bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration
Authors: Leyba K , Martin J M , Aquilante C A , Shalowitz E S , Kudron E K , Reusch J E B R , Regensteiner J G R , Kao D P K
Published: October 2024

Background

Statins have been reported to precipitate diabetes mellitus (DM) in some patients. Limited evidence suggests that this occurs in women more frequently than men, but direct comparisons of rates of reporting of statin-associated DM between men and women are lacking.

Purpose

To determine whether there are sex-specific differences in post-marketing reporting of statin-associated DM.

Methods

We conducted a retrospective pharmacovigilance analysis of spontaneously reported adverse drug events (ADEs) submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System between January 1997 and September 2023. A Proportional Reporting Ratio (PRR) was used to identify the rate of reported statin-associated DM ADEs relative to the rate of DM ADEs reported with all other medications. We compared signals of disproportionate reporting (SDRs) between men and women using a modified relative odds ratio (ROR).

Results

During the study period, there were two-fold as many reports of statin-associated DM in women than in men (14,793 versus 7,307, respectively), despite the fact there were only 7% more non-DM statin ADEs reported in women compared to men (512,134 versus 480,849, respectively). Compared to the background rate of reporting for all ADEs (0.6%), statin-induced DM was disproportionally reported for all subjects in aggregate (2.1%, PRR=3.7) as well as for men only (1.5%, PRR=2.4) and for women only (2.9%, PRR=5.3). Significant PRRs for DM were observed with each statin and for all statins collectively (Figure 1). Statins were reported as the primary- or secondary-suspected cause of DM in women with considerably greater frequency than in men (58% versus 29%, respectively). Rates of reporting of statin-associated DM were higher in women than in men for all statins, with the greatest difference being observed with atorvastatin (ROR 3.0), and the lowest difference being observed with rosuvastatin (ROR 1.2) (Figure 1).

Conclusions

Post-marketing ADE surveillance data suggest a markedly higher rate of incident DM associated with statins than with other medications and a higher rate of reporting of statin-associated DM in women than in men. Future studies should consider sex-moderated mechanisms of statin-associated DM.Figure 1
Association of obesity and metabolic health status with cerebral small vessel disease in stroke-free individuals
Authors: Ishida A , Nakanishi R , Miyagi T , Yamazato M , Ohya Y , Kusunose K
Published: October 2024

Background

It remains unclear whether obesity itself or metabolic abnormalities coexisting with obesity, are associated with stroke.

Purpose

We aimed to investigate the association of obesity and metabolic health status with cerebral small vessel disease (SVD) in stroke-free participants from a brain health check-up.

Methods

We conducted a cross-sectional study of 6088 stroke-free participants who underwent brain magnetic resonance imaging at a brain check-up between 2013 and 2020. Participants were categorised according to sex-specific waist circumference and metabolic health status. A metabolically healthy status was defined as the absence of components of metabolic syndrome other than a large waist circumference, such as high blood pressure, hyperglycaemia, and dyslipidaemia. The total SVD score was derived from four magnetic resonance imaging markers: silent lacunar infarcts, cerebral microbleeds, moderate-to-severe white matter hyperintensities, and enlarged perivascular spaces.

Results

The mean age of the participants was 55±12 years and 46% were women. The prevalence of metabolically healthy obesity was 650 (11%) and the proportion of metabolically healthy obesity among individuals with obesity was 24%. The prevalence of metabolically unhealthy obesity was 2043 (34%), and the proportion of metabolically unhealthy obesity among individuals with metabolically unhealthy individuals was 58%. The prevalence of moderate-to-severe SVD scores (≥2) was 348 (6%), which was higher in metabolically unhealthy individuals, regardless of obesity status. Compared with the metabolically healthy non-obesity group, the metabolically unhealthy non-obesity (odds ratio 2.22 [95% CI, 1.44–3.42]) and metabolically unhealthy obesity (odds ratio, 2.76 [95% CI, 1.80–4.24]) groups had a significantly higher multivariable-adjusted risk for a total SVD score of ≥2. Further sensitivity analyses using BMI-defined obesity instead of waist circumference-defined obesity yielded similar results.

Conclusions

Abdominal and general obesity alone are not associated with higher total SVD scores in stroke-free individuals. Unhealthy metabolic components, especially high blood pressure and hyperglycaemia, are important risk factors for SVD.
The epicardial adipose tissue volume is in patients with type 2 diabetes mellitus associated with a lowered myocardial perfusion reserve
Authors: Johansen A O , Eldin A S , Bojer A S , Soerensen M H , Gaede P H , Madsen P L
Published: October 2024

Introduction

The epicardial adipose tissue (EAT) has unobstructed vascular connection to the myocardium and has a secretome very different from that of other fat depots. The EAT fat pad and its paracrine and vasocrine secretion of pro-inflammatory and profibrotic cytokines is suggested to contribute to heart failure with preserved ejection fraction (HFpEF) pathogenesis albeit via unknown mechanisms. Animal studies and magnetic resonance imaging studies in patients with type 2 diabetes mellitus (T2DM) have documented that important myocardial changes linking diabetic cardiomyopathy to systolic and diastolic dysfunction are myocardial microvascular dysfunction and myocardial fibrosis.

Purpose

To investigate whether a high volume of EAT is associated with impaired myocardial perfusion reserve (MPR) or disperse fibrosis in patients with T2DM.

