John J V Mcmurray

University of Glasgow | UofG · BHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences

Background and Aims The epidemiology of peripartum cardiomyopathy (PPCM) in Europe is poorly understood and data on long-term outcomes are lacking. A retrospective, observational, population-level study of validated cases of PPCM in Scotland from 1998 to 2017 was conducted. Methods Women hospitalized with presumed de novo left ventricular systolic...

Aims Subcutaneous (SC) furosemide has potential advantages over intravenous (IV) furosemide by enabling self-administration or administration by a lay caregiver, such as facilitating early-discharge, preventing hospitalizations and in palliative care. A high concentration, pH neutral furosemide formulation has been developed for SC administration v...

Introduction COVID‐19 may affect clinical risk in patients with heart failure. DELIVER began before and was conducted during the COVID‐19 pandemic. Objective We evaluated the association between COVID‐19 and outcomes among DELIVER participants. Methods Participants with chronic HFmrEF/HFpEF were randomized to dapagliflozin or placebo across 350 s...

Aims Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) are often treated with calcium channel blockers (CCBs) although the safety of CCBs in these patients is uncertain. To investigate the association between CCB and clinical outcomes in patients with HFmrEF/HFpEF; CCBs were exami...

Importance The US Food and Drug Administration expanded labeling of sacubitril-valsartan from the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (EF) to all patients with HF, noting the greatest benefits in those with below-normal EF. However, the upper bound of below normal is not clearly defined, and value de...

Background and aims Randomised controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with COVID-19. This meta-analysis provides estimates of the safety and efficacy of treatment with (versus without) RAS blockers from these trials. Methods PubMed, Web of Science, and ClinicalTrials.gov were searche...

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Aims: Although trials have proven the group-level effectiveness of various therapies for heart failure with reduced ejection fraction (HFrEF), important differences in absolute effectiveness exist between individuals. We developed and validated the LIFEtime-perspective for Heart Failure (LIFE-HF) model for the prediction of individual (lifetime) r...

Importance: Valsartan has shown promise in attenuating cardiac remodeling in patients with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Genetic testing can identify individuals at risk of HCM in a subclinical stage who could benefit from therapies that prevent disease progression. Objective: To explore the potential for valsartan to...

Background: In the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial, omecamtiv mecarbil, compared with placebo, reduced the risk of worsening heart failure (HF) events or cardiovascular death in patients with HF and reduced ejection fraction (HFrEF). The primary aim of this p...

Background and aims: There is little information on the incremental prognostic importance of frailty beyond conventional prognostic variables in heart failure (HF) populations from different country income levels. Methods: 3429 adults with HF (age 61±14 years, 33% women) from 27 high-, middle- and low-income countries were prospectively studied....

Background: Hospitalization is recognized as a sentinel event in the disease trajectory of patients with heart failure (HF), but not all patients experiencing clinical decompensation are ultimately hospitalized. Outpatient intensification of diuretics is common in response to symptoms of worsening HF, yet its prognostic and clinical relevance, spec...

Aims The Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial demonstrated the SGLT2i dapagliflozin to be beneficial in patients with symptomatic heart failure with improved ejection fraction (HFimpEF; those with prior LVEF ≤ 40% that had improved to >40% by enrollment). Whether th...

Open in new tabDownload slide Task Force structure and summary of clinical evidence of 2022 ESC/EACTS review of the 2018 guideline recommendations on the revascularization of left main coronary artery disease. CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; LM, left main; SYNTAX, Synergy Between Percutaneous Coronar...

In October 2021, the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) jointly agreed to establish a Task Force (TF) to review recommendations of the 2018 ESC/EACTS Guidelines on myocardial revascularization as they apply to patients with left main (LM) disease with low-to-intermediate SYNTAX scor...

Introduction: Chronic obstructive pulmonary disease (COPD) is common in heart failure (HF) with a mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and is associated with worse outcomes. Methods and results: In a prespecified analysis of DELIVER, we investigated the relationship between COPD status and outcomes, and the efficacy and s...

