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This article discusses the use of calcium channel blockers (CCBs) in the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF). The article highlights that while certain therapies have been approved for heart failure with reduced ejection fraction (HFrEF) and have shown benefits for HFmrEF and HFpEF, the evidence base for beta-blockade in HFpEF is poor. The article presents a study that analyzes the association of CCBs on outcomes in patients with HFmrEF and HFpEF, finding that CCB use was associated with no difference in cardiovascular death or heart failure hospitalization. However, CCB use was associated with a lower risk of death due to pump failure and a higher risk of non-fatal stroke. The article suggests that dihydropyridine CCBs could be considered for managing comorbidities in patients with HFmrEF and HFpEF without increasing the risk of heart failure-related outcomes. The study has limitations, and further research is needed to fully understand the effects of CCBs in these patient populations. Overall, the article provides valuable insights into the use of medications in heart failure treatment and calls for a reconsideration of traditional concepts regarding indicated and contraindicated therapies. [Extracted from the article]

B This article refers to 'Dosing of losartan in men versus women with heart failure with reduced ejection fraction: the HEAAL trial' by J.P. Ferreira I et al i ., published in this issue on pages 1477-1484. b It is well known that women have been under-represented in early clinical trials of heart failure (HF). The authors noted that clinical factors associated with female sex may have suggested more frail patients, who were possibly less able to tolerate high-dose medical therapy - a plausible underlying reason for the difference in dose-response relationship. [Extracted from the article]

B This article refers to 'A machine learning risk score predicts mortality across the spectrum of left ventricular ejection fraction' by B. Greenberg I et al i ., published in this issue on pages 995-999. b The desire to predict future events has been a basic human quality. It is therefore not surprising that numerous attempts to estimate mortality from heart failure (HF) have been made.1,2 In most cases, a predictive model is constructed by performing one or more regression techniques upon a clinical dataset and validated in a different dataset. In this context, risk prediction for HF outcomes would seem a particularly good fit for ML applications. [Extracted from the article]

Background: Left ventricular (LV) circumferential and longitudinal strain provide important insight into LV mechanics and function, each contributing to volumetric changes throughout the cardiac cycle. We sought to explore this strain-volume relationship in more detail, by mathematically integrating circumferential and longitudinal strain and strain rate to predict LV volume and volumetric rates of change. Methods: Cardiac magnetic resonance (CMR) imaging from 229 participants from the Alberta HEART Study (46 healthy controls, 77 individuals at risk for developing heart failure [HF], 70 patients with diagnosed HF with preserved ejection fraction [HFpEF], and 36 patients with diagnosed HF with reduced ejection fraction [HFrEF]) were evaluated. LV volume was assessed by the method of disks and strain/strain rate were assessed by CMR feature tracking. Results: Integrating endocardial circumferential and longitudinal strain provided a close approximation of LV ejection fraction (EFStrain), when compared to gold-standard volumetric assessment (EFVolume: r = 0.94, P < 0.0001). Likewise, integrating circumferential and longitudinal strain rate provided a close approximation of peak ejection and peak filling rates (PERStrain and PFRStrain, respectively) compared to their gold-standard volume-time equivalents (PERVolume, r = 0.73, P < 0.0001 and PFRVolume, r = 0.78, P < 0.0001, respectively). Moreover, each integrated strain measure differentiated patients across the HF continuum (all P < 0.01), with the HFrEF group having worse EFStrain, PERStrain, and PFRStrain compared to all other groups, and HFpEF having less favorable EFStrain and PFRStrain compared to both at-risk and control groups. Conclusions: The data herein establish the theoretical framework for integrating discrete strain components into volumetric measurements across the cardiac cycle, and highlight the potential benefit of this approach for differentiating patients along the heart failure continuum. [ABSTRACT FROM AUTHOR]

Aims: To compare the cost‐effectiveness of immediate and 12‐month delayed initiation of dapagliflozin treatment in patients with a history of hospitalization for heart failure (HHF) from the UK, Canadian, German, and Spanish healthcare perspectives. Methods and results: A cost‐utility analysis was conducted using a decision‐analytic Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire scores, type 2 diabetes mellitus status and incidence of heart failure (HF) events. Patient‐level data for patients with prior HHF from the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial were used to inform the model inputs on clinical events and utility values. Healthcare costs were sourced from the relevant national reference databases and the published literature. Compared to standard therapy, immediate initiation of dapagliflozin decreased HHF (187 events), urgent HF visits (32 events) and cardiovascular mortality (18 events). Standard therapy was associated with lifetime costs of £13 224 and 4.02 quality‐adjusted life years (QALYs). Twelve‐month delayed initiation of dapagliflozin was associated with total discounted lifetime costs and QALYs of £16 660 and 4.61, respectively, compared to £16 912 and 4.66, respectively, for immediate initiation. Compared to standard therapy, immediate and 12‐month delayed initiation of dapagliflozin yielded an incremental cost‐effectiveness ratio (ICER) of £5779 and £5821, respectively. Compared to 12‐month delayed initiation, immediate initiation of dapagliflozin had an ICER of £5263. Results were similar from the Canadian, German, and Spanish healthcare perspectives. Conclusion: Both immediate and 12‐month delayed initiation of dapagliflozin are cost‐effective. However, immediate initiation provides greater clinical benefits, with almost 10% additional QALYs gain, compared to 12‐month delayed initiation of dapagliflozin and should be considered standard of care. [ABSTRACT FROM AUTHOR]

