Publications by authors named "Mark C Petrie"

220 Publications

Response by Lee et al to Letter Regarding Article, "Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF)".

Circulation 2021 Jul 19;144(3):e40. Epub 2021 Jul 19.

Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.M.Y.L., J.J.V.M., P.S.J., M.C.P., N.S.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055067DOI Listing
July 2021

Efficacy of dapagliflozin in heart failure with reduced ejection fraction according to body mass index.

Eur J Heart Fail 2021 Jul 16. Epub 2021 Jul 16.

BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.

Background: In heart failure with reduced ejection fraction (HFrEF), there is an "obesity paradox", where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a SGLT2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF).

Methods And Results: BMI was examined using standard categories i.e. underweight (<18.5 kg/m ); normal weight (18.5-24.9 Kg/m ); overweight (25.0-29.9 Kg/m ); obesity class I (30.0-34.9 Kg/m ); class II (35.0-39.9 Kg/m ) and class III (≥40 Kg/m ). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal-weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% CI) for the primary outcome with obesity category 1, the lowest risk group, as reference was: under-/normal-weight 1.41 (1.16-1.71), overweight 1.18 (0.97-1.42), obesity class II/III 1.37 (1.10-1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI e.g., HR for primary outcome: under-/normal-weight 0.74 (0.58-0.94), overweight 0.81 (0.65-1.02), obesity class I 0.68 (0.50-0.92), obesity class II/III 0.71 (0.51-1.00); P for interaction=0.79. The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7-1.1) Kg (p<0.001).

Conclusion: We confirmed an "obesity survival paradox" in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied.

Clinical Trial Registration: ClinicalTrials.gov number NCT03036124 (https://clinicaltrials.gov/ct2/show/NCT03036124).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2308DOI Listing
July 2021

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction.

JAMA Cardiol 2021 Jun 23. Epub 2021 Jun 23.

British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.

Importance: Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied.

Objective: To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF.

Design, Setting, And Participants: A total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index.

Main Outcomes And Measures: The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis.

Results: Of 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%]).

Conclusions And Relevance: In this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2021.1825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223134PMC
June 2021

Inhibition of myocardial cathepsin-L release during reperfusion following myocardial infarction improves cardiac function and reduces infarct size.

Cardiovasc Res 2021 Jun 16. Epub 2021 Jun 16.

Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, UK.

Aims: Identifying novel mediators of lethal myocardial reperfusion injury that can be targeted during primary percutaneous coronary intervention (PPCI) is key to limiting the progression of patients with ST-elevated myocardial infarction (STEMI) to heart failure. Here we show through parallel clinical and integrative preclinical studies the significance of the protease cathepsin-L on cardiac function during reperfusion injury.

Methods And Results: We found that direct cardiac release of cathepsin-L in STEMI patients (n = 76) immediately post-PPCI leads to elevated serum cathepsin-L levels and that serum levels of cathepsin-L in the first 24 hour post-reperfusion are associated with reduced cardiac contractile function and increased infarct size. Preclinical studies, demonstrate that inhibition of cathepsin-L release following reperfusion injury with CAA0225 reduces infarct size and improves cardiac contractile function by limiting abnormal cardiomyocyte calcium handling and apoptosis.

Conclusion: Our findings suggest that cathepsin-L is a novel therapeutic target that could be exploited clinically to counteract the deleterious effects of acute reperfusion injury after an acute STEMI.

Translational Perspective: New therapeutic targets are urgently required to limit myocardial damage after reperfusion injury. We identified cardiac release of the protease cathepsin-L among patients following primary percutaneous coronary intervention (PPCI). Elevated serum levels of cathepsin-L were associated with reduced contractile function and increased infarct size at 24 hour and 6 months post-PPCI. Work conducted using animal models indicated that cardiac release of cathepsin-L mediated cardiac dysfunction following reperfusion injury. Specific inhibition of cathepsin-L prevented abnormal calcium handling, reduced infarct size and improved contractile function. These novel findings offer the prospect of targeting cathepsin-L-mediated cardiac dysfunction after PPCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvab204DOI Listing
June 2021

Sodium-glucose cotransporter 2 inhibitors as a treatment for heart failure.

Heart 2021 Jun 14. Epub 2021 Jun 14.

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-318658DOI Listing
June 2021

Heart Failure Hospitalization in Adults Receiving Hemodialysis and the Effect of Intravenous Iron Therapy.

JACC Heart Fail 2021 Jul 9;9(7):518-527. Epub 2021 Jun 9.

Department of Renal Medicine, King's College Hospital, London, United Kingdom.

Objectives: This study sought to examine the effect of intravenous iron on heart failure events in hemodialysis patients.

Background: Heart failure is a common and deadly complication in patients receiving hemodialysis and is difficult to diagnose and treat.

Methods: The study analyzed heart failure events in the PIVOTAL (Proactive IV Iron Therapy in Hemodialysis Patients) trial, which compared intravenous iron administered proactively in a high-dose regimen with a low-dose regimen administered reactively. Heart failure hospitalization was an adjudicated outcome, a component of the primary composite outcome, and a prespecified secondary endpoint in the trial.

