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Take a look at a selection of our recent media coverage:

Increased NT-proBNP levels over time linked to greater risk of heart failure and death

1st March 2023

Increased levels of NT-proBNP over time lead to an elevated risk of both heart failure and mortality among those without heart failure

Increases in the level of N-terminal B-type natriuretic peptide (NT-proBNP) over time are associated with a higher risk of incident heart failure and death among those initially without the disease according to the findings of a study by US researchers.

NT-proBNP levels serve as an important biomarker for patients with chronic heart failure. In fact, higher levels of the protein upon admission to hospital with COVID-19, have also been associated with an increased mortality risk and other complications in patients with and without heart failure. However, in many studies, NT-proBNP has been assessed at a single time-point and in the current work, researchers looked at changes in the biomarker over time and whether this might be prognostic for the development of heart failure among those who were initially free of the disease.

The team used data from the Atherosclerosis in the Communities (ARIC) study and included participants who had measurements of the biomarker at year 2 and 6 (i.e., 4 years apart) but had not been diagnosed with heart failure. The primary exposure variable was the change in NT-proBNP between visits 2 and 4, categorised as either <125 pg/mL or ≥125 pg/mL and the primary outcome measures were set as incident heart failure (HF) hospitalisation and all-cause mortality.

NT-proBNP and risk of heart failure

Data were available for 9,776 individuals (mean age = 57.1 years, 56.5% female) and who were included in the analysis.

Individuals with NT-proBNP levels of 125 pg/mL or higher at both visits had a significantly higher risk of incident HF compared to those with levels below this threshold (adjusted Hazard Ratio, aHR = 2.40, 95% CI 2.00 – 2.88). Similarly, there was an elevated risk of mortality (aHR = 1.68, 95% CI 1.47 – 1.91). Interestingly, those with NT-proBNP levels of 125 pg/mL or higher at visit 2 but which was lower at visit 4, still had a higher risk of HF although the result was not significant (HR = 1.01, 95% 0.71 – 1.43) when compared to those who levels were below the threshold at both visits. There was also a significant increase in HF and mortality risk based on the percent change in the biomarker per 1 standard deviation increase. There were also significant associations with cardiovascular risk factors such as systolic blood pressure, body mass index, triglyceride and low-density lipoprotein cholesterol and the change in NT-proBNP.

The authors concluded that the changes in NT-proBNP over time, reflected a dynamic change in the risk of HF events and death among those without prevalent clinical HF. They added that serial measurements of NT-proBNP could be use to improve risk stratification of patients pre-heart failure.

Citation
Jia X et al. Association of Long-term Change in N-Terminal Pro-B-Type Natriuretic Peptide With Incident Heart Failure and Death. JAMA Cardiol 2023

Torsemide and furosemide all-cause mortality similar in heart failure

24th January 2023

Torsemide treatment leads to similar levels of all-cause mortality as furosemide among patients hospitalised with heart failure

Treatment with the loop diuretic torsemide (TM) leads to a similar level of all-cause mortality and all-cause hospitalisations as furosemide (FM) following hospital discharge in patients with heart failure according to the findings of a randomised trial by US researchers.

Heart failure is growing public health concern with an estimated global prevalence exceeding 37.7 million people. Both fluid retention and congestion are key features of the condition which are treated with loop diuretics and this approach is recommended in therapy guidelines. Although furosemide is an established loop diuretic, another agent, torsemide, has both a longer half-life and greater oral bioavailability than furosemide. Moreover, some evidence points to a lower mortality in patients with congestive heart failure treated with torsemide compared to furosemide. However, studies have not been sufficiently powered to address mortality differences between the two agents.

In the present study, researchers undertook an open-label, randomised trial to examine the comparative effectiveness of TM and FM in patients discharged from hospital following an admission for heart failure, irrespective of their ejection fraction. The researchers hypothesised that torsemide would lower all-cause mortality by 20% compared to furosemide. Patients were eligible if they were hospitalised for either de novo heart failure or a worsening of chronic heart failure and randomised 1:1 to either furosemide or torsemide. The researchers set the primary effectiveness outcome as all cause mortality whereas one of the main secondary outcomes was all-cause hospitalisations.

Torsemide and all-cause mortality

A total of 2,859 patients with a mean age of 64.5 years (36.9% female) were randomised to either diuretic and followed for a median of 17.4 months.