Background: In North America and other industrialized countries, heart failure (HF) has become a national public health priority. Studies indicate there is significant heterogeneity in approaches to treat and manage HF and suggest targeted changes in health care delivery are needed to reduce unnecessary health care utilization and to optimize patient outcomes. Most recent published studies have reported on the care of HF patients in tertiary care hospitals and the perspective of non-specialist stakeholders on HF management, such as general practitioners and clinics or hospital administrators is rarely considered. This study explores the current state of community-based HF care in Canada as experienced by various healthcare stakeholders providing or coordinating care to HF patients. Methods: This study employed a qualitative exploratory research design consisting of semi-structured telephone interviews conducted with health care providers and health care administrators working outside of tertiary care in the four most populous Canadian provinces. A modified thematic analysis process was used and the different data sources were triangulated. Findings were collectively interpreted by the authors. Results: Twenty-eight participants were recruited in the study: eight cardiologists, five general practitioners/family physicians, eight nurse practitioners/registered nurses, four hospital pharmacists and three health care administrators/directors. Participants reported a lack of stakeholder engagement throughout the continuum of care, which hinders the implementation of a coordinated approach to quality HF care. Four substantive themes emerged that indicated challenges and gaps in the optimal treatment and management of HF in community settings: 1) challenges in the risk assessment and early diagnosis of HF, 2) challenges in ensuring efficient and consistent transition from acute care setting to the community, 3) challenges of primary care providers to optimally treat and manage HF patients, and 4) challenges in promoting a holistic approach in HF management. Conclusions: As health systems evolve from tertiary-based care to community-based outpatient services for the management of chronic diseases, this study's findings pinpoint challenges that have been observed in the Canadian context and can stimulate and orient dialogue toward solutions for a more coordinated approach to improve the care of HF patients and reduce pressure on the healthcare system. [ABSTRACT FROM AUTHOR]

Background: In North America and other industrialized countries, heart failure (HF) has become a national public health priority. Studies indicate there is significant heterogeneity in approaches to treat and manage HF and suggest targeted changes in health care delivery are needed to reduce unnecessary health care utilization and to optimize patient outcomes. Most recent published studies have reported on the care of HF patients in tertiary care hospitals and the perspective of non-specialist stakeholders on HF management, such as general practitioners and clinics or hospital administrators is rarely considered. This study explores the current state of community-based HF care in Canada as experienced by various healthcare stakeholders providing or coordinating care to HF patients. Methods: This study employed a qualitative exploratory research design consisting of semi-structured telephone interviews conducted with health care providers and health care administrators working outside of tertiary care in the four most populous Canadian provinces. A modified thematic analysis process was used and the different data sources were triangulated. Findings were collectively interpreted by the authors. Results: Twenty-eight participants were recruited in the study: eight cardiologists, five general practitioners/family physicians, eight nurse practitioners/registered nurses, four hospital pharmacists and three health care administrators/directors. Participants reported a lack of stakeholder engagement throughout the continuum of care, which hinders the implementation of a coordinated approach to quality HF care. Four substantive themes emerged that indicated challenges and gaps in the optimal treatment and management of HF in community settings: 1) challenges in the risk assessment and early diagnosis of HF, 2) challenges in ensuring efficient and consistent transition from acute care setting to the community, 3) challenges of primary care providers to optimally treat and manage HF patients, and 4) challenges in promoting a holistic approach in HF management. Conclusions: As health systems evolve from tertiary-based care to community-based outpatient services for the management of chronic diseases, this study’s findings pinpoint challenges that have been observed in the Canadian context and can stimulate and orient dialogue toward solutions for a more coordinated approach to improve the care of HF patients and reduce pressure on the healthcare system. [ABSTRACT FROM AUTHOR]