Results: Overall, 2,141 participants were followed for a median of 2.1 years. A first fatal or nonfatal heart failure event occurred in 51 (4.7%) of 1,093 patients in the high-dose iron group and in 70 (6.7%) of 1,048 patients in the low-dose group (HR: 0.66; 95% CI: 0.46-0.94; P = 0.023). There was a total of 63 heart failure events (including first and recurrent events) in the high-dose iron group and 98 in the low-dose group, giving a rate ratio of 0.59 (95% CI: 0.40-0.87; P = 0.0084). Most patients presented with pulmonary edema and were mainly treated by mechanical removal of fluid. History of heart failure and diabetes were independent predictors of a heart failure event.

Conclusions: Compared with a lower-dose regimen, high-dose intravenous iron decreased the occurrence of first and recurrent heart failure events in patients undergoing hemodialysis, with large relative and absolute risk reductions. (UK Multicentre Open-label Randomised Controlled Trial Of IV Iron Therapy In Incident Haemodialysis Patients; 2013-002267-25).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchf.2021.04.005DOI Listing
July 2021

Hypertensive disorders in women with peripartum cardiomyopathy: insights from the ESC Peripartum Cardiomyopathy Registry.

Eur J Heart Fail 2021 Jun 11. Epub 2021 Jun 11.

Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.

Aims: Hypertensive disorders occur in women with peripartum cardiomyopathy (PPCM). How often hypertensive disorders co-exist, and to what extent they impact outcomes, is less clear. We describe differences in phenotype and outcomes in women with PPCM with and without hypertensive disorders during pregnancy.

Methods: The European Society of Cardiology PPCM Registry enrolled women with PPCM from 2012-2018. Three groups were examined: 1) women without hypertension ('PPCM-noHTN'); 2) women with hypertension but without pre-eclampsia ('PPCM-HTN'); 3) women with pre-eclampsia ('PPCM-PE'). Maternal (6-month) and neonatal outcomes were compared.

Results: Of 735 women included, 452 (61.5%) had PPCM-noHTN, 99 (13.5%) had PPCM-HTN and 184 (25.0%) had PPCM-PE. Compared to women with PPCM-noHTN, women with PPCM-PE had more severe symptoms (NYHA IV in 44.4% and 29.9%, p<0.001), more frequent signs of heart failure (pulmonary rales in 70.7% and 55.4%, p=0.002), higher baseline LVEF (32.7% and 30.7%, p=0.005) and smaller left ventricular end diastolic diameter (57.4mm [±6.7] and 59.8mm [±8.1], p<0.001). There were no differences in the frequencies of death from any cause, re-hospitalization for any cause, stroke, or thromboembolic events. Compared to women with PPCM-noHTN, women with PPCM-PE had a greater likelihood of left ventricular recovery (LVEF≥50%) (adjusted OR 2.08 95% CI 1.21-3.57) and an adverse neonatal outcome (composite of termination, miscarriage, low birth weight or neonatal death) (adjusted OR 2.84 95% CI 1.66-4.87).

Conclusion: Differences exist in phenotype, recovery of cardiac function and neonatal outcomes according to hypertensive status in women with PPCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2264DOI Listing
June 2021

Impact of Percutaneous Coronary Intervention on Outcomes in Patients With Heart Failure: JACC State-of-the-Art Review.

J Am Coll Cardiol 2021 May;77(19):2432-2447

Department of Medicine, University of Mississippi, Jackson, Mississippi, USA. Electronic address:

Coronary artery disease (CAD) is highly prevalent in patients with heart failure (HF) and accounts for nearly two-thirds of cases. The use of percutaneous coronary intervention (PCI) in HF patients with CAD has markedly increased and has been suggested to be associated with improved outcomes in numerous observational studies. Randomized data comparing the impact of PCI with that of coronary artery bypass graft (CABG) or contemporary guideline-directed medical therapy alone on clinical outcomes and myocardial recovery in patients with HF are lacking. The purpose of this review is to describe the available evidence regarding the impact of PCI in acute HF (in the presence and absence of an acute coronary syndrome), chronic HF with reduced ejection fraction, and HF with preserved ejection fraction. Adequately-powered randomized clinical trials examining the outcomes with PCI in these distinct HF populations are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2021.03.310DOI Listing
May 2021

Effect of Neprilysin Inhibition on Left Ventricular Remodeling in Patients With Asymptomatic Left Ventricular Systolic Dysfunction Late After Myocardial Infarction.

Circulation 2021 Jul 13;144(3):199-209. Epub 2021 May 13.

Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (K.F.D., R.T.C., K.J.M.B., R.L.G., T.H., A.M.J., M.M.Y.L., G.R., P.W., P.S.J., M.C.P., J.J.V.M.), University of Glasgow, United Kingdom.

Background: Patients with left ventricular (LV) systolic dysfunction after myocardial infarction are at a high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system inhibition may result in greater attenuation of adverse LV remodeling as a result of increased levels of substrates for neprilysin with vasodilatory, antihypertrophic, antifibrotic, and sympatholytic effects.