Background Studies demonstrated sex differences in outcomes following acute myocardial infarction, with women more likely to develop heart failure (HF). Sacubitril/valsartan has been shown to reduce cardiovascular death and HF hospitalizations in patients with HF with reduced ejection fraction. Methods and Results A total of 5661 patients (1363 wo...

Aim To estimate the lifetime benefit of a combination treatment of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors and mineralocorticoid‐receptor antagonists (MRA) in patients with type 2 diabetes and chronic kidney disease (CKD). Materials and Methods The cumulative effect of combination treatment was derived from trial‐level estimates of the...

Background: Heart failure (HF) readmission rates are low in some jurisdictions. However, international comparisons are lacking and could serve as a foundation for identifying regional patient management strategies that could be shared to improve outcomes. Objectives: This study sought to summarize 30-day and 1-year all-cause readmission and mort...

Open in new tabDownload slide Critical comparison between REVIVED-BCIS2 and STICH(ES) trials. NYHA, New York Heart Association; MI, myocardial infarction; LVEF, left ventricular ejection fraction; CAD, coronary artery disease; ACEi, angiotensin converting enzyme inhibitor; ARBs, angiotensin receptor blockers; ICD, implantable cardio-defibrillator;...

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP-1 RAs) reduce adverse cardiovascular outcomes in type 2 diabetes (T2D). However, the efficacy of combination therapy is unclear. Objectives: The aim of this study was to evaluate the effects of GLP-1 RAs on cardiovascular outcomes in patients with T2D...

Background: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level. Methods: Adults with CKD, with/without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m 2 and urinary albumi...

Background: Because clinical characteristics and prognosis vary by geographic region in patients with heart failure (HF), the response to treatment may also vary. A previous report suggested that the efficacy of sodium-glucose cotransporter-2 inhibitor efficacy in heart failure with reduced ejection fraction (HFrEF) may be modified by region. Obj...

Background: SGLT-2 inhibitors are guideline-recommended in the management of heart failure(HF). While these therapies can be initiated even in patients with comorbid CKD, some patients may face deterioration in kidney function over time. Objectives: To examine the safety and efficacy of continuing SGLT-2 inhibitors in HF when eGFR falls below th...

Background: It is unknown how the efficacy and safety of mineralocorticoid receptor antagonists vary according to duration of heart failure with reduced ejection fraction (HFrEF). Objectives: In this study, we sought to evaluate the safety and efficacy of eplerenone according to duration of HFrEF. Methods: In the EMPHASIS-HF trial, 3 patient g...

Background: Mortality from acute myocardial infarction (AMI) has declined, increasing the pool of survivors at risk of later development of heart failure (HF). However, coronary reperfusion limits infarct size and secondary prevention therapies have improved. In light of these competing influences, we examined long-term trends in the risk of HF ho...

Background: Adrenomedullin is a vasodilatory peptide with a role in microcirculatory and endothelial homeostasis. Adrenomedullin is a substrate for neprilysin and may therefore play a role in beneficial effects of sacubitril/valsartan (Sac/Val) treatment. Methods: Mid-regional pro-peptide of adrenomedullin (MR-proADM) was measured in 156 patient...

Background: Patients with heart failure (HF) often suffer from a range of comorbidities, which may affect their health status. Objectives: To assess the impact of different comorbidities on health status in patients with HF and reduced and preserved ejection fraction (HFrEF and HFpEF). Methods: Using individual patient data from HFrEF (ATMOSPH...

Background: Elevated circulating carbohydrate antigen 125 (CA125) is a marker of congestion and a predictor of outcomes in acute heart failure (HF). Less is known about CA125 in chronic ambulatory HF with reduced ejection fraction. Objectives: This study examined the association between baseline CA125 (and changes in CA125) and outcomes in patie...