During follow-up, death occurred in 26.1% of the TM group and 26.2% of the FM group and this difference was not significant (hazard ratio, HR = 1.02, 95% CI 0.89 – 1.18, p = 0.76). In addition, all-cause mortality or all-cause hospitalisations occurred in 47.3% of those assigned to TM and 49.3% of patients in the FM group (HR = 0.92, 95% CI 0.83 – 1.02). There were also no significant differences in any of the subgroups analysed, including patients with differing levels of ejection fractions.

Although there were no significant differences between the two loop diuretics, the researchers did acknowledge at least two potentially important study limitations including treatment discontinuation (9.5% of any agent at 6 months) and cross-over (7% for TM to FM) between the two agents could have had an effect.

They concluded that while torsemide did not lower all-cause mortality compared to furosemide, these findings should be interpreted with caution given the rates of discontinuation and cross-over.

Citation
Mentz RJ et al. Effect of torsemide vs furosemide after discharge on all-cause mortality in patients hospitalized with heart failure: The TRANSFORM-HF randomized clinical trial. JAMA 2023

Higher plant omega-3 levels reduce death and hospitalisation risk in heart failure

4th November 2022

Higher plant omega-3 levels in heart failure (HF) patients reduces mortality and first HR hospitalisation risk more than marine-based omega-3

A higher level of plant omega-3 levels in ambulatory heart failure patients significantly reduced all-cause mortality and first heart failure hospitalisation risk compared to levels of marine-based omega-3 according to the findings of a study by Spanish researchers.

The supplementation with marine-based omega-3 fatty acids can provide a small beneficial advantage in terms of mortality and cardiovascular-related hospital admission in patients with heart failure. Other work has suggested that omega-3 fatty acid supplements also offer benefits on recurrent heart failure hospitalisation although further work is required to confirm these findings. However, not everyone eats fish or wants to take supplements and for such individuals, omega-3 fatty acids can be obtained through the diet via other sources. For example, plant omega-3 sources include alpha-linolenic acid (ALA) which is present in flaxseed and walnut oil. But whether this plant-based source of fatty acids provides the same benefits to heart failure patients as marine-based acids is unclear.

In the present study, the Spanish team speculated that regular consumption of ALA foods would provide a beneficial effect in terms of morbidity and mortality for patients with heart failure. To provide a more accurate measure of intake, rather than relying on self-reporting, the Spanish team assessed ALA levels in serum phospholipids which provides a more objective measure of ALA intake. For comparative purposes, they also measured serum levels of marine-based omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The team recruited patients who attended a heart failure unit with a tertiary hospital in Barcelona. The primary outcome was a composite of all-cause mortality or first heart failure hospitalisation although the researchers also separately examined the components of the composite as secondary outcomes. The levels of ALA were split into quartiles and multivariable regression analysis was used and focused on a comparison of the lowest (Q1) versus the highest (Q2 – Q4) levels.

Plant omega 3 levels and heart failure outcomes

A total of 905 patients with a mean age of 67 years (31.7% female) were included and followed up for a median of 2.4 years.

The primary endpoint occurred in 184 patients during follow-up including141 heart failure hospitalisations. When comparing ALA levels between Q1 and Qs 2-Q4, there was a 39% lower risk of the primary endpoint (Hazard ratio, HR = 0.61, 95% CI 0.46 – 0.81, p = 0.001). There were similarly significant reductions for the components of the composite, i.e., all-cause mortality (HR = 0.58, 95% CI 0.41 – 0.82, p = 0.002) and first heart failure hospitalisation (HR = 0.58, 95% CI 0.40 – 0.84).

Interestingly, when looking at the combined levels of EPA and DHA there was no significant effect on the primary endpoint when comparing Q1 with Q2 – Q4 (HR = 1.11, 95% CI 0.82 – 1.51, p = 0.502). The effect on both all-cause mortality and heart failure hospitalisation were also non-significant.

The authors concluded that elevated levels of plant omega-3 fatty acids in serum were related to a lower risk of incident adverse clinical outcomes in patients with heart failure.