Methods

198 patients with T2DM but without ischemic heart disease were identified from a cross-sectional cardiovascular magnetic resonance imaging cohort study. 25 healthy controls were included for characterization of baseline characteristics. With gadolinium for contrast, MPR was determined by perfusion sequences and disperse fibrosis was determined from the myocardial extracellular volume (ECV). Volumes of EAT and pericardial adipose tissue (PAT) were determined from cine images.

Results

The T2DM patients (69% male) had a median age 59 IQR [50, 67] yrs, BMI 30.7 IQR [27.8, 33.7] kg/m2, and EAT of 17.3 IQR [14.2, 22.4] cm2. All patients had normal left ventricle ejection fraction. Compared to the healthy controls, patients with T2DM had higher BMI, abdominal circumference, ECV, EAT, and PAT volumes, and lower MPR (all p<0.001). In univariable regression analysis, EAT and PAT were both associated with higher BMI, abdominal circumference, and age (all p<0.02). In multivariable regression analysis, however, with adjustments for age, sex, BMI, and T2DM-duration, only EAT and MPR were significantly associated (P<0.01), whereas EAT and ECV were not. The PAT volume was not associated with MPR nor ECV. High-sensitive CRP was associated with the EAT volume (p<0.001), but hs-CRP was not associated with MPR or ECV.

Conclusion

An increased epicardial adipose tissue volume is in patients with T2DM associated with myocardial microvascular dysfunction. Irrespective of a generally heightened inflammatory level, the mechanism by which EAT contribute to development of HFpEF is therefore possibly via an EAT-induced impairment of the myocardial perfusion reserve. Randomized studies targeting a decreased epicardial adipose tissue volume are needed to demonstrate if this will improve myocardial microvascular dysfunction and hence limit development of HFpEF in patients with T2DM.Univariable analysis of EAT and ECVUnivariable analysis of EAT and MPR
Persistence and Adherence to GLP-1 RA treatment in Type 2 Diabetes Mellitus: a Nationwide registry study
Authors: Lassen M C H , Johansen N D , Modin D , Catarig A M , Vistisen B K , Amadid H , Zimmermann E , Gislason G , Biering-Soerensen T
Published: October 2024

Background

The use of glucagon-like peptide-1 receptor agonsists (GLP-1 RA) continues to rise and is increasingly important in the treatment of type-2 diabetes mellitus (T2DM). Though the use of GLP-1 RA continues to increase, persistence and adherence to therapy remains suboptimal.

Purpose

We aimed to assess the level of adherence and persistence to GLP-1 RA using real-world data and to investigate sociodemographic and clinical factors associated with discontinuation of GLP-1 RA therapy.

Methods

In this retrospective cohort study, all first-time users of GLP-1 RA with T2DM ≥18 years from 2007-2020 were identified using the Danish registries (Figure 1A-1B). All participants had 18 months of follow-up. Medication possession ratio (MPR) was calculated by summing days of medication supply from all dispensed prescription made during the study period divided by number of days in study period. MPR ≥0.80 was used to define adherence. Discontinuation was defined as >90 days between the last day of prescription coverage and the first day of a new dispensed prescription. Adherence to GLP-1 RA therapy and the risk of discontinuing therapy was estimated at 6- and 12-months of follow-up. Multivariable logistic regression was used to identify sociodemographic and clinical factors associated with discontinuing GLP-1 RA therapy.

Results

In total, 44,343 first-time users of GLP-1 RA with T2DM were identified (mean age: 58.6 years, 42.7% female, 21.3% had cardiovascular disease, median duration of T2DM was 6.8 years, median HbA1c was 65 mmol/mol). The absolute risk of discontinuing GLP-1 RA at 6 and 12 months was 14.2% (95%CI: 13.9-14.6) and 21.4% (95%CI: 21.1-21.8), respectively (Figure 2A). Of the 9,520 (21.5%) who discontinued therapy during the 12-month follow-up, 1,947 (20.5%) occurred within the first 31 days of treatment. At 6 months, 58.5% were adherent to GLP-1 RA therapy with a median MPR of 0.84 [IQR: 0.70-0.95]. At 12 months, 61.1% were adherent to therapy with a median MPR of 0.85 [IQR: 0.71, 0.94]. In the multivariable model, low (<40 years) and high age (>75 years), lower household income, educational level, longer diabetes duration, and higher comorbidity burden were associated with a higher risk of discontinuing GLP-1 RA whereas baseline HbA1c was not (Figure 2B-2E).

Conclusion

Approximately one in five patients discontinued therapy within 12 months and a little over 60% were adherent. Sociodemographic factors, including household income, age, and comorbidity burden were associated with risk of discontinuing GLP-1 RA therapy. Given the changing landscape of who should be treated with GLP-1 RA, the cardio-renal benefits reported in recent trials, and the ongoing trials in the field, future research into adherence and persistence to GLP-1 RA and possible interventions to improve these, are needed.
Association of insulin resistance with cardiovascular disease and all-cause mortality in type 1 diabetes mellitus: systematic review and meta-analysis
Authors: Sun R , Wang J , Li M , Lip G Y H , Liu B , Pan Y , Zhang L , Sun R
Published: October 2024

Background

Insulin resistance (IR) is a key factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and is associated with a higher risk of cardiovascular disease (CVD) and mortality. However, the association between IR and these outcomes in type 1 diabetes mellitus (T1DM) is less clear. This systematic review and meta-analysis aimed to investigate the associations between CVD outcomes and IR in T1DM.

