Guideline-directed Medical Therapy Research Articles

Contemporary guideline-directed medical therapy in de novo, chronic, and worsening heart failure patients: First data from the TITRATE-HF study.

Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real-world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE-HF study started to prospectively investigate the use, sequencing, and titration of guideline-directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers. TITRATE-HF is an ongoing long-term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and median ejection fraction was 35% (IQR 25-40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non-use in HFrEF patients was related to side-effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF. This first analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management.

Differences in provider approach to initiating and titrating guideline directed medical therapy in heart failure with reduced ejection fraction

BackgroundDespite the strong evidence supporting guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF), prescription rates in clinical practice are still lacking.MethodsA survey containing 20 clinical vignettes of patients with HFrEF was answered by a national sample of 127 cardiologists and 68 internal/family medicine physicians. Each vignette had 4–5 options for adjusting GDMT and the option to make no medication changes. Survey respondents could only select one option. For analysis, responses were dichotomized to the answer of interest.ResultsCardiologists were more likely to make GDMT changes than general medicine physicians (91.8% vs. 82.0%; OR 1.84 [1.07–3.19]; p = 0.020). Cardiologists were more likely to initiate beta-blockers (46.3% vs. 32.0%; OR 2.38 [1.18–4.81], p = 0.016), angiotensin receptor blocker/neprilysin inhibitor (ARNI) (63.8% vs. 48.1%; OR 1.76 [1.01–3.09], p = 0.047), and hydralazine and isosorbide dinitrate (HYD/ISDN) (38.2% vs. 23.7%; OR 2.47 [1.48–4.12], p < 0.001) compared to general medicine physicians. No differences were found in initiating angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARBs), initiating mineralocorticoid receptor antagonist (MRA), sodium-glucose transporter protein 2 (SGLT2) inhibitors, digoxin, or ivabradine.ConclusionsOur results demonstrate cardiologists were more likely to adjust GDMT than general medicine physicians. Future focus on improving GDMT prescribing should target providers other than cardiologists to improve care in patients with HFrEF.

Rediscovery of the implication of albuminuria in heart failure: emerging classic index for cardiorenal interaction.

The development of new drugs and device therapies has led to remarkable advancements in heart failure (HF) treatment in the past couple of decades. However, it becomes increasingly evident that guideline-directed medical therapy cannot be one-size-fits-all across a wide range of ejection fractions (EFs) and various aetiologies. Therefore, classifications solely relying on EF and natriuretic peptide make optimization of treatment challenging, and there is a growing exploration of new indicators that enable efficient risk stratification of HF patients. Particularly when considering HF as a multi-organ interaction syndrome, the cardiorenal interaction plays a central role in its pathophysiology, and albuminuria has gained great prominence as its biomarker, independent from glomerular filtration rate. Albuminuria has been shown to exhibit a linear correlation with cardiovascular disease and HF prognosis in multiple epidemiological studies, ranging from normal (<30mg/g) to high levels (>300mg/g). However, on the other hand, it is only recently that the details of the pathological mechanisms that give rise to albuminuria have begun to be elucidated, including the efficient compaction/tightening of the glomerular basement membrane by podocytes and mesangial cells. Interestingly, renal disease, diabetes, and HF damage these components associated with albuminuria, and experimental models have demonstrated that recently developed HF drugs reduce albuminuria by ameliorating these pathological phenotypes. In this review, facing the rapid expansion of horizons in HF treatment, we aim to clarify the current understanding of the pathophysiology of albuminuria and explore the comprehensive understanding of albuminuria by examining the clinically established evidence to date, the pathophysiological mechanisms leading to its occurrence, and the outcomes of clinical studies utilizing various drug classes committed to specific pathological mechanisms to put albuminuria as a novel axis to depict the pathophysiology of HF.

Spontaneous Coronary Artery Dissection in a Male Patient With Fibromuscular Dysplasia

Abstract A male patient presented with cardiac arrest attributed to anterior ST-segment elevation myocardial infarction from type 1 spontaneous coronary artery dissection. Subsequent imaging confirmed fibromuscular dysplasia in noncoronary arterial segments. The patient was started on guideline-directed medical therapy and referred to cardiac rehabilitation, showing substantial improvements in clinical status. With greater awareness and advancements in imaging, spontaneous coronary artery dissection has been more frequently recognized, and although as many as 81% to 92% of all cases occur in female patients, it can be seen among men, as well. Adjunctive imaging for arteriopathies may help establish the diagnosis for equivocal causes of acute coronary syndrome in women and men.

Utilizing median and maximum QTc values improves prediction of breakthrough cardiac events in pediatric long QT syndrome.

Although prior studies indicate that a QTc > 500 ms on a single baseline 12-lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS. We performed a retrospective analysis of 433 patients with LQTS evaluated, risk-stratified, and undergoing active guideline-based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF-terminating ICD shock, and sudden cardiac death (SCD). During the median follow-up of 5.5 years (interquartile range [IQR] = 3-9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c-statistic = 0.93-0.95). Patients in the high-risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%-81%) when compared to patients in both medium-risk (93%-97%) and low-risk (98%-99%) groups. The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12-lead ECGs are at the highest risk of BCE while on guideline-directed medical therapy.