Aim Eplerenone reduces the risk of cardiovascular death or first hospitalization for heart failure (HF) in patients with HF and a reduced ejection fraction (HFrEF), but it is still frequently underused in routine practice. We evaluated the time course of benefits of eplerenone after its initiation in HFrEF patients from EMPHASIS-HF trial. Methods...

Background: Recent guidelines proposed a classification for heart failure (HF) on the basis of left ventricular ejection fraction (LVEF), although it remains unclear whether the divisions chosen were biologically rational. Using patients spanning the full range of LVEF, we examined whether there was evidence of LVEF thresholds in patient character...

Background: Although education in self-management is thought to be an important aspect of the care of patients with heart failure, little is known about whether self-rated knowledge of self-management is associated with outcomes. Objectives: To assess the relationship between patient-reported knowledge of self-management and clinical outcomes in...

Aims: Stroke is an important problem in patients with heart failure (HF), but the intersection between the two conditions is poorly studied across the range of ejection fraction. The prevalence of history of stroke and related outcomes were investigated in patients with HF. Methods and results: Individual patient meta-analysis of seven clinical...

Background The rate of stroke in patients with heart failure (HF) and preserved ejection fraction but without atrial fibrillation (AF), is uncertain as is whether it is possible to reliably predict the risk of stroke in these patients. Methods We validated a previously developed simple risk model for stroke among patients enrolled in the I-Preserv...

Aims: Determine the cost-effectiveness of dapagliflozin, added to usual care, in patients with heart failure (HF) with mildly reduced or preserved ejection fraction for the UK, German and Spanish payers using detailed patient-level data from the Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failur...

Background and Aims Higher ambient temperatures have been associated with higher rates of admission for kidney stones and acute kidney injury. Occupational heat stress is also a risk factor for impaired kidney function in several rural resource-poor settings. It is unclear if higher ambient heat exposure is associated with a faster loss of kidney f...

Background and Aims The SGLT2 inhibitor dapagliflozin reduces the risk of progressive kidney disease and cardiovascular events in patients with and without type 2 diabetes. Among patients with CKD, baseline risks of cardiovascular disease and CKD progression vary based on age and sex. Whether the effects of dapagliflozin are uniform among patients...

Background and Aims The DAPA-CKD trial demonstrated that dapagliflozin reduced the risk of kidney failure in patients with chronic kidney disease (CKD) with or without type 2 diabetes. In contrast to most other trials, participants who reached dialysis were allowed to continue study medication with dapagliflozin or placebo. In this pre-specified an...

BACKGROUND Guideline‐recommended therapies that improve prognosis remain underused in clinical practice. Physical frailty may lead to underprescription of life‐saving therapy. We aimed to investigate the association between physical frailty and the use of evidence‐based pharmacological therapy for heart failure with reduced ejection fraction and th...

Background: Heart failure (HF) is associated with impaired physical function and poor quality of life and affects health status more profoundly than many other chronic diseases. Objectives: The authors examined the effects of dapagliflozin on specific physical and social limitations as reported by patients in the DAPA-HF (Dapagliflozin And Preve...

Background A rise in the incidence of selected autoimmune disorders has been described, raising the question as to whether the overall incidence of autoimmune disorders might be on the rise due to environmental factors. However, reliable estimates of disease incidence and trends over time, particularly as pertains to autoimmune diseases as a group,...

Aims: Because an increased risk of amputation with canagliflozin was reported in the CANVAS trials, there has been a concern about the safety of sodium-glucose cotransporter 2 inhibitors in patients with peripheral artery disease (PAD) who are at higher risk of amputation. Methods and results: A patient-level pooled analysis of the DAPA-HF and D...

Aims: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure with mildly reduced or preserved ejection fraction. In this study, the safety and efficacy of dapagliflozin according to background diuretic therapy and the influence of dapagliflozin on longitudinal diuretic use were...