Citation
Lazaro I et al. Relationship of Circulating Vegetable Omega-3 to Prognosis in Patients With heart failure J Am Coll Cardiol 2022

Heart failure patients benefit from telemedicine

13th October 2022

Heart failure patients who receive remote disease monitoring and consultations may experience short-term cardiovascular and mortality benefits

Digital health interventions (DHIs) have contributed to the transformation of healthcare delivery in the past decade and especially since the COVID-19 pandemic when interventions such as telemedicine for remote consultations became the ‘norm’ in many specialities. Nevertheless, while imposed in many therapy areas during the pandemic, there are actually potential benefits for patients cardiovascular disease. For example, connected health technologies e.g., mobile phones, smartphones, tablets, wearable devices, smartwatches, personal health sensors, all provide an opportunity to revolutionise cardiovascular disease prevention through personalised, convenient, and easily accessible patient education and behaviour change support. The value of DHIs for the prevention of cardiovascular disease was explored in a systematic review and meta-analysis in 2015, in which the authors concluded that the available data provide evidence that DHIs can reduce cardiovascular disease (CVD) outcomes and have a positive impact on risk factors for CVD. However, given that the data used in the aforementioned meta-analysis was collected more than 8 years ago and the COVID-19 pandemic lead to enforced telemedicine and remote monitoring, for the present study, a Malaysian team of researchers sought to update the effectiveness of DHIs for patients with cardiovascular disease.

The researchers included randomised trials, observational and cohort studies that specifically addressed the effect of a telemedicine intervention on cardiovascular outcomes for those either at risk (i.e., for primary prevention) or those with established CVD (secondary prevention). The primary outcome was cardiovascular-related mortality, whereas secondary outcomes included hospitalisation, all-cause mortality and all-cause hospitalisation. Interventions were categorised as remote consultations; remote monitoring of health or diagnostic measures; transmission of medical data and finally remote case management.

Heart failure and cardiovascular outcomes

A total of 72 studies with 127,869 participants (65% male) were included in the analysis. The duration of studies ranged from 1 to 79 months and 49 were short-term (< 12 months) and 22 long-term (> 12 months). Overall, 39 studies included patients with heart failure, 19 addressed secondary prevention and 12 primary prevention.

For heart failure patients, combined remote monitoring and consultation were associated with a 17% reduced risk of cardiovascular mortality (risk ratio, RR = 0.83, 95% CI 0.70 – 0.99, p = 0.036). In addition, this combination significantly reduced hospitalisation for a cardiovascular cause (RR = 0.71, 95% CI 0.58 – 0.87, p = 0.0002) though this was largely in short-term (i.e., < 12 month) studies. However, telemedicine had no effect on all-cause hospitalisation among those with heart failure (RR = 1.02, 95% CI 0.94 – 1.10, p = 0.71).

In secondary prevention studies, the combination of remote monitoring and consultation was associated with a small reduction in systolic blood pressure (mean difference = -3.59, p < 0.0001) but not on diastolic pressure. There was also a small but significant effect of remote consultations on body-mass index (p < 0.0064) in primary prevention.

The authors concluded that a combination of remote disease monitoring and consultation appeared to reduce cardiovascular-related hospitalisation and mortality risk among patients with heart failure in the short-term. They called for future research to evaluate the sustained effect of telemedicine interventions.

Citation

Kuan PX et al. Efficacy of telemedicine for the management of cardiovascular disease: a systematic review and meta-analysis Lancet Digit Health 2022

Different heart failure exercise-based cardiac rehabilitation programs equally beneficial

17th June 2022

An analysis suggests that different exercise-based cardiac rehabilitation programs in heart failure provide broadly similar patient benefits

The different exercise-based cardiac rehabilitation programs available for those with heart failure all appear to provide broadly similar benefits to patients. This was the main conclusion of a network meta-analysis by Australian researchers.

A 2020 analysis found that the current worldwide prevalence of heart failure is 64.34 million cases and which account for 9.91 million years lost due to disability. Heart failure patients have a reduced exercise capacity and one important aspect of a cardiac rehabilitation program is physical activity and exercise. In fact, exercise-based cardiac rehabilitation programs have demonstrated numerous benefits for people with heart failure including improvements in exercise capacity, quality of life and better clinical outcomes. There are several different types of exercise-based cardiac rehabilitation programs including home-based (HB), centre-based (CB), hybrid-based (HB), where more two delivery modes were included in the program and finally, technology-enabled (TE) where > 50% of the program was delivered via text messaging or video calls.

