Publications by authors named "Subodh Verma"

581 Publications

Risk Factors for Post-Repair Elevated Mitral Gradient: A Post-Hoc Analysis of a Randomized Trial.

Ann Thorac Surg 2022 Jun 29. Epub 2022 Jun 29.

Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada; Department of Surgery, University of Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, ON, Canada. Electronic address:

Background: Pre-discharge elevated mean mitral gradients (>5mmHg) may occur after repair for degenerative mitral regurgitation. We sought to identify risk factors associated with elevated gradients as well as to evaluate its impact on functional outcomes at 12 months in this sub-analysis of the Canadian Mitral Research Alliance (CAMRA) CardioLink-2 trial.

Methods: 104 degenerative mitral regurgitation patients undergoing mitral repair were randomized to either a leaflet resection or preservation strategy. Logistic regression was used to identify risk factors associated with an elevated gradient. Functional outcomes at 12 months were compared between participants with and without elevated gradients.

Results: Elevated gradients was identified in 15 participants (14.4%), which was not significantly different based on allocation to each repair strategy (p=0.10). Patients with elevated gradients were more likely to be female (OR 4.28 [95%CI:1.29-14.19] p=0.02) and had a lower preoperative hemoglobin level (0.93 [0.89-0.98] p=0.01) and smaller inter-commissural diameter (0.86 [0.76-0.97] p=0.02) and mitral annuloplasty size (0.71 [0.57-0.87] p=0.001). The ratio of inter-commissural diameter to annuloplasty size was similar between those with and without elevated gradients (both 0.8±0.1; p=0.69). At 12 months, those with elevated gradients had worse NYHA functional status (p=0.0001), lower peak oxygen saturation in exercise test (p=0.01), smaller body weight-walk distance product (p=0.02) and higher Borg Scale (p=0.01) in 6-minute walk test.

Conclusions: Female gender, smaller mitral anatomy sizes and lower preoperative hemoglobin levels were associated postoperative elevated mitral gradients, which was in turn associated with reduced functional status. Further research is warranted to investigate these potential risk factors.
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http://dx.doi.org/10.1016/j.athoracsur.2022.05.053DOI Listing
June 2022

Benefits of icosapent ethyl for enhancing residual cardiovascular risk reduction: A review of key findings from REDUCE-IT.

J Clin Lipidol 2022 Jun 4. Epub 2022 Jun 4.

VA Boston Healthcare System, Division of Cardiovascular Medicine, Boston University School of Medicine, Boston, MA, United States (Dr Boden).

Background: REDUCE-IT was a multinational, double-blind trial that randomized 8179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides to icosapent ethyl (IPE) or placebo. IPE was associated with a substantial reduction in the primary composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. Since the original publication of the trial, there have been a myriad of additional analyses confirming the benefit of IPE in various patient groups. Our objectives in this review are to summarize the key findings of the REDUCE-IT trial and its subsequent analyses as well as to call for the reevaluation and expansion of current guidelines to incorporate IPE as a therapy for patients at elevated cardiovascular risk with mild or moderate hypertriglyceridemia.
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http://dx.doi.org/10.1016/j.jacl.2022.05.067DOI Listing
June 2022

Stage-based approach to predict left ventricular reverse remodeling after mitral repair.

Clin Cardiol 2022 Jun 24. Epub 2022 Jun 24.

Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.

Background: Although predictors of reverse left ventricular (LV) remodeling postmitral valve repair are critical for guiding perioperative decision-making, there remains a paucity of randomized, prospective data to support the criteria that potential predictor variables must meet.

Methods And Results: The CAMRA CardioLink-2 randomized trial allocated 104 patients to either leaflet resection or preservation strategies for mitral repair. The correlation of indexed left ventricular end-systolic volume (LVESVI), indexed left ventricular end-diastolic volume (LVEDVI), and left ventricular ejection fraction (LVEF) were tested with univariate analysis and subsequently with multivariate analysis to determine independent predictors of reverse remodeling at discharge and at 12 months postoperatively. At discharge, both LVESVI and LVEDVI were independently associated with their preoperative values (p < .001 for both) and LVEF by preoperative LVESVI (p < .001). Mitral ring size was favorably associated with the change in LVESVI (p < .05) and LVEF (p < .01) from predischarge to 12 months, while the mean mitral valve gradient after repair was adversely associated with the change in LVESVI (p < .05) and LVEDVI (p < .05). No significant associations were found between reverse remodeling and coaptation height nor mitral repair technique.

Conclusions: Beyond confirming the lack of impact of mitral repair technique on reverse remodeling, this investigation suggests that recommending surgery before significant LV dilatation or dysfunction, as well as higher postoperative mitral valve hemodynamic performance, may enhance remodeling capacity following mitral repair.
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http://dx.doi.org/10.1002/clc.23879DOI Listing
June 2022

Non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease.

Eur Heart J 2022 Jun 17. Epub 2022 Jun 17.

Division of Cardiac Surgery, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Despite existing treatments, patients with heart failure and chronic kidney disease (CKD) remain at high risk for adverse outcomes and progression to end-stage disease. Steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone and eplerenone reduce mortality but remain under-prescribed due to the perceived risk of hyperkalaemia and hormonal side effects. The discovery of non-steroidal MRAs represents a major new dimension in cardiorenal disease therapy. Non-steroidal MRAs have high affinity and specificity for the mineralocorticoid receptor (MR) and differ from both steroidal agents and each other with respect to important physiochemical, pharmacodynamic, and pharmacokinetic parameters. Similar to their steroidal counterparts, they have beneficial anti-inflammatory, anti-remodelling, and anti-fibrotic properties in the kidneys, heart, and vasculature. There are several non-steroidal MRAs under development and clinical assessment; of these, only esaxerenone and finerenone are approved for treatment globally. In Japan, esaxerenone is approved for essential hypertension and has been studied in diabetic nephropathy. Compared with steroidal MRAs, finerenone more potently inhibits MR co-regulator recruitment and fibrosis and distributes more evenly between the heart and kidneys. The landmark Phase III trials FIGARO-DKD and FIDELIO-DKD demonstrated that finerenone-reduced major kidney and cardiovascular events on top of maximally tolerated renin-angiotensin-aldosterone system inhibition in patients with CKD associated with Type 2 diabetes. Non-steroidal MRAs are currently under evaluation in heart failure and for synergistic treatment with sodium-glucose contransporter 2 inhibitors. These ground-breaking agents could become an important therapy across the spectrum of cardiorenal disease.
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http://dx.doi.org/10.1093/eurheartj/ehac299DOI Listing
June 2022

Dealing With the Epidemic of Endocarditis in People Who Inject Drugs.