Methods

PubMed, EMBASE, and the Cochrane Library databases were searched from inception to 15 March 2023 and updated on 31 October 2023. Observational studies (cohort studies or post hoc analysis of clinical trials) reporting the associations between IR measured by estimated glucose disposal rate (eGDR) level and the risk of CVD and all-cause mortality in individuals with T1DM were eligible. Data, pooled by random effects models, were presented as hazard ratios (95% confidence intervals, CI). The primary outcomes were the composite CVD outcome and all-cause mortality.

Results

Eight studies involving 21,930 individuals were included, of which five studies involving 19,960 T1DM individuals reported the risk of CVD. During a median follow-up of 10 years, there were 2,149 cases of incident CVD. The pooled hazard ratio for composite CVD outcome per 1-unit increase in the eGDR index was 0.83 (95% CI 0.78–0.90, I2 = 58.9%). Five studies involving 19,403 T1DM individuals reported the risk of all-cause mortality. During a median follow-up of 10 years, a total of 1,279 deaths were observed. The pooled hazard ratio for all-cause mortality per 1-unit increase in the eGDR index was 0.84 (95% CI 0.81–0.87, I2 = 0%).

Conclusions

IR as measured by eGDR may be an additional risk factor for cardiovascular disease and all-cause mortality in individuals with T1DM. Modification of IR by lifestyle interventions or pharmacological treatments could be a viable therapeutic target to lower the risk of CVD in T1DM.Figure 1 Literature flowchartFigure2 Forest plot
Influence of urban noise exposure on early-onset myocardial infarction risk prediction
Authors: Kerniss H , Mata Marin L A M M , Clemens K C , Litfin C L , Seidel A S , Ruehle S R , Osteresch R O , Fach A F , Hambrecht R H , Wienbergen H W
Published: October 2024

Results from the DECIBEL-MI (Determination of Environmental CIty-noise's Burden, Exposure, and Link to Myocardial Infarction) Study

Background

Urban noise has not been incorporated into existing risk scores for cardiovascular events. The present study endeavors to explore the impact of noise exposure on the individual risk of early-onset myocardial infarction (MI).

Methods

All consecutive patients aged ≤ 50 years with acute MI who were admitted to a heart center between 2015 and 2023 and were residing in our city were included. The LIFE-CVD model was used to predict the 10-year cardiovascular risk of the patients based on traditional risk factors at the time of MI. The Geoportal Bremen was used to calculate both the daytime (Lden) and nighttime (Lnight) residential noise exposure levels.

Results

Among the 430 patients aged 50 years or younger diagnosed with MI, an elevated incidence of noise exposure compared to the general population in the same region was observed. This result was observed in both Lden (65% vs. 53%, p < 0.01) and Lnight (55% vs. 41%, p < 0.01).

Patients with MI and a low LIFE-CVD score (≤2.5%) exhibited significantly higher noise exposure in comparison to those with a high LIFE-CVD score (2.32 vs. 1.36, p < 0.01 for Lden, and 1.72 vs. 1.00, p < 0.01 for Lnight).

The average noise exposure increased with decreasing traditional risk factors exposure (see Figure 1). This inverse relationship persisted significantly in a linear regression analysis, even after adjusting for potential confounding factors such as socioeconomic status, PM10 and renal function (p < 0.01). Consequently, the incorporation of urban noise exposure contributes to optimizing the stratification of risk groups within LIFE-CVD risk categories.

Conclusion

Young patients with myocardial infarction (MI) who had fewer traditional risk factors were exposed to higher noise levels. Through comprehensive multivariate analysis, we identified a consistent inverse association between residential noise and the estimated cardiovascular risk based on traditional risk factors. Incorporating noise exposure into clinical care considerations has the potential to enhance the accuracy of MI prediction.

Figure 1: Comparison of Lden in patients with MI ≤ 50 years with different 10-year LIFE-CVD risk categories (based on traditional risk factors)
Life course cumulative PM2.5 exposure since childhood and albuminuria in midlife: a 30-year prospective cohort study
Authors: Li Y , Lu Y A O
Published: October 2024

Background

Previous studies have confirmed the adverse effect of ambient fine particulate matter (PM2.5) on kidney and cardiovascular diseases. However, the effects of long-term cumulative PM2.5 exposure on albuminuria, particularly from childhood to middle age, remains uncertain.

Purposes

We aimed to investigate the association between cumulative PM2.5 exposure and albuminuria across three distinct time frames using data from the 30-year population-based cohort study.

Methods

Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 1643 children and adolescents were followed with 6 visits over 30 years. The annual mean PM2.5 concentration for the period 1987-2017, at the address of each participant, was obtained from the MERRA-2 and CHAP datasets in China. We assessed cumulative PM2.5 exposure as the area under the curve (AUC) and used the linear regression models to estimate the association between cumulative PM2.5 exposure and urinary albumin-to-creatinine ratio (uACR) in 2017.

Results

In full adjustment for potential confounders, childhood and life course cumulative PM2.5 exposure was positively associated with uACR in midlife [childhood: β=0.103 (95%CI: 0.003, 0.202); life course: β=0.078 (95%CI: 0.004, 0.153)]. However, the relationship between adulthood cumulative PM2.5 exposure and uACR in middle age was not statistically significant. In addition, the associations of adulthood and life course cumulative PM2.5 exposure with uACR in middle age were only observed in non-smokers [β=0.109 (95% CI: 0.002, 0.216)], but not in smokers.

