Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19 : nationwide self-controlled cases series and matched cohort study

Y OBJECTIVE To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19. DESIGN Self-controlled case series and matched cohort study. SETTING National registries in Sweden. PARTICIPANTS 1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants. MAIN OUTCOMES MEASURES Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event). RESULTS Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding. CONCLUSIONS The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.Peer reviewe

Eligibility of sacubitril–valsartan in a real-world heart failure population : a community-based single-centre study

Aims: This study aims to investigate the eligibility of the Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor (ARNI) with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM‐HF) study to a real‐world heart failure population. Methods and results: Medical records of all heart failure patients living within the catchment area of Umeå University Hospital were reviewed. This district consists of around 150 000 people. Out of 2029 patients with a diagnosis of heart failure, 1924 (95%) had at least one echocardiography performed, and 401 patients had an ejection fraction of ≤35% at their latest examination. The major PARADIGM‐HF criteria were applied, and 95 patients fulfilled all enrolment criteria and thus were eligible for sacubitril–valsartan. This corresponds to 5% of the overall heart failure population and 24% of the population with ejection fraction ≤ 35%. The eligible patients were significantly older (73.2 ± 10.3 vs. 63.8 ± 11.5 years), had higher blood pressure (128 ± 17 vs. 122 ± 15 mmHg), had higher heart rate (77 ± 17 vs. 72 ± 12 b.p.m.), and had more atrial fibrillation (51.6% vs. 36.2%) than did the PARADIGM‐HF population. Conclusions: Only 24% of our real‐world heart failure and reduced ejection fraction population was eligible for sacubitril–valsartan, and the real‐world heart failure and reduced ejection fraction patients were significantly older than the PARADIGM‐HF population. The lack of data on a majority of the patients that we see in clinical practice is a real problem, and we are limited to extrapolation of results on a slightly different population. This is difficult to address, but perhaps registry‐based randomized clinical trials will help to solve this issue

Safety and Tolerability of Initiating Maximum-Dose Sacubitril-Valsartan in Patients on Target Dose Renin-Angiotensin System Inhibitors

Aim. Sacubitril-valsartan has proven beneficial in heart failure with reduced ejection fraction. Guidelines recommend initiating half-dose sacubitril-valsartan before up-titration even to patients already on target dose angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). To reduce the number of titration steps needed in order to simplify for the patient as well as the clinic, we aimed to investigate the safety and tolerability of switching patients on target dose ACE inhibitors or ARBs directly to maximum-dose sacubitril-valsartan. Methods. This prospective cohort study was conducted between April 2016 and November 2017. A total of 66 patients with heart failure and reduced ejection fraction already on guideline-recommended target dose ACE inhibitors or ARBs (equivalent to enalapril 10 mg twice daily) were switched to maximum-dose sacubitril-valsartan (200 mg twice daily). The patients were followed for twelve months. Results. Patients had a mean age of 72 +/- 10 years, mean systolic blood pressure of 121 +/- 17 mmHg, and 92% were male. At 12-month follow-up, nine patients (14%) had discontinued sacubitril-valsartan, four patients (6%) had a dose reduction, and 17 patients (26%) had developed symptomatic hypotension. No angioedema occurred within the 12-month follow-up and there were no hospitalizations or emergency room visits within the first 14 days. Conclusions. Switching directly from target dose ACE inhibitors or ARBs to maximum-dose sacubitril-valsartan was safe and generally well tolerated

Right ventricular systolic dysfunction and remodelling in Nigerians with peripartum cardiomyopathy : a longitudinal study

BACKGROUND: The literature on right ventricular systolic dysfunction (RVSD) in peripartum cardiomyopathy (PPCM) patients is scanty, and it appears that RV reverse remodelling in PPCM has not been previously described. This study thus aimed to assess RVSD and remodelling in a cohort of PPCM patients in Kano, Nigeria. METHODS: A longitudinal study carried out in 3 referral hospitals in Kano, Nigeria. Consecutive PPCM patients who had satisfied the inclusion criteria were recruited and followed up for 12 months. RVSD was defined as the presence of either tricuspid annular plane systolic excursion (TAPSE) <16 mm or peak systolic wave (S') tissue Doppler velocity of RV free wall <10 cm/s. For the purpose of this study, recovery of RV systolic function was defined as an improvement of reduced TAPSE to ≥16 mm or S' to ≥10 cm/s, without falling to reduced levels again, during follow-up. RESULTS: A total of 45 patients were recruited over 6 months with a mean age of 26.6 ± 7.0 years. RV systolic function recovery occurred in a total of 8 patients (8/45; 17.8 %), of whom 6 (75.0 %) recovered in 6 months after diagnosis. The prevalence of RVSD fell from 71.1 % at baseline to 36.4 % at 6 months (p = 0.007) and 18.8 % at 1 year (p = 0.0008 vs baseline; p = 0.41 vs 6 month). Patients with RVSD had higher serum creatinine, and TAPSE accounted for 19.2 % (p = 0.008) of the variability of serum creatinine at 6 months. Although 83.3 % of the deceased had RVSD, it didn't predict mortality in the regression models (p > 0.05). CONCLUSION: RVSD and reverse remodelling were common in Nigerians with PPCM, in whom the first 6 months after diagnosis seem to be critical for RV recovery and survival

Eligibility of Dapagliflozin and Empagliflozin in a Real-World Heart Failure Population