Can J Cardiol 2022 Jun 9. Epub 2022 Jun 9.

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada; Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

North America is facing an opioid epidemic and growing illicit drug supply, contributing to growing numbers of injection drug use-related infective endocarditis (IDU-IE). Patients with IDU-IE have high early and late mortality. Patients with IDU-IE more commonly present with right-side IE compared with those with non-IDU IE, and a majority are a result of Streptococcus aureus. Although most patients can be successfully managed with intravenous antibiotic treatment, surgery is often required in part owing to high relapse rates, potential treatment biases, and more aggressive pathophysiology in some. Multidisciplinary management as endocarditis teams, including not only cardiologists and cardiac surgeons, but also infectious disease specialists, drug addiction experts, social workers, neurologists, and neurosurgeons, is essential to best manage substance use disorder and facilitate safe discharge to home and society. Structural and population-level interventions, such as harm-reduction programs, are necessary to reduce IDU-IE relapse rates in the community and other IDU-related health concerns, such as overdoses. In this review, we describe the pathophysiologic, clinical, surgical, social, and ethical characteristics of IDU-IE and their management. We present the most recent clinical guidelines for this condition and discuss existing gaps in knowledge to guide future research, practice changes, and policy interventions.
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http://dx.doi.org/10.1016/j.cjca.2022.06.004DOI Listing
June 2022

Epidemiology of the diabetes-cardio-renal spectrum: a cross-sectional report of 1.4 million adults.

Cardiovasc Diabetol 2022 Jun 10;21(1):104. Epub 2022 Jun 10.

Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, P.O. Box 12000, 9112001, Jerusalem, Israel.

Background: Type-2 diabetes (T2D), chronic kidney disease, and heart failure (HF) share epidemiological and pathophysiological features. Although their prevalence was described, there is limited contemporary, high-resolution, epidemiological data regarding the overlap among them. We aimed to describe the epidemiological intersections between T2D, HF, and kidney dysfunction in an entire database, overall and by age and sex.

Methods: This is a cross-sectional analysis of adults ≥ 25 years, registered in 2019 at Maccabi Healthcare Services, a large healthcare maintenance organization in Israel. Collected data included sex, age, presence of T2D or HF, and last estimated glomerular filtration rate (eGFR) in the past two years. Subjects with T2D, HF, or eGFR < 60 mL/min/1.73 m were defined as within the diabetes-cardio-renal (DCR) spectrum.

Results: Overall, 1,389,604 subjects (52.2% females) were included; 445,477 (32.1%) were 25- < 40 years, 468,273 (33.7%) were 40- < 55 years, and 475,854 (34.2%) were ≥ 55 years old. eGFR measurements were available in 74.7% of the participants and in over 97% of those with T2D or HF. eGFR availability increased in older age groups. There were 140,636 (10.1%) patients with T2D, 54,187 (3.9%) with eGFR < 60 mL/min/1.73m, and 11,605 (0.84%) with HF. Overall, 12.6% had at least one condition within the DCR spectrum, 2.0% had at least two, and 0.23% had all three. Cardiorenal syndrome (both HF and eGFR < 60 mL/min/1.73m) was prevalent in 0.40% of the entire population and in 2.3% of those with T2D. In patients with both HF and T2D, 55.2% had eGFR < 60 mL/min/1.73m and 15.8% had eGFR < 30 mL/min/1.73m. Amongst those within the DCR spectrum, T2D was prominent in younger participants, but was gradually replaced by HF and eGFR < 60 mL/min/1.73m with increasing age. The congruence between all three conditions increased with age.

Conclusions: This large, broad-based study provides a contemporary, high-resolution prevalence of the DCR spectrum and its components. The results highlight differences in dominance and degree of congruence between T2D, HF, and kidney dysfunction across ages.
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http://dx.doi.org/10.1186/s12933-022-01521-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188046PMC
June 2022

Emerging role for SGLT2 inhibitors in mitigating the risk of hyperkalaemia in heart failure.

Eur Heart J 2022 Jun 10. Epub 2022 Jun 10.

Cardiology Unit, Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.

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http://dx.doi.org/10.1093/eurheartj/ehac304DOI Listing
June 2022

Forecasting Heart Failure Risk in Diabetes.

J Am Coll Cardiol 2022 06;79(23):2294-2297

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1016/j.jacc.2022.04.011DOI Listing
June 2022

Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T in EMPEROR-Preserved.

JACC Heart Fail 2022 Jul 1;10(7):512-524. Epub 2022 Jun 1.

Department of Cardiology (CVK), and the Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research Partner Site Berlin, Charité Universitätsmedizin, Berlin, Germany.

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with disease severity and outcomes among patients with heart failure (HF) with preserved ejection fraction.

Objectives: The authors evaluated associations between both biomarkers and clinical outcomes in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) trial.

Methods: Of 5,988 study participants, 5,986 (99.9%) and 5,825 (97.3%) had available baseline NT-proBNP and hs-cTnT; postbaseline NT-proBNP was also available. Baseline characteristics were expressed by biomarker quartiles. The effect of empagliflozin on cardiovascular death/ HF hospitalization, the individual components, total HF hospitalizations, slope of decline of estimated glomerular filtration rate (eGFR), and a composite renal endpoint were examined across biomarker quartiles. Change in NT-proBNP across study visits as a function of treatment assignment was also assessed.