Conclusions

Cumulative PM2.5 exposure during childhood and over the life course is associated with higher uACR in midlife, especially for children and non-smokers. Lowering PM2.5 pollution early in life could prevent the development of renal dysfunction and cardiovascular disease in later life.
Blood pressure and renal function responses in workers exposed to lead for up to six years
Authors: Yu Y , An D W , Yang W Y , Verhamme P , Allegaert A , Nawrot T S , Staessen J A
Published: October 2024

Background

Lead is a widespread environmental toxicant. However, there is currently no consensus whether low-level lead exposure raises blood pressure (BP) or induces kidney dysfunction.

Purpose

The Study for Promotion of Health in Recycling Lead (SPHERL) assessed the BP and renal function (RF) responses for up to six years in the workers without previous occupational lead exposure.

Methods

BP was the average of 5 consecutive readings and the estimated glomerular filtration rate was derived from serum creatinine (eGFRcrt) and cystatin C (eGFRcys). Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 mg/dL). The statistical methods included multivariable-adjusted mixed models and interval-censored Cox regression analysis.

Results

The 234 workers analyzed were on average 28.5 years old and included 91.9% men. The baseline BL concentration was 4.35 µg/dL and increased 3.17-fold over follow-up (median: 2.03 years; range: 0.92-6.45 years). The changes in BP and RF were not significantly correlated with the follow-up-to-baseline BL ratio (p≥0.51 and p≥0.18, respectively). The fully-adjusted changes in systolic/diastolic BP associated with a doubling of BL were -0.25/-0.12 mm Hg (CI: -0.94 to 0.44/-0.66 to 0.42 mm Hg). Accordingly, the incidence of stage-1 or -2 hypertension was not associated with the BL change (p≥0.063). Similarly, the changes in eGFRcrt and eGFRcys associated with a 3-fold BL increment were not significant, amounting to -0.70 mL/min/1.73 m2(CI: -1.70 to 0.30 mL/min/1.73 m2) and -1.06 ml/min/1.73 m2 (-2.16 to 0.03 mL/min/1.73 m2).

Conclusion

The BP and RF responses to an over 3-fold BL increment were small and not significant confirming the safety of modern lead-handing facilities operating under current safety rules.Figure 1Figure 2
Development of a predictive model for adherence to pharmacological treatment in ischemic heart disease: consideration of psychosociocultural, neuropsychological, and mental health variables
Authors: Flores-Mendoza J B , Salvador-Cruz J , Robles-Garcia R , Aceves Chimal J L , Diaz-Loving R
Published: October 2024

Introduction

Adherence to pharmacological treatment recommendations is the main preventable cause of rehospitalization and premature mortality in patients diagnosed with ischemic heart disease, which in turn, is permeated by modifiable psychosocial risk factors such as anxiety, depression, stress, type A behavior pattern, inhibitory control, attitudes and behavioral beliefs towards the disease and treatment. The objective of this study was to develop and test a model to predict adherence to pharmacological treatment in patients with ischemic heart disease undergoing coronary revascularization surgery based on psychosocial, neuropsychological and mental health variables.

Material and Methods

Cross-sectional study with a sample of 691 patients between 45 and 82 years of age (M= 52 years, SD= 12.15), 46% women and 54% men, diagnosed with ischemic heart disease and undergoing coronary revascularization surgery. Anthropometric, cardiovascular and psychosocial risk factors were evaluated. The scales were designed and validated to assess adherence to pharmacological treatment in ischemic heart disease by means of EFA and CFA, which showed adequate internal consistency indicators and psychometric properties.

Results

Using the AMOS v.24 statistical package, a path analysis was performed for the variable of adherence to pharmacological treatment, with attitudes toward the disease and treatment, behavioral beliefs, and inhibitory control (executive function) as direct predictors, explaining 54% of the variance in adherence to pharmacological treatment in ischemic heart disease, and the model fit indices were: χ2(33) =261. 19; CMIN/DF= 7.91; TLI= .893; NFI= .815; IFI= .901; CFI= .900; AGFI= .822, SRMR= 2.727; RMSEA=.053.

Conclusions

The findings of this research contribute to the understanding of adherence to pharmacological treatment in ischemic heart disease as a process and not only as an isolated construct, in which mental health intervenes interacting with psychosocial and cultural aspects of the patient with respect to their disease and pharmacological treatment and in turn provides evidence that inhibitory control as an executive function. This provides evidence that inhibitory control as an executive function is useful for understanding adherence to pharmacological treatment, which shows the need to incorporate in the hospital setting comprehensive psychological evaluations and interventions that allow us to predict adherence to pharmacological treatment of ischemic heart disease in order to intervene in the processes involved, which could contribute to the prevention of rehospitalization and premature mortality.
Correlation analysis of self-rated health and net adverse clinical events in patients with acute myocardial infarction
Authors: Cao S , Liu J Y , Gu T S , Hu S T , Zhang Y K , Jiang C , Zhang J K , Wu X , Liu X , Liu T , Chen K Y
Published: October 2024

Backgrounds

Self-rated health (SRH） is a recognized standard risk factor for myocardial infarction, but its impact on prognosis remains uncertain.

Purpose

This study aims to investigate the impact of self-rated health on the long-term clinical outcomes of myocardial infarction patients.

Methods

The data for this study were derived from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023, Patients were divided into satisfied and unsatisfied groups based on their responses to an SRH questionnaire. Propensity score matching (PSM) was utilized to balance covariates between the two groups and analyze the relationship between SRH and clinical outcomes. The primary endpoint was net adverse clinical events (NACE), comprising cardiac death, recurrent myocardial infarction, revascularization, ischemic stroke, and bleeding events (BARC ≥3). The secondary endpoint comprised the individual components of the primary endpoint.

