Cardiovascular Hospitalization Research Articles

Rhythm vs Rate Control Strategy for Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

BackgroundRhythm control, either with antiarrhythmic drugs or catheter ablation, and rate control strategies are the cornerstones of atrial fibrillation (AF) management. Despite the increasing role of rhythm control over the past few years, it remains inconclusive which strategy is superior in improving clinical outcomes. ObjectivesThis study summarizes the total and time-varying evidence regarding the efficacy of rhythm- vs rate-control strategies in the management of AF. MethodsWe systematically perused the MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science databases for randomized controlled trials from inception to November 2023. We included studies that compared the efficacy of rhythm control (ie, antiarrhythmic drugs classes Ia, Ic, or III, AF catheter ablation, and electrical cardioversion) and rate control (ie, beta-blocker, digitalis, or calcium antagonist) strategies among patients with nonvalvular AF. The primary outcome was cardiovascular (CV) death, whereas secondary outcomes included all-cause death, stroke, hospitalization for heart failure (HF), sinus rhythm at the end of the follow-up, and rhythm control–related adverse events. A cumulative meta-analysis to assess temporal trends and a meta-regression analysis using the percentage of ablation use was performed. ResultsWe identified 18 studies with a total of 17,536 patients (mean age: 68.6 ± 9.7 years, 37.9% females) and a mean follow-up of 28.5 months. Of those, 31.9% had paroxysmal AF. A rhythm control strategy reduced CV death (HR: 0.78; 95% CI: 0.62-0.96), stroke (HR: 0.801; 95% CI: 0.643-0.998), and hospitalization for HF (HR: 0.80; 95% CI: 0.69-0.94) but not all-cause death (HR: 0.86; 95% CI: 0.73-1.02) compared with a rate control strategy. This benefit was driven by contemporary studies, whereas more ablation use within the rhythm control arm was associated with improved outcomes, except stroke. ConclusionsIn patients with AF, a contemporary rhythm control strategy leads to reduced CV mortality, HF events, and stroke compared with a rate control strategy.

Depressive symptoms are associated with clinical outcomes in heart failure with reduced ejection fraction.

The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. One hundred forty-two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6months, depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and HFrEF disease activity by B-type natriuretic peptide (BNP). The Self-Care of Heart Failure Index (SCHFI) was used to assess HF self-care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow-up period of 4years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI-II scores were associated with poorer HF self-care maintenance behaviours (R=-0.30, P<0.001) and fewer daily steps (R=-0.19, P=0.04), suggesting that elevated depressive symptoms may diminish important health behaviours. Increases in plasma BNP over 6months were associated with worse outcomes. Changes in BDI-II and plasma BNP over 6months were positively related (R=0.25, P=0.004). This study confirms that elevated depressive symptoms are associated with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Poor health behaviours may contribute to the adverse association of elevated depressive symptoms with the increased hazard of adverse clinical outcomes.

Echocardiographic predictors of cardiovascular outcome in heart failure with preserved ejection fraction.

The optimal echocardiographic predictors of cardiovascular outcome in heart failure (HF) with preserved ejection fraction (HFpEF) are unknown. We aimed to identify independent echocardiographic predictors of cardiovascular outcome in patients with HFpEF. Systematic literature search of three electronic databases was conducted from date of inception until November 2022. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for echocardiographic variables from multivariate prediction models for the composite primary endpoint of cardiovascular death and HF hospitalization were pooled using a random effects meta-analysis. Specific subgroup analyses were conducted for studies that enrolled patients with acute versus chronic HF, and for those studies that included E/e', pulmonary artery systolic pressure (PASP), renal function, natriuretic peptides and diuretic use in multivariate models. Forty-six studies totalling 20 056 patients with HFpEF were included. Three echocardiographic parameters emerged as independent predictors in all subgroup analyses: decreased left ventricular (LV) global longitudinal strain (HR 1.24, 95% CI 1.10-1.39 per 5% decrease), decreased left atrial (LA) reservoir strain (HR 1.30, 95% CI 1.13-1.1.50 per 5% decrease) and lower tricuspid annular plane systolic excursion (TAPSE) to PASP ratio (HR 1.17, 95% CI 1.07-1.25 per 0.1 unit decrease). Other independent echocardiographic predictors of the primary endpoint were a higher E/e', moderate to severe tricuspid regurgitation, LV mass index and LA ejection fraction, although these variables were less robust. Impaired LV global longitudinal strain, lower LA reservoir strain and lower TAPSE/PASP ratio predict cardiovascular death and HF hospitalization in HFpEF and are independent of filling pressures, clinical characteristics and natriuretic peptides. These echocardiographic parameters reflect key functional changes in HFpEF, and should be incorporated in future prospective risk prediction models.