Methods: We performed a prospective, multicenter, randomized, double-blind, active-comparator trial comparing sacubitril/valsartan 97/103 mg twice daily with valsartan 160 mg twice daily in patients ≥3 months after myocardial infarction with a LV ejection fraction ≤40% who were taking a renin angiotensin system inhibitor (equivalent dose of ramipril ≥2.5 mg twice daily) and a β-blocker unless contraindicated or intolerant. Patients in New York Heart Association class ≥II or with signs and symptoms of heart failure were excluded. The primary outcome was change from baseline to 52 weeks in LV end-systolic volume index measured using cardiac magnetic resonance imaging. Secondary outcomes included other magnetic resonance imaging measurements of LV remodeling, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin I, and a patient global assessment of change questionnaire.

Results: From July 2018 to June 2019, we randomized 93 patients with the following characteristics: mean age, 60.7±10.4 years; median time from myocardial infarction, 3.6 years (interquartile range, 1.2-7.2); mean LV ejection fraction, 36.8%±7.1%; and median NT-proBNP, 230 pg/mL (interquartile range, 124-404). Sacubitril/valsartan, compared with valsartan, did not significantly reduce LV end-systolic volume index; adjusted between-group difference, -1.9 mL/m (95% CI, -4.9 to 1.0); =0.19. There were no significant between-group differences in NT-proBNP, high-sensitivity cardiac troponin I, LV end-diastolic volume index, left atrial volume index, LV ejection fraction, LV mass index, or patient global assessment of change.

Conclusions: In patients with asymptomatic LV systolic dysfunction late after myocardial infarction, treatment with sacubitril/valsartan did not have a significant reverse remodeling effect compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03552575.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.121.054892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284373PMC
July 2021

Clonal haematopoiesis of indeterminate potential: intersections between inflammation, vascular disease and heart failure.

Clin Sci (Lond) 2021 Apr;135(7):991-1007

BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, U.K.

Ageing is a major risk factor for the development of cardiovascular disease (CVD) and cancer. Whilst the cumulative effect of exposure to conventional cardiovascular risk factors is important, recent evidence highlights clonal haematopoiesis of indeterminant potential (CHIP) as a further key risk factor. CHIP reflects the accumulation of somatic, potentially pro-leukaemic gene mutations within haematopoietic stem cells over time. The most common mutations associated with CHIP and CVD occur in genes that also play central roles in the regulation of inflammation. While CHIP carriers have a low risk of haematological malignant transformation (<1% per year), their relative risk of mortality is increased by 40% and this reflects an excess of cardiovascular events. Evidence linking CHIP, inflammation and atherosclerotic disease has recently become better defined. However, there is a paucity of information about the role of CHIP in the development and progression of heart failure, particularly heart failure with preserved ejection fraction (HFpEF). While systemic inflammation plays a role in the pathophysiology of both heart failure with reduced and preserved ejection fraction (EF), it may be of greater relevance in the pathophysiology of HFpEF, which is also strongly associated with ageing. This review describes CHIP and its pathogenetic links with ageing, inflammation and CVD, while providing insight into its putative role in HFpEF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/CS20200306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055963PMC
April 2021

Dapagliflozin and Recurrent Heart Failure Hospitalizations in Heart Failure With Reduced Ejection Fraction: An Analysis of DAPA-HF.

Circulation 2021 May 9;143(20):1962-1972. Epub 2021 Apr 9.

BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (P.S.J., K.F.D., M.C.P., J.J.V.M.).

Background: Patients with heart failure (HF) and reduced ejection fraction will experience multiple hospitalizations for heart failure during the course of their disease. We assessed the efficacy of dapagliflozin on reducing the rate of total (ie, first and repeat) hospitalizations for heart failure in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure).

Methods: The total number of HF hospitalizations and cardiovascular deaths was examined by using the proportional-rates approach of Lei-Wei-Yang-Ying and a joint frailty model for each of recurrent HF hospitalizations and time to cardiovascular death. Variables associated with the risk of recurrent hospitalizations were explored in a multivariable Lei-Wei-Yang-Ying model.

Results: Of 2371 participants randomly assigned to placebo, 318 experienced 469 hospitalizations for HF; of 2373 assigned to dapagliflozin, 230 patients experienced 340 admissions. In a multivariable model, factors associated with a higher risk of recurrent HF hospitalizations included higher heart rate, higher N-terminal pro-B-type natriuretic peptide, and New York Heart Association class. In the Lei-Wei-Yang-Ying model, the rate ratio for the effect of dapagliflozin on recurrent HF hospitalizations or cardiovascular death was 0.75 (95% CI, 0.65-0.88), =0.0002. In the joint frailty model, the rate ratio for total HF hospitalizations was 0.71 (95% CI, 0.61-0.82), <0.0001, whereas, for cardiovascular death, the hazard ratio was 0.81 (95% CI, 0.67-0.98), =0.0282.

Conclusions: Dapagliflozin reduced the risk of total (first and repeat) HF hospitalizations and cardiovascular death. Time-to-first event analysis underestimated the benefit of dapagliflozin in HF and reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.121.053659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126492PMC
May 2021

Efficacy and Safety of Dapagliflozin in Men and Women With Heart Failure With Reduced Ejection Fraction: A Prespecified Analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure Trial.

JAMA Cardiol 2021 Jun;6(6):678-689

Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Importance: Women may respond differently to certain treatments for heart failure (HF) with reduced ejection fraction (HFrEF) than men.

