Cardiology Research Review Issue 109 2023 PDF

Cardiology RESEARCH REVIEW ™ Making Education Easy In this issue: The HARMS2-AF risk score for prediction of new-onset AF Home telemonitoring systems for patients with HF Widening ethnic inequities in HF hospitalisations in NZ Upgrade from right ventricular pacing to CRT in patients with HF Sema...

Cardiology RESEARCH REVIEW ™ Making Education Easy In this issue: The HARMS2-AF risk score for prediction of new-onset AF Home telemonitoring systems for patients with HF Widening ethnic inequities in HF hospitalisations in NZ Upgrade from right ventricular pacing to CRT in patients with HF Semaglutide in patients with HFpEF and obesity Optical coherence tomography vs angiography guidance for PCI in complex bifurcation lesions Impact of ferric carboxymaltose in HF patients with iron deficiency Issue 109 – 2023 Welcome to the latest issue of Cardiology Research Review. In this issue, we report a novel lifestyle risk score that may help identify individuals at risk for AF in the general community and assist population screening, a Dutch group looks at the use of home telemonitoring systems in patients with HF, and a local study finds that ethnic inequities in HF incidence are widening in NZ and need to be addressed. I hope you find these and the other selected articles interesting and look forward to receiving any feedback you may have. Kind regards, Professor Alexander Sasse [email protected] New-onset atrial fibrillation prediction: The HARMS2-AF risk score Authors: Segan L et al. Summary: This study developed and validated an AF lifestyle risk score to identify individuals at risk for AF in the general population. A weighted score was developed using UK Biobank (UKB) data and externally validated using Framingham Heart Study data. Among 314,280 UKB participants, the incidence of AF was 5.7%, with median time to AF of 7.6 years. Hypertension, age, BMI, male sex, sleep apnoea, smoking, and alcohol were found to be predictive variables for AF, and were used to develop a HARMS2-AF risk score. A higher HARMS2-AF score (≥5 points) was associated with heightened AF risk. The risk score outperformed the Framingham-AF and ARIC risk models and was comparable to the CHARGE-AF risk score. Comment: How to characterise and quantify the risk for AF, how about developing a score. The UKB gives access to 500,000 patients, also included and validated was the model with patients from the Framingham Heart study. UKB patients had an AF incidence of 5.7%. Univariate and multivariate analysis helped to identify main predictors of AF: Hypertension (4 points), Age (1–2 points), Raised BMI (1 point), Male sex (2 points), Sleep Apnoea (2 points), Smoking (1 point) and Alcohol (1–2 points), the F must be for Fibrillation, giving us HARMS2-AF. The benefit is risk prediction, but at the same time identifying risk factors, some of which are modifiable. Intermediate risk is a score of 5–9, high risk is 10–14 points. Give it a try, it would be interesting to see how it compares to ECG monitoring and anticoagulation treatment decision-making. Effectiveness of aortic valve replacement in patients with Heyde syndrome Reference: Eur Heart J 2023;44(36):3443-52 Abstract Complete or culprit-only PCI in older patients with MI? Telemonitoring for heart failure Catheter ablation for coexisting AF in patients with end-stage HF Abbreviations used in this issue AF = atrial fibrillation BMI = body mass index CRT = cardiac resynchronisation therapy ECG = electrocardiogram HF = heart failure HFpEF = HF with preserved ejection fraction HFrEF = HF with reduced ejection fraction HR = hazard ratio LVEF = left ventricular ejection fraction MI = myocardial infarction NYHA = New York Heart Association OR = odds ratio PCI = percutaneous coronary intervention STEMI = ST-elevation MI www.researchreview.co.nz Authors: Scholte NTB et al. Summary: This meta-analysis investigated the effect of home telemonitoring systems (hTMS) on clinical outcomes in patients with HF. A search of four bibliographic databases identified 65 studies of non-invasive hTMS and 27 studies of invasive hTMS involving a total of 36,549 patients with HF. During follow up (mean 11.5 months), all-cause mortality was reduced by 16% in patients using hTMS compared with standard of care (pooled OR 0.84, 95% CI 0.77–0.93), first HF hospitalisations were reduced by 19% (OR 0.81, 95% CI 0.74–0.88), and total