Results: Higher baseline NT-proBNP and hs-cTnT concentrations were associated with more comorbidities and worse HF severity. Incidence rates for cardiac and renal outcomes were 2- to 5-fold higher among those in the highest vs lowest NT-proBNP or hs-cTnT quartiles. Empagliflozin consistently reduced the risk for cardiovascular events and reduced slope of eGFR decline across NT-proBNP or hs-cTnT quartiles. Empagliflozin treatment modestly lowered NT-proBNP; by 100 weeks, the adjusted mean difference in NT-proBNP from placebo was 7%. Increase in NT-proBNP from baseline to 12 weeks was strongly associated with risk of cardiovascular death/HF hospitalization.

Conclusions: The benefit of empagliflozin on cardiac outcomes and decline of eGFR is preserved across the wide range of baseline NT-proBNP and hs-cTnT evaluated. Empagliflozin modestly reduces NT-proBNP in HF with preserved ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT03057951).
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http://dx.doi.org/10.1016/j.jchf.2022.05.004DOI Listing
July 2022

Optimizing Foundational Therapies in Patients With HFrEF: How Do We Translate These Findings Into Clinical Care?

JACC Basic Transl Sci 2022 May 2;7(5):504-517. Epub 2022 Mar 2.

Department of Medicine, University of Mississippi, Jackson, Mississippi, USA.

Given the high risk of adverse outcomes in patients with heart failure and reduced ejection fraction (HFrEF), there is an urgent need for the initiation and titration of guideline-directed medical therapy (GDMT) that can reduce the risk of morbidity and mortality. Clinical practice guidelines are now emphasizing the need for early and rapid initiation of therapies that have cardiovascular benefit. Recognizing that there are many barriers to GDMT initiation and optimization, health care providers should aim to introduce the 4 pillars of quadruple therapy now recommended by most clinical practice guidelines: angiotensin receptor-neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors. A large proportion of patients with HFrEF do not have clinical contraindications to GDMT but are not treated with these therapies. Early initiation of low-dose combination therapy should be tolerated by most patients. However, patient-related factors such as hemodynamics, frailty, and laboratory values will need consideration for maximum tolerated GDMT. GDMT initiation in acute heart failure hospitalization represents another important avenue to improve use of GDMT. Finally, removal of therapies that do not have clear cardiovascular benefit should be considered to lower polypharmacy and reduce the risk of adverse side effects. Future prospective studies aimed at guiding optimal implementation of quadruple therapy are warranted to reduce morbidity and mortality in patients with HFrEF.
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http://dx.doi.org/10.1016/j.jacbts.2021.10.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156437PMC
May 2022

The Morphology of Coronary Artery Disease in South Asians vs White Caucasians and Its Implications.

Can J Cardiol 2022 May 11. Epub 2022 May 11.

Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

South Asians (SAs) experience a higher prevalence and earlier onset of coronary artery disease and have worse outcomes compared with White Caucasians (WCs) following invasive revascularisation procedures, a mainstay of coronary artery disease (CAD) management. We sought to review the differences in the CAD pattern and risk factors between SA and WC patients and to discuss their potential impact on the development of coronary disease, acute coronary syndrome, and revascularisation outcomes. SAs have a more diffuse pattern with multivessel involvement compared with WCs. However, less is known about other morphologic characteristics, such as calcification of atherosclerotic plaque and coronary diameter in SA populations. Despite a similar coronary calcification burden, higher noncalcified plaque composition, elevated thrombosis, and inflammatory markers likely contribute to the disease pattern. Although the current evidence on the role of coronary vessel size remains inconsistent, smaller diameters in SAs could play a potential role in the higher disease prevalence. This is especially important given the impact of coronary artery diameter on revascularisation outcomes. In conclusion, SAs have a unique CAD risk profile composed of traditional and novel risk factors. Our findings highlight the need for additional awareness of health professionals of this specific risk profile and potential therapeutic targets, as well as the need for further research in this vulnerable population.
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http://dx.doi.org/10.1016/j.cjca.2022.05.005DOI Listing
May 2022

Canadian Cardiovascular Society 2022 Guidelines for Peripheral Arterial Disease.

Can J Cardiol 2022 05;38(5):560-587

University of Montreal, Montreal, Quebec, Canada.

Patients with widespread atherosclerosis such as peripheral artery disease (PAD) have a high risk of cardiovascular and limb symptoms and complications, which affects their quality of life and longevity. Over the past 2 decades there have been substantial advances in diagnostics, pharmacotherapy, and interventions including endovascular and open surgical to aid in the management of PAD patients. To summarize the evidence regarding approaches to diagnosis, risk stratification, medical and intervention treatments for patients with PAD, guided by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework, evidence was synthesized, and assessed for quality, and recommendations provided-categorized as weak or strong for each prespecified research question. Fifty-six recommendations were made, with 27% (15/56) graded as strong recommendations with high-quality evidence, 14% (8/56) were designated as strong recommendations with moderate-quality evidence, and 20% (11/56) were strong recommendations with low quality of evidence. Conversely 39% (22/56) were classified as weak recommendations. For PAD patients, strong recommendations on the basis of high-quality evidence, include smoking cessation interventions, structured exercise programs for claudication, lipid-modifying therapy, antithrombotic therapy with a single antiplatelet agent or dual pathway inhibition with low-dose rivaroxaban and aspirin; treatment of hypertension with an angiotensin converting enzyme or angiotensin receptor blocker; and for those with diabetes, a sodium-glucose cotransporter 2 inhibitor should be considered. Furthermore, autogenous grafts are more effective than prosthetic grafts for surgical bypasses for claudication or chronic limb-threatening ischemia involving the popliteal or distal arteries. Other recommendations indicated that new endovascular techniques and hybrid procedures be considered in patients with favourable anatomy and patient factors, and finally, the evidence for perioperative risk stratification for PAD patients who undergo surgery remains weak.
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http://dx.doi.org/10.1016/j.cjca.2022.02.029DOI Listing
May 2022

Aortic valve neocuspidization and its technical nuance.

