Preserved Left Ventricular Ejection Fraction Research Articles

AL–AMYLOIDOSIS RELATED ADVANCED HEART FAILURE DIAGNOSED THROUGH F–18–FLUTEMETANOL PET SCAN

Abstract Background Systemic amyloidosis (SA) is a group of rare diseases in which abnormal misfolded proteins, amyloid fibrils, accumulate in tissue. The gold standard for diagnosis is tissue biopsy of the affected organ, but it is invasive and needs specific proteomic or immunohistochemistry analyses to characterize the involved protein. We report a case of a complex diagnosis of SA in an advanced heart failure (HF) patient. Methods and Results A 68–year–old woman with history of recurrent uveitis started to complain dyspnea in 2022, after Covid19. Since her symptoms worsened, in June 2023 she was diagnosed in another center with restrictive cardiomyopathy with preserved left ventricular (LV) ejection fraction. She underwent coronary angiography (unremarkable), cardiac MRI (aspecific fibrosis), and a FDG–PET scan which showed non–homogeneous LV fixation. The patient was treated with steroids for the suspicion of an immunologic–inflammatory disease, without benefit. Fourteen months after the initial presentation, she was admitted to our centre for advanced inotrope–dependent HF. She had mildly increased LV hypertrophy and severe systolic dysfunction with restrictive physiology and, notably, peri–orbital subcutaneous hemorrhages (Figure 1). Hematological screening for amyloidosis showed elevated serum free lambda light chains. Repeated cardiac MRI scan was consistent with infiltrative disease. A total–body PET scan with dual tracer was performed. The control session with F–18–FDG showed mild aspecific cardiac uptake in the basal septum and lateral wall (Figure 2), while off–label use of F–18–Flutemetanol, an Alzheimer‘s disease approved experimental tracer that binds to amyloid fibrils beta sheets with very high sensitivity and specificity, showed intense cardiac, hepatic, pulmonary and muscular uptake, with wash–out–timing diagnostic for AL–SA (Figure 3). Periumbilical fat biopsy confirmed the clinical suspicion of SA. Hematological investigations led to the diagnosis of stage I–A lambda micromolecular multiple myeloma, with systemic amyloidosis and a IIIb cardiac prognostic score. Conclusions Endomyocardial biopsy is an invasive procedure and periumbilical fat biopsy discriminates the amyloid protein type only by proteomic analysis, which is available in very few Italian centres. The off–label use of Alzheimers’ PET tracers could reduce the delay of cardiac AL–SA diagnosis, allowing early disease identification and prompting timely hematological therapy.

Medical treatment of heart failure with renin–angiotensin–aldosterone system inhibitors and beta-blockers in aortic stenosis: association with long-term outcome after aortic valve replacement

Abstract Aims There is a lack of robust data on the optimal medical treatment of heart failure in patients with severe aortic stenosis, with no randomized controlled trials guiding treatment. The study aimed to study the association between exposure to renin–angiotensin–aldosterone system (RAS) inhibitors or beta-blockers and outcome after aortic valve replacement in patients with aortic stenosis and heart failure. Methods and results The study included all patients with heart failure undergoing aortic valve replacement for aortic stenosis in Sweden between 2008 and 2016 (n = 4668 patients). Exposure to treatment was assessed by a continuous tracking of drug dispensations, and outcome events were all-cause mortality and hospitalization for heart failure collected from national patient registries. After adjustment for age, sex, atrial fibrillation, hypertension, diabetes mellitus, and prior myocardial infarction, Cox regression analysis showed that RAS inhibition was associated with a lower risk of all-cause mortality in patients with reduced left ventricular ejection fraction (LV-EF) [hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.51–0.65] and preserved LV-EF (HR 0.69, 95% CI 0.56–0.85). Beta-blockade was associated with a lower risk of all-cause mortality in patients with reduced LV-EF (HR 0.81, 95% CI 0.71–0.92), but not in preserved LV-EF (HR 0.87, 95% CI 0.69–1.10). There was no association between RAS inhibition or beta-blockade and the risk of hospitalization for heart failure. Conclusion The RAS inhibition was associated with a lower all-cause mortality after valve replacement in patients with both reduced and preserved LV-EF. Beta-blockade was associated with lower all-cause mortality only in patients with reduced LV-EF.