Routine Functional Testing or Standard Care in High-Risk Patients after Percutaneous Coronary Intervention.

This review aimed to collate the available evidence on outcomes following routine functional stress testing vs standard of care (i.e. symptom-guided stress testing) in high-risk patients following percutaneous coronary intervention (PCI). The most recent pragmatic POST-PCI trial provided randomized evidence showing that routine functional stress testing post-PCI did not lead to a reduction in 2-year ischemic cardiovascular events or all-cause mortality, as compared to a symptom-guided standard-of-care approach. This was also true for sub-analyses including multivessel or left main disease, diabetics, as well as following imaging or physiology guided PCI. In the absence of a change in their clinical or functional status suggestive of stent failure, post-PCI routine periodic stress testing in stable patients on guideline-directed medical therapy is currently not recommended by American clinical practice guidelines. While evidence on the cost-effectiveness of routine stress testing strategy is scarce, physician, payer, and policy-level interventions to reduce inappropriate use of routine functional testing need to be addressed.

Recovery of left ventricular systolic function in peripartum cardiomyopathy: an observational study from rural Tanzania

BackgroundThe aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania.MethodsIn this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%).ResultsMedian age of the 110 participants was 28.5 years (range 17–45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15–46). After a median follow-up of 8.98 months (IQR 5.72–29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6–77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10–2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19–0.82, p = 0.012).ConclusionLeft ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care.

Validation of A New Scoring Method to Assess the Efficacy of Rapid Initiation and Titration of Combination Pharmacotherapy for Patients Hospitalized with Acute Decompensated Heart Failure with Reduced and Mildly Reduced Ejection Fraction

Background: Despite the encouragement of early initiation and titration of guideline-di-rected medical therapy (GDMT) for the treatment of heart failure (HF), most patients do not receive an adequate type and dose of pharmacotherapy in the real world. Objectives: This study aimed to determine the efficacy of titrating composite GDMT in patients with HF with reduced and mildly reduced ejection fraction and to identify patient conditions that may benefit from titration of GDMT. Methods: This was a two-center, retrospective study of consecutive patients hospitalized with acute decompensated heart failure (ADHF). Patients were classified into two groups according to a scoring scale determined by combination and doses of four types of HF agents (ACEis/ARBs/ARNis, BBs, MRAs, and SGLT2is) at discharge. A score of 5 or greater was defined as titrated GDMT, and a score of 4 or less was regarded as sub-optimal medical therapy (MT). Results: A total of 979 ADHF patients were screened. After 553 patients were excluded based on exclusion criteria, 426 patients (90 patients in the titrated GDMT group and 336 patients in the sub-optimal MT group) were enrolled for the analysis. The median follow-up period was 612 (453–798) days. Following statistical adjustment using the propensity score weighting method, the 2-year composite endpoint (composite of cardiac death and HF rehospitalization) rate was significantly lower in the titrated GDMT group, at 19%, compared with the sub-optimal MT group: 31% (score 3–4 points) and 43% (score 0–2 points). Subgroup analysis indicated a marked benefit of titrated GDMT in particular patient subgroups: age &lt; 80 years, BMI 19.0–24.9, eGFR &gt; 20 mL/min/1.73 m2, and serum potassium level ≤ 5.5 mmol/L. Conclusions: Prompt initiation and dose adjustment of multiple HF medications, with careful monitoring of the patient’s physiologic and laboratory values, is a prerequisite for improving the prognosis of patients with heart failure.

Multidisciplinary proactive e-consults to improve guideline-directed medical therapies for patients with diabetes and chronic kidney disease: an implementation study

IntroductionWe hypothesized that multidisciplinary, proactive electronic consultation (MPE) could overcome barriers to prescribing guideline-directed medical therapies (GDMTs) for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).Research design...

Real-World Clinical Burden of Newly Diagnosed Heart failure in Thai Patients.

There are limited data on the burden of newly diagnosed patients with heart failure (HF) in Thailand. Thus, this study aimed to fully understand the hospitalization, rehospitalization, mortality rates, demographics and characteristics, and quality of care in these patients. A retrospective review of all eligible adult patients' medical records from 2018 and 2019 was conducted at five hospitals.The patients were newly diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code "I50." Descriptive statistics was used to investigate patients' hospital burden and clinical outcome data. There were 1134 patients newly diagnosed with HF, classified as HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) (44.0, 40.0, and 16.0%, respectively). The male-to-female ratios in HFmrEF and HFpEF were similar. In contrast, the proportion of men with HFrEF was greater. The mean age of all patients was 66.0years. The hospitalization rate was 1.3. Rehospitalization rates for HF-related issues were 0.1, 0.2, 0.4, and 0.5 at 30days, 60days, 180days, and 1year, respectively. The percentage of deaths from all causes among these patients was 9.8%, while the percentage of deaths from cardiovascular-related causes was 8.5%. Only a small proportion of patients received a target dose of guideline-directed medical therapy (GDMT). The study revealed that the characteristics, hospitalization rate for HF, and in-hospital mortality rate among newly diagnosed patients with HF were higher compared to similar studies conducted in Thailand and other countries. Moreover, a high quality of care is needed to improve the morbidity and mortality associated with HF in Thailand.