Background: Patients recently hospitalized for heart failure (HF) often have unstable hemodynamics and experience worsening renal failure, and are at elevated risk for recurrent HF events. In DELIVER, dapagliflozin reduced HF events or cardiovascular death including among patients who were hospitalized or recently hospitalized. Methods: We exami...

Background and aims: The aims of this study were to assess prescription patterns, dosages, discontinuation rates and association with prognosis of conventional heart failure (HF) medications in patients with transthyretin cardiac amyloidosis (ATTR-CA). Methods: A retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the Na...

Aims: Dapagliflozin resulted in significant and sustained reductions in first and recurrent HF hospitalizations among patients with HF across the spectrum of ejection fraction. How treatment with dapagliflozin differentially impacts hospitalization for HF of varying complexity is not well studied. Methods and results: In the DELIVER and DAPA-HF...

Background and aims The PARAGLIDE-HF trial demonstrated reductions in natriuretic peptides with sacubitril/valsartan compared with valsartan in patients with heart failure (HF) with mildly reduced or preserved ejection fraction who had a recent worsening HF event, but was not adequately powered to examine clinical outcomes. PARAGON-HF included a su...

Background and Aims Adjustment of treatment based on remote monitoring of pulmonary artery (PA) pressure may reduce the risk of hospital admission for heart failure (HF). We have conducted a meta-analysis of large randomized trials investigating this question. Methods A systematic literature search was performed for randomized clinical trials (RCT...

Background and Aims To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide. Methods A multi-centre, open-label, randomized, active-comparator trial. Patients w...

Introduction: Patients with heart failure experience a high burden of symptoms, physical limitations, and poor quality-of-life. Dapagliflozin improves heart failure hospitalization and cardiovascular death in patients with reduced, mildly reduced, and preserved ejection fractions. We examined the effects of dapagliflozin on health status, measured...

Importance: Dapagliflozin has been shown to improve overall health status based on aggregate summary scores of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction enrolled in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection F...

Aims: To evaluate the prevalence of pathogenic variants in genes associated with dilated cardiomyopathy (DCM) in a clinical trial population with heart failure and reduced ejection fraction (HFrEF) and describe the baseline characteristics by variant carrier status. Methods and results: This was a post hoc analysis of the Phase 3 PARADIGM-HF tri...

Background: It is uncertain how much candidate biomarkers improve risk prediction when added to comprehensive models including routinely collected clinical and laboratory variables in heart failure. Methods: Aldosterone, cystatin C, high sensitivity-troponin T (hs-TnT), galectin-3, growth differentiation factor-15 (GDF-15), kidney injury molecul...

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, setting, and par...

Background: The goal of this work was to investigate trends (2001-2019) for cardiovascular events and cardiometabolic risk factor levels in individuals with type 2 diabetes (T2D) and matched control subjects. Methods: This study included 679 072 individuals with T2D from the Swedish National Diabetes Register and 2 643 800 matched control subjec...

Background: NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a potent predictor of death and heart failure (HF) across multiple populations. We evaluated the prognostic importance of NT-proBNP in patients with acute myocardial infarction (MI) complicated by left ventricular systolic dysfunction, pulmonary congestion, or both and ≥1 of 8 ri...

Although patients with heart failure with preserved ejection fraction (HFpEF) (left ventricular ejection fraction ≥50%) comprise nearly half of those with chronic heart failure, evidence-based treatment options for this population have historically been limited. Recently, however, emerging data from prospective, randomized trials enrolling patients...

Background: A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time,...

Background: Patients with heart failure (HF) have a high burden of multimorbidity, often necessitating numerous medications. There may be clinical concern about introducing another medication, especially among individuals with polypharmacy. Objectives: This study examined the efficacy and safety of addition of dapagliflozin according to the numb...

Background: Catastrophic disruptions in care delivery threaten the operational efficiency and potentially the validity of clinical research efforts, in particular randomized clinical trials. Most recently, the COVID-19 pandemic affected essentially all aspects of care delivery and clinical research conduct. While consensus statements and clinical...