ECHOCARDIOGRAPHIC AND ELECTROCARDIOGRAPHIC PREDICTORS OF NEW ATRIAL FIBRILLATION IN END-STAGE RENAL DISEASE PATIENTS WITH PRESERVED LEFT VENTRICULAR SYSTOLIC FUNCTION

Objective: We investigated the echocardiographic and electrocardiographic predictors for future development of AF in patients with ESRD and preserved LV EF who had never diagnosed AF. Design and method: Atrial fibrillation (AF) is a common cause which leads to adverse cardiovascular outcome in patients with end-stage renal disease (ESRD). AF is common arrhythmia in patients with reduced left ventricular (LV) ejection fraction (EF). It is unclear the predictor of new AF in patients with preserved LV EF. We enrolled 226 patients with ESRD who has performed transthoracic echocardiography. We excluded the 1) 16 patients who has been received a diagnosis of AF, and 2) 19 patients with LV EF < 50%, and 191 patients (121 males, mean 62 ± 14 years) Results: During a mean follow-up period of 885 ± 720 days, AF occurred in 20 (10.5%) patients. The patients with AF development was older (69 ± 12 vs. 61 ± 14 years, p=0.023). There were no differences in history of hypertension, diabetes, stroke and coronary artery disease between two groups. In univariate Cox regression analysis, left atrial volume index (LAVI), right ventricular systolic pressure, age and QRS duration were associated with future AF events. After multivariate Cox regression analysis, age (HR: 1.015, 95% CI: 1.008-1.105, p value: 0.022) and QRS duration (HR: 1.025, 95% CI: 1.001-1.049, p value: 0.043) significantly predicted the future development of AF. Conclusions: QRS duration is well known predictor of cardiovascular outcome in patients with reduced LV EF. In this study, we demonstrated QRS duration predicted new AF events in ESRD patients with preserved LV EF.

AORTIC STENOSIS AND HEART FAILURE: DIFFERENCES AND SIMILARITIES BEYOND PRESERVED EJECTION FRACTION

Objective: Degenerative aortic stenosis (AS) is highly prevalent in Western countries and shows a strong association with age and other cardiovascular risk factors such as arterial hypertension, diabetes mellitus, dyslipidaemia, and visceral obesity. The same risk factors are involved in the development of heart failure with preserved ejection fraction (HFpEF). Notwithstanding several similarities, patients with AS and preserved left ventricular ejection fraction (ASpEF) are not considered to actually have HFpEF. We sought to investigate the haemodynamic and metabolic features of patients with ASpEF both at rest and during physical effort and highlight similarities and differences with HFpEF. Design and method: We enrolled 148 patients with HFpEF, 150 with ASpEF (with at least moderate aortic transvalvular gradient), and 80 age- and sex-matched healthy controls. All patients received a comprehensive laboratory evaluation, a resting echocardiographic examination, and a combined cardiopulmonary-echocardiographic stress test. Patients with ASpEF who fulfilled the criteria for transcatheter aortic valve replacement (n=125) underwent cardiac computed tomography to measure aortic valve calcium score and volume. Results: Serum levels of N-terminal prohormone of brain natriuretic peptide were similar between HFpEF and ASpEF patients after excluding subjects with atrial fibrillation. As a marker of deregulated inflammation, epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and controls and was inversely related to peak oxygen consumption (VO2) in all subgroups (Figure). Furthermore, all patients showed a significant impairment in peak VO2 caused by a reduction in bith cardiac output (CO) and peripheral arteriovenous oxygen difference (AVO2diff). HFpEF patients displayed increased arterial stiffness, worse left ventricular-arterial coupling, and worse left atrial function. On the other hand, patients with ASpEF showed worse right ventricular-pulmonary arterial coupling. In ASpEF, disease severity, evaluated by aortic transvalvular peak velocity, mean gradient at rest and peak exercise, and aortic valve calcium score and volume, was directly related to EAT thickness. Conclusions: ASpEF shows substantial similarities to HFpEF. ASpEF could represent a separate phenotype in the spectrum of HFpEF; further and larger studies should investigate this hypothesis to give further insight into the pathophysiology of ASpEF.

Role of aortic valve replacement in moderate aortic stenosis: a 10-year outcomes study

ObjectivePatients with moderate aortic stenosis (AS) exhibit high morbidity and mortality. Limited evidence exists on the role of aortic valve replacement (AVR) in this patient population. To investigate the benefit...

Left atrium volume and function changes during stress in patients with primary mitral regurgitation and preserved left ventricular ejection fraction.