While there is clear evidence that exercise-based cardiac rehabilitation programs are effective, what is not so clear is the the relative merits of the different programs, since in most analyses, pairwise comparisons have be used. For the present study, the Australian team turned to the use of a network meta-analysis, which enables the simultaneous comparison of the different interventions to overcome the limitations imposed by using a pairwise approach. They searched for randomised trials (with usual care as a comparator) in which there was a comparison of exercise-based cardiac rehabilitation programs in adult, heart failure patients with either a preserved or reduced ejection fraction and where the program lasted for a minimum of 4 weeks. In addition, studies were included if these reported on several different outcomes such as exercise capacity (peak oxygen uptake, Vo2 peak), the 6 minute walk distance, the Kansas City Cardiomyopathy questionnaire (KCCQ) and the physical component summary score of the short form survey 36 (SF-36). Additionally, the researchers considered the impact of programs on clinical outcomes such as heart failure-related hospitalisation and mortality.

Exercise-based cardiac rehabilitation an heart failure outcomes

A total 139 randomised controlled trials including 18,670 participants with a median age of 61.1 years (71.4% male) were analysed. The median duration of the exercise program was 12 weeks and median length of follow-up in studies was 16 weeks.

Only CB, HB and TE programs were associated with an increase in Vo2 peak compared to usual care and there were no statistically significant differences between these three modes of delivery.

The six minute walk distance was improved only by hybrid, CB and HB programs and again, there were no significant differences between the programs. Only HB programs improved the KCCQ and none of the delivery modes improved the SF-36 physical component summary score compared to usual care.

Heart failure-related hospitalisation (odds ratio, OR = 0.41, 95% CI 0.17 – 0.76) and mortality (OR = 0.42, 95% CI 0.16 – 0.90) were only reduced after CB programs.

The authors concluded that exercise-based cardiac rehabilitation programs appeared to improve functional capacity and clinical outcomes in those with heart failure. They added that since the different programs were comparably beneficial, the selection of a program should be tailored to the needs of the individual patient.

Citation
Tegegne TK et al. Effects of exercise-based cardiac rehabilitation delivery modes on exercise capacity and health-related quality of life in heart failure: a systematic review and network meta-analysis Open Heart 2022

Reduced sodium intake does not lower clinical events in heart failure patients

12th April 2022

A reduced sodium intake has no impact on clinical events in heart failure patients but does slightly improves QOL and disease functional class

A randomised trial by researchers from the Canadian VIGOUR Centre, University of Alberta, Canada showed that reduced sodium intake had no effect on clinical events including cardiovascular-related hospitalisations or mortality in ambulatory heart failure patients compared with usual care, but did have a small, but significant, positive effect on quality of life and improved disease functional class.

In patients with congestive heart failure, the reduced low cardiac output decreases the fullness of the arterial circulation initiates several internal mechanisms to increase vascular resistance and enhance sodium and water renal retention. In fact, in a study that examined factors associated with a worsening of heart failure, noncompliance with salt restriction, was a factor in over a fifth (22%) of cases.

As a result, dietary advice advocating a reduced sodium intake is arguably the most frequent self-care behaviour recommendation to patients with heart failure and is endorsed by all heart failure guidelines. Currently, the American Heart Association recommends a reduction of sodium intake to <2300 mg/d for general cardiovascular health promotion but notes how there are no trials to support this level of restriction in patients with heart failure.

Nevertheless, the beneficial effect of lowering sodium intake is not clear cut and some evidence suggests that a reduced sodium intake to less than 2g/day is unwarranted in mild heart failure. In contrast, other data shows that sodium restriction (< 2.5 g/day) was associated with a significantly higher risk of death or heart failure hospitalisation

With some uncertainties over whether a reduced sodium intake was beneficial to those with heart failure, for the present study, the Canadian team examined the effect of a dietary intervention of less than 1.5 g/day (1500 mg) of sodium compared to usual care, i.e., where no such recommendation was in place. Included patients had chronic heart failure (New York Heart Association functional class, 2 – 3) and had optimal medical therapy. Individuals were then randomised 1:1 to the low sodium diet or usual care. The low sodium intervention was supported by behavioural counselling and meal plans and menus for a period of 12 months. Dietary sodium intake was assessed using a 3-day food record at baseline and again after 6 and 12 months for both groups. The primary outcome of interest was a composite of cardiovascular-related hospitalisation, cardiovascular-related emergency department visits and all-cause mortality within 12 months of randomisation. In addition, to the clinical outcomes, quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, as well any changes in the New York Heart Association functional class.