J Card Surg 2022 Aug 9;37(8):2475-2476. Epub 2022 May 9.

Division of Cardiac Surgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Aortic valve neocuspidization or Ozaki procedure represents an advanced surgical strategy for the management of patients with aortic valvulopathy. It has been shown to have clinical and hemodynamic outcomes that compare favorably with aortic valve replacement as it restores physiological aortic valve function and left ventricular remodeling. There are, however, a new set of issues including structural valve deterioration, leaflet tear/perforation, and need for reoperation. A keen understanding of the technical nuances involved with the Ozaki procedure may help in reducing the incidence of such adverse outcomes.
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http://dx.doi.org/10.1111/jocs.16604DOI Listing
August 2022

Healthcare costs and hospitalizations in US patients with type 2 diabetes and cardiovascular disease: A retrospective database study (OFFSET).

Diabetes Obes Metab 2022 07 3;24(7):1300-1309. Epub 2022 May 3.

Division of Cardiac Surgery, St Michael's Hospital, University of Toronto, Toronto, Canada.

Aim: To investigate the budget implications of treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus other glucose-lowering treatment (here termed 'standard of care' [SoC]) during 2012-2019.

Materials And Methods: GLP-1 RA-naïve adults with type 2 diabetes (T2D) in the IBM MarketScan database with at least one glucose-lowering medication claim within 6 months after their first cardiovascular disease (CVD) hospitalization were included (index date was the date of first claim for a GLP-1 RA for the GLP-1 RA group, and the date of the first claim, independent of medication type, for the SoC group). Monthly healthcare costs and hospitalization risk over 12 months postindex date were compared for those who initiated a GLP-1 RA posthospitalization versus those with a claim for any other glucose-lowering medication.

Results: Postindex date, mean observed total costs were lower for patients receiving a GLP-1 RA compared with SoC ($3853 vs. $4288). In adjusted analysis, both groups had similar total healthcare costs (P = .56). This was driven by significantly lower inpatient and outpatient costs and higher drug costs in the GLP-1 RA group compared with SoC (P < .001). Risks of all-cause (adjusted hazard ratio: 0.85) and CVD-related hospitalization (0.76) were significantly lower in the GLP-1 RA group compared with SoC (P < .001). Similar results were observed in a subgroup with atherosclerotic CVD.

Conclusions: These findings suggest that, in US patients with T2D and a CVD-related hospitalization, the added medical cost of treatment with GLP-1 RAs is offset by lower inpatient and outpatient care costs, resulting in budget neutrality against SoC.
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http://dx.doi.org/10.1111/dom.14703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324926PMC
July 2022

An Arrow Through the Heart.

J Invasive Cardiol 2022 05;34(5):E414-E415

St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada. subodh.

A 54-year-old man suffered a self-inflicted penetrating chest wound from an automated crossbow used for hunting large animals. The arrow was in the plane of the diaphragm and penetrated the left ventricle, although no hemopericardium, hemothorax, or pneumothorax were identified. Intraoperative transesophageal echocardiography showed no significant mitral regurgitation despite the proximity of the arrow to the base of a papillary muscle. This case details his subsequent successful treatment with the assistance of cardiopulmonary bypass.
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May 2022

Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection: An Analysis of the DARE-19 Randomized Controlled Trial.

Clin J Am Soc Nephrol 2022 Apr 28. Epub 2022 Apr 28.

The George Institute for Global Health, Newtown, NSW, Australia.

Background And Objectives: Patients who were hospitalized with coronavirus disease 2019 (COVID-19) infection are at high risk of AKI and KRT, especially in the presence of CKD. The Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial showed that in patients hospitalized with COVID-19, treatment with dapagliflozin versus placebo resulted in numerically fewer participants who experienced organ failure or death, although these differences were not statistically significant. We performed a secondary analysis of the DARE-19 trial to determine the efficacy and safety of dapagliflozin on kidney outcomes in the overall population and in prespecified subgroups of participants defined by baseline eGFR.

Design, Setting, Participants, & Measurements: The DARE-19 trial randomized 1250 patients who were hospitalized (231 [18%] had eGFR <60 ml/min per 1.73 m) with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. Dual primary outcomes (time to new or worsened organ dysfunction or death, and a hierarchical composite end point of recovery [change in clinical status by day 30]), and the key secondary kidney outcome (composite of AKI, KRT, or death), and safety were assessed in participants with baseline eGFR <60 and ≥60 ml/min per 1.73 m.

Results: The effect of dapagliflozin versus placebo on the primary prevention outcome (hazard ratio, 0.80; 95% confidence interval, 0.58 to 1.10), primary recovery outcome (win ratio, 1.09; 95% confidence interval, 0.97 to 1.22), and the composite kidney outcome (hazard ratio, 0.74; 95% confidence interval, 0.50 to 1.07) were consistent across eGFR subgroups ( for interaction: 0.98, 0.67, and 0.44, respectively). The effects of dapagliflozin on AKI were also similar in participants with eGFR <60 ml/min per 1.73 m (hazard ratio, 0.71; 95% confidence interval, 0.29 to 1.77) and ≥60 ml/min per 1.73 m (hazard ratio, 0.69; 95% confidence interval, 0.37 to 1.29). Dapagliflozin was well tolerated in participants with eGFR <60 and ≥60 ml/min per 1.73 m.

Conclusions: The effects of dapagliflozin on primary and secondary outcomes in hospitalized participants with COVID-19 were consistent in those with eGFR below/above 60 ml/min per 1.73 m. Dapagliflozin was well tolerated and did not increase the risk of AKI in participants with eGFR below or above 60 ml/min per 1.73 m.
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http://dx.doi.org/10.2215/CJN.14231021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269587PMC
April 2022

Initial Decline (Dip) in Estimated Glomerular Filtration Rate After Initiation of Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction: Insights From DAPA-HF.

Circulation 2022 Aug 20;146(6):438-449. Epub 2022 Apr 20.