Objective: To investigate the efficacy and safety of dapagliflozin compared with placebo in men and women with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).

Design, Setting, And Participants: Prespecified subgroup analysis of a phase 3 randomized clinical trial conducted at 410 sites in 20 countries. Patients with New York Heart Association functional class II through IV with an ejection fraction of 40% or less and elevated N-terminal pro-B-type natriuretic peptide were eligible. Data were analyzed between June 2020 and January 2021.

Interventions: Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy.

Main Outcomes And Measures: The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death.

Results: A total of 4744 patients were randomized in DAPA-HF, of whom 1109 were women (23.4%). Compared with placebo, dapagliflozin reduced the risk of worsening HF events or cardiovascular death to a similar extent in both men and women (hazard ratios, 0.73 [95% CI, 0.63-0.85] and 0.79 [95% CI, 0.59-1.06], respectively; P for interaction = .67). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement in symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score of ≥5 points; men, 59% vs 50%; women, 57% vs 54%; P for interaction = .14) and decreased the proportion with worsening symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score decrease of ≥5 points; men, 25% vs 34%; women, 27% vs 31%; P for interaction = .15), irrespective of sex. Results were consistent for the Kansas City Cardiomyopathy Questionnaire clinical summary score and overall summary score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either men or women.

Conclusions And Relevance: Dapagliflozin reduced the risk of worsening HF, cardiovascular death, and all-cause death and improved symptoms, physical function, and health-related quality of life similarly in men and women with heart failure and reduced ejection fraction. In addition, dapagliflozin was safe and well-tolerated irrespective of sex.

Trial Registration: ClinicalTrials.gov Identifier: NCT03036124.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2021.0379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014207PMC
June 2021

Intravenous iron for heart failure with evidence of iron deficiency: a meta-analysis of randomised trials.

Clin Res Cardiol 2021 Mar 23. Epub 2021 Mar 23.

Robertson Centre for Biostatistics, University of Glasgow, Boyd Orr Building, University Avenue, Glasgow, UK.

Background: The recent AFFIRM-AHF trial assessing the effect of intravenous (IV) iron on outcomes in patients hospitalised with worsening heart failure who had iron deficiency (ID) narrowly missed its primary efficacy endpoint of recurrent hospitalisations for heart failure (HHF) or cardiovascular (CV) death. We conducted a meta-analysis to determine whether these results were consistent with previous trials.

Methods: We searched for randomised trials of patients with heart failure investigating the effect of IV iron vs placebo/control groups that reported HHF and CV mortality from 1st January 2000 to 5th December 2020. Seven trials were identified and included in this analysis. A fixed effect model was applied to assess the effects of IV iron on the composite of first HHF or CV mortality and individual components of these.

Results: Altogether, 2,166 patients were included (n = 1168 assigned to IV iron; n = 998 assigned to control). IV iron reduced the composite of HHF or CV mortality substantially [OR 0.73; (95% confidence interval 0.59-0.90); p = 0.003]. Outcomes were consistent for the pooled trials prior to AFFIRM-AHF. Whereas first HHF were reduced substantially [OR 0.67; (0.54-0.85); p = 0.0007], the effect on CV mortality was uncertain but appeared smaller [OR 0.89; (0.66-1.21); p = 0.47].

Conclusion: Administration of IV iron to patients with heart failure and ID reduces the risk of the composite outcome of first heart failure hospitalisation or cardiovascular mortality, but this outcome may be driven predominantly by an effect on HHF. At least three more substantial trials of intravenous iron are underway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00392-021-01837-8DOI Listing
March 2021

Invasive versus medically managed acute coronary syndromes with prior bypass (CABG-ACS): insights into the registry versus randomised trial populations.

Open Heart 2021 02;8(1)

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK

Background: Coronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS).

Methods: ACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated.

Results: Of 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558-841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year.

Conclusions: Compared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar.

Trial Registration Number: NCT01895751.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/openhrt-2020-001453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919592PMC
February 2021

Risk stratification and management of women with cardiomyopathy/heart failure planning pregnancy or presenting during/after pregnancy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy.

Eur J Heart Fail 2021 04 17;23(4):527-540. Epub 2021 Mar 17.

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

This position paper focusses on the pathophysiology, diagnosis and management of women diagnosed with a cardiomyopathy, or at risk of heart failure (HF), who are planning to conceive or present with (de novo or previously unknown) HF during or after pregnancy. This includes the heterogeneous group of heart muscle diseases such as hypertrophic, dilated, arrhythmogenic right ventricular and non-classified cardiomyopathies, left ventricular non-compaction, peripartum cardiomyopathy, Takotsubo syndrome, adult congenital heart disease with HF, and patients with right HF. Also, patients with a history of chemo-/radiotherapy for cancer or haematological malignancies need specific pre-, during and post-pregnancy assessment and counselling. We summarize the current knowledge about pathophysiological mechanisms, including gene mutations, clinical presentation, diagnosis, and medical and device management, as well as risk stratification. Women with a known diagnosis of a cardiomyopathy will often require continuation of drug therapy, which has the potential to exert negative effects on the foetus. This position paper assists in balancing benefits and detrimental effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2133DOI Listing
April 2021

Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial.