Reduced sodium intake and cardiovascular outcomes

A total of 806 patients with median age of 67 years (66% male) were randomised to the low sodium arm (397) or usual care. At baseline the median sodium intake was 2286 mg/day for the low sodium group and 2119 mg/day for control arm. After 12 months, the sodium intake reduced by 4% in the control arm but by 28% in the low sodium group.

Within 12 months, the primary outcome occurred in 15% of those in the low sodium arm and 17% in the usual care group (adjusted hazard ratio, HR = 0.99, 95% CI 0.66 – 1.47, p = 0.95). All-cause mortality rates were also similar (6% vs 4%, low sodium vs usual care), giving a hazard ratio of 1.35 (95% CI 0.64 – 2.82, p = 0.43).

Whilst there were no significant differences in clinical outcomes, participants assigned to the low sodium group did see a small, but significant increase in the overall KCCQ summary score of 3.38 points (p = 0.011) and those in the low sodium group had a greater odds of improving by one NYHA functional class compared to the usual care group (odds ratio, OR = 0.59, 95% CI 0.40 – 0.86, p = 0.006).

The authors concluded that while a low sodium diet did not impact significantly on clinical outcomes, it did produce small but significant improvements in quality of life and NYHA functional class.

Citation
Ezekowitz JA et al. Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial Lancet 2022

Heart failure patients at increased risk of cancer and cancer-related mortality

28th January 2022

Heart failure (HF) patients have a higher risk of cancer and cancer-related mortality compared to matched-controls according to research by a team from the Cardiovascular Disease Unit, Genoa, Italy.

There is emerging evidence that the incidence of cancer is higher among those with cardiovascular disease and heart failure and this latter group frequently die from cancer. In fact, research has uncovered the increased risk of cancer among HF patients, persists beyond the first year after their HF diagnosis and that their prognosis is worse compared to non-heart failure patients with cancer. Despite this purported association, other work among 28,341 Physicians’ Health Study participants, has shown that HF is not associated with an increased risk of cancer among male physicians. It has also been suggested that while heart failure patients did have a slightly increased risk of various cancer subtypes, these increased risks were largely drive by comorbidities.

Given this potential uncertainty over the HF-cancer association, the Italian team attempted to provide greater clarity by undertaking a retrospective cohort study of healthcare records in Puglia, a region of southern Italy. They included patients aged 50 years and older, diagnosed with heart failure but without a history of cancer in the three years prior to their inclusion in the analysis. The team included a control group without HF who were matched on age and sex. The primary outcomes of the study were cancer incidence as well as mortality. In an effort to examine whether HF severity influenced the study outcomes, the researchers also explored patients use of doses in excess of 80 mg/day of furosemide and equivalents for longer than 30 days in the year before the index date.

Heart failure patients and cancer

A total of 104,020 HF patients with a mean age of 76 years were matched to an equal number of control patients. The researchers identified a total of 12,036 new diagnoses of cancer in HF patients and 7,045 in controls after a median follow-up period of 5 years. This gave an incidence cancer rate of 21.36 per 1000 person-years among those with HF and 12.42 in the control arm (Hazard ratio, HR = 1.76, 95% CI 1.71 – 1.81).

The cancer mortality rate was also higher among HF patients compared with controls (HR = 4.11, 95% CI 3.86 – 4.38). This difference was also seen among HF patients aged less than 70 years (HR = 1.66, 95% CI 1.58 – 1.75) and in those over 80 years of age (HR = 2.07).

High dose loop diuretics also showed an important effect with a higher cancer incidence (HR = 1.11, 95% CI 1.03 – 1.21) and cancer-related mortality (HR = 1.35).

The authors concluded that HF patients had both a higher incidence of cancer and cancer mortality than matched controls and speculated that given that the risk was elevated among those with high dose loop diuretics, it was possible that the overall cancer risks were potentially higher in those with decompensated, i.e., more severe HF.

Citation

Bertero E et al. Cancer Incidence and Mortality According to Pre-Existing Heart Failure in a Community-Based Cohort JACC CardioOncology 2022

Sodium-glucose cotransporter 2 inhibitors associated with cardiovascular benefits

26th January 2022

Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) reduce adverse cardiovascular outcomes according to a meta-analysis of clinical trials

SGLT2-Is can be considered as an effective class of drugs to improve cardiovascular morbidity and mortality. This was the conclusion of a meta-analysis by researchers from the Division of Cardiology, Southern Illinois University School of Medicine, US.