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

Background: In a post hoc analysis, the frequency of occurrence of an early decline (dip) in estimated glomerular filtration rate (eGFR) after initiation of dapagliflozin and its association with outcomes were evaluated in patients with heart failure and reduced ejection fraction randomized in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial.

Methods: Patients with heart failure with reduced ejection fraction with or without type 2 diabetes and an eGFR ≥30 mL·min·1.73 m were randomized to placebo or dapagliflozin 10 mg daily. The primary outcome was the composite of worsening heart failure or cardiovascular death. The extent of the dip in eGFR between baseline and 2 weeks, patient characteristics associated with a >10% decline, and cardiovascular outcomes and eGFR slopes in participants experiencing this decline were investigated. Time-to-event outcomes were assessed in Cox regression from 14 days; eGFR slopes were assessed with repeated-measures mixed-effect models.

Results: The mean change in eGFR between day 0 and 14 was -1.1 mL·min·1.73 m (95% CI, -1.5 to -0.7) with placebo and -4.2 mL·min·1.73 m (95% CI, -4.6 to -3.9) with dapagliflozin, giving a between-treatment difference of 3.1 mL·min·1.73 m (95% CI, 2.6-3.7). The proportions of patients randomized to dapagliflozin experiencing a >10%, >20%, and >30% decline in eGFR were 38.2%, 12.6%, and 3.4%, respectively; for placebo, they were 21.0%, 6.4%, and 1.3%, respectively. The odds ratio for a >10% early decline in eGFR with dapagliflozin compared with placebo was 2.36 (95% CI, 2.07-2.69; <0.001). Baseline characteristics associated with a >10% decline in eGFR on dapagliflozin were older age, lower eGFR, higher ejection fraction, and type 2 diabetes. The hazard ratio for the primary outcome in patients in the placebo group experiencing a >10% decline in eGFR compared with ≤10% decline in eGFR was 1.45 (95% CI, 1.19-1.78). The corresponding hazard ratio in the dapagliflozin group was 0.73 (95% CI, 0.59-0.91; <0.001). A >10% initial decline in eGFR was not associated with greater long-term decline in eGFR or more adverse events.

Conclusions: The average dip in eGFR after dapagliflozin was started was small and associated with better clinical outcomes compared with a similar decline on placebo in patients with heart failure with reduced ejection fraction. Large declines in eGFR were uncommon with dapagliflozin.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT03036124.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.058910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354593PMC
August 2022

Complete transcatheter versus complete surgical management for combined aortic stenosis and coronary artery disease: A false dichotomy?

J Card Surg 2022 Jul 17;37(7):2084-2085. Epub 2022 Apr 17.

Division of Cardiac Surgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Coronary artery disease and aortic stenosis often occur concomitantly owing to their shared risk factor profile. While standard management of these patients has been through surgical methods including surgical aortic valve replacement and coronary artery bypass grafting, recent studies have investigated the potential role of complete transcatheter management (i.e., transcatheter aortic valve implantation and percutaneous coronary intervention) for these patients. In this editorial, we discuss the growing body of evidence suggesting long-term risks of transcatheter interventions despite their short-term benefits and also look to the future of hybrid approaches for multifaceted structural heart pathologies.
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http://dx.doi.org/10.1111/jocs.16531DOI Listing
July 2022

Ketones regulate endothelial homeostasis.

Cell Metab 2022 04;34(4):513-515

Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.

In a recent paper in EMBO Molecular Medicine, Weis et al. reveal that cardiac endothelial cells can oxidize ketone bodies, which enhances cell proliferation, migration, and vessel sprouting. Furthermore, increasing ketone body levels with a ketogenic diet can increase endothelial cell proliferation and prevent blood vessel rarefication in hypertrophied mouse hearts. This suggests that increasing endothelial cell ketone oxidation has potential in treating heart failure.
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http://dx.doi.org/10.1016/j.cmet.2022.03.008DOI Listing
April 2022

Effect of Vupanorsen on Non-High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70.

Circulation 2022 05 3;145(18):1377-1386. Epub 2022 Apr 3.

TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (B.A.B., N.A.M., A.J., J.F.K., J.-G.P., S.A.M., M.S.S., S.D.W.).

Background: Genetic loss-of-function variants in are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis.

Methods: Adults with non-high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 mg/dL on statin therapy were randomized in a double-blind fashion to placebo or 1 of 7 vupanorsen dose regimens (80, 120, or 160 mg SC every 4 weeks, or 60, 80, 120, or 160 mg SC every 2 weeks). The primary end point was placebo-adjusted percentage change from baseline in non-HDL-C at 24 weeks. Secondary end points included placebo-adjusted percentage changes from baseline in triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and ANGPTL3.

Results: Two hundred eighty-six subjects were randomized: 44 to placebo and 242 to vupanorsen. The median age was 64 (interquartile range, 58-69) years, 44% were female, the median non-HDL-C was 132.4 (interquartile range, 118.0-154.1) mg/dL, and the median triglycerides were 216.2 (interquartile range, 181.4-270.4) mg/dL. Vupanorsen resulted in significant decreases from baseline over placebo in non-HDL-C ranging from 22.0% in the 60 mg every 2 weeks arm to 27.7% in the 80 mg every 2 weeks arm (all <0.001 for all doses). There were dose-dependent reductions in triglycerides that ranged from 41.3% to 56.8% (all <0.001). The effects on LDL-C and ApoB were more modest (7.9%-16.0% and 6.0%-15.1%, respectively) and without a clear dose-response relationship' and only the higher reductions achieved statistical significance. ANGPTL3 levels were decreased in a dose-dependent manner by 69.9% to 95.2% (all <0.001). There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen. Injection site reactions and >3× elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively), and there was a dose-dependent increase in hepatic fat fraction (up to 76%).

Conclusions: Vupanorsen administered at monthly equivalent doses from 80 to 320 mg significantly reduced non-HDL-C and additional lipid parameters. Injection site reactions and liver enzyme elevations were more frequent at higher doses, and there was a dose-dependent increase in hepatic fat fraction.

Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT04516291.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.122.059266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047643PMC
May 2022

Usage récent de cannabis et infarctus du myocarde chez de jeunes adultes: étude transversale.

CMAJ 2022 03;194(12):E464-E472

Service d'anesthésie (Ladha, Mistry, Wijeysundera, Hare, Mazer), Hôpital St. Michael, Réseau hospitalier Unity Health de Toronto et Institut des politiques, de la gestion et de l'évaluation de la santé (Ladha, Wijeysundera), Institut des sciences médicales (Mistry, Mazer), Service d'anesthésie et de gestion de la douleur, Hôpital général de Toronto, Réseau universitaire de santé (Clarke) et Division de chirurgie cardiaque (Verma), Hôpital St. Michael, Réseau hospitalier Unity Health de Toronto, et Département de chirurgie (Verma) et Département de physiologie (Hare, Mazer), Université de Toronto, Toronto, Ont.

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http://dx.doi.org/10.1503/cmaj.202392-fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967434PMC
March 2022

Cardiovascular efficacy of liraglutide and semaglutide in individuals with diabetes and peripheral artery disease.

Diabetes Obes Metab 2022 07 11;24(7):1288-1299. Epub 2022 Apr 11.

CPC Clinical Research, University of Colorado School of Medicine, Aurora, Colorado, USA.

Aim: To evaluate the cardiovascular (CV) efficacy of liraglutide and semaglutide in patients with type 2 diabetes (T2D) and peripheral artery disease (PAD).

Materials And Methods: LEADER and SUSTAIN 6 trials investigated subcutaneous liraglutide (≤1.8 mg/day) and semaglutide (0.5 or 1.0 mg/week), respectively, versus placebo in patients with T2D and high CV risk (median follow-up: 3.8 and 2.1 years, respectively). The primary outcome was a composite of CV death, non-fatal myocardial infarction or non-fatal stroke (major adverse CV event [MACE]) according to the presence of PAD at baseline.

Results: Overall, 1184/9340 (12.7%) patients in LEADER and 460/3297 (14.0%) in SUSTAIN 6 had PAD at baseline. Patients with PAD were at an ~35% increased risk of MACE versus those without (LEADER: hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.17-1.58; SUSTAIN 6: HR 1.33, 95% CI 0.94-1.83). The effects of both therapies on MACE were consistently beneficial in patients with PAD (liraglutide: HR 0.77, 95% CI 0.58-1.01; semaglutide: 0.61, 0.33-1.13) and without (liraglutide: HR 0.89, 95% CI 0.79-1.00; semaglutide: HR 0.77, 95% CI 0.58-1.01; P  = .34 for liraglutide and .49 for semaglutide). Absolute risk reductions for MACE were higher in patients with PAD (liraglutide: 4.13%-point, 95% CI -0.15-8.42; semaglutide: 4.63%-point, 95% CI -0.58-9.84) versus without (liraglutide:1.42%-point, 95% CI -0.03-2.87; semaglutide: 1.90%-point, 95% CI 0.00-3.80).

Conclusion: Both liraglutide and semaglutide reduce MACE with consistent CV efficacy regardless of PAD status.
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http://dx.doi.org/10.1111/dom.14700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325529PMC
July 2022

Transcriptional control of Arabidopsis seed development.

Planta 2022 Mar 23;255(4):90. Epub 2022 Mar 23.

Mendel Centre for Genomics and Proteomics of Plants Systems, CEITEC MU - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

Main Conclusion: The entire process of embryo development is under the tight control of various transcription factors. Together with other proteins, they act in a combinatorial manner and control distinct events during embryo development. Seed development is a complex process that proceeds through sequences of events regulated by the interplay of various genes, prominent among them being the transcription factors (TFs). The members of WOX, HD-ZIP III, ARF, and CUC families have a preferential role in embryonic patterning. While WOX TFs are required for initiating body axis, HD-ZIP III TFs and CUCs establish bilateral symmetry and SAM. And ARF5 performs a major role during embryonic root, ground tissue, and vasculature development. TFs such as LEC1, ABI3, FUS3, and LEC2 (LAFL) are considered the master regulators of seed maturation. Furthermore, several new TFs involved in seed storage reserves and dormancy have been identified in the last few years. Their association with those master regulators has been established in the model plant Arabidopsis. Also, using chromatin immunoprecipitation (ChIP) assay coupled with transcriptomics, genome-wide target genes of these master regulators have recently been proposed. Many seed-specific genes, including those encoding oleosins and albumins, have appeared as the direct target of LAFL. Also, several other TFs act downstream of LAFL TFs and perform their function during maturation. In this review, the function of different TFs in different phases of early embryogenesis and maturation is discussed in detail, including information about their genetic and molecular interactors and target genes. Such knowledge can further be leveraged to understand and manipulate the regulatory mechanisms involved in seed development. In addition, the genomics approaches and their utilization to identify TFs aiming to study embryo development are discussed.
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http://dx.doi.org/10.1007/s00425-022-03870-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8940821PMC
March 2022

Empagliflozin in patients with type 2 diabetes mellitus and chronic obstructive pulmonary disease.

Diabetes Res Clin Pract 2022 Apr 18;186:109837. Epub 2022 Mar 18.

Yale University School of Medicine, New Haven, CT, USA.

Aims: Type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) often co-exist, yielding increased risk of cardiovascular (CV) complications including heart failure (HF). We assessed risk of cardiorenal outcomes, mortality and safety in patients with versus without COPD in the EMPA-REG OUTCOME trial.

Methods: Patients (n = 7,020) with T2DM and CV disease (CVD) were treated with empagliflozin (10 mg or 25 mg) or placebo. Cox regression was used to assess COPD subgroup (placebo only) associations with, and treatment effects of empagliflozin versus placebo on first hospitalization for HF (HHF), CV death, all-cause mortality, incident/worsening nephropathy, and all-cause hospitalization.