EFFECT OF DAPAGLIFLOZIN ON CARDIOVASCULAR OUTCOMES IN HFREF PATIENTS: IMPACT OF DIABETES MELLITUS TYPE 2 STATUS

Dapagliflozin has shown promise in the treatment of heart failure with reduced ejection fraction (HFrEF), but its effects in patients with and without diabetes remain unclear. Objective: This study aimed to assess the effects of dapagliflozin in HFrEF patients, both with and without diabetes. Methods: From January to July 2023, a six-month case-control study was conducted in the cardiology department of a Tertiary Care Hospital in Peshawar, Pakistan. All patients received an additional dose of dapagliflozin (10 mg) alongside their usual treatment plans. The primary outcome was a composite of heart failure exacerbation or cardiovascular death. Data analysis was performed using SPSS version 22. Results: Patients with diabetes mellitus type 2 (DMT2) exhibited a higher rate of cardiovascular death (22%) and hospitalization for heart failure (14.4%) compared to those without diabetes. The hospitalisation rate for heart failure was also higher in the DMT2 group (12.21%) than in the non-diabetic group (8.6%). Over the trial period, cardiovascular death occurred in 12.44% of patients with DMT2 compared to 7.30% in those without DMT2. Patients with diabetes experienced a significantly higher number of first and recurrent hospitalizations for heart failure and cardiovascular death compared to those without diabetes (32.45% vs. 19.20%, p=0.021). Conclusion: Dapagliflozin therapy in HFrEF patients demonstrated varying effects between those with and without diabetes. The study underscores the importance of personalised management strategies considering comorbid medical conditions. Despite dapagliflozin treatment, patients with both heart failure and diabetes continued to experience cardiovascular complications, highlighting the need for individualised treatment plans that account for a patient's complete medical profile.

Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial.

Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers (SCBs) flecainide and propafenone in patients with cardiovascular disease. Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) and primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of heart failure (HF) or acute coronary syndrome) during SCB intake for patients with ERC (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3/100 (99/3316) patient-years] than in patients who never received SCB [SCBnever 4.9/100 (150/3083) patient-years, P < 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9/100 (96/3359) patient-years] than in SCBnever patients [4.2/100 (135/3220) patient-years, adjusted P = 0.015]. Sinus rhythm at 2 years was similar between groups [SCB 537/610 (88); SCBnever 472/579 (82)]. Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable HF. Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.

Potential Spatial Accessibility to Cardiovascular Hospitals in Romania

Cardiovascular diseases (CVDs) represent the leading cause of death globally. Romania recorded the highest mortality rate due to CVDs in the EU in 2022, with 162,984 deaths, while the number of registered patients with CVDs surpassed 4 million. This study aims to measure the population’s potential spatial accessibility to cardiovascular hospitals in Romania, as timely access to such healthcare facilities is crucial to minimise avoidable mortality due to CVDs. Although distance is an essential parameter of spatial accessibility, time-based analysis is more reflective of real-world scenarios due to the unpredictability of travel. The potential spatial accessibility was measured using the Application Program Interface (API) offered through the Google Maps platform and a personal car as the transportation mode. The country’s cardiovascular hospital network comprises 161 units, of which 84 can provide complex care. Because all of them are located in urban areas, three different time slots were considered to distinguish between high and low traffic congestion situations. We created hierarchies of ten-minute and five km intervals for travel time and distance, respectively, to emphasize the population percentages with better or low potential spatial accessibility. Results showed that only 15% of the population can reach the nearest cardiovascular hospital in less than 20 min, and 23% must travel for over 60 min, while 45.7% live farther than 20 km from a cardiovascular hospital. Inhabitants living in remote areas, especially rural ones, are the most vulnerable, having to travel for the longest time and distance. Actions like improving the existing transport infrastructure and upgrading healthcare facilities and equipment are needed to ensure better medical care and an adequate response to population needs. This study can support local authorities in optimising spatial accessibility to cardiovascular care by identifying the most burdened hospitals in the context of low medical specialised staff and large catchment areas.