Aims: Among patients with heart failure (HF) and reduced ejection fraction (HFrEF), those with atrial fibrillation (AF) may respond differently to certain treatments than patients without AF. We investigated the efficacy and safety of dapagliflozin in patients with HFrEF with and without AF in the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF). We also examined the effect of dapagliflozin on new‐onset AF. Methods and results: The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized, 1910 (40.3%) had 'any AF' (history of AF or AF on enrolment electrocardiogram). Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in patients with and without any AF [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.62–0.92 and 0.74, 95% CI 0.62–0.88, respectively; p for interaction = 0.88]. Consistent benefits were observed for the components of the primary outcome, all‐cause mortality, and improvement of Kansas City Cardiomyopathy Questionnaire total symptom score. Among patients without AF at baseline, dapagliflozin did not significantly reduce the risk of new‐onset AF compared with placebo (HR 0.86, 95% CI 0.60–1.22). However, patients with new‐onset AF had a 5 to 6‐fold higher risk of adverse outcomes when compared to those without incident AF. Conclusions: Dapagliflozin, compared with placebo, reduced the risk of worsening HF events, cardiovascular death, and all‐cause death, and improved symptoms, in patients with and without AF. Dapagliflozin did not reduce the risk of new‐onset AF. [ABSTRACT FROM AUTHOR]

Aims Among patients with heart failure (HF) and reduced ejection fraction (HFrEF), those with atrial fibrillation (AF) may respond differently to certain treatments than patients without AF. We investigated the efficacy and safety of dapagliflozin in patients with HFrEF with and without AF in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on new-onset AF. Methods and results The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized, 1910 (40.3%) had 'any AF' (history of AF or AF on enrolment electrocardiogram). Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in patients with and without any AF [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.62-0.92 and 0.74, 95% CI 0.62-0.88, respectively; p for interaction = 0.88]. Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and improvement of Kansas City Cardiomyopathy Questionnaire total symptom score. Among patients without AF at baseline, dapagliflozin did not significantly reduce the risk of new-onset AF compared with placebo (HR 0.86, 95% CI 0.60-1.22). However, patients with new-onset AF had a 5 to 6-fold higher risk of adverse outcomes when compared to those without incident AF. Conclusions Dapagliflozin, compared with placebo, reduced the risk of worsening HF events, cardiovascular death, and all-cause death, and improved symptoms, in patients with and without AF. Dapagliflozin did not reduce the risk of new-onset AF. [ABSTRACT FROM AUTHOR]

Background: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo.Methods: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms.Results: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization.Conclusions: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article about heart failure with reduced and preserved ejection fraction that highlight common and practical issues by patients and clinicians, which appeared in the previous issue of the magazine.

Background: Heart failure is a costly health condition and a major public health concern. We sought to examine the costs of hospital admissions for heart failure between fiscal years 2004 and 2013 in Canada and to model the future costs to 2030. Methods: Canadian Institutes for Health Information Discharge Abstract Database was used to identify admissions to hospital with heart failure as the primary diagnosis between fiscal years 2004 and 2013. Multiple linear regression models were used to calculate the trend in prevalence and extrapolate these to 2030. Canadian Institutes for Health Information patient cost estimates were used to identify costs of hospital admissions for heart failure. Generalized linear models were used to estimate average annual costs per heart failure patient. We conducted a sensitivity analysis including all admissions for heart failure in any diagnostic field. Results: In 2013, 45 600 (95% confidence interval [CI]: 43 800-47 200) patients were admitted with heart failure as the primary diagnosis, accounting for $482 (95% CI $464-$500) million. By 2030, we estimate 54 000 (95% CI 49 000-60 000) patients and costs of $722 (95% CI $650-$801) million, with older adults (age ≥ 80 yr) accounting for 52% of costs. Including admissions for which heart failure was a secondary diagnosis increases the total cost to $2.8 (95% CI $2.6-$3.0) billion in 2030. Interpretation: As in other developed countries, hospital costs related to heart failure in Canada are on the rise. Older adults are the main consumers of such hospital services. Strategies to improve outpatient care to reduce rates of admission for heart failure are needed. [ABSTRACT FROM AUTHOR]