Results: At baseline, patients with COPD (n = 707) had more HF and used insulin more frequently than those without COPD. During follow-up in the placebo group, those with baseline COPD had increased risk of HHF (HR 2.15 [95% CI 1.32, 3.49]), HHF/CV death (1.60 [1.10, 2.33]), incident/worsening nephropathy (1.68 [1.26, 2.24]), all-cause hospitalization (1.44 [1.19, 1.74]) and all-cause death (1.60 [1.09, 2.35]) compared to those without COPD. Empagliflozin consistently reduced all clinical outcomes, irrespective of COPD status (interaction p-values 0.14 to 0.96), with a confirmed safety profile.

Conclusions: In patients with T2DM and CVD, COPD increased the risk of mortality and cardiorenal outcomes, including HF. Empagliflozin consistently reduced these outcomes versus placebo regardless of COPD, suggesting that empagliflozin's benefits in patients with T2DM and CVD are not mitigated by the presence of COPD.
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http://dx.doi.org/10.1016/j.diabres.2022.109837DOI Listing
April 2022

Sodium-Glucose Cotransporter 2 Inhibitors and Cardiac Remodeling.

J Cardiovasc Transl Res 2022 Mar 15. Epub 2022 Mar 15.

Division of Cardiology, Department of Medicine, Duke University, 2301 Erwin Road, Durham, NC, USA.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have evident cardiovascular benefits in patients with type 2 diabetes with or at high risk for atherosclerotic cardiovascular disease, heart failure with reduced ejection fraction, heart failure with preserved ejection fraction (only empagliflozin and dapagliflozin have been investigated in this group so far), and chronic kidney disease. Prevention and reversal of adverse cardiac remodeling is one of the mechanisms by which SGLT2 inhibitors may exert cardiovascular benefits, especially heart failure-related outcomes. Cardiac remodeling encompasses molecular, cellular, and interstitial changes that result in favorable changes in the mass, geometry, size, and function of the heart. The pathophysiological mechanisms of adverse cardiac remodeling are related to increased apoptosis and necrosis, decreased autophagy, impairments of myocardial oxygen supply and demand, and altered energy metabolism. Herein, the accumulating evidence from animal and human studies is reviewed investigating the effects of SGLT2 inhibitors on these mechanisms of cardiac remodeling.
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http://dx.doi.org/10.1007/s12265-022-10220-5DOI Listing
March 2022

Treatment With Icosapent Ethyl to Reduce Ischemic Events in Patients With Prior Percutaneous Coronary Intervention: Insights From REDUCE-IT PCI.

J Am Heart Assoc 2022 03 9;11(6):e022937. Epub 2022 Mar 9.

Department of Medicine Baylor College of MedicineCenter for Cardiovascular Disease PreventionMethodist DeBakey Heart and Vascular Center Houston TX.

Background Patients who undergo percutaneous coronary intervention (PCI) are at increased risk for recurrent cardiovascular events despite aggressive medical therapy. Methods and Results This post hoc analysis focused on the subset of patients with prior PCI enrolled in REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), a multicenter, randomized, double-blind, placebo-controlled trial of icosapent ethyl versus placebo. Icosapent ethyl was added to statins in patients with low-density lipoprotein cholesterol <100 mg/dL and fasting triglycerides 135-499 mg/dL. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. There were 8179 patients randomized in REDUCE-IT followed for a median of 4.9 years, and 3408 (41.7%) of them had a prior PCI with a median follow-up of 4.8 years. These patients were randomized a median of 2.9 years (11 days to 30.7 years) after PCI. Among patients treated with icosapent ethyl versus placebo, there was a 34% reduction in the primary composite end point (hazard ratio [HR], 0.66; 95% CI, 0.58-0.76; <0.001; number needed to treat=12) and a 34% reduction in the key secondary composite end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR, 0.66; 95% CI, 0.56-0.79; <0.001; NNT=19) versus placebo. Similarly, large reductions occurred in total coronary revascularizations and revascularization subtypes. There was also a 39% reduction in total events (rate ratio, 0.61; 95% CI, 0.52-0.72; <0.001). Conclusions Among patients treated with statins with elevated triglycerides and a history of prior PCI, icosapent ethyl substantially reduced the risk of recurrent events during an average of ~5 years of follow-up with a number needed to treat of only 12. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.
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http://dx.doi.org/10.1161/JAHA.121.022937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075300PMC
March 2022

Benefits of GLP-1 (Glucagon-Like Peptide 1) Receptor Agonists for Stroke Reduction in Type 2 Diabetes: A Call to Action for Neurologists.

Stroke 2022 05 9;53(5):1813-1822. Epub 2022 Mar 9.

Sunnybrook Health Sciences Centre, University of Toronto, Canada (J.J.H.).

People living with diabetes are at higher risk for stroke and have a poorer prognosis following a stroke event than those without diabetes. Data from cardiovascular outcome trials and meta-analyses indicate that GLP-1RAs (glucagon-like peptide 1 receptor agonists) reduce the risk of stroke in individuals with type 2 diabetes. Accordingly, many guidelines now recommend the addition of GLP-1RAs to ongoing antihyperglycemic regimens to lower the risk of stroke in type 2 diabetes. The current work summarizes evidence supporting the use of GLP-1RAs for stroke reduction in people with type 2 diabetes and offers 2 new resources for neurologists who are considering GLP-1RAs for their patients-a list of frequently asked questions with evidence-based answers on safely initiating and managing GLP-1RAs, and a practical decision-making algorithm to assist in using GLP-1RAs as part of a stroke reduction strategy.
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http://dx.doi.org/10.1161/STROKEAHA.121.038151DOI Listing
May 2022

Baseline Characteristics of Patients With HF With Mildly Reduced and Preserved Ejection Fraction: DELIVER Trial.

JACC Heart Fail 2022 03;10(3):184-197

Jefe de Unidad de Insuficiencia Cardíaca, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Argentina.

Objectives: This report describes the baseline clinical profiles and management of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial participants and how these compare with those in other contemporary heart failure with preserved ejection fraction trials.