Relevance of Cardiovascular Exercise in Cancer and Cancer Therapy-Related Cardiac Dysfunction.

Cancer therapy-related cardiac dysfunction (CTRCD) has been identified as a threat to overall and cancer-related survival. Although aerobic exercise training (AET) has been shown to improve cardiorespiratory fitness (CRF), the relationship between specific exercise regimens and cancer survival, heart failure development, and reduction of CTRCD is unclear. In this review, we discuss the impact of AET on molecular pathways and the current literature of sports in the field of cardio-oncology. Cardio-oncological exercise trials have focused on variations of AET intensity by using moderate continuous and high intensity interval training, which are applicable, safe, and effective approaches to improve CRF. AET increases CRF, reduces cardiovascular morbidity and heart failure hospitalization and should thus be implemented as an adjunct to standard cancer therapy, although its long-term effect on CTRCD remains unknown. Despite modulating diverse molecular pathways, it remains unknown which exercise regimen, including variations of AET duration and frequency, is most suited to facilitate peripheral and central adaptations to exercise and improve survival in cancer patients.

Active Arrhythmia Pattern: A Novel Predictor of ICD Shocks-A Subanalysis From the PARTITA Study.

In the PARTITA trial (Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator?), antitachycardia pacing (ATP) predicted the occurrence of implantable cardioverter defibrillator (ICD) shocks. Catheter ablation of ventricular tachycardia after the first shock reduced the risk of death or worsening heart failure. A threshold of ATPs that might warrant an ablation procedure before ICD shocks is unknown. Our aim was to identify a threshold of ATPs and clinical features that predict the occurrence of shocks and cardiovascular events. We analyzed data from 517 patients in phase A of the PARTITA study. We used classification and regression tree analysis to develop and test a risk stratification model based on arrhythmia patterns and clinical data to predict ICD shocks. Secondary end points were worsening heart failure and cardiovascular hospitalization. Classification and regression tree classified patients into 6 leaves by increasing shock probability. Patients treated with ≥5 ATPs in 6 months (active arrhythmia pattern) had the highest risk of ICD shocks (93% and 86%, training and testing samples, respectively). Patients without ATPs had the lowest (1% and 2%). Other predictors included left ventricle ejection fraction<35%, age of <60 years, and obesity. Survival analysis revealed a higher risk of worsening heart failure (hazard ratio, 5.45 [95% CI, 1.62-18.4]; P=0.006) and cardiovascular hospitalization (hazard ratio, 7.29 [95% CI, 3.66-14.5]; P<0.001) for patients with an active arrhythmia pattern compared with those without ATPs. Patients with an active arrhythmia pattern (≥5 ATPs in 6 months) are associated with an increased risk of ICD shocks, as well as heart failure hospitalization and cardiovascular hospitalization. These data suggest that additional treatments may be helpful to this high-risk group as a preventive strategy to reduce the incidence of major events. Further prospective randomized trials are needed to confirm the benefits of early ventricular tachycardia ablation in this setting.

Relationship of TAPSE Normalized by Right Ventricular Area With Pulmonary Compliance, Exercise Capacity, and Clinical Outcomes.