Aims: In this post hoc analysis of the PARAGON-HF trial, we evaluated clinical outcomes and response to sacubitril/valsartan by duration of heart failure (HF) with left ventricular ejection fraction ≥45% from initial diagnosis. Methods and results: The primary outcome was a composite of total HF hospitalizations and cardiovascular death, analyze...

Background: Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction(HFpEF). Objectives: To assess the clinical implications of RV function, the association with N-terminal pro-B-type-natriuretic-p...

Background: Cardio-renal-metabolic (CRM) conditions are individually common among patients with HF, but the prevalence and influence of overlapping CRM conditions in this population have not been well-studied. Objectives: To evaluate the impact of overlapping CRM conditions on clinical outcomes and treatment effects of dapagliflozin in HF. Meth...

Background The DAPA‐CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular...

Importance: In the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, dapagliflozin reduced the risk of time to first worsening heart failure (HF) event or cardiovascular death in patients with HF with mildly reduced or preserved ejection fraction (EF). Objective: To evaluate...

Aims Multimorbidity, the coexistence of two or more chronic conditions, is synonymous with heart failure(HF). How risk related to comorbidities compare at individual and population levels is unknown. The aim of this study is to examine the risk related to comorbidities, alone and in combination, both at individual and population levels. Methods Us...

Aims: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are effective across the spectrum of the left ventricular ejection fraction (LVEF) in heart failure (HF); however, population-wide medication use in eligible patients remains suboptimal. We evaluated the potential implications of optimal global implementation of SGLT-2 inhibitors in HF. Met...

Although the development of therapies and tools for the improved management of heart failure (HF) continues apace, day-to-day management in clinical practice is often far from ideal. A Cardiovascular Round Table workshop was convened by the European Society of Cardiology (ESC) to identify barriers to the optimal implementation of therapies and guid...

Aims: The 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation combining creatinine and cystatin C provides a better estimation of glomerular filtration rate (GFR) compared to the creatinine-only equation. Methods and results: CKD-EPI creatinine-cystatin C equation (creatinine-cystatin) was compared to creatinine-only (creat...

Aims: Hypertensive heart disease (HHD) is recognized as a key clinical precursor to heart failure with preserved ejection fraction (HFPEF). However, pathophysiological transition from HHD to HFPEF is not well understood. We sought determine whether regional differences in impaired myocardial function may underlie the greater mechanical dysfunction...

Background: ET-1 (endothelin-1) is implicated in the pathophysiology of heart failure and renal disease. Its prognostic importance and relationship with kidney function in patients with heart failure with reduced ejection fraction receiving contemporary treatment are uncertain. We investigated these and the efficacy of dapagliflozin according to E...

Introduction: The globalization of clinical trials has highlighted geographic differences in patient characteristics, treatments, and outcomes. We examined these differences in PARADISE-MI. Methods and results: 23.0% were randomized in Eastern Europe/Russia, 17.5% in Western Europe, 12.2% in Southern Europe, 10.1% in Northern Europe, 12.0% in La...

Background: Global longitudinal (GLS) and global circumferential strain (GCS) have been shown to be impaired in HFpEF. Objectives: To assess whether treating HFpEF patients with sacubitril/valsartan would significantly improve GLS and GCS compared to valsartan alone. Methods: PARAMOUNT was a phase 2, randomized, parallel-group, double-blind mu...

Background: Anemia is common in patients with heart failure with reduced ejection fraction and is associated with poor clinical outcomes. Renin-angiotensin system blockers lower hemoglobin and may induce anemia. Objectives: The authors investigated whether concomitant neprilysin inhibition might ameliorate this effect of renin-angiotensin system...

Background: Impaired quality of life is common in patients with end-stage kidney disease. We report the baseline quality of life measures in participants from the PIVOTAL randomized controlled trial and the potential relationship with the primary outcome (all-cause mortality, myocardial infarction, stroke, and heart failure hospitalisation), and a...