SGLT2-Is were developed and licensed as a class of drugs for the management of type 2 diabetes and one agent in particular, dapagliflozin, has been shown, as an add-on drug to conventional anti-diabetic drugs, to improve glycaemic control. However, with more widespread use of these drugs, it became apparent that there were potential cardioprotective effects, such as a reduction in the worsening of heart failure, irrespective of whether or not the patients were diabetic.

For the present study, the US researchers, set out to establish whether the magnitude of any cardiovascular benefit from SGLT2-Is were generalisable to patients of different ages and ethnicities. They searched for placebo-controlled randomised clinical trials in patients with existing atherosclerotic cardiovascular disease (ASCVD) or the presence of risk factors for ASCVD such as diabetes or heart failure. They set the primary outcome as cardiovascular death or hospitalisation for heart failure (HHF) and major cardiovascular events (MACE), HHF, cardiovascular death, acute myocardial infarction and all-cause mortality as secondary outcomes. They included gender, age (< 65 or > 65) and ethnicity as subgroups for separate analyses.

Findings

A total of 10 trials including 71,553 patients were analysed with 39,053 who received SGLT2-Is.

The primary outcome of cardiovascular death or HHF was reported in all trials and there were 6921 incidents, 8.1% occurring in those given SGLT2-Is and 11.6% in the placebo group. The use of SGLT2-Is was calculated to be associated with 33% reduced risk of the primary outcome (odds ratio, OR = 0.67, 95% CI 0.55 – 0.80, p < 0.01).

There was also a reduced risk of MACE in those taking SGLT2-Is (OR = 0.90, 95% CI 0.81 – 0.99, p = 0.03). However, there was no difference in the rate of acute myocardial infarction in those taking SGLT2-Is compared to placebo (OR = 0.95, 95% CI 0.87 – 1.03). Moreover, subgroup analysis favoured the use of SGLT2-Is in all groups compared and all-cause mortality was also lower in those taking SGLT2-Is (OR = 0.87, 95% CI 0.80 – 0.96, p = 0.04).

The authors concluded that the ‘cardiovascular outcomes of SGLT2-I therapy can be compared across all trials, and it demonstrates remarkable consistency of class benefit, despite the variations in populations enrolled.’

Citation

Bhattarai M et al. Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Patients With Type 2 Diabetes and Other Risk Factors for Cardiovascular Disease: A Meta-analysis. JAMA 2022

Sex-related heart failure mortality influenced by left ventricular ejection fraction

4th January 2022

Sex-related differences in mortality in patients with heart failure hospitalisations appear to be affected by the left ventricular ejection fraction according to researchers from the Cardiology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain.

Although the risk of heart failure (HF) is similar between men and women, there are some notable sex-related differences, with men being predisposed to HF with reduced ejection fraction and women with preserved ejection fraction. Although there is some evidence that women with HF live longer than men, they experience more psychological and physical disability. However, much of the available data is derived from patients with stable HF and what is less clear, is if there are any sex-related prognostic differences among patients hospitalised following decompensated heart failure.

For the present study, the Spanish team retrospectively examined gender differences in mortality across the left ventricular ejection fraction spectrum in a cohort of patients after a hospitalisation for acute HF. The researchers used a multi-centre prospective registry of those hospitalised and collected demographics, medical history, laboratory and echocardiographic parameters and followed patients over a 6-month period. The primary study endpoints were all-cause, cardiovascular and HF-related mortality. Cardiovascular death was considered secondary to a worsening of HF, acute myocardial infarction, stroke or transient ischaemic attack, whereas HF-related deaths were considered secondary to a worsening of the HF or a sudden cardiac death.

Findings

A total of 4812 patients with a mean age of 74.2 years (46.6% women) were included in the analysis. The proportion of patients with a left ventricular ejection fraction (LVEF) of < 40%, 41 – 49% and > 50% was 31.5%, 14.3% and 54.2% respectively. Women were generally older with a mean age of 76.8 years compared to 71.9 years for men and had a higher preserved ejection fraction (70.5% vs 39.9%, female vs male, p < 0.001).