While tricuspid annular plane systolic excursion (TAPSE) captures the predominant longitudinal motion of the right ventricle (RV), it does not account for ventricular morphology and radial motion changes in various forms of pulmonary hypertension. This study aims to account for both longitudinal and radial motions by dividing TAPSE by RV area and to assess its clinical significance. We performed a retrospective analysis of 71 subjects with New York Heart Association class II to III dyspnea who underwent echocardiogram and invasive cardiopulmonary exercise testing (which defined 4 hemodynamic groups: control, isolated postcapillary pulmonary hypertension, combined postcapillary pulmonary hypertension, and pulmonary arterial hypertension). On the echocardiogram, TAPSE was divided by RV area in diastole (TAPSE/RVA-D) and systole (TAPSE/RVA-S). Analyses included correlations (Pearson and linear regression), receiver operating characteristic, and survival curves. On linear regression analysis, TAPSE/RVA metrics (versus TAPSE) had a stronger correlation with pulmonary artery compliance (r=0.48-0.54 versus 0.38) and peak VO2 percentage predicted (0.23-0.30 versus 0.18). Based on the receiver operating characteristic analysis, pulmonary artery compliance ≥3 mL/mm Hg was identified by TAPSE/RVA-D with an under the curve (AUC) of 0.79 (optimal cutoff ≥1.1) and by TAPSE/RVA-S with an AUC of 0.83 (optimal cutoff ≥1.5), but by TAPSE with only an AUC of 0.67. Similarly, to identify peak VO2 <50% predicted, AUC of 0.66 for TAPSE/RVA-D and AUC of 0.65 for TAPSE/RVA-S. Death or cardiovascular hospitalization at 12 months was associated with TAPSE/RVA-D ≥1.1 (HR, 0.38 [95% CI, 0.11-0.56]) and TAPSE/RVA-S ≥1.5 (HR, 0.44 [95% CI, 0.16-0.78]), while TAPSE was not associated with adverse outcomes (HR, 0.99 [95% CI, 0.53-1.94]). Among 31 subjects with available cardiac magnetic resonance imaging, RV ejection fraction was better correlated with novel metrics (TAPSE/RVA-D r=0.378 and TAPSE/RVA-S r=0.328) than TAPSE (r=0.082). In a broad cohort with suspected pulmonary hypertension, TAPSE divided by RV area was superior to TAPSE alone in correlations with pulmonary compliance and exercise capacity. As a prognostic marker of right heart function, TAPSE/RVA-D <1.1 and TAPSE/RVA-S <1.5 predicted adverse cardiovascular outcomes.

MINIMUM NUMBER OF READINGS NEEDED TO DETERMINE LONG-TERM VISIT-TO-VISIT SYSTOLIC BLOOD PRESSURE VARIABILITY FOR PREDICTING CARDIOVASCULAR OUTCOMES IN DIABETIC PATIENTS

Objective: In clinical practice, office blood pressure (BP) measurements are used for assessing long-term, visit-to-visit variability (VVV) of BP and the consistency of BP control in patients treated for hypertension. We aimed to determine the reproducibility of VVV and the minimum number of BP measurements required to estimate VVV for predicting cardiovascular outcomes. Design and method: This multicenter, retrospective study used data from the Korea University Medical Center database built on electronic health records. A total of 10,475 diabetic patients with &gt;9 readings of BP during a minimum of two years were identified. Patients were followed up for 3 years after determining the coefficient of variation (CV), and the primary outcome was major adverse cardiovascular events (MACE), including cardiovascular mortality, myocardial infarction, stroke, and hospitalization for heart failure. Results: In diabetic patients, the average age of the patients was 65.2 years; 53.2% were men; and 87.4% had hypertension. The mean CV of systolic BP (SBP) was 9.0 ± 3.6. The mean CV of multiple readings that best predicted 3-year MACE were 8.4 for the 3 SBP readings (area under the curve [AUC], 0.57), 9.5 for the 5 readings (AUC, 0.61), 9.0 for the 7 readings (AUC, 0.63), 9.0 for the 9 readings (AUC, 0.64), and 9.7 for all readings (AUC, 0.66). In univariable analysis, 3-year MACE was significantly associated with high VVV from all SBP readings (HR 2.44, p&lt;0.001) and 5 SBP readings (HR 2.03, p&lt;0.001). Hence, a minimum of 5 SBP readings (median time 252 days) is needed for determining intraindividual VVV. Conclusions: In clinical practice, long-term VVV is reliably reproducible in diabetic patients. We recommend a minimum of five BP measurements for the estimation of intraindividual VVV. It is important to consider the number and duration of BP measurements used to calculate VVV when predicting cardiovascular outcomes.