Eur J Heart Fail 2021 04 10;23(4):601-613. Epub 2021 Mar 10.

Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Aims: We examined the efficacy and safety of dapagliflozin, compared with placebo, according to aetiology in patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF).

Methods And Results: Aetiology was investigator-reported and categorized as ischaemic or non-ischaemic. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. A total of 4744 patients were randomized in DAPA-HF, of whom 2674 (56.4%) patients had an ischaemic aetiology. Participants with an ischaemic aetiology had a higher risk of cardiovascular mortality [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.13-1.63], but lower risk of HF hospitalization (HR 0.83, 95% CI 0.70-0.98) than non-ischaemic patients. Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in both patients with ischaemic and non-ischaemic aetiology (HR 0.77, 95% CI 0.65-0.92, and HR 0.71, 95% CI 0.58-0.87, respectively; P for interaction = 0.55). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Dapagliflozin, as compared with placebo, increased the proportion of patients with an improvement of Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) of ≥5 points (P for interaction = 0.32) and decreased the proportion with a deterioration in KCCQ-TSS of ≥5 points (P for interaction = 0.76), irrespective of aetiology. Study drug discontinuation and serious adverse events were similar according to treatment groups, irrespective of aetiology.

Conclusions: Dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, similarly in patients with ischaemic and non-ischaemic aetiology. In addition, dapagliflozin was safe and well-tolerated, irrespective of aetiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2124DOI Listing
April 2021

Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists: An Analysis of DAPA-HF.

JACC Heart Fail 2021 Apr 3;9(4):254-264. Epub 2021 Feb 3.

BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. Electronic address:

Objectives: The purpose of this study was to assess the efficacy and safety of dapagliflozin in patients taking or not taking an mineralocorticoid receptor antagonist (MRA) at baseline in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial.

Background: MRAs and sodium glucose co-transporter 2 inhibitors each have diuretic activity, lower blood pressure, and reduce glomerular filtration rate (GFR). Therefore, it is important to investigate the safety, as well as efficacy, of their combination.

Methods: A total of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) were randomized to placebo or dapagliflozin 10 mg daily. The efficacy of dapagliflozin on the primary composite outcome (cardiovascular death or episode of worsening heart failure) and its components was examined according to MRA use, as were predefined safety outcomes.

Results: A total of 3,370 patients (71%) were treated with an MRA and they were younger (65 vs. 69 years of age), less often from North America (9% vs. 26%), had worse New York Heart Association functional class (35% vs. 25% in class III/IV), lower left ventricular ejection fraction (30.7% vs. 31.9%) and systolic blood pressure (120.3 vs. 125.5 mm Hg), but higher estimated GFR (67.1 vs. 62.6 ml/min/1.73 m), than patients not taking an MRA. The benefit of dapagliflozin compared with placebo was similar in patients taking or not taking an MRA: hazard ratio: 0.74 (95% confidence interval [CI]: 0.63 to 0.87) versus 0.74 (95% CI: 0.57 to 0.95), respectively, for the primary endpoint (p value for interaction = 0.97); similar findings were observed for secondary endpoints. In both MRA subgroups, safety outcomes were similar in patients randomized to dapagliflozin or placebo.

Conclusions: Dapagliflozin was similarly efficacious and safe in patients with HFrEF taking or not taking an MRA, supporting the use of both drugs together. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchf.2020.11.009DOI Listing
April 2021

Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM-HF.

J Am Heart Assoc 2021 Feb 30;10(4):e019238. Epub 2021 Jan 30.

Division of Cardiology University of British Columbia Vancouver Canada.

Background Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. Methods and Results We examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Blocker-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non-COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; <0.001), with similar left ventricular ejection fraction (29.9% versus 29.4%), but higher NT-proBNP (N-terminal pro-B-type natriuretic peptide; median, 1741 pg/mL versus 1591 pg/mL; P=0.01), worse functional class (New York Heart Association III/IV 37% versus 23%; <0.001) and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (73 versus 81; <0.001), and more congestion and comorbidity. Medical therapy was similar in patients with and without COPD except for beta-blockade (87% versus 94%; <0.001) and diuretics (85% versus 80%; <0.001). After multivariable adjustment, COPD was associated with higher risks of heart failure hospitalization (hazard ratio [HR], 1.32; 95% CI, 1.13-1.54), and the composite of cardiovascular death or heart failure hospitalization (HR, 1.18; 95% CI, 1.05-1.34), but not cardiovascular death (HR, 1.10; 95% CI, 0.94-1.30), or all-cause mortality (HR, 1.14; 95% CI, 0.99-1.31). COPD was also associated with higher risk of all cardiovascular hospitalization (HR, 1.17; 95% CI, 1.05-1.31) and noncardiovascular hospitalization (HR, 1.45; 95% CI, 1.29-1.64). The benefit of sacubitril/valsartan over enalapril was consistent in patients with and without COPD for all end points. Conclusions In PARADIGM-HF, COPD was associated with lower use of beta-blockers and worse health status and was an independent predictor of cardiovascular and noncardiovascular hospitalization. Sacubitril/valsartan was beneficial in this high-risk subgroup. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01035255.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.019238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955331PMC
February 2021

Sodium-glucose co-transporter 2 inhibitors-the first successful treatment for heart failure with preserved ejection fraction?