Aims: This study is aimed at investigating the eligibility in a real-world heart failure population for the DAPA-HF (testing dapagliflozin) and EMPEROR-reduced (testing empagliflozin) trials, comparing the eligible real-world patients to trial participants and to characterize the noneligible patients. Methods: Medical records of all heart failure patients who had a diagnosis of heart failure from the Heart Centre or Department of Internal Medicine at Umea University Hospital were reviewed. Results: 2433 of the hospital's uptake population of 150 000 had a diagnosis of heart failure. 681 patients had left ventricle ejection fraction <= 40%, and of these 352 (52%) and 268 (39%) patients met eligibility criteria for DAPA-HF and EMPEROR-reduced, respectively. Comparing eligible patients in our population with the DAPA-HF- and EMPEROR-reduced trial populations, we found that eligible real-world patients were older (79.0 vs. 66.2 years and 80.3 vs. 67.2 years, respectively), had worse renal function (eGFR 54.4 vs. 66.0 ml/min/1.73m(2) and 49.5 vs. 61.8 ml/min/1.73m(2), respectively), higher prevalence of atrial fibrillation (56.0% vs. 36.1% and 53.0% vs. 35.6%, respectively), and lower prevalence of diabetes mellitus (21.0% vs. 41.8% and 26.1% vs. 49.8%, respectively). The main reasons for ineligibility were low NT-proBNP or low eGFR. Noneligible patients differed according to reason for ineligibility, where patients with low NT-proBNP were generally younger and healthier, and patients with low eGFR were older and had more comorbidities. Conclusions: 39-52% of patients with heart failure and reduced ejection fraction in this real-world heart failure population were eligible for SGLT2-inhibitor treatment, corresponding to 11-14% of all heart failure patients. Compared to trial participants, eligible real-world patients were significantly older with worse renal function, more atrial fibrillation, and less diabetes mellitus. Trial entry criteria exclude comparatively young and healthy patients, as well as comparatively old patients with more comorbid conditions

Differences in medical treatment and clinical characteristics between men and women with heart failure : a single-centre multivariable analysis

Purpose: The aims of this study were to examine sex differences in a heart failure population with regards to treatment and patient characteristics and to investigate the impact of sex on achieved doses of heart failure medications. Methods and results: A total of 1924 patients with heart failure in a regional hospital were analysed, 622 patients had ejection fraction <= 40% of which 30% were women. In patients with reduced ejection fraction, women were older (79 +/- 11 vs. 74 +/- 12 years, P < 0.001), had lower body weight (70 +/- 17 vs. 86 +/- 18 kg, P < 0.001), lower estimated glomerular filtration rate (eGFR) (49 +/- 24 vs. 71 +/- 30 ml/min, P < 0.001) and received lower doses of heart failure medications than men. Multivariable linear regression on patients with reduced ejection fraction showed that sex was not associated with achieved dose of any heart failure medication. For angiotensin-converting enzyme inhibitors and angiotensin receptor blockers associated factors were eGFR, systolic blood pressure, age, ejection fraction, and heart rate. For beta-blockers associated factors were body weight, atrial fibrillation and age. For mineralocorticoid receptor antagonists associated factors were eGFR, serum potassium, age, systolic blood pressure, ejection fraction and heart rate. Conclusion: Women with heart failure and reduced ejection fraction were prescribed lower doses of heart failure medications, were older, had worse renal function, and lower body weight than men. Sex was not independently associated with achieved doses of heart failure medications, instead age, renal function and body weight explained the differences in treatment

Heart Failure: The Dilemma of the 40-50% Ejection Fraction Range

The common pathophysiology contributing to fluid retention and dyspnoea in heart failure is a non-compliant and stiff myocardium with raised left ventricular end-diastolic pressure. With the rapid development of newer imaging technologies, particularly echocardiography, our understanding of the syndrome of heart failure has significantly changed. The most important imaging sign in the early eighties was reduced ejection fraction (HFrEF), with low values being used as an explanation for the development of signs and symptoms. In the early 2000s, similar Doppler echocardiographic signs became frequently recognised in patients with heart failure symptoms and signs who proved to have a relatively maintained ejection fraction (EF) of >40%, hence the description of the syndrome of “diastolic heart failure”. This was later rephrased as heart failure with normal ejection fraction (HFnEF) and more recently as heart failure with preserved ejection fraction (HFpEF). Since then, HFpEF has attracted the interest of many cardiologists and scientists worldwide, searching for specific features and treatment options for the syndrome. As for the features, two important findings have now been established, the first showed that LV systolic function mainly at the subendocardial level was abnormal in HFpEF, particularly manifesting during stress/exercise when the increase in heart rate was not associated with a commensurate increase in stroke volume and a second observation of a significant impairment of left atrial function (i.e. myocardial strain) and emptying fraction associated with increased left atrial pressures and the potential development of atrial arrhythmia in HFpEF. Such atrial abnormalities have been shown to be commonly associated with cavity enlargement and poor compliance. The latter observation has similarly been reported in patients with reduced EF. Despite the above similarities in cardiac physiology between HFpEF and HFrEF, treatments of the two conditions differ markedly. When comparing HFrEF and HFpEF, we can easily see that some patients fall into the grey area on the EF spectrum with values fluctuating above and below 40%, suggesting that the substrate for the expected drug effect may differ, possibly explaining the lack of consistent response in these patients.. In addition, it should not be forgotten that most heart failure medications work on the circulation rather than the heart itself, hence the need for shared circulatory disturbances between the two conditions before we can reasonably expect identical treatment benefits when using the same medications in different clinical settings. Therefore, it is clear that classifying heart failure patients according to a single measure of LV function i.e. ejection fraction fails to help at least 50% of patients presenting with this syndrome. In contrast, aggregating such patients based on clear evidence for raised LA pressures, irrespective of EF, might show evidence for a more consistent response to vasodilators and conventional heart failure therapy, particularly those patients currently described as HFpEF