Patients with primary mitral regurgitation (MR) usually remain asymptomatic for a long time due to compensatory mechanisms and an adequate treatment could be delayed. Stress echocardiography and speckle-tracking analysis could help to evaluate impaired left atrium (LA) function before the manifestation of clinically significant myocardial changes in asymptomatic patients with primary MR and preserved left ventricular (LV) ejection fraction (EF). This study prospectively enrolled 91 patients with preserved LV EF (≥60%) at rest, of which 60 patients had moderate-to-severe MR and 31 were healthy controls. Rest and stress (bicycle ergometry) echocardiography and speckle-tracking offline analysis were performed. In MR group LA volume indices were higher at rest and during stress, while LA reservoir, conduit, and contractile fractions were decreased (p < .005). LA deformation parameters at rest were similar in both groups. During maximum stress LA conduit, contractile fractions and reservoir strain were lower (p < .05) in patients with MR. Indices of LA volume were related to SPAP at rest and during stress. Higher NT-proBNP concentrations was associated with higher LA volume indices, decreased contractile and reservoir functions during peak stress (p < .05). LA volume indices, LA EF, and filling index at rest could predict exercise-induced pulmonary hypertension (EIPH) (p < .05). In patients with primary MR and preserved LV EF, LA parameters are related to SPAP and NT-pro-BNP concentration. LA volume indices, LA EF and LA filling index are predictors of EIPH.

Non-invasive imaging in acute decompensated heart failure with preserved ejection fraction.

Non-invasive imaging plays an increasingly important role in emergency medicine, given the trend towards smaller, portable ultrasound devices, the integration of ultrasound imaging across diverse medical disciplines, and the growing evidence supporting its clinical benefits for the patient. Heart failure with preserved ejection fraction (HFpEF) provides a compelling illustration of the impactful role that imaging plays in distinguishing diverse clinical presentations of heart failure with numerous associated comorbidities, including pulmonary, renal, or hepatic diseases. While a preserved left ventricular ejection fraction might misguide the clinician away from diagnosing cardiac disease, there are several clues provided by cardiac, vascular, and lung ultrasonography, as well as other imaging modalities, to rapidly identify (decompensated) HFpEF. Congestion remains the primary reason why patients with heart failure (irrespective of ejection fraction) seek emergency care. Furthermore, comprehensive phenotyping is becoming increasingly important, considering the development of targeted treatments for conditions exhibiting HFpEF physiology, such as cardiac amyloidosis. Timely recognition in such cases has lasting implications for long-term outcomes.

The impact of renal tubulointerstitial dysfunction on the early and long-term prognosis in chronic heart failure patients with preserved left ventricular ejection fraction

Aim. To study the dependence of the early-term (1 year) and long-term (5 years) prognosis in patients with chronic heart failure (CHF) of ischemic origin with preserved left ventricular ejection fraction (LVEF) depending on renal tubulointerstitial functional disorders. Materials and methods. The study involved 88 patients (men – 46.6 % (n = 41); women – 53.4 % (n = 47)) with CHF of ischemic origin, stage II A–B, stage II–IV according to NYHA, 67 % (n = 59) with sinus rhythm, and 33 % (n = 29) with atrial fibrillation. Patients with sinus rhythm and atrial fibrillation were matched in age (p = 0.483), height (p = 0.345), weight (p = 0.317), body surface area (p = 0.153). NGAL levels were analyzed using an ELISA kit (E-EL-H0096, Elabscience, USA). NAG levels were analyzed using an ELISA kit (SEA 069 Hu, Cloud-Clone Corp., USA). KIM-1 levels were analyzed using an ELISA kit (SEA 785 Hu, Cloud-Clone Corp., USA). Kaplan–Meier curves and Cox proportional hazards regression analysis were performed. Results. No significant difference was found in the frequency of the cumulative endpoint during the first-year follow-up from the initial level of two markers of tubulointerstitial injury – KIM-1 (Log-Rank Test: p = 0.57529) and NAG (Log-Rank Test: p = 0.86001). According to the results of analysis of the Cox proportional hazards, only a tendency to increase in the risk factors of adverse events were observed in case of elevated KIM-1 (HR = 1.66; p = 0.5795) and NAG levels (HR = 1.1712; p = 0.8626) in this CHF patients’ cohort. Kaplan–Meier analysis revealed a probable (Log-Rank Test; p = 0.00141) increase in the frequency of the cumulative endpoint during the first year of follow-up in CHF patients with preserved LVEF due to increased serum NGAL level more than 168 ng/ml. According to the univariate model, an elevated serum NGAL level is associated with an increase in the relative risk by 4.2 times (95 % CI 1.78–16.89; p = 0.014). A reduced sodium level less than 142.5 mmol/l was associated with an increase in number of adverse cardiovascular events during the first-year follow- ups by 22 % (HR = 1.22, p = 0.029). After 5 years of follow-up, a decrease in sodium level less than 142.3 mmol/l is also characterized by a probable difference of the cumulative Kaplan–Meier’s curves (Cox–Mantel F-Test, p = 0.00287). According to the univariate model of Cox proportional hazards, the relative risk of adverse cardiovascular events in patients with CHF during the 5-year follow-up has a tendency to increase by 1.04 times (95 % CI 0.85–1.27; p = 0.72). Serum NGAL, a marker of renal tubulo-interstitial injury, doesn’t lose its properties as a powerful marker of an unfavorable long-term prognosis in patients with CHF with preserved LVEF (HR = 5.96; 95 % CI 1.17–30.50; p = 0.032). Conclusions. The most powerful factors of the early (1-year) prognosis of adverse cardiovascular events in CHF patients with preserved left ventricular ejection fraction are the marker of tubulointerstitial injury, serum NGAL over 168 ng/ml, as well as the marker of tubulointerstitial dysfunction – the serum sodium level less than 142.5 mmol/l. The electrolyte imbalance, decreased sodium level less than 142.3 mmol/l, remains a powerful marker of an unfavorable long-term 5-year prognosis in CHF patients with preserved left ventricular ejection fraction, meanwhile serum NGAL, a marker of renal tubulointerstitial injury, besides doesn’t lose its prognostic value (HR = 5.96; 95 % CI 1.17–30.50; p = 0.032), but also is independent from the parameters of the age (p = 0.409) and gender (p = 0.397) in such patients.

Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction

BackgroundMost trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin–angiotensin–aldosterone system antagonists.MethodsIn a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction.ResultsFrom September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no–beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P=0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no–beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no–beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%.ConclusionsAmong patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.)

Clinical significance of echocardiographic signs of right heart dysfunction in patients with chronic heart failure with preserved left ventricular ejection fraction

Aim: To analyze the features of clinical signs, quality of life and psycho-emotional state in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and non-obstructive atherosclerosis of the coronary arteries, depending on the presence of echocardiographic criteria for dysfunction of the right heart.Material and Methods. Patients underwent an extended protocol of echocardiography with an assessment of the structure and function of the right heart; ultrasound examination of the lungs with the determination of the number of B-lines; a six-minute walk test, a test for the presence of a symptom of bendopnea with the determination of blood oxygen saturation (SpO2) before and during the test. In addition, quality of life was assessed using the Minnesota questionnaire and the SF-36 questionnaire (The Short Form-36); the psycho-emotional state of patients was analyzed according to the HADS (Hospital Anxiety and Depression Scale), the level of adherence to treatment was analyzed according to the Morisky – Green questionnaire. Patients were divided into two groups depending on signs of right heart dysfunction: Tei index more than 0.54, tricuspid annulus systolic excursion (TAPSE) less than 17 mm, tricuspid annulus systolic velocity (RV S’) less than 9,5 cm/sec.Results. Echocardiographic signs of right heart dysfunction in patients with HFpEF was associated with lower quality of life indicators according to the SF-36 questionnaire, in particular, general health status (p = 0.008) and role limitations due to emotional problems (p = 0.03). During the bendopnea test (p = 0.04), the majority of patients with signs of dysfunction of the right heart (66.7%) had a decrease in SpO2, while in the comparison group the proportion of such patients was 36.7% (p = 0.04). The psycho-emotional state according to the HADS scale and adherence to treatment did not differ in both groups (p &gt; 0.05). The frequency of detection of B-lines according to lung ultrasound was also comparable.

The effect of hyperlipidemia and body fat distribution on subclinical left ventricular function in obesity: a cardiovascular magnetic resonance study

BackgroundObesity is often associated with multiple comorbidities. However, whether obese subjects with hyperlipidemia in the absence of other complications have worse cardiac indices than metabolically healthy obese subjects is unclear. Therefore, we aimed to determine the effect of hyperlipidemia on subclinical left ventricular (LV) function in obesity and to evaluate the association of cardiac parameters with body fat distribution.Materials and methodsNinety-two adults were recruited and divided into 3 groups: obesity with hyperlipidemia (n = 24, 14 males), obesity without hyperlipidemia (n = 25, 13 males), and c ntrols (n = 43, 25 males). LV strain parameters (peak strain (PS), peak diastolic strain rate (PDSR), peak systolic strain rate) derived from cardiovascular magnetic resonance tissue tracking were measured and compared. Dual-energy X-ray absorptiometer was used to measure body fat distribution. Correlations of hyperlipidemia and body fat distribution with LV strain were assessed by multivariable linear regression.ResultsObese individuals with preserved LV ejection fraction showed lower global LV longitudinal, circumferential, and radial PS and longitudinal and circumferential PDSR than controls (all P < 0.05). Among obese patients, those with hyperlipidemia had lower longitudinal PS and PDSR and circumferential PDSR than those without hyperlipidemia (− 12.8 ± 2.9% vs. − 14.2 ± 2.7%, 0.8 ± 0.1 s−1 vs. 0.9 ± 0.3 s−1, 1.2 ± 0.2 s−1 vs. 1.4 ± 0.2 s−1; all P < 0.05). Multivariable linear regression demonstrated that hyperlipidemia was independently associated with circumferential PDSR (β = − 0.477, P < 0.05) in obesity after controlling for growth differences, other cardiovascular risk factors, and central fat distribution. In addition, android fat had an independently negative relationship with longitudinal and radial PS (β = − 0.486 and β = − 0.408, respectively; all P < 0.05); and visceral fat was negatively associated with longitudinal PDSR (β = − 0.563, P < 0.05). Differently, gynoid fat was positively correlated with circumferential PS and PDSR and radial PDSR (β = 0.490, β = 0.481, and β = 0.413, respectively; all P < 0.05).ConclusionHyperlipidemia is independently associated with subclinical LV diastolic dysfunction in obesity. Central fat distribution (android and visceral fat) has a negative association, while peripheral fat distribution (gynoid fat) has a positive association on subclinical LV function. These results suggest that appropriate management of hyperlipidemia may be beneficial for obese patients, and that the differentiation of fat distribution in different regions may facilitate the precise management of obese patients.Clinical trials registration Effect of lifestyle intervention on metabolism of obese patients based on smart phone software (ChiCTR1900026476).