Sex differences in the prognostic role of achieving target doses of heart failure medications: Data from the Swedish Heart Failure Registry.

Guidelines recommend target doses (TD) of heart failure (HF) with reduced ejection fraction (HFrEF) medications regardless of sex. Differences in pharmacokinetics and pharmacodynamics may explain heterogeneity in treatment response, adverse reactions, and tolerability issues across sexes. The aim of this study was to explore sex-based differences in the association between TD achievement and mortality/morbidity in HFrEF. Patients with HFrEF and HF duration ≥6 months registered in the Swedish HF Registry between May 2000 and December 2020 (follow-up until December 2021) were analysed. Treatments of interest were renin-angiotensin system inhibitors (RASI) or angiotensin receptor-neprilysin inhibitors (ARNI), and beta-blockers. Multivariable Cox regression models were performed to explore the risk of cardiovascular mortality or hospitalization for HF across dose categories in females versus males. A total of 17 912 patients were analysed (median age 77.0 years, interquartile range [IQR] 70.0-83.0), 29% were female. Over a median follow-up of 1.33 years (IQR 0.29-3.22), for RASI/ARNI there was no significant difference in outcome for females achieving 50-99% versus 100% of TD (hazard ratio 0.92, 95% confidence interval 0.83-1.03), whereas males showed a gradual lowering in risk together with the achievement of higher % of TD (p-interaction = 0.030). For beta-blockers the achievement of TD was associated with the lowest risk of outcome regardless of sex. Our findings suggest that females and males might differently benefit from the same dose of RASI/ARNI, and do represent a general call for randomized controlled trials to consider sex-specific up-titration schemes when testing HFrEF treatments in need of up-titration.

Influence of multimorbidity and socioeconomic position on long-term healthcare utilization and prognosis in patients after cardiac resynchronization therapy implantation.

We aimed to investigate the influence of socioeconomic position (SEP) and multimorbidity on cross-sectional healthcare utilization and prognosis in patients after cardiac resynchronization therapy (CRT) implantation. We included first-time CRT recipients with left ventricular ejection fraction ≤35% implanted between 2000 and 2017. Data on chronic conditions, use of healthcare services, and demographics were obtained from Danish national administrative and health registries. Healthcare utilization (in- and outpatient hospitalizations, activities in general practice) was compared by multimorbidity categories and SEP by using a negative binomial regression model. The association between SEP, multimorbidity, and prognostic outcomes was analysed using Cox proportional hazards regression. We followed 2007 patients (median age of 70 years), 79% were male, 75% were on early retirement or state pension, 37% were living alone, and 41% had low education level for a median of 5.2 [inter-quartile range: 2.2-7.3) years. In adjusted regression models, a higher number of chronic conditions were associated with increased healthcare utilization. Both cardiovascular and non-cardiovascular hospital contacts were increased. Patients with low SEP had a higher number of chronic conditions, but SEP had limited influence on healthcare utilization. Patients living alone and those with low educational level had a trend towards a higher risk of all-cause mortality [adjusted hazard ratio (aHR): 1.17, 95% confidence interval (CI) 1.03-1.33, and aHR 1.09, 95% CI 0.96-1.24). Multimorbidity increased the use of cross-sectional healthcare services, whereas low SEP had minor influence on the utilizations. Living alone and low educational level showed a trend towards a higher risk of mortality after CRT implantation.

CARDIOVASCULAR IMPACT OF DISCONTINUATION OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN ADVANCED CHRONIC KIDNEY DISEASE