Eur J Heart Fail 2021 Jan 27. Epub 2021 Jan 27.

British Heart Foundation Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2108DOI Listing
January 2021

Electrocardiographic features and their echocardiographic correlates in peripartum cardiomyopathy: results from the ESC EORP PPCM registry.

ESC Heart Fail 2021 04 16;8(2):879-889. Epub 2021 Jan 16.

Division of Cardiology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Aims: In peripartum cardiomyopathy (PPCM), electrocardiography (ECG) and its relationship to echocardiography have not yet been investigated in large multi-centre and multi-ethnic studies. We aimed to identify ECG abnormalities associated with PPCM, including regional and ethnic differences, and their correlation with echocardiographic features.

Methods And Results: We studied 411 patients from the EURObservational PPCM registry. Baseline demographic, clinical, and echocardiographic data were collected. ECGs were analysed for rate, rhythm, QRS width and morphology, and QTc interval. The median age was 31 [interquartile range (IQR) 26-35] years. The ECG was abnormal in > 95% of PPCM patients. Sinus tachycardia (heart rate > 100 b.p.m.) was common (51%), but atrial fibrillation was rare (2.27%). Median QRS width was 82 ms [IQR 80-97]. Left bundle branch block (LBBB) was reported in 9.30%. Left ventricular (LV) hypertrophy (LVH), as per ECG criteria, was more prevalent amongst Africans (59.62%) and Asians (23.17%) than Caucasians (7.63%, P < 0.001) but did not correlate with LVH on echocardiography. Median LV end-diastolic diameter (LVEDD) was 60 mm [IQR 55-65] and LV ejection fraction (LVEF) 32.5% [IQR 25-39], with no significant regional or ethnic differences. Sinus tachycardia was associated with an LVEF < 35% (OR 1.85 [95% CI 1.20-2.85], P = 0.006). ECG features that predicted an LVEDD > 55 mm included a QRS complex > 120 ms (OR 11.32 [95% CI 1.52-84.84], P = 0.018), LBBB (OR 4.35 [95% CI 1.30-14.53], P = 0.017), and LVH (OR 2.03 [95% CI 1.13-3.64], P = 0.017).

Conclusions: PPCM patients often have ECG abnormalities. Sinus tachycardia predicted poor systolic function, whereas wide QRS, LBBB, and LVH were associated with LV dilatation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006717PMC
April 2021

Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial.

Heart 2021 Jan 12. Epub 2021 Jan 12.

Department of Cardiology, Golden Jubilee National Hospital, Glasgow, UK

Objectives: Persistently impaired culprit artery flow (
Methods: In T-TIME (trial of low-dose adjunctive alTeplase during primary PCI), patients ≤6 hours from onset of ST-elevation myocardial infarction (STEMI) were randomised to placebo, alteplase 10 mg or alteplase 20 mg, administered by infusion into the culprit artery, pre-stenting. In this prespecified, secondary analysis, coronary flow was assessed angiographically at the point immediately before drug administration. Microvascular obstruction, myocardial haemorrhage and infarct size were assessed by cardiovascular magnetic resonance (CMR) at 2-7 days and 3 months.

Results: TIMI flow was assessed after first treatment (balloon angioplasty/aspiration thrombectomy), immediately pre-drug administration, in 421 participants (mean age 61±10 years, 85% male) and was 3, 2 or 1 in 267, 134 and 19 participants respectively. In patients with TIMI flow ≤2 pre-drug, there was higher incidence of microvascular obstruction with alteplase (alteplase 20 mg (53.1%) and 10 mg (59.5%) combined versus placebo (34.1%); OR=2.47 (95% CI 1.16 to 5.22, p=0.018) interaction p=0.005) and higher incidence of myocardial haemorrhage (alteplase 20 mg (53.1%) and 10 mg (57.9%) combined vs placebo (27.5%); OR=3.26 (95% CI 1.44 to 7.36, p=0.004) interaction p=0.001). These effects were not observed in participants with TIMI 3 flow pre-drug. There were no interactions between TIMI flow pre-drug, alteplase and 3-month CMR findings.

Conclusion: In patients with impaired culprit artery flow (
Trial Registration Number: NCT02257294.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-317828DOI Listing
January 2021

Coronary revascularisation in patients with ischaemic cardiomyopathy.

Heart 2021 Apr 12;107(8):612-618. Epub 2021 Jan 12.