HF hospitalisations were reduced by 15% (pooled incidence rate ratio 0.85, 95% CI 0.76–0.96). Comment: This Dutch group conducted a meta-analysis asking the question if hTMS can improve outcome in HF patients. They looked at different hTMS modalities including the use of implanted devices. About 10,000 patients had non-invasive and 9400 patients invasive hTMS – comparison was standard of care. hTMS did reduce mortality by about 16%, however the main driver was structural telephone support (STS), rather than just the technical monitoring. HF admissions were reduced by about 19% with STS plus telemonitoring. Overall, telemonitoring did affect outcomes in HF patients, but there was considerable heterogeneity in the study outcomes likely driven by quite different approaches of health systems to HF care. So for NZ application it would have to be part of an integrated HF service. Reference: Eur Heart J 2023;44(31):2911-26 Abstract CLICK HERE to read previous issues of Cardiology Research Review a RESEARCH REVIEW™ publication 1 Cardiology RESEARCH REVIEW ™ Widening ethnic inequities in heart failure incidence in New Zealand Authors: Chan DZL et al. FULLY FUNDED with Special Authority criteria* for the treatment of T2D For your patients with type 2 diabetes † THE POWER TO ACCOMPLISH MORE Above and beyond glycaemic control‡1,2 Not an actual patient. 38% RRR in CV death in patients with established CV disease (CAD, PAD, MI or stroke) and T2D (HR=0.62; p<0.001).#2 *JARDIANCE is a funded medicine. Restrictions apply: Pharmaceutical Schedule, Hospital Medicines List. Jardiance is fully funded for the treatment of T2DM. Jardiance is not funded for the treatment of heart failure with reduced ejection fraction. †In adult patients with insufficiently controlled type 2 diabetes and CAD, PAD, or a history of MI or stroke. #The absolute risk for CV death was reduced from 5.9% in patients receiving standard of care plus placebo to 3.7% in patients receiving standard of care plus JARDIANCE® (p<0.001).1,2 1.JARDIANCE® Data Sheet 2021 2.Zinman B et al. N Engl J Med. 2015;373(22):2117-2128 JARDIANCE® empagliflozin 10mg, 25mg film coated tablets. Before prescribing, please review full Data Sheet which is available on request from Boehringer Ingelheim or from http://www.medsafe.govt.nz/profs/datasheet/dsform.asp INDICATION: Type 2 diabetes mellitus - Glycaemic control: Treatment of type 2 diabetes mellitus (T2DM) to improve glycaemic control in adults as: Monotherapy - When diet and exercise alone do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate due to intolerance; Add-on combination therapy - With other glucoselowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control. Prevention of cardiovascular (CV) events: In patients with T2DM and established CV disease to reduce the risk of CV death. To prevent CV deaths, Jardiance should be used in conjunction with other measures to reduce CV risk in line with the current standard of care. Heart failure - In adult patients with heart failure (NYHA class II-IV) and reduced ejection fraction, with or without type 2 diabetes mellitus: -to reduce the risk of hospitalisation for heart failure; -to slow kidney function decline. DOSAGE AND ADMINISTRATION: Type 2 diabetes mellitus: Recommended starting dose is 10mg once daily . Patients with type 2 diabetes mellitus tolerating 10mg once daily and requiring additional glycaemic control, increase dose to 25mg once daily. Heart failure: Recommended dose is 10mg once daily. Can be taken with or without food. No dose adjustment is recommended based on age, patients with eGFR ≥30mL/min/1.73m2 (T2DM) or ≥20mL/min/1.73m2 (HF), or hepatic impairment. When Jardiance is used in combination with a sulfonylurea (SU) or with insulin, a lower dose of the sulfonylurea or insulin may be considered. CONTRAINDICATIONS: Hypersensitivity to empagliflozin or any of the excipients; patients with severe renal impairment (T2DM: eGFR <30mL/min/1.73m2). WARNINGS AND PRECAUTIONS: Patients with type 1 diabetes; ketoacidosis; necrotising fasciitis of the perineum (Fournier’s gangrene); contraindicated when eGFR <30mL/min/1.73m2 (T2DM); not recommended when eGFR <20mL/ min/1.73m2 (HF); assess renal function before treatment and regularly thereafter; patients for whom a drop in BP could pose a risk (e.g. those with known CV disease, on anti-hypertensive therapy with a history of hypotension, or aged ≥75 