Rationale and design of the PACIFIC-PRESERVED (PhenomApping, ClassIFication and Innovation for Cardiac dysfunction in patients with heart failure and PRESERVED left ventricular ejection fraction) study

BackgroundHeart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that is poorly defined, reflecting an incomplete understanding of its pathophysiology. AimTo redefine the phenotypic spectrum of HFpEF. MethodsThe PACIFIC-PRESERVED study is a prospective multicentre cohort study designed to perform multidimensional deep phenotyping of patients diagnosed with HFpEF (left ventricular ejection fraction≥50%), patients with heart failure with reduced ejection fraction (left ventricular ejection fraction≤40%) and subjects without overt heart failure (3:2:1 ratio). The study proposes prospective investigations in patients during a 1-day hospital stay: physical examination; electrocardiogram; performance-based tests; blood samples; cardiac magnetic resonance imaging; transthoracic echocardiography (rest and low-level exercise); myocardial shear wave elastography; chest computed tomography; and non-invasive measurement of arterial stiffness. Dyspnoea, depression, general health and quality of life will be assessed by dedicated questionnaires. A biobank will be established. After the hospital stay, patients are asked to wear a connected garment (with digital sensors) to collect electrocardiography, pulmonary and activity variables in real-life conditions (for up to 14 days). Data will be centralized for machine-learning-based analyses, with the aim of reclassifying HFpEF into more distinct subgroups, improving understanding of the disease mechanisms and identifying new biological pathways and molecular targets. The study will also serve as a platform to enable the development of innovative technologies and strategies for the diagnosis and stratification of patients with HFpEF. ConclusionsPACIFIC-PRESERVED is a prospective multicentre phenomapping study, using novel analytical techniques, which will provide a unique data resource to better define HFpEF and identify new clinically meaningful subgroups of patients.

The perpetual need of randomized clinical trials: challenges and uncertainties in emulating the REDUCE-AMI trial.

Trial emulations in observational data analyses can complement findings from randomized clinical trials, inform future trial designs, or generate evidence when randomized studies are not feasible due to resource constraints and ethical or practical limitations. Importantly, trial emulation designs facilitate causal inference in observational data analyses by enhancing counterfactual thinking and comparisons of real-world observations (e.g. Mendelian Randomization) to hypothetical interventions. In order to enhance credibility, trial emulations would benefit from prospective registration, publication of statistical analysis plans, and subsequent prospective benchmarking to randomized clinical trials prior to their publication. Confounding by indication, however, is the key challenge to interpreting observed intended effects of an intervention as causal in observational data analyses. We discuss the target trial emulation of the REDUCE-AMI randomized clinical trial (ClinicalTrials.gov ID NCT03278509; beta-blocker use in patients with preserved left ventricular ejection fraction after myocardial infarction) to illustrate the challenges and uncertainties of studying intended effects of interventions without randomization to account for confounding. We furthermore directly compare the findings, statistical power, and clinical interpretation of the results of the REDUCE-AMI target trial emulation to those from the simultaneously published randomized clinical trial. The complexity and subtlety of confounding by indication when studying intended effects of interventions can generally only be addressed by randomization.

Age-Dependent Detection of Atrial Fibrillation with Implantable Cardiac Monitors in Patients with Cryptogenic Stroke.