Cardiovascular Division, King's College London, London, UK

Heart failure resulting from ischaemic heart disease is associated with a poor prognosis despite optimal medical treatment. Despite this, patients with ischaemic cardiomyopathy have been largely excluded from randomised trials of revascularisation in stable coronary artery disease. Revascularisation has multiple potential mechanisms of benefit, including the reversal of myocardial hibernation, suppression of ventricular arrhythmias and prevention of spontaneous myocardial infarction. Coronary artery bypass grafting is considered the first-line mode of revascularisation in these patients; however, evidence from the Surgical Treatment of Ischaemic Heart Failure (STICH) trial showed a reduction in mortality, though this only became apparent with extended follow-up due to an excess of early adverse events in the surgical arm. There is currently no randomised controlled trial evidence for percutaneous coronary intervention in patients with ischaemic cardiomyopathy; however, the REVIVED-BCIS2 trial has recently completed recruitment and will address this gap in the evidence. Future directions include (1) clinical trials of revascularisation in patients hospitalised with heart failure, (2) defining the role of viability and ischaemia testing in heart failure, (3) studies to enhance the understanding of the mechanistic effects of revascularisation and (4) generating models to refine pre- and post-revascularisation risk prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-316856DOI Listing
April 2021

Renin-angiotensin-aldosterone inhibitors and COVID-19: nearing the end of a media-fuelled controversy.

Eur J Heart Fail 2021 03 25;23(3):486-488. Epub 2021 Jan 25.

Cardiology and Cardiac Catheterization Laboratory, ASST Spedali Civili and Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013611PMC
March 2021

Cardiotoxic effects of angiogenesis inhibitors.

Clin Sci (Lond) 2021 01;135(1):71-100

BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, United Kingdom, G12 8TA.

The development of new therapies for cancer has led to dramatic improvements in survivorship. Angiogenesis inhibitors represent one such advancement, revolutionising treatment for a wide range of malignancies. However, these drugs are associated with cardiovascular toxicities which can impact optimal cancer treatment in the short-term and may lead to increased morbidity and mortality in the longer term. Vascular endothelial growth factor inhibitors (VEGFIs) are associated with hypertension, left ventricular systolic dysfunction (LVSD) and heart failure as well as arterial and venous thromboembolism, QTc interval prolongation and arrhythmia. The mechanisms behind the development of VEGFI-associated LVSD and heart failure likely involve the combination of a number of myocardial insults. These include direct myocardial effects, as well as secondary toxicity via coronary or peripheral vascular damage. Cardiac toxicity may result from the 'on-target' effects of VEGF inhibition or 'off-target' effects resulting from inhibition of other tyrosine kinases. Similar mechanisms may be involved in the development of VEGFI-associated right ventricular (RV) dysfunction. Some VEGFIs can be associated with QTc interval prolongation and an increased risk of ventricular and atrial arrhythmia. Further pre-clinical and clinical studies and trials are needed to better understand the impact of VEGFI on the cardiovascular system. Once mechanisms are elucidated, therapies can be investigated in clinical trials and surveillance strategies for identifying VEGFI-associated cardiovascular complications can be developed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/CS20200305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812690PMC
January 2021

Effects of dapagliflozin in heart failure with reduced ejection fraction and chronic obstructive pulmonary disease: an analysis of DAPA-HF.

Eur J Heart Fail 2021 04 18;23(4):632-643. Epub 2021 Jan 18.

BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.

Aims: Chronic obstructive pulmonary disease (COPD) is an important comorbidity in heart failure (HF) with reduced ejection fraction (HFrEF), associated with worse outcomes and often suboptimal treatment because of under-prescription of beta-blockers. Consequently, additional effective therapies are especially relevant in patients with COPD. The aim of this study was to examine outcomes related to COPD in a post hoc analysis of the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial.

Methods And Results: We examined whether the effects of dapagliflozin in DAPA-HF were modified by COPD status. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. Overall, 585 (12.3%) of the 4744 patients randomized had a history of COPD. Patients with COPD were more likely to be older men with a history of smoking, worse renal function, and higher baseline N-terminal pro B-type natriuretic peptide, and less likely to be treated with a beta-blocker or mineralocorticoid receptor antagonist. The incidence of the primary outcome was higher in patients with COPD than in those without [18.9 (95% confidence interval 16.0-22.2) vs. 13.0 (12.1-14.0) per 100 person-years; hazard ratio (HR) for COPD vs. no COPD 1.44 (1.21-1.72); P < 0.001]. The effect of dapagliflozin, compared with placebo, on the primary outcome, was consistent in patients with [HR 0.67 (95% confidence interval 0.48-0.93)] and without COPD [0.76 (0.65-0.87); interaction P-value 0.47].

Conclusions: In DAPA-HF, one in eight patients with HFrEF had concomitant COPD. Participants with COPD had a higher risk of the primary outcome. The benefit of dapagliflozin on all pre-specified outcomes was consistent in patients with and without COPD.

Clinical Trial Registration: ClinicalTrials.gov ID NCT03036124.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247863PMC
April 2021

EMPEROR-REDUCED reigns while EMPERIAL whimpers.

Eur Heart J 2021 02;42(6):711-714

BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehaa965DOI Listing
February 2021

Renin-angiotensin system blockers, risk of SARS-CoV-2 infection and outcomes fromCoViD-19: systematic review and meta-analysis.

Eur Heart J Cardiovasc Pharmacother 2020 Dec 18. Epub 2020 Dec 18.

British Heart Foundation Cardiovascular Research Centre, University of Glasgow.

Aims: This meta-analysis provides summary odds ratio (OR) estimates for associations between treatment with (vs. without) renin-angiotensin system (RAS) blockers and risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and coronavirus disease 2019 (CoViD-19) severity (including case-fatality) in patients with hypertension, and in all patients (irrespective of hypertension).