Results

The study included a total of 55,054 AMI patients, with 54,049 rating their health as satisfactory and 1,005 patients as unsatisfactory. In the satisfactory group, patients tended to be younger, had fewer females, better Killip classification, a higher proportion of STEMI cases, a higher rate of undergoing PCI, and a lower prevalence of concomitant disease such as diabetes, hypertension, chronic kidney disease, cerebrovascular disease, peripheral vascular disease, thyroid disease, and chronic lung disease. Additionally, patients in the satisfactory group had a higher proportion of antiplatelet therapy use (aspirin, ticagrelor). 1,005 pairs were well matched after PSM. After a median follow-up of 1626 days, the proportion of all-cause death, cardiac death, and recurrent myocardial infarction in the satisfied group was significantly lower than that in the unsatisfied group. Multivariable Cox regression analysis revealed that satisfactory SRH was associated with a reduced risk of NACE (aHR 0.809, 95%CI 0.704-0.930, P=0.002), cardiac death (aHR 0.790, 95%CI 0.665-0.939, P=0.007), and recurrent myocardial infarction (aHR 0.734, 95%CI 0.563-0.955, P=0.021).

Conclusions

Good SRH can decrease the risk of NACE in myocardial infarction patients, underscoring the importance of considering SRH in clinical assessment.
Association of pulsatile venous waveform pattern in the venous studies of lower extremities to 2d-echocardiographic parameters for right heart function and right atrial pressure
Authors: Maderazo D , Sindiong M K
Published: October 2024

Introduction

To date, the detection of pulsatile venous waveform (PVW) pattern in venous duplex scans are read as suggestive of increased central venous pressure (CVP) and/or right-sided heart failure. In the advent of point of care ultrasound, non-invasive measures can be used to determine systemic hemodynamics in emergent clinical settings.

Purpose

This study aims to determine the association of PVW pattern to echocardiographic parameters of right ventricular (RV) function and right atrial pressure (RAP).

Methods

A single center retrospective study of adult patients with venous studies of the lower extremities and 2d-echocardiogram done from January 2019 to October 2023. Logistic regression analyses were performed to determine the association of PVW pattern with RV dysfunction based on TAPSE, S’ and FAC, as well as with increased RAP.

Results

A total of 2086 adult patients were included with median for age of 67 years of which 1141 (55%) were females, and 728 (35%) were hypertensive. PVW pattern was noted from 163 participants (7.8%) of which a higher proportion had heart failure, kidney disease, COVID-19, pneumonia and valvular heart disease. Patients with PVW pattern had a significantly lower median TAPSE [18 (IQR 15-20) vs 20 (IQR 18-22)] and median S’ [11.1 (IQR 8.6-13.20) vs 12.3 (IQR 10.6-14.40)] with FAC 27.1 + 11.9%. Increased RAP was noted in 7% of the study population. Patients with PVW pattern had a higher median inferior vena cava (IVC) diameter [1.9 ( IQR 1.5-2.3) vs 1.5 (IQR 1.3-1.8)] and lower median IVC collapsibility [39.9 (IQR 23.5-51.4) vs 50 (IQR 38.9-58.80]. PVW pattern is significantly associated with TAPSE (crude OR 3.89; CI 2.67-5.66, p<0.0001), S’ (crude OR 3.26, CI 2.30-4.62, p<0.0001) and increased RAP (adjusted OR 6.06, CI 4.02-9.14, p<0.0001).

Conclusion

Patients with PVW pattern had about 4 times and 3 times higher odds of developing RV systolic dysfunction based on TAPSE and S’, respectively. Its presence confers about 6 times higher odds of developing increased RAP. These parameters can direct further diagnostic work-up and guide assessment of response to decongestive therapy in critical units and other areas where 2d-echocardiogram is not readily accessible.
Heart rate response and recovery in bicycle exercise testing - reference values and association with mortality
Authors: Jou J , Zhou X , Lindow T , Brudin L , Hedman K , Ekstrom M , Malinovschi A
Published: October 2024

Introduction

Chronotropic incompetence and impaired heart rate (HR) recovery are related to mortality. Guidelines lack specific recommendations for reference values on HR recovery assessment.

Purpose

To define normal values for HR response and recovery in individuals referred for a bicycle exercise stress test and to relate these factors to risk of mortality.

Methods

We included 9,917 subjects (46% females) aged 18–85 years who performed a bicycle exercise test. We defined age- and sex-specific reference equations for peak HR, HR reserve, and HR recovery at 1 and 2 minutes (HRR1 and HRR2) using a subgroup of individuals without apparent cardiovascular (CV) risk nor comorbidities (N=2,774). Associations between blunted HR indices (<5thpercentile) and mortality were analysed using Cox regression in all subjects and in individuals with normal exercise capacity (N=8,070).

Results

All HR indices were age-dependent. The 5th percentiles of HR reserve, HRR1, and HRR2 correlated weakly with previously reported reference values. During median follow-up of 8.6 years 1,110 (11%) died. HR recovery variables were the strongest predictors of all-cause (HRR1, hazard ratio 1.66 (95% confidence interval, 1.45–1.90)) and CV mortality (HRR2, 1.59 (1.26–2.00)) after adjustments for potential confounders. Blunted HR response (peak HR) increased risk of all-cause (1.32 (1.14–1.53)) and CV mortality (1.41 (1.09–1.83)). Combined blunted HRR1 and HRR2 or HR response and HRR1 further increased risk of all-cause (1.92 (1.64–2.24) and 1.85 (1.55–2.22), respectively) and CV mortality (1.95 (1.50–2.54) and 1.94 (1.42–2.65), respectively). HR recovery variables (HRR1, 1.97 (1.63–2.39) and HRR2, 1.76 (1.46–2.12)) remained stronger predictors of mortality than peak HR (1.38 (1.10–1.72)) in individuals with normal exercise capacity.