years); complicated urinary tract infections (UTIs); rare hereditary conditions of galactose intolerance, e.g. galactosaemia; pregnancy; lactation; children (<18 years). INTERACTIONS: Diuretics; insulin and SU; interference with 1,5-anhydroglucitol assay. ADVERSE REACTIONS: Very common: hypoglycaemia (when used with metformin in combination with SU or insulin - patients with T2DM); volume depletion (patients with HF). Common: hypoglycaemia (combination with metformin; pioglitazone with or without metformin; metformin and linagliptin – patients with T2DM); hypoglycaemia (patients with HF); vaginal moniliasis, vulvovaginitis, balanitis and other genital infections; UTIs (including pyelonephritis and urosepsis); pruritus (patients with T2DM); allergic skin reactions (e.g. rash, urticaria); increased urination (patients with T2DM); thirst (patients with T2DM); serum lipids increased; volume depletion (patients aged ≥75 years); constipation. For other adverse reactions, see full Data Sheet. ACTIONS: Empagliflozin is a reversible competitive inhibitor of sodium-glucose co-transporter 2 (SGLT2), which is responsible for glucose absorption in the kidney. It improves glycaemic control in patients with type 2 diabetes by reducing renal glucose reabsorption. Through inhibition of SGLT2, excessive glucose is excreted in the urine. Empagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, increasing tubuloglomerular feedback and reducing intraglomerular pressure, lowering both pre- and afterload of the heart, and downregulating sympathetic activity. PRESCRIPTION MEDICINE – JARDIANCE is a funded medicine – Restrictions apply: Pharmaceutical Schedule, Special Authority. Jardiance is fully funded for the treatment of T2DM. Jardiance is not funded for the treatment of heart failure with reduced ejection fraction. JARDIANCE® is a registered trademark of Boehringer Ingelheim. BOEHRINGER INGELHEIM (N.Z.) Ltd. Level 3, 2 Osterley Way, Manukau, Auckland 2104. TAPS MR8157/PC-NZ-100168 April 2022 BOE000418 ‡ Boehringer Ingelheim (NZ) Ltd. PO Box 76216 Manukau City, Auckland 2241. Phone 0800 802 461 Eli Lilly and Company (NZ) Ltd. PO Box 109197 Newmarket, Auckland 1149. Phone 0800 500 056 NZBN 9429039560643 Summary: This study investigated ethnic disparities in incident HF hospitalisations in NZ. Incident HF hospitalisations in patients aged ≥20 years were identified through International Classification of Diseases, 10th Revision (ICD-10)-coded national hospitalisation records. Of 116,113 incident HF hospitalisations in 2006–2018, 12.8% of patients were Māori, 5.7% were Pasifika, 3.0% were Asian and 78.6% were European/other. Overall, 64% of Māori and Pacific patients were aged <70 years, compared with 37% of Asian and 19% of European/others. In 2018, incidence rate ratios compared with European/others were 6.0, 7.5 and 0.5 for Māori, Pacific people and Asians aged 20–49 years; 3.7, 3.6 and 0.5 for Māori, Pacific people and Asians aged 50–69 years; and 1.5, 1.5 and 0.5 for Māori, Pacific people and Asians aged ≥70 years. Between 2006 and 2018, ethnicity-specific rates diverged in older patients (≥70 years) due to a decline in rates in European/others and Asians, but no change in rates in Māori and Pacific people. Comment: This paper characterised 116,113 incident HF admissions in NZ between 2006 and 2018. HF was the primary ICD diagnosis code in about a third of patients. The paper contains a wealth of information, and is a great baseline for assessing where we stand. The most apparent finding is the discrepancy between a fall in HF incidence in patients with European and Asian ethnicity compared to higher rates for Māori and Pacific ethnicities, rates that also do not show a decline. Not only that, but age of HF onset was 17 years younger for Māori and Pacific patients. For most clinicians this paper vividly confirms our experiences, the very clearly presented information should help guide policy decisions. Reference: Heart 2023; published online Aug 3 Abstract Kindly Supported by RACP MyCPD Program participants can claim the time spent reading and evaluating research reviews as CPD in the online MyCPD program. Please contact [email protected] for any assistance. For more information, please go to www.medsafe.govt.nz www.researchreview.co.nz a RESEARCH REVIEW™ publication 2 Cardiology RESEARCH REVIEW ™ Upgrade of right ventricular pacing to cardiac resynchronisation therapy in heart failure OCT or angiography guidance for PCI in complex bifurcation lesions Authors: Merkely B et al. Authors: Holm NR et al., for the OCTOBER Trial Group Summary: This multicentre, randomised controlled trial investigated the effects of upgrading to CRT with defibrillator (CRT-D) in patients with HFrEF currently receiving right ventricular pacing. 