Background Continuous monitoring using implantable cardiac monitors (ICMs) results in atrial fibrillation (AF) detection rates of up to 30% in patients with cryptogenic stroke (CS). Although higher age is an independent risk factor for AF, there are no age-specific recommendations for the implantation of ICM. Objective The aim of this study was to analyze age-related AF rates in patients with CS and continuous rhythm monitoring, to determine the rates of oral anticoagulation (OAC) and recurrent cerebrovascular events (stroke or transient ischemic attack) in patients with ICM-detected AF, and to describe the temporal relationship of AF detection and recurrent cerebrovascular events. Methods In this observational study, patients with CS provided with ICMs were systematically followed. All patients underwent 72-hour electrocardiography monitoring, transcranial Doppler ultrasound, and transthoracic echocardiography prior to ICM insertion. Follow-up included a regular outpatient presentation every 3 months with medical history, physical examination, and interrogation of the ICM. Results One-hundred eighty-six patients (mean age: 65 ± 12 years, 54% female) were included in this analysis. AF was detected in 6, 27, 56, and 65% ( p < 0.001) of patients aged less than 60, 60 to 69, 70 to 79, and more than or equal to 80 years, respectively. All patients with AF under 60 years had an impaired left ventricular systolic function. OAC was initiated in 85% of the patients with AF. Recurrent cerebrovascular events occurred in 34 patients of whom 14 had a diagnosis of AF. In nine patients, AF was diagnosed before the occurrence of a recurrent cerebrovascular event. Conclusion AF prevalence increased with age and was absent in CS patients younger than 60 years and with preserved left ventricular ejection fraction. The temporal relationship of AF and recurrent cerebrovascular events was weak.

Heart failure with preserved left ventricular ejection fraction (HFpEF)

Heart failure with preserved left ventricular ejection fraction (HFpEF) is a common and very important disease entity because of its association with frequent repeat hospitalization and high mortality. Hallmarks of the underlying pathophysiology include a small left ventricular cavity due to concentric remodeling, impaired left ventricular compliance and left atrial dysfunction. This leads to an increase in left atrial and pulmonary pressure on exertion and in advanced stages of the disease already at rest with consecutive exertional dyspnea and exercise intolerance. Additional cardiovascular mechanisms including atrial fibrillation, chronotropic incompetence and coronary artery disease as well as non-cardiac co-morbidities contribute to a variable extent to the clinical picture. The diagnostic work-up is demanding and complex but the concepts have significantly improved during the last years. The study results of the Sodium Glucose cotransporter-2 inhibitors (SGLT-2-inhibitors) have revolutionized the treatment of HFpEF. In the present article, we provide an overview about the current understanding of the pathophysiology of HFpEF, the principles of the diagnostic pathways and a summary of the intervention studies in the field, and we propose an approach for the treatment in clinical practice.

Prospective benchmarking of an observational analysis in the SWEDEHEART registry against the REDUCE-AMI randomized trial

Prospective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning the protocol of the trial and the observational analysis, while the trials findings are unavailable. The Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction (REDUCE-AMI, ClinicalTrials.gov ID: NCT03278509) trial started recruitment in September 2017 and results are expected in 2024. REDUCE-AMI aimed to estimate the effect of long-term use of beta blockers on the risk of death and myocardial following a myocardial infarction with preserved left ventricular systolic ejection fraction. We specified the protocol of a target trial as similar as possible to that of REDUCE-AMI, then emulated the target trial using observational data from Swedish healthcare registries. Had everyone followed the treatment strategy as specified in the target trial protocol, the observational analysis estimated a reduction in the 5-year risk of death or myocardial infarction of 0.8 percentage points for beta blockers compared with no beta blockers; effects ranging from an absolute reduction of 4.5 percentage points to an increase of 2.8 percentage points in the risk of death or myocardial infarction were compatible with our data under conventional statistical criteria. Once results of REDUCE-AMI are published, we will compare the results of our observational analysis against those from the trial. If this prospective benchmarking is successful, it supports the credibility of additional analyses using these observational data, which can rapidly deliver answers to questions that could not be answered by the initial trial. If benchmarking proves unsuccessful, we will conduct a “postmortem” analysis to identify the reasons for the discrepancy. Prospective benchmarking shifts the investigator focus away from an endeavour to use observational data to obtain similar results as a completed randomized trial, to a systematic attempt to align the design and analysis of the trial and the observational analysis.

Chronic Heart Failure in Patients Hospitalized in 2002 and 2021: Comparative Analysis of Prevalence, Clinical Course and Drug Therapy.