Background: The DELIVER trial was designed to evaluate the effects of the sodium-glucose cotransporter-2 inhibitor dapagliflozin on cardiovascular death, heart failure (HF) hospitalization, or urgent HF visits in patients with HF with mildly reduced and preserved left ventricular ejection fraction (LVEF).

Methods: Adults with symptomatic HF and LVEF >40%, with or without type 2 diabetes mellitus, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and evidence of structural heart disease were randomized to dapagliflozin 10 mg once daily or matching placebo.

Results: A total of 6,263 patients were randomized (mean age: 72 ± 10 years; 44% women; 45% type 2 diabetes mellitus; 45% with body mass index ≥30 kg/m; and 57% with history of atrial fibrillation or flutter). Most participants had New York Heart Association functional class II symptoms (75%). Baseline mean LVEF was 54.2 ± 8.8% and median NT-proBNP of 1,399 pg/mL (IQR: 962 to 2,210 pg/mL) for patients in atrial fibrillation/flutter compared with 716 pg/mL (IQR: 469 to 1,281 pg/mL) in those who were not. Patients in both hospitalized and ambulatory settings were enrolled, including 10% enrolled in-hospital or within 30 days of a hospitalization for HF. Eighteen percent of participants had HF with improved LVEF.

Conclusions: DELIVER is the largest and broadest clinical trial of this population to date and enrolled high-risk, well-treated patients with HF with mildly reduced and preserved LVEF. (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [NCT03619213]).
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http://dx.doi.org/10.1016/j.jchf.2021.11.006DOI Listing
March 2022

Sodium-glucose cotransporter 2 inhibitors in heart failure with reduced or preserved ejection fraction: a meta-analysis.

ESC Heart Fail 2022 04 2;9(2):942-946. Epub 2022 Feb 2.

Division of Cardiac Surgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Aims: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to be an effective therapy in improving heart failure outcomes. We conducted a meta-analysis of randomized controlled trials to evaluate the efficacy of SGLT2 inhibitors in heart failure patients with either a reduced or preserved ejection fraction.

Methods And Results: We searched MEDLINE and EMBASE for large (≥1000 patients) randomized controlled trials evaluating the effects of SGLT2 inhibitors compared with placebo in the setting of heart failure until September 2021. Our primary outcome was the composite of heart failure hospitalization and cardiovascular death, and secondary outcomes included all-cause mortality and total heart failure hospitalizations. We pooled hazard ratios and risk ratios and evaluated risk of bias with the Cochrane Collaboration tool. Four randomized controlled trials (DAPA HF, EMPEROR-Preserved, EMPEROR-Reduced, and SOLOIST-WHF) were included (n = 15 684); two of which evaluated patients with a reduced LVEF, one of which evaluated patients with a preserved LVEF, and one of which included both. Treatment with SGLT2 inhibitors resulted in a significant reduction in the composite of CV death and heart failure hospitalization (HR: 0.76, 95% CI: 0.70, 0.82, I : 0%, P < 0.00001). This was consistent in sub-groups of patients with LVEF ≤40% (n = 9199, HR: 0.74, 95% CI: 0.68, 0.81, I : 0%) and LVEF >40% (n = 6482, HR: 0.78, 95% CI: 0.68, 0.89, I : 0%, P-for-interaction: 0.57), as well as in sub-groups of patients with and without diabetes mellitus at baseline (P-for-interaction: 0.81). SGLT2 inhibitors were associated with a significant reduction in cardiovascular death (HR: 0.87, 95% CI: 0.79, 0.97, I : 0%, P < 0.00001) and total heart failure hospitalization (RR: 0.71, 95% CI: 0.67, 0.76, I : 0%, P < 0.00001); although a potential trend towards reduced all-cause mortality was noted with SGLT2 inhibitors, no statistically significant difference was observed (HR: 0.91, 95% CI: 0.83, 1.00, I : 14%, P = 0.05).

Conclusions: Sodium-glucose cotransporter 2 inhibitors reduce cardiovascular death and heart failure hospitalization among patients with heart failure, regardless of LVEF status.
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http://dx.doi.org/10.1002/ehf2.13805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934917PMC
April 2022

Leaflet Resection vs Preservation for Degenerative Mitral Regurgitation: Functional Outcomes and Mitral Stenosis at 12 Months in a Randomized Trial.

Can J Cardiol 2022 06 21;38(6):808-814. Epub 2022 Jan 21.

Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Ontario, Canada. Electronic address:

Background: Mitral valve repair is the gold standard treatment for degenerative mitral regurgitation (MR). The Canadian Mitral Research Alliance (CAMRA) CardioLink-2 trial showed no significant association between repair strategy, that is, leaflet resection vs preservation, and risk of functional mitral stenosis. In this subanalysis, we compared outcomes and functional tests at 12 months.

Methods: CAMRA CardioLink-2 was a multicentre randomized controlled trial that allocated patients with degenerative MR and posterior leaflet prolapse to leaflet resection (n = 54) or preservation (n = 50). Stress echocardiography and functional status assessments, including the 6-minute walk test, were compared 12 months after repair.

Results: Baseline demographics, stress echocardiographic findings, and mitral annuloplasty prosthesis size (33.0 ± 3.0 vs 33.6 ± 3.4 mm; P = 0.4) were similar between the two groups. There were no readmissions for heart failure or deaths during the follow-up period. At 12 months, a larger percentage of patients were in NYHA functional class ≥ 2 in the resection group compared with the preservation group (P = 0.01). Exercise capacity, rate-pressure product, 6-minute walk distance, and mean mitral valve gradients were not significantly different between the groups at 12 months. A more prominent increase in mean mitral gradient with smaller annuloplasty sizes was observed in the resection group at both rest (P = 0.03) and peak exercise (P = 0.005) in the linear regression model.

Conclusions: At 12 months, there were no significant differences in mitral valve gradient, exercise capacity, and 6-minute walk test between repair strategies. Leaflet preservation may offer a larger mitral valve orifice with improved gradients in patients requiring smaller annuloplasty sizes.
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http://dx.doi.org/10.1016/j.cjca.2022.01.013DOI Listing
June 2022
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