Methods And Results: PubMed, EMBASE, Web of Science, Google Scholar, medRxiv and SSRN were searched (May 02, 2020 to August 12, 2020) for non-randomised observational CoViD-19 studies. Event/patient numbers were extracted, comparing ACE inhibitor/ARB treatment (and each separately), to treatment with neither drug, for the outcomes: (a) Likelihood of SARS-CoV-2 infection; (b) CoViD-19 severity (including hospitalisation, Intensive Therapy Unit (ITU), ventilation); (c) Case-fatality. Risk of bias was assessed (ROBINS-I). Random-effects meta-analysis estimates were pooled. Eighty six studies including 459,755 patients (103,317 with hypertension), were analysed. In patients with hypertension, ACE inhibitor or ARB treatment was not associated with a greater likelihood of SARS-CoV-2 infection in 60,141 patients (OR 1.06, 95% CI 0.99-1.14), hospitalisation in 5,925 patients (OR 0.90, 0.62-1.31), ITU in 7,218 patients (OR 1.06, 0.73-1.56), ventilation (or ITU/ventilation/death) in 13,163 patients (OR 0.91, 0.72-1.15) or case-fatality in 18,735 patients with 2,893 deaths (OR 0.75, 0.61-0.92).

Conclusion: ACE inhibitors and ARBs appear safe in the context of SARS-CoV-2 infection and should not be discontinued. PROSPERO registration number: CRD42020186996.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjcvp/pvaa138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799280PMC
December 2020

Rationale and methods of a randomized trial evaluating the effect of neprilysin inhibition on left ventricular remodelling.

ESC Heart Fail 2021 02 10;8(1):129-138. Epub 2020 Dec 10.

Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK.

Aims: In patients at high risk of heart failure following myocardial infarction (MI) as a result of residual left ventricular systolic dysfunction (LVSD), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan may result in a greater attenuation of adverse left ventricular (LV) remodelling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti-hypertrophic, anti-fibrotic, and sympatholytic effects.

Methods: We designed a randomized, double-blinded, active-comparator trial to examine the effect of sacubitril/valsartan to the current standard of care in reducing adverse LV remodelling in patients with asymptomatic LVSD following MI. Eligible patients were ≥3 months following MI, had an LV ejection fraction ≤40% as measured by echocardiography, were New York Heart Association functional classification I, tolerant of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at equivalent dose of ramipril 2.5 mg twice daily or greater, and taking a beta-blocker unless contraindicated or intolerant. Patients were randomized to sacubitril/valsartan (target dose 97/103 mg twice daily) or valsartan (target dose 160 mg twice daily). The primary endpoint will be change in LV end-systolic volume indexed for body surface area measured using cardiac magnetic resonance imaging over 52 weeks from randomization. Secondary endpoints include other magnetic resonance imaging-based metrics of LV remodelling, biomarkers associated with LV remodelling and neurohumoral activation, and change in patient well-being assessed using a patient global assessment questionnaire.

Conclusions: This trial will investigate the effect of neprilysin inhibition on LV remodelling and the neurohumoral actions of sacubitril/valsartan in patients with asymptomatic LVSD following MI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835504PMC
February 2021

Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF).

Circulation 2021 Feb 13;143(6):516-525. Epub 2020 Nov 13.

Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (M.M.Y.L., K.J.M.B., K.M., G.R., R.T.C., C.B., L.C., K.F.D., N.N.L., C.J.P., J.R.P., P.W., A.R., P.B.M., J.J.V.M., P.S.J., M.C.P., N.S.), University of Glasgow, United Kingdom.

Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain.

Methods: We designed a multicenter, randomized, double-blind, placebo-controlled trial (the SUGAR-DM-HF trial [Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus, or Prediabetes, and Heart Failure]) to investigate the cardiac effects of empagliflozin in patients in New York Heart Association functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomly assigned 1:1 to empagliflozin 10 mg once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The coprimary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area and LV global longitudinal strain both measured using cardiovascular magnetic resonance. Secondary efficacy outcomes included other cardiovascular magnetic resonance measures (LV end-diastolic volume index, LV ejection fraction), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, B-lines on lung ultrasound, and biomarkers (including N-terminal pro-B-type natriuretic peptide).

Results: From April 2018 to August 2019, 105 patients were randomly assigned: mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LV ejection fraction 32.5% (9.8%), and 81 (77.1%) New York Heart Association II and 24 (22.9%) New York Heart Association III. Patients received standard treatment for HFrEF. In comparison with placebo, empagliflozin reduced LV end-systolic volume index by 6.0 (95% CI, -10.8 to -1.2) mL/m (=0.015). There was no difference in LV global longitudinal strain. Empagliflozin reduced LV end-diastolic volume index by 8.2 (95% CI, -13.7 to -2.6) mL/m (=0.0042) and reduced N-terminal pro-B-type natriuretic peptide by 28% (2%-47%), =0.038. There were no between-group differences in other cardiovascular magnetic resonance measures, diuretic intensification, Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, or B-lines.

Conclusions: The sodium-glucose cotransporter 2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which sodium-glucose cotransporter 2 inhibitors reduce heart failure hospitalization and mortality in HFrEF. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03485092.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864599PMC
February 2021