Objective: Hypertension is a major problem in chronic kidney disease (CKD) with a prevalence approaching 100%, contributing to the risk of CKD progression, cardiovascular events and all-cause mortality. Renin-angiotensin system inhibitors (RASi) are the first-line therapy for antihypertensive treatment in patients with CKD, due to its protective effects. However, it is common practice stopping RASi in advanced CKD to attempt to delay kidney replacement therapy (KRT) initiation and/or to prevent drug-related acute kidney injury. Design and method: From the CKD-Rein prospective cohort, which included 3033 outpatients from nephrology clinics in France, we selected participants with an estimated glomerular filtration rate (eGFR) &lt;30 mL/min/1.73m2 and who were treated with RASi for at least 3 months. We used the G-formula to deal with time-fixed (age, sex, diabetes, heart failure, lung diseases) and time-varying confounding (eGFR, systolic blood pressure, serum sodium and potassium, diuretic prescription) to compare two treatment strategies: to discontinue or to continue RASi. The outcome, MACE, was the composite of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure. Competing risks were initiation of KRT and non-cardiovascular death. Results: From the 1,472 patients included (median age 69 years, median eGFR 25mL/min/1.73m2, 34% women), 27% discontinued RASi over a median follow-up of 35 [17-51] months. The crude rate of RASi discontinuation was higher in the presence of cardiovascular comorbidities and more severe CKD. The number of reported serious adverse reactions over the follow-up (such as acute kidney injury or hyperkalemia) was low, but higher in the discontinuation than in the continuation group (47 versus 23 per 1,000 person-years). After taking the afore-mentioned potential confounders into account, the 36-month risk of MACE was twice as high in the discontinuation group as that in the continuation group (RR 2.13, 95%CI 1.60-2.85). Conclusions: RASi discontinuation was significantly associated with MACE risk, the leading cause of morbidity and mortality in advanced CKD. Our results, along with other published data, suggest that the risk-benefit balance favors continued use of RASi in this population.

Effects of trimetazidine on heart failure with reduced ejection fraction and associated clinical outcomes: a systematic review and meta-analysis

BackgroundDespite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy...

The Long-Term Prognostic Role of Nighttime Resting Heart Rate in Obstructive Sleep Apnea in Patients with Acute Coronary Syndrome.

A close relationship exists between resting heart rate (RHR) and obstructive sleep apnea (OSA). Still, the prognostic importance of nighttime RHR in patients with acute coronary syndrome (ACS) with or without OSA remains unclear. In this prospective cohort study, OSA was defined as an apnea-hypopnea index of ≥ 15 events/h, and the high nighttime RHR (HNRHR) was defined as a heart rate of ≥ 70 bpm. The primary endpoint was a major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for heart failure. Among the 1875 enrolled patients, the mean patient age was 56.3±10.5 years, 978 (52.2%) had OSA, and 425 (22.7%) were in HNRHR. The proportion of patients with HNRHR is higher in the OSA population than in the non-OSA population (26.5% vs. 18.5%; P＜0.001). During 2.9 (1.5, 3.5) years of follow-up, HNRHR was associated with an increased risk of MACCE in patients with OSA (adjusted HR: 1.56, 95% CI: 1.09-2.23, P=0.014), but not in patients without OSA (adjust HR: 1.13, 95% CI: 0.69-1.84, P=0.63). In patients with ACS, a nighttime RHR of ≥ 70 bpm was associated with a higher risk of MACCE in those with OSA but not in those without it. This identifies a potential high-risk subgroup where heart rate may interact with the prognosis of OSA. Further research is needed to determine causative relationships and confirm whether heart rate control impacts cardiovascular outcomes in patients with ACS-OSA.

Microbiological and molecular genetic characteristics of Klebsiella pneumoniae isolates, extracted under conditions of cardiac surgery hospital