Comparative analysis of the prevalence of chronic heart failure (CHF), clinical and medical history data, and drug therapy of patients admitted to a cardiology hospital in 2002 and 2021. The study analyzed the medical records of patients with a confirmed diagnosis of CHF who were admitted in 2002 (n=210) and 2021 (n=381) to a specialized cardiology hospital. According to medical records of 2021, the proportion of patients with a confirmed diagnosis of CHF (87.6%) in the cohort of patients admitted to a cardiology hospital was twice as high as in 2002 (46.4%; p&lt;0.001). The majority of patients with CHF in the study sample were patients with preserved left ventricular ejection fraction (HFpEF). The proportion of such patients significantly increased to reach 75.9% in 2021 compared to 58.6% in 2002 (p&lt;0.001). At the same time, the number of severe forms of CHF (NYHA functional class (FC) IV) decreased by 10% and was 13.2% in 2002 and 1.3% in 2021 (p&lt;0.001). In the majority of patients, ischemic heart disease (98.1 and 91.1% in 2002 and 2021, respectively, p&lt;0.001) and hypertension (80.5 and 98.2%, respectively, p&lt;0.001) were diagnosed as the cause for CHF. Furthermore, the incidence of comorbidity increased significantly: atrial fibrillation was detected in 12.3% of patients in 2002 and 26.4% in 2021 (p &lt; 0.001); type 2 diabetes mellitus, in 14.3 and 32% of patients (p &lt;0.001); and obesity, in 33.3 and 43.7% of patients, respectively (p=0.018). The frequency of using the major groups of drugs increased during the analyzed period: renin-angiotensin-aldosterone system blockers were administered to 71.9% of patients in 2002 and to 87.7% in 2021 (p&lt;0.001); beta-blockers were administered to 53.3 and 82.4% of patients (p&lt;0.001); and mineralocorticoid receptor antagonists, to 1.9 and 18.6% of patients, respectively (p=0.004). In 2021, the proportion of patients with a confirmed diagnosis of CHF in the patient cohort admitted to a cardiology hospital was twice as high as in 2002; the phenotype with preserved left ventricular ejection fraction predominated in the CHF structure. During the analyzed twenty-year period, the prevalence of comorbidities increased among CHF patients. The prescription frequency of pathogenetic evidence-based therapy has significantly increased by 2021, however, it remains insufficient even in patients with CHF with reduced left ventricular ejection fraction.

THE VALUE OF HOLTER MONITORING AND THE LEVEL OF SYSTEMIC INFLAMMATION IN PATIENTS WITH STABLE ISCHEMIC HEART DISEASE COMBINED WITH TYPE 2 DIABETES, DEPENDING ON THE NUMBER OF AFFECTED CORONARY ARTERIES

Diabetes mellitus (DM) is one of the significant medical and social problems of modern society, which is due to high morbidity and prevalence, frequent occurrence of chronic micro- and macrovascular complications. Coronary heart disease (CHD) in patients with type 2 diabetes is 2-4 times more common than in people of the same age without diabetes [1]. In the absence of apparent signs of atherosclerosis, the risk of developing coronary artery disease in the next 10 years is 30% [2]. To date, the course and prognosis of this group of patients have not been sufficiently studied, objective clinical and diagnostic criteria for the development of complications of myocardial infarction have not been developed, and the problem of choosing pathogenetically based methods of treatment of CHD in combination with type 2 diabetes remains unresolved [3].The aim of the work was to investigate the informativeness of Holter monitoring (HM), the correlation of HM indicators, C-reactive protein (CRP) and carbohydrate metabolism in patients with stable coronary heart disease (CHD) in combination with type 2 diabetes for the prognosis of the course of this pathology, timely individual treatment and prevention occurrence of endpoints.Material and methods. The study involved 95 patients with coronary heart disease with angina pectoris functional class (FC) III and heart failure (HF FC III with a preserved left ventricular ejection fraction (LVEF); of them, 60 patients had concomitant type 2 DM in the compensation stage.Results. In patients with comorbidity (a combination CHD and type 2 diabetes), episodes of ST depression/elevation, tachycardia, and extrasystoles were more often registered in patients with multivessel lesions of CA (р&lt;0.05), according to HM; the content of CRP in blood serum increased in proportion to the severity of the course of the disease, which depended on the number of affected CA.Conclusions. The nature and severity of the course of CHD correlate with comorbid pathology and the number of CAs affected by atherosclerosis. In the case of multivessel damage, according to the data of clinical, functional and laboratory research, an aggressive progression of cardiac pathology was noted.

Effects of Premature Ventricular Complex Burden on Left Ventricular Global Longitudinal Strain in Patients without Structural Heart Disease.

