnosed with HFrEF prior to the use of sacubitril/valsartan or SGLT2 inhibitors. Identification of patients with historical HF diagnosis is time-consuming. Artificial intelligence approaches using deep learning might allow rapid identification of such patients. Aim To develop an artificial intelligence deep-learning algorithm for rapid identification of HF from electronic health records (EHRs) and to determine the potential benefit of our AI-driven algorithm for the detection of undertreated HFrEF patients in the community. Methodology In this study data was collected from EHRs of 1,200 patients who underwent transthoracic echocardiography. The records were screened to identify HF diagnosis through an AI deep-learning algorithm using a Convolutional Neural Network (CNN). Medication status of patients identified as having HFrEF was assessed to determine whether they were on optimal guideline-directed medical therapy. Accuracy of the AI algorithm was assessed by a manual clinician review in a subset of 150 patients. Eligible patients not on optimal medical therapy where no further optimisation was planned (judged to be "stable" at last visit) were invited for a clinical evaluation including NT-proBNP and Kansas City Cardiomyopathy Questionnaire (KCCQ) and offered a treatment optimization that could include either uptitration or initiation of a new medication if symptomatic. NT-proBNP and KCCQ were repeated at 12 week, pre- and post-optimization results were compared to evaluate patient outcomes. Results The deep-learning algorithm accurately identified HFrEF patients (99%) and use of RAAS inhibitors (97%) and beta-blockers (92%). 73 patients attended for initial clinical assessment (mean age 70 years, 77% male) and demonstrated a moderate level of HF-symptom burden (median NT-proBNP was 679 pg/mL, interquartile range was from 220 to 1300) and mean KCCQ overall summary score was 70, indicating a moderate level of HF symptom burden. 27 patients agreed to treatment optimisation. After 12 weeks there was a significant 22% reduction in NT-proBNP (from 1991 pg/mL (SD+/- 1796) to 1630 pg/mL (SD +/- 1588),p=0.049) and improvements in KCCQ (total symptom score 79 (+/-22) to 85 (+/-20), p=0.005; clinical summary score 78 (+/-23) to 82 (+/-20); overall summary score from 75 (+/- 24) to 80 (+/-22), both p=0.04). 23 patients (85%) and 18 patients (67%) out of 27 had an improvement in NT-proBNP and KCCQ overall summary scores respectively. Conclusion In our study we demonstrated the feasibility and potential benefits incorporating AI into a clinical workflow, allowing optimising treatment of patients with HF, with improvements in biomarkers and quality of life that could translate to long-term patient benefits.Changes in NT-proBNP after treatmentChanges in KCCQ after treatment

Assessing the alignment of obstructive hypertrophic cardiomyopathy pharmacological treatments with ESC guidelines in Germany

Abstract Introduction The European Society of Cardiology (ESC) recently updated treatment guidelines for hypertrophic cardiomyopathy (HCM). Purpose The aim of this study was to describe the treatment of obstructive HCM in Germany and assess alignment with the 2014 and 2023 ESC guidelines. Methods Adults with HCM were identified using a nationally representative administrative claims dataset (WIG2 Benchmark database) from several German Statutory Health Insurances between 2012 and 2018. Obstructive HCM was identified as any obstructive HCM diagnosis (ICD-10: I42.1) or any HCM diagnosis (I42.2, I42.9) with septal reduction therapy. The index date was defined as the date where the patient met all eligibility criteria for HCM. Minimum follow-up time was set to one year. Patients had at least 1 year of baseline data prior to the index HCM diagnosis and were followed up for at least 1 year after the diagnosis (or until death within 1 year). Patients with phenocopies were excluded. ESC guideline-directed pharmacological treatments for HCM included beta-blockers (BB), calcium channel blockers (CCB), disopyramide, and/or mavacamten (approved by EMA June 2023). While the 2014 ESC Guidelines on Diagnosis and Management of HCM were applicable during the study, recommendations pertaining to the use of non-vasodilating BBs and non-dihydropyridine (DHP) CCBs did not change in the 2023 ESC Guidelines for the Management of Cardiomyopathies; thus, this study applies to both. Results Out of 6793 patients with HCM analysed in the period 2012-2018, 1,141 had obstructive HCM. The average follow-up was 5 years. Patients were mostly male (62%) with a mean age of 60 years. Hypertension, hyperlipidaemia, coronary artery disease, heart failure, and atrial fibrillation were among the most common comorbidities; the mean Charlson Comorbidity Index score was 2.3. At index, 46% of patients were on BB monotherapy, 23% were on CCB monotherapy, <1% were on a combination of BBs or a combination of CCBs, 9% were on a combination of BBs and CCBs, and as many as 22% received no HCM treatment. Patients experienced 1615 unique treatment combinations throughout the study across all lines of therapy (Table 1). The most common treatments were bisoprolol (24%), metoprolol (19%), amlodipine (12%), and verapamil (12%). The use of propranolol was negligible (1%). 43% of pharmacological treatments were not in line with ESC guidelines. The most common reason for not aligning was using DHP-CCBs or vasodilating BBs. Conclusion This study shows that 57% of obstructive HCM treatments received by patients during the study were aligned with recommendations from the 2023 ESC guidelines on cardiomyopathies. Research is needed to investigate barriers and enablers to implementing the guideline including awareness of recommended treatments, as well as the management of comorbidities.