360 patients with symptomatic HFrEF (NYHA class II–IVa) with a pacemaker or implantable cardioverter defibrillator (ICD), high right ventricular pacing burden (≥20%), and QRS complex duration ≥150 ms were randomised 3:2 to receive CRT-D upgrade or ICD. The primary outcome was a composite of all-cause mortality, HF hospitalisation, or <15% reduction in left ventricular end-systolic volume at 12 months. During a median follow-up of 12.4 months, the primary outcome occurred in 32.4% of patients in the CRT-D arm and 78.9% in the ICD arm (OR 0.11, 95% CI 0.06–0.19; p<0.001). All-cause mortality or HF hospitalisation occurred in 10% and 32% of patients in the respective arms (HR 0.27, 95% CI 0.16–0.47; p<0.001). The incidence of procedure- or device-related complications did not differ significantly between groups. Summary: The multicentre OCTOBER trial investigated whether routine optical coherence tomography (OCT)-guided PCI is better than angiography-guided PCI for lesions involving coronary-artery branch points (bifurcations). At 38 centres in Europe, 1201 patients with a clinical indication for PCI and a complex bifurcation lesion identified by coronary angiography were randomised 1:1 to OCT-guided PCI or angiographyguided PCI. The primary end-point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion MI, or ischaemia-driven target-lesion revascularisation. During 2 years of follow up, a primary end-point event occurred in 10.1% of patients in the OCT-guided PCI group and 14.1% in the angiography-guided PCI group (HR 0.70, 95% CI 0.50–0.98; p=0.035). Procedurerelated complications occurred in 6.8% and 5.5% of patients in the respective groups. Semaglutide in patients with heart failure with preserved ejection fraction and obesity Authors: Kosiborod MN et al., for the STEP-HFpEF Trial Committees and Investigators Summary: This analysis of the STEP-HFpEF trial investigated the efficacy and tolerability of subcutaneous semaglutide in patients with obesity-related HFpEF. 529 patients with HFpEF and BMI ≥30 kg/m2 were randomised to receive onceweekly semaglutide 2.4mg or placebo for 52 weeks. The dual primary end-points were change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; higher scores indicating fewer symptoms and physical limitations) and change in body weight. The mean change in KCCQ-CSS after 52 weeks was +16.6 points with semaglutide and +8.7 points with placebo (p<0.001), the mean percentage change in body weight was −13.3% with semaglutide and −2.6% with placebo (p<0.001), and the mean change in 6-min walk distance was +21.5m and +1.2m in the respective groups (p<0.001). Serious adverse events were reported in 13.3% of semaglutide recipients and 26.7% of placebo recipients. Comment: You can’t escape publications on this new drug, one every week it seems. Here semaglutide was given to obese HFpEF patients. BMI >30, treatment for one year, 529 patients, outcome was a HF questionnaire and weight. Somewhat unusually there were almost twice as many serious adverse events in the placebo group compared to the semaglutide group (13.3% vs 26.7%). Weight dropped by 13.3% on semaglutide (compared to 2.6%; p<0.001). The questionnaire score improved by 16.6 points on treatment compared to 8.7 points on placebo, and 6-min walk outcomes were also better. So, in obese HFpEF patients, significant weight loss reduces symptoms – as such not a surprising clinical outcome. Will semaglutide achieve a longer term benefit though? Reference: N Engl J Med 2023;389:1069-84 Abstract This Research Review has been endorsed by The Royal New Zealand College of General Practitioners (RNZCGP) and has been approved for up to 1 CME credit for the General Practice Educational Programme (GPEP) and Continuing Professional Development (CPD) purposes. You can record your CME credits in your RNZCGP Dashboard. Time spent reading this publication has been approved for CNE by The College of Nurses Aotearoa (NZ) for RNs and NPs. For more information on how to claim CNE hours please CLICK HERE. www.researchreview.co.nz Reference: N Engl J Med 