Background: Evaluation of left ventricular (LV) function in patients with idiopathic premature ventricular contraction (PVC) with preserved LV ejection fraction (LVEF), especially in the subclinical stage, may be of great importance in terms of directing early treatment. Methods: A total of 122 patients, retrospectively recruited, were divided into three groups according to PVC burden: Group 1; 5% ≤ PVC < 10%, Group 2; 10% ≤ PVC < 15%, and Group 3; 15% ≤ PVC. Transthoracic echocardiography (TTE) was performed to evaluate LV parameters. Results: LV-GLS (Global longitudinal strain) was found to be significantly lower in groups 2 and 3 with high PVC burden (18.9% ± 1.4, 17.5% ± 2.1, 16.3% ± 1.3; p < 0.001, respectively). Correlation analysis revealed a positive and significant correlation between PVC burden and deterioration in LV-GLS (r: 0.536; p < 0.001). In addition, PVC burden was found to be an independent predictor of LV-GLS deterioration in multiple linear regression analysis (β: 0.525, p < 0.001). The ROC curve analysis demonstrated that a PVC burden cut-off value of 8.4% was associated with a LV-GLS deterioration greater than -18, with a specificity of 75.4% and a sensitivity of 75.4% (AUC: 0.81 [0.73-0.88] 95% CI; p < 0.001). Conclusions: PVC burden was an independent predictor of deterioration in LV-GLS. The presence of LV-GLS deterioration due to PVC burden emphasizes the necessity for closer patient monitoring, observation of the response to pharmacological treatment, and evaluation of early invasive treatment strategies in selected patient groups.

Optimization of Cardiorespiratory Fitness and Quality of Life in Women with Chronic Heart Failure after a Cardiac Rehabilitation Program

Introduction: Women with heart failure (HF) tend to experience a greater symptom burden and lower quality of life, possibly due to phenotypic differences and unique gender-associated risk factors. Despite evidence on the effects of cardiac rehabilitation programs (CRP) in the general population, there is underrepresentation of women in these programs. Additionally, the impact of CRP on cardiorespiratory variables obtained through cardiopulmonary exercise testing (CPET) and health-related quality of life (HRQoL) in women with HF remains unknown. Objective: To assess the impact of a CRP on cardiorespiratory fitness (CRF) in cardiorespiratory variables obtained through CPET and HRQoL in women with HF. Methods: A quasi-experimental study included HF patients who completed a CRP from June 2019 to December 2023. The CRP involved nutritional assessment, psychosocial evaluation, educational sessions, and concurrent training. It comprised 30 minutes of aerobic resistance training at 65-80% of heart rate reserve (HRR) and 30 minutes of strength training at 30-50% of 1-repetition maximum (1RM), with a frequency of 3 sessions per week for 4 to 6 weeks. CPET was conducted at the beginning and end of the program, analyzing cardiorespiratory variables. HRQoL was assessed using the SF-36 questionnaire. Gains in CRF and HRQoL at the end of the program in both men and women were analyzed. Results: Out of 217 included patients, 29.9% were women. At the program's onset, women showed lower exercise tolerance than men (workload 5.4±2.57 METs vs. 6.62±2.53 METs) and worse HRQoL (62.03%±18.37 vs. 68.38%±18.37). However, post-intervention, they optimized their CRF (%predicted VO2 [%VO2p] initial 56.62%±20.11 vs final 80.12%±30.32, p=&lt;0.001). Significant improvements in cardiorespiratory variables were observed in both cases: delta METs-load 3.02, p=&lt;0.001, delta peak oxygen consumption (VO2peak) 1.83 ml/kg/min, p=&lt;0.001, delta oxygen pulse (PO2) 1.21, p=0.021, delta cardiac power output (CPO) 1917, p=0.004, with a rightward shift in ventilatory thresholds and improvement in HRQoL (62.03%±18.37 vs. 78.81%±12.9, p=&lt;0.001) post-CRP. The only variable with no significant changes in either case was VE/VCO2 slope (delta -0.51, p=0.736). Additionally, in women with reduced left ventricular ejection fraction (&lt;50%), variables with no significant improvement included CPO (delta 959.22, p=0.283) and time to recovery of VO2 kinetics (TRCVO2) (delta -0.74, p=0.957). In patients with preserved left ventricular ejection fraction (≥50%), variables with no significant change included PO2 (delta 1.08, p=0.173), TRCVO2 (delta 26.82, p=0.099), and the first ventilatory threshold (VT1) (delta 0.09, p=0.504). Program attendance was 87.5% in both groups. Conclusion: Implementing a CRP in women with HF resulted in significant improvements in all evaluated cardiorespiratory variables (except for VE/VCO2 slope) and quality of life. These findings support the importance of ensuring women's access and participation in cardiac rehabilitation programs. Addressing existing barriers is crucial to maximize the long-term benefits of CRP in the female population with HF.