Prognostic implications of guideline-directed medical therapy in functional mitral regurgitation: a meta-analysis

Abstract Background Randomized evidence of the role of heart failure medical therapy for patients with functional mitral regurgitation (FMR) is lacking. Purpose The present meta-analysis sought to investigate the independent long-term prognostic impact of the different medical categories recommended in heart failure, for subjects with FMR. Methods A systematic literature review was conducted in electronic databases to identify studies reporting the association of renin angiotensin system inhibitors (RASi), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) with outcomes in FMR. A random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome in each medical category. Results The final sample comprised 12 studies with 6,715 FMR patients (Picture 1). The use of RASi and BBs was associated with a significantly lower risk for all-cause mortality (HR 0.52 [0.39-0.68]; p <0.00001, I2 =62 % and HR 0.62 [0.49-0.77]; p <0.0001, I2 =44 % respectively) and for the composite outcome (HR 0.54 [0.44-0.67]; p <0.00001, I2 =33 % and HR 0.62 [0.52-0.75], p <0.00001, I2 =35% respectively) in unadjusted models (Picture 2). Both RASi (aHR 0.73 [0.56-0.95], p =0.02, I2 =52%) and BBs (aHR 0.60 [0.41-0.88], p = 0.009, I2 =55%) retained their association with the composite outcome in pooled adjusted models (Picture 2). The prognostic benefit of using RASi or BBs was retained in subgroup analysis including only patients with moderate of severe FMR. MRAs did not demonstrate a significant association with improved outcomes in FMR. Conclusions RASi and BBs appear to have a favorable prognostic impact in patients with FMR, regardless of regurgitation severity.Study flow chart for study selectionPharmacotherapy and prognosis in FMR

Use of Beta-Blockers as a First-Line Treatment for Primary Hypertension

Background: Even though beta-blockers had been used as a first-line therapy for hypertension, since the late 1960s, the Eighth Joint National Committee, JNC 8, decided to recommend them no longer. This decision was based on relatively weak evidence from previous studies, which found that first-line beta-blockers were less effective in reducing stroke and heart failure, the main outcomes of hypertension. Despite the general perception, the most common events caused by hypertension are death and MI, not stroke or heart failure. Therefore, this study aimed to clarify beta-blocker efficacy by incorporating the data from all relevant beta-blocker trials, using the composite outcome of major cardiovascular events. Method: A search was conducted on MEDLINE, PubMed, Embase, and the Cochrane Library, restricted to published, peer-reviewed, human, meta-analysis, and controlled clinical trials. The term words used were “beta-blockers or adrenergic beta antagonists”, “hypertension”, and “death or coronary heart disease or stroke or congestive heart failure or myocardial infarction”. For this research, we selected six randomized controlled trials, and three meta-analyses were also chosen. Results: The results showed that beta-blockers were as effective as other first-line medications in younger hypertensive patients. On the other hand, in the patients aged above 60, the results were mixed. Beta-blockers were more effective than diuretics, but inferior to angiotensin receptor blockers. Also, beta-blockers were as safe and effective as angiotensin-converting enzyme inhibitors in reducing coronary heart disease, myocardial infarction, heart failure, and sudden death. However, beta-blockers were inferior to calcium channel blockers in reducing strokes. Conclusions: Beta-blockers were found to be the most effective in many aspects except for strokes. Further studies are needed to assess beta-blockers’ effectiveness in treating primary hypertension.

Ventricular arrhythmias occurring in myocardial infarction patients with acute ST-segment elevation within the first 24 hours after primary percutaneous coronary intervention and their prognostic value

Reperfusion therapy in myocardial infarction patients with acute ST-segment elevation significantly reduced the frequency of ventricular tachycardia and ventricular fibrillation, however, such arrhythmias still occur in 6-8% of patients, posing a threat to their lives.The aim of the study was to determine the nature of ventricular arrhythmias occurring in myocardial infarction patients with acute ST-segment elevation within the first 24 hours after primary percutaneous coronary intervention, and their prognostic value regarding the development of complications during the inpatient treatment phase. The study involved 82 individuals (mean age: 62,4±10,2 years; male: 69,23 (58,6-78,92)%, female: 30,77 (21,08-41,4)%). Within 24 hours after the infarct-related artery stenting, all patients underwent a 24-hour Holter ECG monitoring. The course of the disease was analyzed based on the presence of risk factors such as hypertension, diabetes mellitus, past COVID-19, and obesity. Ventricular rhythm disturbances were represented mainly by premature contractions. They occurred significantly more frequently in patients with arterial hypertension (883,71 (96,0; 986.0); p=0,02; p=0,03; p=0,02, compared to patients with a history of COVID-19, diabetes, and obesity, respectively) and in those with past COVID-19 (711,3 (125,0; 846,5); p=0,01; p=0,04, compared to indi­viduals with diabetes and obesity, respectively). Isolated premature ventricular complexes, pairs, triplets were recorded, and in individuals with arterial hypertension and past COVID-19 “runs” of ventricular extrasystoles and episodes of nonsustained monomorphic and even polymorphic ventricular tachycardia, such as Torsades de Pointes, (under the condition of combined risk factors) were noted; predominantly in these patients during the hospital phase such сom­plications as ventricular fibrillation and asystole,with sudden cardiac arrest developed. The obtained results is an evidence of electrical myocardial instability and indicate that myocardial infarction patients with acute ST-segment elevation, in addition to myocardial revascularization, require optimization of pharmacological treatment. The use of intravenous beta-blockers as part of complex treatment prevented the occurrence of life-threatening ventricular arrhythmias during the inpatient treatment phase.