2023; published online Aug 27 Abstract Independent commentary by Professor Alexander Sasse Professor Alexander Sasse is Consultant Cardiologist and Clinical Director of the Cardiology Department at Wellington Hospital/CCDHB. His clinical interests include the various modalities of cardiac imaging, structural heart disease and intervention, general cardiology and the prevention of stroke. He went to Medical School in Bonn and did his training at the RWTH Aachen (Germany) and has been a Cardiologist since 2004. In 2007 he moved to Wellington and has been there since. Appointments include being a senior lecturer at Wellington School of Medicine (University of Otago) since 2007, and adjunct Professor at the School of Biological Sciences (Victoria University) Wellington since 2012. CLICK HERE to read our latest SPEAKER SERIES: How to welcome the fantastic four This publication summarises a Novartissponsored breakfast symposium presentation by Professor Andrew Sindone, held in June 2023, in Auckland at the Cardiac Society of Australia and New Zealand Annual Scientific Meeting. In this symposium, Professor Sindone provided a summary of international heart failure guidelines for starting the four pillars of heart failure therapy – angiotensin receptor/neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 (SGLT2) inhibitors – and rapidly up-titrating these agents. How to welcome the fantastic four A RESEARCH REVIEW™ SPEAKER SERIES Making Education Easy About the speaker Professor Andrew Sindone BMed (Hons), MD, FRACP, FCSANZ Andrew Sindone is a practicing cardiologist with private practice in Ryde and Westmead and is the Director of the Heart Failure Unit and Department of Cardiac Rehabilitation at Concord Hospital and Head of Department of Cardiology at Ryde Hospital, Sydney, NSW. He has a long history of cardiovascular research having presented over one hundred research papers both nationally and internationally. He has been principal investigator in more than 45 international multicentre clinical trials and is an advisor to the NSW Ministry of Health, as well as being co-author of the Australian Guidelines for the Management of Chronic Heart Failure. 2023 This publication summarises a Novartis-sponsored breakfast symposium presentation by Professor Andrew Sindone, held in June 2023, in Auckland at the Cardiac Society of Australia and New Zealand Annual Scientific Meeting. In this symposium, Professor Sindone provided a summary of international heart failure guidelines for starting the four pillars of heart failure therapy – angiotensin receptor/neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 (SGLT2) inhibitors – and rapidly up-titrating these agents. He provided a brief overview of why use of the ‘fantastic four’ is important in heart failure and how to implement such therapy. The complete CSANZ symposium presentation video can also be viewed here. In 2013, there were three main pillars of heart failure therapy, the angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), the beta blockers, and the MRAs. Now, in 2023, there are four main pillars of heart failure therapy, the ARNIs, the beta-blockers, MRAs and the SGLT2 inhibitors. So how do we use the ‘fantastic four’, how do we manage them and how do we introduce them? The European guidelines lack detail on how to introduce these agents, so Professor Sindone and colleagues developed guidelines for when to introduce each pillar based on whether patients are congested or euvolaemic (Figure 1).1, 2 Additionally, these guidelines highlight the importance of multidisciplinary care for all patients and point out that diuretics should be used only to manage congestion. * ARNI/ACE inhibitor , beta blocker†, MRA and SGLT2 inhibitor‡ recommended in ALL patients with HFrEF ARNI is preferred to ACEi ABOUT RESEARCH REVIEW Research Review is an independent medical publishing organisation producing electronic publications in a wide variety of specialist areas. A Research Review Speaker Series is a summary of a speaking engagement by a medical expert. Research Review has no control over the content of these presentations, which has been developed and presented by the featured expert. SUBSCRIBE AT NO COST TO ANY RESEARCH REVIEW We offer over 50 different Reviews in various clinical areas. NZ health professionals can subscribe to or download previous editions of Research Review publications at www.researchreview.co.nz Privacy Policy: Research Review will record your email details on a secure database and will not release them to anyone without your prior approval. Research Review and you have the right to inspect, update or delete your details at any time. Diuretics to manage congestion Reference: Eur Heart J 2023; published online Aug 26 Abstract Multidisciplanry heart failure service and exercise training Comment: This was a collaboration of Eastern European centres with US cooperation. 