Conclusions

All HR variables were age-dependent and associated with mortality. Blunted HR recovery was more strongly related to mortality than chronotropic incompetence, and their combination added prognostic value. Furthermore, blunted HR recovery variables, rather than blunted HR response, remained strongly associated with mortality even in the presence of normal exercise capacity.
Third ventilatory threshold in heart failure patients undergoing CPET: a prognostic analysis
Authors: Certo Pereira J , Amador R , Carvalho R , Bello R , Lima R , Maltes S , A Gomes D , Rocha B , Durazzo A , Mendes M , Adragao P , Cunha G
Published: October 2024

Introduction

One crucial element in cardiopulmonary exercise testing (CPET) involves identifying the first and second ventilatory thresholds (VT), VT1 and VT2, which hold known prognostic implications. If the individual can sustain exercise considerably beyond VT2, a third breakpoint (VT3 – Figure A) may emerge, coinciding with heightened hyperventilation to counter metabolic acidosis. Historically, this point has been mainly described among athletes and its meaning is still not entirely clear. We aimed to assess the prognostic value of VT3 in patients with heart failure (HF).

Methods

Retrospective, single-center study enrolling HF patients undergoing CPET from 2015 to 2021. We evaluated the typical CPET parameters along with the three ventilatory thresholds: VT1, VT2, and the newly introduced VT3. The primary outcome was a composite of cardiovascular death, urgent heart transplant, need for left ventricle assistance device and HF hospitalizations.

Results

We included 221 patients (82% men, mean age 58±12 years), among whom 69% had ischemic heart failure aetiology. The mean left ventricular ejection fraction (LVEF) was 34±9%, with a mean respiratory exchange ratio 1.15±0.082, mean pVO2 18.5±6.3, and a mean VE/VCO2 slope of 41.3±12.9. VT3 was attained by 43% (n = 94) of the patients.

In comparison to those who did not achieve VT3, patients who reached this threshold were younger (56±11 vs 60±12; p = 0.05), had a higher pVO2 (20.5±6.9 vs 17±5.4; p = 0.05), higher RER (1.16±0.86 vs 1.13±0.78; p = 0.05), and lower VE/VCO2 slope (39±10.3 vs 43±14.3; p = 0.05).

Regarding the three ventilatory thresholds (VT1, VT2, VT3), 7% (n=17) achieved a maximum of one threshold, 50% (n=110) achieved two thresholds, and 43% (n=94) reached all three thresholds. After a median follow-up of 2,3 years patients with identifiable VT3 had significantly better prognosis (HR 0,434; 95%CI 0,246-0,767; p=0,004) than those without this threshold. Furthermore, the number of identifiable ventilatory thresholds correlated positively with prognosis. In fact, patients with only 2 thresholds have twice the probability of developing an event and those with one or zero identifiable thresholds have a 4-fold increase in the probability of events (Figure C).

Conclusion

In a cohort of patients with HF, those with identifiable VT3 had a lower incidence of events. This parameter may aid in prognostic stratification in this population. However, this findings warrant further prospective validation.Figure 1
Signal-morphology impedance cardiography is a non-invasive tool to predict responses to exercise based cardiac rehabilitation in chronic heart failure patients
Authors: Bour F , Iliou M C , Vitiello D , Lepretre P M
Published: October 2024

Background

All the studies and meta-analyses showed beneficial effects of the exercise based cardiac rehabilitation (ExBCR) on peak value of oxygen uptake (VO2peak) in patient with chronic heart failure (CHF). It is widely recognized that changes in VO2peak induced by training (ΔVO2peak) have a prognostic value. A 5.0% increase in ΔVO2peak has been associated with a significant clinical improvement1. However, 20 to 30 % of CHF are non-responders to ExBCR. The Signal-Morphology Impedance Cardiography (SM-ICGTM) technology has allowed previous researchers to show the role of cardiac output (CO) on DVO2peak2. CO responses may be partly attributed to the peak ejection flow velocity that can explain the impaired response to ExBCR.

Purpose

The study aimed to establish whether SM-ICGTM is an appropriate technology to predict responses to ExBCR in CHF patients.

Methods

A retrospective study was conducted on 65 CHF patients (LVEF: 29.0±8.3%). All patients performed a cardiopulmonary exercise test (CPET) on bicycle to determine ventilation (VE) and VO2peak before and after 20 ExBCR sessions. In addition, stroke volume (SV), heart rate (HR), and CO were continuously monitored by SM-ICGTM (PhysioFlow® Lab1). The value of peak ejection flow velocity, so called CTi by the manufacturer, was calculated as the peak of the first mathematical derivative over the time of the impedance waveform during the systole and measured by PhysioFlow® throughout the test. For the analysis of training response patients were divided in two groups: the normal CTi profile which was characterized by an initial increase followed by a plateau until CPET exhaustion, and the abnormal CTi response if CTi decreased at the onset of CPET or increased then decreased before exhaustion. Statistical analyses were performed with JASP. The significant level was set at p value < 0.05 for 95% confidence interval.