Klebsiella pneumoniae is one of the main causative agents of healthcare-associated infections (HAI) worldwide. The study was aimed at molecular characterization of beta-lactam antibiotic resistance in K. pneumoniae isolated in the cardiac surgery hospital, identify hypervirulent isolates and assess isolate genetic relatedness. K. pneumoniae isolated from the clinical material of patients (n = 50) at cardiac surgery departments as well as anesthesiology and reanimation department treated at the cardiovascular surgery hospital in Perm from July 2021 to December 2022 were analyzed. Bacteriological studies were performed on an automatic analyzer WalkAway-96Plus (Beckman Coulter, USA). The sensitivity to thirteen antimicrobials, production of extended-spectrum beta-lactamases (ESBL) and multidrug resistance (MDR) phenotype were assessed. The string test was used to screen hypermucoviscous K. pneumoniae. Isolate relatedness (ERIC-PCR), presence of beta-lactamase genes (blaTEM, blaCTX-M, blaSHV, blaOXA, blaKPC, blaVIM-2, blaIMP-1, blaNDM-1), as well as genes associated with hypervirulence (prmpA, iucA, peg-344, wzyK2, magA) were analyzed by PCR. Amplifications were performed in a DNA Engine Dyad Thermal Cycler (Bio-Rad, USA). Gel documentation system Gel-Doc XR (Bio-Rad, USA) was used for band visualization and data documentation. According to the study results, it was found that carbapenem-resistant isolates accounted for almost 76% of all isolates, the ESBL-phenotype had 90%, and MDR-phenotype — 88% of studied isolates. According to the string test results, 8% of K. pneumoniae isolates had a hypermucoviscous phenotype. As for genes associated with hypervirulence, it was shown that the iucA gene was the most common, amplified in 54% of isolates, prmpA was detected in 38% of isolates, 48% of isolates had wzyK2 or magA genes encoding capsular type K1/K2. Almost a third of K. pneumoniae samples contained a combination of the rmpA and iucA genes, and they were isolated more often in the group of patients with active infection. Only carbapenem-sensitive microorganisms had hypermucoviscous phenotype, K1 capsular type, and a combination of prmpA, iucA, peg-344 genes, whereas the K2 capsular type was most common among carbapenem-resistant K. pneumoniae. Based on molecular genetic typing, it was found that 24% of K. pneumoniae isolates were assigned to four genome groups of identical cultures, 76% of the isolates had individual profiles. Closely related isolates were found among patients from different departments that indicates a potential pathogen circulation in the closed circuit “surgery department–department of anesthesiology” and “reanimation–surgery department”.

Applications of SGLT2 inhibitors beyond glycaemic control.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were initially developed for their glucose-lowering effects and have shown a modest glycaemic benefit in people with type 2 diabetes mellitus (T2DM). In the past decade, a series of large, robust clinical trials of these therapies have demonstrated striking beneficial effects for various care goals, transforming the chronic disease therapeutic landscape. Cardiovascular safety studies in people with T2DM demonstrated that SGLT2 inhibitors reduce cardiovascular death and hospitalization for heart failure. Subsequent trials in participants with heart failure with reduced or preserved left ventricular ejection fraction demonstrated that SGLT2 inhibitors have beneficial effects on heart failure outcomes. In dedicated kidney outcome studies, SGLT2 inhibitors reduced the incidence of kidney failure among participants with or without diabetes. Post hoc analyses have suggested a range of other benefits of these drugs in conditions as diverse as metabolic dysfunction-associated steatotic liver disease, kidney stone prevention and anaemia. SGLT2 inhibitors have a generally favourable adverse effect profile, although patient selection and medication counselling remain important. Concerted efforts are needed to better integrate these agents into routine care and support long-term medication adherence to close the gap between clinical trial outcomes and those achieved in the real world.

Right ventricular dysfunction in chronic heart failure: clinical laboratory and echocardiographic characteristics. (the RIVED-CHF registry).

Right ventricular dysfunction (RVD) and pulmonary hypertension have been recognized as two important prognostic features in patients with left side heart failure. Current literature does not distinguish between right heart failure (RHF) and RVD, and the two terms are used indiscriminately to describe pulmonary hypertension and RVD as well as clinical sign of RHF. Therefore, the right ventricle (RV) adaptation across the whole spectrum of left ventricular ejection fraction (LVEF) values has been poorly investigated. This is a multicenter observational prospective study endorsed by the Italian Society of Cardiology aiming to analyze the concordance between the signs and symptoms of RHF and echocardiographic features of RVD. The protocol will assess patients affected by chronic heart failure in stable condition regardless of the LVEF threshold by clinical, laboratory, and detailed echocardiographic study. During the follow-up period, patients will be observed by direct check-up visit and/or virtual visits every 6 months for a mean period of 3 years. All clinical laboratory and echocardiographic data will be recorded in a web platform system accessible for all centers included in the study. The main study goals are: to investigate the concordance and discordance between clinical signs of RHF and RVD measured by ultrasonographic examination; to evaluate prognostic impact (in terms of cardiovascular mortality and heart failure hospitalization) of RVD and RHF during a mean follow-up period of 3 years; to investigate the prevalence of different right ventricular maladaptation (isolated right ventricular dilatation, isolated pulmonary hypertension, combined pattern) and the related prognostic impact. With this protocol, we would investigate the three main RVD patterns according to heart failure types and stages; we would clarify different RVD and pulmonary hypertension severity according to the heart failure types. Additionally, by a serial multiparametric analysis of RV, we would provide a better definition of RVD stage and how much is it related with clinical signs of RHF (ClinicalTrials.gov Identifier: NCT06002321).