360 HFrEF patients with broad complex right ventricular pacing (>20%, >150 ms) were randomised 3:2 to CRT-D or ICD upgrade. Average LVEF was 24.8% at baseline. After a year of observation 32.4% in the CRT-D arm and 78.9% in the ICD arm reached an unfavourable end-point (p<0.001), though mortality alone was not different. The main driver for the outcome was recurrent hospitalisation. Probably not a surprising result, but it confirms that more physiological pacing should be considered in HF patients. Comment: A recurrent theme at conferences and in cath labs: intravascular imaging for PCI and if so for what types of procedures? 1201 patients were randomised to PCI with and without OCT – looking in particular at 227 bifurcation PCIs. After 2 years, 10.1% of the OCT-PCI patients had an adverse outcome compared with 14.1% of angiography PCI patients (p=0.035). Mortality and target vessel revascularisation was individually not statistically significant. There is lots of fine-print in the paper, for example 64% of OCT-PCI patients showed a degree of stent malaposition. OCT-PCI was shown to be safe regarding procedurerelated complications. So, a 30% reduction of the composite end-point, with fine significance margins. Each to draw their own conclusions. * Congested Euvolaemic ARNI/ACE inhibitor*and SGLT2 inhibitor‡ ARNI/ACE inhibitor* and beta blocker † Add MRA Add MRA and SGLT2 inhibitor‡ Add beta blocker†Once euvolaemic Up-titrate heart failure therapy to maximum tolerated dose (generally favour up-titrating beta blocker † initially unless congested or heart rate <50 bpm) If LVEF ≤35% after 3 months: ICD and/or CRT (if QRS ≥130ms) If SR ≥70 bpm + LVEF ≤35%: add ivabradine ADDITIONAL TREATMENT OPTIONS FOR PERSISTENT HFrEF: Consider nitrates + hydralazine if ARNI/ACE inhibitor/ARB contraindicated or not tolerated Consider nitrates +/- hydralazine and/or digoxin if refractory symptoms Consider vericiguat§ if recent hospitalisation and high risk of readmission Consider omecamtiv mecarbil§ if persistent LVEF ≤35% Consider IV ferric carboxymaltose if ferritin <100 or if ferritin 100-299 and transferrin saturation <20% The key overarching theme is to commence all patients on the four destination therapies of ARNI/ACE inhibitor*, beta blocker†, MRA and SGLT2 inhibitor‡ as soon as clinically possible, given their early morbidity and mortality benefit. *ARNI preferred. ACE inhibitor can be considered as an alternative if problematic hypotension, and consider switching to ARNI later. † Use beta blocker with outcome trial proven HFrEF efficacy (carvedilol, bisoprolol, metoprolol succinate or nebivolol). ‡ Use SGLT2 inhibitor with outcome trial proven HFrEF efficacy (dapagliflozin or empagliflozin). § Unavailable in New Zealand. Figure 1. Heart failure with reduced ejection fraction management algorithm, with one of several possible d rug initiation regimens based on presence or absence of clinical congestion.1 Abbreviations used in this review ACC = American College of Cardiology ACE = angiotensin-converting enzyme ACEI = angiotensin-converting enzyme inhibitors ACEI/ARB = angiotensin converting enzyme inhibitor/angiotensin receptor blocker AHA = American Heart Association ARB = angiotensin receptor blockers ARNI = angiotensin receptor/neprilysin inhibitors BB = beta-blockers www.researchreview.co.nz CI = confidence interval COR = class of recommendation CRT = cardiac resynchronisation therapy CV = cardiovascular ESC = European Society of Cardiology GDMT = guideline-directed medical therapy HF = heart failure HFrEF = heart failure with reduced ejection fraction HFSA = Heart Failure Society of America HR = hazard ratio ICD = implantable cardioverter defibrillator LVEF = left ventricular ejection fraction MRA = mineralocorticoid receptor antagonists SGLT2 = sodium–glucose cotransporter 2 SGLT2I = sodium-glucose cotransporter-2 inhibitors SR = sinus rhythm a RESEARCH REVIEW™ publication 1 a RESEARCH REVIEW™ publication 3 Cardiology RESEARCH REVIEW ™ Ferric carboxymaltose in heart failure with iron deficiency Complete or culprit-only PCI in older patients with myocardial infarction Authors: Mentz RJ et al., for the HEART-FID Investigators Authors: Biscaglia S et al., for the FIRE Trial Investigators Summary: The HEART-FID study investigated the clinical effects of ferric carboxymaltose in patients with HFrEF and iron deficiency. 