Results

Our study population consisted in 32 patients who presented a normal CTi profile and 33 with an abnormal CTi profile. As shown in Table 1, no significant difference was found at baseline between both groups. ExBCR induced significant changes in VO2peak even if 29 % patients were non-responders. Patients with normal CTi profile presented a greater DVO2peak compared to patients with abnormal CTi profile (28 ± 30 vs. 14 ± 19 %, p<0.01). 78% of patients with normal CTi profile versus only 64% of patients with abnormal CTi profile were ExBCR responders. The logistic regression showed that patient with normal CTi profile were 3.3 time more likely to present a ΔVO2peak ≥ 5%.

Conclusion

Exercise CTi profiles determined by SM-ICGTM prove to be an interesting tool to help predicting ExBCR responses in CHF patients and maybe highlighting the hemodynamic determinants of VO2 responses to exercise training.
Achieving theorical cardiorespiratory fitness is associated with high-volumen training in a phase II cardiac rehabilitation program
Authors: Lara Vargas J , Palomeque C A , Zamora I K , Avalos J V , Leyva E A , Rodriguez L V , Lastra V J , Juarez M , Camas L , Gomez A E , Morales P J D
Published: October 2024

Background and Puropose

Cardiac Rehabilitation (CR) is an interdisciplinary therapeutic program with demonstrated success rates in reducing cardiovascular outcomes. To obtain these benefits, it is important to achieve a level of cardiorespiratory fitness (CRFIt) that should be close to the ideal according to age and gender (theorical). The best way to measure it, is through VO2p, or with its surrogate value in METs-load. In our Phase II CR program, both aerobic and strength training is supervised 3 times per week, but emphasis is placed on weekly aerobic training volume (TVol) for a sufficient dose, in order to guarantee outcomes. Our hypothesis is that with adequate TVol, CRFit will be achieved at ideal levels (theorical). The aim of the study is to evaluate the safety and achievement in CRFit measured by METs-load in patients with heart disease during a high-volume Phase II CR program.

Methods

Quasi-experimental study of a comprehensive Phase II CR program in which patients were evaluated by initial and final exercise testing. Depending on the result, they were assigned for 4-6 weeks (4 to those patients with >5METs and 6 to those with <5METs) to 3 weekly concurrent training sessions (30 mins of aerobic at 70-85% of their heart rate reserve plus strength training), in addition to the corresponding educational, nutritional and psychological intervention. TVol was calculated by METs/week (METs-minute obtained by ergo or treadmill multiplied by 90 minutes). Progressions were made to achieve a weekly program average TVol>500 METs/week according to guidelines recomendations. An adverse event was defined as malignant ventricular arrhythmias, cardiorespiratory arrest, or death.

Results

A population of 522 patients was analyzed, 72% men, average age of 58.8 years (+-0.59), with coronary ischemic disease, heart failure and cardiomyopathies as the most common heart diseases. Regarding the average theorical METs (8.23, +-0.6), our patients achieved final average METs of 10.2 (+-0.26) and 90.02% (+-0.53) of attendace (Figure 1). The average of TVol were 637.4 (+-37.35) METs/week. The differential between the initial and final METs (Delta1) was correlated by Spearman with the differential between the final METs and its theorical (Delta2) and a significant moderate correlation was found (r=0.32 Spearman, p <0.001). TVol and Delta2 shows a strong and significant correlation (r=0.72 Spearman, p<0.001) (Figure 2). No adverse events were reported in any of the training sessions.

Conclusion

The Phase II CR program with concurrent training only 3 times per week but with TVol>600 METs/week is safe and guarantees a CRFit above the ideal level (theorical). We recommend to measure and fullfill training volume as a strategy to achieve promising results in exercise tolerance and functional capacity in patients with heart disease.
Effectiveness of hybrid comprehensive telerehabilitation in women with heart failure - subanalysis of the TELEREH-HF RCT
Authors: Piotrowicz E , Kowalik I , Opolski G , Banach M , Zareba W , Orzechowski P , Szalewska D , Glowczynska R , Irzmanski R , Kalarus Z , Pluta S , Mierzynska A , Jaworska I , Piotrowicz R
Published: October 2024

Background

Despite the known benefits of cardiac rehabilitation, it remains underutilized among women. In particular, little is known about the effectiveness of hybrid comprehensive telerehabilitation (HCTR) in women with heart failure (HF).

Purpose: The purpose of this study was to assess effectiveness and safety of HCTR in women with HF.

Methods: The present analysis formed part of TELEREH-HF multicenter, randomized trial that enrolled 850 HF patients (NYHA I-III, LVEF ≤ 40%). Patients were randomized 1:1 to HCTR plus usual care (UC) or UC alone. Patients underwent either an HCTR (1 week in hospital and 8 weeks at home, five times weekly) or UC with observation. The effectiveness of HCTR was assessed by changes in

peak oxygen consumption (VO2 peak), workload duration (t) in cardiopulmonary exercise test and quality of life (QoL) based on Medical Outcome Survey Short Form 36 Questionnaire (SF-36). Measurements were made before and after intervention/observation.

Results: Women constituted 11.5 % of population in the TELEREH-HF study. Forty women in HCTR group and 44 women in UC group completed HCTR and observation respectively. HCTR resulted in significant improvement in VO2peak, workload duration and QoL. We did not observe these favorable results in the UC group except for an increase workload duration. In the HCTR group, there was a significantly greater improvement in physical component of QoL than in the UC group. All results are presented in Table 1. In neither group were there deaths nor major adverse events related to exercise training.