After 6 months, 645 (13.4%) of the patients had died with mortality rates of 13.3% and 13.5% (women vs men, p = 0.82) and there were no significant sex-related differences in all-cause mortality. Moreover, LVEF was not an independent predictor of mortality (HR = 1.02, 95% CI 0.99 – 1.05, p = 0.13). Similarly, rates of cardiovascular mortality were not different between the sexes. However, there was a significant interaction between sex and levels of LVEF (p for interaction = 0.030) and women had a significantly lower risk of cardiovascular mortality at lower LVEF levels (< 25%). There were also no differences between the sexes in HF-related mortality although as with cardiovascular mortality, there were differences across the levels of LVEF and women had a reduced risk of HR-related death. For example, compared to men, women had a reduced risk of HF death at a LVEF of < 43% (HR = 0.77, 95% CI 0.59 – 0.99) In contrast, this risk of death in women became higher as the LVEF increased above 80%.

Commenting on these findings, the authors noted that while sex was not a determinant of 6 month all-cause mortality, women had a lower risk of cardiovascular and HR-related mortality where the LVEF was < 25% and < 43% but higher where the LVEF was > 80%. They concluded that further work is required to confirm these findings and to evaluate the potential negative implications of a supra-normal LVEF in women with a preserved ejection fraction.

Citation

Santas E et al. Sex-Related Differences in Mortality Following Admission for Acute Heart Failure Across the Left Ventricular Ejection Fraction Spectrum J Am Heart Assoc 2021

Aspirin use linked to increased risk of heart failure

29th November 2021

Aspirin use among patients both with and without cardiovascular disease is associated with an increased risk of incident heart failure

Aspirin use is associated with an more than a 20% increased risk of heart failure in those with and without cardiovascular disease according to the results of an analysis by researchers from the Research Unit Hypertension and Cardiovascular Epidemiology, University of Leuven, Belgium.

Heart failure (HF) is best described as a clinical syndrome and which is characterised by symptoms including breathlessness, ankle swelling and fatigue, due to structural and/or functional cardiac abnormality, leading to a reduced cardiac output and/or intra-cardiac pressures at rest or during stress. Furthermore, HF is associated with a associated with a hyper coagulable state and autopsy studies have found that acute coronary events are frequent in HF patients who die suddenly, highlighting the potential value of using anti-thrombotic therapy. Although low dose aspirin is no longer recommended for the primary prevention of cardiovascular disease, the role of anti-thrombotic therapy in heart failure is less clear with one study concluding that there was ‘no evidence that aspirin is effective or safe in patients with heart failure.’ In contrast, a 2014 study concluded that ‘low-dose aspirin therapy was associated with a significant reduction in mortality and morbidity risk’ in patients with heart failure.

With some uncertainty over the value of aspirin use in patients with HF, the Belgian researchers sought to gain a better understanding of the role and value of aspirin. They turned to the Heart ‘Omics’ in aGEing (HOMAGE) database, which contains patient-level data for over 30,000 individuals from 21 studies and developed models to examine the impact of aspirin using both a derivation and validation set. At baseline all participants were free of heart failure and at the time of entry into studies, aspirin use was recorded and patients dichotomised as either ‘users’ or ‘non-users’. Other data included in the subsequent analysis were demographics and relevant clinical information such as the presence of co-morbidities and any history of cardiovascular disease.

Findings

In the HOMAGE dataset, the study population included 30,827 individuals (19,257 in the derivation set) with a mean age of 66.8 years (33.9% women). Overall, 26.4% had a a history of coronary artery disease and the biggest co-morbidity was hypertension (85.8%).

After a median follow-up period of 5.3 years, 1330 patients experienced either fatal or non-fatal HF with an incident rate of 14.5% (95% CI 13.4 – 15.7%) in the aspirin use group versus 5.9% (95% CI 5.5 – 6.4%) in the ‘non-aspirin’ group. In the HOMAGE dataset, the fully adjusted hazard ratio for aspirin use in those with cardiovascular disease was 1.26 (95% CI 1.12 – 1.41, p < 0.001) and 1.23 (95% CI 1.06 – 1.41, p = 0.004) among those without cardiovascular disease.

Commenting on these findings, the authors concluded that aspirin use increased the risk of incident HF in patients with and without prior cardiovascular disease, adding that ‘our observations suggest that aspirin should be prescribed with caution in patients at risk of HF or having HF.’

Citation

Mujaj B et al. Aspirin use is associated with increased risk for incident heart failure: a patient‐level pooled analysis. ESC Heart Fail 2021