Prediabetes is associated with increased cardiac events in patients with cancer who are prescribed anthracyclines.

Prediabetes, which is a precedent of overt diabetes, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in patients with cancer who are prescribed anthracycline-containing chemotherapy (ACT) is uncertain. The objective of this study was to evaluate the association of prediabetes with cardiovascular events in patients with cancer who are prescribed ACT. The authors identified patients with cancer who received ACT from 2000 to 2019 from Clinical Data Analysis Reporting System of Hong Kong. Patients were divided into diabetes, prediabetes, and normoglycemia groups based on their baseline glycemic profile. The Primary outcome, a major adverse cardiovascular event (MACE), was the composite event of hospitalization for heart failure and cardiovascular death. Among 12,649 patients at baseline, 3997 had prediabetes, and 5622 had diabetes. Over median follow-up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycemia group, 358 (9.0%) in the prediabetes group, and 728 (12.9%) in the diabetes group. Compared with normoglycemia, prediabetes (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.01-1.43) and diabetes (adjusted HR, 1.46; 95% CI, 1.24-1.70) were associated with an increased risk of MACE. In the prediabetes group, 475 patients (18%) progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR, 1.76; 95% CI, 1.31-2.36) compared with patients who remained prediabetic. In patients with cancer who received ACT, those who had prediabetes at baseline and those who progressed to diabetes at follow-up had an increased risk of MACE. The optimization of cardiovascular risk factor management, including prediabetes, should be considered in patients with cancer who are treated before and during ACT to reduce cardiovascular risk. Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked. In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure. Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease. These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow-up strategies, and consideration of prediabetes management in cancer care.

The Effect of SGLT2 Inhibitor Therapy on Endothelial Progenitor Cell Function in Patients With Heart Failure.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to reduce the risk of cardiovascular mortality and hospitalizations in patients with heart failure (HF) with preserved or reduced ejection fraction (HFpEF or HFrEF). The mechanism for this benefit is not clear. Endothelial progenitor cells (EPCs) are bone marrow-derived cells able to differentiate into functional endothelial cells and participate in endothelial repair. The aim of this study was to evaluate the effect of SGLT-2 inhibitors on the level and function of EPCs in patients with HF. We enrolled 20 patients with symptomatic HF, 12 with HFrEF and 8 with HFpEF (aged 73.3 ± 10.2 years, 95% men). Blood samples were drawn at 2 time points: baseline and ≥3 months after initiation of SGLT-2 inhibitor therapy. Circulating EPC levels were evaluated by expression of vascular endothelial growth factor receptor-2 (VEGFR-2), CD34, and CD133 by flow cytometry. EPC colony forming units (CFUs) were quantified after 7 days in culture. The proportion of cells that coexpressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was higher following 3 months of SGLT-2 inhibitors [0.26% (interquartile range, IQR 0.10-0.33) versus 0.55% (IQR 0.28-0.91), P = 0.002; 0.12% (IQR 0.07-0.15) versus 0.24% (IQR 0.15-0.39), P = 0.001, respectively]. EPC CFUs were also increased following SGLT-2 inhibitor treatment [23 (IQR 3.7-37.8) versus 79.4 (IQR 25.1-110.25) colonies/10 6 cells, P = 0.0039]. In patients with symptomatic HF, both HFpEF and HFrEF, treatment with SGLT-2 inhibitors is associated with an increase in the level and function of circulating EPCs. This augmentation in EPCs may be a contributing mechanism to the clinical benefit of SGLT-2 inhibitors in patients with HF.