Conclusion

In women with HF, hybrid comprehensive telerehabilitation is safe and resulted in a significant improvement in physical capacity and QoL.
Effect of sacubitril/valsartan and dapagliflozin on athletic performance; can the popular cardiac medications of recent years be used as doping agents?
Authors: Kilic S , Asal S , Torun A , Babaoglu M , Yavuz S , Demirtas C , Dilmen S , Orhan A L , Uzun M
Published: October 2024

Background/Introduction

Recent guidelines have highlighted the positive impacts of sacubitril/valsartan and dapagliflozin on heart failure management [1]. Given their potential misuse as doping agents in professional sports, this study evaluates their effects on athletic performance.

Purpose

To investigate the effects of sacubitril/valsartan and dapagliflozin on athletic performance and cardiac functions in a rodent model.

Methods

The study had a randomized double-blind design. 24 Sprague-Dawley male rats aged 4 months, divided into control, sacubitril/valsartan, and dapagliflozin groups. The rats were weighed at the start of the experiment. The medications (dapagliflozin 1,5 mg/kg/1 ml/once a day, sacubitril/valsartan 60 mg/kg/1 ml/once a day to their respective groups, and normal saline for control group) were administered via gastric gavage for 30 days. The rats were weighed, examined with transthoracic echocardiography and put on rotarod at the start of the experiment, and on 15th and 30th days. The rats were put on forced swimming tests for 20 days. Exhaustion, loss of coordinated movements and failure to surface for 3 seconds after submersion in the water were defined as indications for ending the test as per the guidelines regarding rat exercise testing [2]. M-mode and Doppler measurements, forced swimming test durations, rotarod durations and weight were recorded on 0th, 15th and 30th days.

Results

Initial performance metrics, including echocardiography, weight, and rotarod tests, showed no significant differences among the groups at baseline. The distributions in data were non-normal. Over the course of the study, median swimming times significantly differed from the 9th session, with dapagliflozin-treated rats exhibiting a substantial increase in endurance. Specifically, dapagliflozin group's swimming times increased to a median of 3580 seconds by the 20th session, compared to 2382 seconds in the control group and 2591 seconds in the sacubitril/valsartan group, indicating a pronounced improvement in exercise capacity (P<0.0001)(Figure-1). Echocardiographic assessments revealed enhanced cardiac output and ejection fraction, particularly in the sacubitril/valsartan group, suggesting increased cardiac efficiency and potential athletic performance enhancement.

Conclusion(s)

The study demonstrates a significant improvement in athletic performance with dapagliflozin compared to sacubitril/valsartan. These findings suggest a potential for misuse in sports doping, emphasizing the need for stringent regulation and monitoring within competitive athletics.Figure-1
Cardiac screening with ECG in the young: significance of T wave inversion, T wave depth and T wave/QRS ratio
Authors: Alzarka A , Abioye D , Maclachlan H , Bhatia R , Sharma S , Papadakis M , Finocchiaro G
Published: October 2024

Background

In young apparently healthy individuals, repolarization changes at the ECG may suggest an underlying cardiomyopathy.

Purpose

This study aims to investigate the clinical significance of T waves depth and T/QRS ratio in young individuals who underwent cardiac screening and exhibited T wave inversion (TWI) at the ECG.

Methods

We analysed a database of individuals aged 14 to 35 years who underwent cardiac screening, which included a health questionnaire and 12-lead ECG with a charitable organisation, between 2008 and 2013. All individuals included had recently responded to a follow-up online health questionnaire or had documented outcomes on a national digital database. The amplitudes of QRS (peak to peak) and T waves (mV) were measured in the leads where TWI was present; the average T/QRS ratio and average TWI depth were calculated.

Results

Our cohort comprised 5360 subjects (mean age of 21 ± 6 years, 61% males). Of the 358 (7%) who were referred for further investigations based on their screening findings, 255 (5%) had an abnormal ECG. TWI was documented in 120 (2%) individuals [anterior TWI in 78, inferior TWI in 16, lateral TWI in 6, and overlaps in 20 cases]. After further investigations, 16/120 (13%) individuals were diagnosed with cardiomyopathy [9 hypertrophic cardiomyopathy (HCM), 5 arrhythmogenic cardiomyopathy (ACM), 1 dilated cardiomyopathy (DCM), and 1 left ventricular non-compaction cardiomyopathy (LVNC)]. Of the remaining 104/120 individuals, 18 were diagnosed with other cardiac conditions and 86 were not found to have a cardiac disease. During a mean follow-up of 8.1 ± 1.2 years, no deaths were documented among the 16 individuals diagnosed with a cardiomyopathy, but 3 of them experienced a sudden cardiac arrest (all of them had ACM). In individuals diagnosed with a cardiomyopathy both average T/QRS ratio and average TWI depth were higher compared to the rest (0.128 vs 0.117; p = 0.54 and 0.281 vs 0.162 mV; p = 0.03, respectively). Average T/QRS ratio and average TWI depth were higher in individuals diagnosed with HCM compared with the ones diagnosed with other cardiomyopathies (0.133 vs 0.115; p = 0.68 and 0.336 vs 0.164 mV; p = 0.05, respectively).

Conclusion

T wave inversion is a relatively common ECG finding in young apparently healthy individuals and this feature leads to a diagnosis of cardiomyopathy in 13% of cases. Among subjects exhibiting TWI, T/QRS ratio and T wave depth appear higher in the ones who are eventually diagnosed with cardiomyopathies.Figure 1.Flowchart of patient selection