Background: The STICH (Surgical Treatment for Ischemic Heart Failure) trial compared a strategy of routine coronary artery bypass grafting (CABG) with guideline-based medical therapy for patients with ischemic left ventricular dysfunction.Objective: To describe treatment-related quality-of-life (QOL) outcomes, a major prespecified secondary end point in the STICH trial.Design: Randomized trial. (ClinicalTrials.gov: NCT00023595).Setting: 99 clinical sites in 22 countries.Patients: 1212 patients with a left ventricular ejection fraction of 0.35 or less and coronary artery disease.Intervention: Random assignment to medical therapy alone (602 patients) or medical therapy plus CABG (610 patients).Measurements: A battery of QOL instruments at baseline (98.9% complete) and 4, 12, 24, and 36 months after randomization (collection rates were 80% to 89% of those eligible). The principal prespecified QOL measure was the Kansas City Cardiomyopathy Questionnaire, which assesses the effect of heart failure on patients' symptoms, physical function, social limitations, and QOL.Results: The Kansas City Cardiomyopathy Questionnaire overall summary score was consistently higher (more favorable) in the CABG group than in the medical therapy group by 4.4 points (95% CI, 1.8 to 7.0 points) at 4 months, 5.8 points (CI, 3.1 to 8.6 points) at 12 months, 4.1 points (CI, 1.2 to 7.1 points) at 24 months, and 3.2 points (CI, 0.2 to 6.3 points) at 36 months. Sensitivity analyses to account for the effect of mortality on follow-up QOL measurement were consistent with the primary findings.Limitation: Therapy was not masked.Conclusion: In this cohort of symptomatic high-risk patients with ischemic left ventricular dysfunction and multivessel coronary artery disease, CABG plus medical therapy produced clinically important improvements in quality of life compared with medical therapy alone over 36 months.Primary Funding Source: National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]

Background: Patients with ischemic left ventricular dysfunction have higher operative risk with coronary artery bypass graft surgery (CABG). However, those whose early risk is surpassed by subsequent survival benefit have not been identified.Objectives: This study sought to examine the impact of anatomic variables associated with poor prognosis on the effect of CABG in ischemic cardiomyopathy.Methods: All 1,212 patients in the STICH (Surgical Treatment of IsChemic Heart failure) surgical revascularization trial were included. Patients had coronary artery disease (CAD) and ejection fraction (EF) of ≤35% and were randomized to receive CABG plus medical therapy or optimal medical therapy (OMT) alone. This study focused on 3 prognostic factors: presence of 3-vessel CAD, EF below the median (27%), and end-systolic volume index (ESVI) above the median (79 ml/m(2)). Patients were categorized as having 0 to 1 or 2 to 3 of these factors.Results: Patients with 2 to 3 prognostic factors (n = 636) had reduced mortality with CABG compared with those who received OMT (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.56 to 0.89; p = 0.004); CABG had no such effect in patients with 0 to 1 factor (HR: 1.08; 95% CI: 0.81 to 1.44; p = 0.591). There was a significant interaction between the number of factors and the effect of CABG on mortality (p = 0.022). Although 30-day risk with CABG was higher, a net beneficial effect of CABG relative to OMT was observed at >2 years in patients with 2 to 3 factors (HR: 0.53; 95% CI: 0.37 to 0.75; p<0.001) but not in those with 0 to 1 factor (HR: 0.88; 95% CI: 0.59 to 1.31; p = 0.535).Conclusions: Patients with more advanced ischemic cardiomyopathy receive greater benefit from CABG. This supports the indication for surgical revascularization in patients with more extensive CAD and worse myocardial dysfunction and remodeling. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595). [ABSTRACT FROM AUTHOR]

Background Patients with ischemic left ventricular dysfunction have higher operative risk with coronary artery bypass graft surgery (CABG). However, those whose early risk is surpassed by subsequent survival benefit have not been identified. Objectives This study sought to examine the impact of anatomic variables associated with poor prognosis on the effect of CABG in ischemic cardiomyopathy. Methods All 1,212 patients in the STICH (Surgical Treatment of IsChemic Heart failure) surgical revascularization trial were included. Patients had coronary artery disease (CAD) and ejection fraction (EF) of ≤35% and were randomized to receive CABG plus medical therapy or optimal medical therapy (OMT) alone. This study focused on 3 prognostic factors: presence of 3-vessel CAD, EF below the median (27%), and end-systolic volume index (ESVI) above the median (79 ml/m²). Patients were categorized as having 0 to 1 or 2 to 3 of these factors. Results Patients with 2 to 3 prognostic factors (n = 636) had reduced mortality with CABG compared with those who received OMT (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.56 to 0.89; p = 0.004); CABG had no such effect in patients with 0 to 1 factor (HR: 1.08; 95% CI: 0.81 to 1.44; p = 0.591). There was a significant interaction between the number of factors and the effect of CABG on mortality (p = 0.022). Although 30-day risk with CABG was higher, a net beneficial effect of CABG relative to OMT was observed at >2 years in patients with 2 to 3 factors (HR: 0.53; 95% CI: 0.37 to 0.75; p<0.001) but not in those with 0 to 1 factor (HR: 0.88; 95% CI: 0.59 to 1.31; p = 0.535). Conclusions Patients with more advanced ischemic cardiomyopathy receive greater benefit from CABG. This supports the indication for surgical revascularization in patients with more extensive CAD and worse myocardial dysfunction and remodeling. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595) [ABSTRACT FROM AUTHOR]