3065 patients were randomised 1:1 to receive intravenous ferric carboxymaltose or placebo in addition to standard HF therapy. Ferric carboxymaltose or placebo was given every 6 months as needed, based on iron indices and haemoglobin levels. The primary outcome was a hierarchical composite of death within 12 months, hospitalisations for HF within 12 months, or change from baseline to 6 months in the 6-min walk distance. Death by month 12 occurred in 8.6% and 10.3% of patients in the ferric carboxymaltose and placebo groups, respectively; a total of 297 and 332 hospitalisations for HF occurred by month 12 in the respective groups; and the mean change from baseline to 6 months in 6-min walk distance was 8m and 4m, respectively (p=0.02). Repeated dosing of ferric carboxymaltose had an acceptable tolerability profile. Summary: The multicentre FIRE trial investigated the benefits of complete revascularisation in older patients (≥75 years) with MI and multivessel disease. 1445 patients (aged 77–84 years, 36.5% female) with MI and multivessel disease who were undergoing PCI of the culprit lesion were randomised to receive either physiologyguided complete revascularisation of nonculprit lesions or to receive no further revascularisation. The primary outcome was a composite of death, MI, stroke, or any revascularisation at 1 year. A primary outcome event occurred in 15.7% of patients in the complete-revascularisation group compared with 21.0% in the culprit lesion-only group (HR 0.73, 95% CI 0.57–0.93; p=0.01); cardiovascular death or MI occurred in 8.9% and 13.5% of patients in the respective groups (HR 0.64, 95% CI 0.47–0.88). The safety outcome (a composite of contrast-associated acute kidney injury, stroke, or bleeding) did not differ significantly between groups. Comment: Iron deficiency can have a negative effect on HF, but oral replacement of iron has disappointed in the past. Enrolled in this study were HFrEF patients with low iron parameters. In a 1:1 ratio, patients received intravenous ferric carboxymaltose or placebo, in addition to usual therapy for HF. There was no difference in mortality (8.6% vs 10.3%) and no difference in hospitalisations (297 vs 332). Six-min walking test results were moderately better after iron therapy. There was no difference in the hierarchical composite end-point. There was no safety concern with the iron injection. What does this mean for iron treatment in HF? Patient selection was slightly different from other iron trials. It will be interesting to follow further discussions on this topic. Comment: Older patients with MI are a growing population, and they tend to have more comorbidities and more coexisting coronary artery disease. So how completely should they be revascularised – in this trial also guided by coronary physiology. Compared with culprit lesion-only PCI in 1445 older patients (≥75 years of age) with acute MI. Median patient age was 80 years, and one-third were female. 50% of the complete revascularisation group actually had a second PCI – an important parameter. 15.7% of complete revascularisation patients had adverse outcomes, compared to 21% in the culprit lesion-only group (p=0.01). The number-neededto-treat was 19. There was no difference in safety outcomes. The accompanying editorial discusses the role of frailty rather than age to make the decision for an invasive strategy. 35% of patients had a STEMI, so one could argue about the role of medical treatment in some of the remaining patients. But overall the trial would favour comprehensive invasive management in this group of patients. Reference: N Engl J Med 2023;389(11):975-86 Abstract Effectiveness of aortic valve replacement in Heyde syndrome Authors: Goltstein LCMJ et al. Summary: This systematic review and meta-analysis investigated the impact of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding in patients with Heyde syndrome. A search of various databases found 25 trials that reported on acquired von Willebrand syndrome (n=1054), and ten that reported on gastrointestinal bleeding (n=300) after aortic valve replacement in patients with Heyde syndrome that were suitable for inclusion. Meta-analysis of the data showed that acquired von Willebrand syndrome recovered in 86% of patients within 24h of aortic valve replacement, in 90% after 24–72h, in 92% after 3–21 days, and in 87% after 4 weeks to 2 years. Gastrointestinal bleeding stopped in 73% of patients postoperatively. Comment: Heyde Syndrome – I’m sure you will have come across it. Severe aortic stenosis and bleeding from a gastrointestinal bleed, and an acquired von Willebrand syndrome driven by high shear stress from the aortic stenosis. This meta-analysis looked at 35 studies with a total of 1354 patients; about one-third had surgical aortic valve replacement and two-thirds had transcatheter aortic valve replacement. Across studies, about 87% showed a recovery from the acquired von Willebrand syndrome, and 73% had cessation of gastrointestinal bleeding. Some trials were lacking longer term follow up, but overall the message was quite clear: if the aortic stenosis/acquired von Willebrand syndrome was the cause of the gastrointestinal bleeding it will likely improve after valve replacement. And the patient will also get a functioning valve at the same time. Reference: Eur Heart J 2023;44(33):3168-77 Abstract Independent Content: The selection of articles and writing of summaries and commentary in this publication is completely independent of the advertisers/sponsors and their products. Privacy Policy: Research Review will record your email details on a secure database and will not release them to anyone without your prior approval. Research Review and you have the right to inspect, update or delete your details at any time. Disclaimer: This publication is not intended as a replacement for regular medical education but to assist in the process. The reviews are a summarised interpretation of the published study and reflect the opinion of the writer rather than those of the research group or scientific journal. It is suggested readers review the full trial data before forming a final conclusion on its merits. Research Review publications are intended for New Zealand health professionals. www.researchreview.co.nz © 2023 RESEARCH REVIEW Reference: N Engl J Med 2023;389:889-98 Abstract Catheter ablation in end-stage heart failure with atrial fibrillation Authors: Sohns C et al., for the CASTLE HTx Investigators Summary: The CASTLE-HTx trial investigated whether catheter ablation is superior to medical therapy in patients with AF and end-stage HF. 194 patients (mean age 64 years, 19% female) with symptomatic AF and end-stage HF who were eligible for heart transplantation were randomised 1:1 to receive either first-time catheter ablation or medical therapy for AF (rate or rhythm control). Both groups also received guidelinedirected HF therapy. The primary end-point (a composite of all-cause mortality, worsening HF requiring urgent heart transplantation, or implantation of a left ventricular assist device) occurred in 8% of patients in the ablation group and 30% in the medical therapy group during 1 year of follow-up (HR 0.24, 95% CI 0.11–0.52; p<0.001). Allcause mortality occurred in 6% of patients in the ablation group and 20% of patients in the medical therapy group (HR 0.29, 95% CI 0.12–0.72). Comment: End-stage HF and AF are common combinations, usually the clinical impression is that this would be too advanced to consider ablation. But this single centre in Germany randomised such patients 1:1 to AF ablation, 97 in each group. These were patients considered for transplant or assist devices, both were primary study end-points together with mortality. Actually ablated were 84% in the ablation group and 16% in the medical group. Follow up was 18 months, primary end-points occurred in 8% in the ablation group and 30% in the medical group, mortality alone was 6% and 20%. Overall interesting discussion points, but access to urgent transplant and left ventricular assist devices are a more uncommon option in NZ. And access to pulmonary vein isolation is limited as it is, but maybe there is a subgroup in this study cohort that is relevant to our practice. Reference: N Engl J Med 2023; published online Aug 27 Abstract Research Review New Zealand is on LinkedIn. FOLLOW US TO KEEP UP TO DATE a RESEARCH REVIEW™ publication 4