Titration of Medications after Acute Heart Failure is Safe, Tolerated, and Effective Regardless of Risk.

Guideline-directed medical therapy decisions may be less affected by single patient variables such as blood pressure or kidney function and more by overall risk profile. In STRONG-HF, high intensity care (HIC) in the form of rapid uptitration of heart failure (HF) guideline-directed medical therapy (GDMT) was effective overall, but the safety, tolerability and efficacy of HIC across the spectrum of HF severity is unknown. Evaluating this with a simple risk-based framework offers an alternative and more clinically translatable approach than traditional subgroup analyses. To assess safety, tolerability, and efficacy of HIC according to the simple, powerful, and clinically translatable Meta-Analysis Global Group in Chronic (MAGGIC) HF risk score. In STRONG-HF, 1078 patients with acute HF were randomized to HIC (uptitration of treatments to 100% of recommended doses within 2 weeks of discharge and 4 scheduled outpatient visits over the 2 months after discharge) versus usual care (UC). The primary endpoint was the composite of all-cause death or first HF rehospitalization at Day 180. Baseline HF risk profile was determined by the previously validated MAGGIC risk score. Treatment effect was stratified according to MAGGIC risk score both as a categorical and continuous variable. Among 1062 patients (98.5%) with complete data for whom a MAGGIC score could be calculated at baseline, GDMT use at baseline was similar across MAGGIC tertiles. Overall GDMT prescriptions achieved for individual medication classes were higher in the HIC versus UC group and did not differ by MAGGIC risk score tertiles (interaction non-significant). The incidence of all-cause death or HF readmission at Day 180 was, respectively, 16.3%, 18.9%, and 23.2% for MAGGIC risk score tertiles 1-3. The HIC arm was at lower risk of all-cause death or HF readmission at Day 180 (HR 0.66, 95% CI 0.50-0.86) and this finding was robust across MAGGIC risk score modeled as a categorical (HR 0.51, 0.62, 0.68 in tertile 1, 2, and 3, respectively, (interaction non-significant) for all comparisons) and continuous (p-interaction=NS) variable. The rate of adverse events was higher in the HIC group, but this observation did not differ based on MAGGIC risk score tertile (interaction non-significant). HIC led to better use of GDMT and lower HF-related morbidity and mortality compared to UC regardless of underlying HF risk profile.

Deciphering mortality risk of diabetes medications in heart failure patients with diabetes mellitus under triple guideline-directed medical therapy

BackgroundScientific evidence regarding the impact of different combinations of diabetes medications in heart failure patients with diabetes mellitus (HFwDM) remains limited. AimWe aimed to investigate the effect of monotherapy and combination therapy for DM on all-cause mortality in HFwDM under triple guideline-directed medical therapy (GDMT). MethodThis nationwide retrospective cohort study included adult HFwDM under triple GDMT between January 1, 2016 and December 31, 2022.We collected the data from the National Electronic Database of the Turkish Ministry of Health.We created various combination including different diabetes medications based on the current guidelines for DM.The primary endpoint was all-cause mortality. ResultsA total of 321,525 HFwDM under triple GDMT (female:49%, median age:68[61–75] years) were included. The highest rate of prescribed combination therapy was metformin and sulfonylureas (n = 55,266). In Cox regression analysis, insülin monotherapy had the highest risk for all-cause mortality (HR:2.25, 95CI%:2.06–2.45), whereas combination therapy including metformin, SGLT2i, and sulfonylureas provided the most beneficial effect on survival (HR:0.29, 95CI%:0.22–0.39) when compared to patients not receiving diabetes medication. Among patients taking diabetes medications, the inclusion of SGLT2i demonstrated a survival benefit (p < 0.05), despite concurrent use of volume-retaining medications such as insulin and thiazolidinediones. Conversely, combinations of diabetes medications without SGLT2i did not demonstrate any survival benefit compared to patients not taking diabetes medication (p > 0.05). ConclusionThis study underscored the use of SGLT2i as monotherapy or as a part of combination diabetes medications to improve survival among HFwDM, while also highlighting that combinations lacking SGLT2i did not confer any survival benefit.

Supra-normal and mildly reduced ejection fraction in women -An overlooked vulnerable subpopulation in heart failure

BackgroundRecently, patients with supra-normal left ventricular ejection fraction (snEF) are reported to have high risk of adverse outcomes, especially in women. We sought to evaluate sex-related differences in the association between LVEF and long-term outcomes in heart failure (HF) patients. MethodsThe multicenter WET-HF Registry enrolled all patients hospitalized for acute decompensated HF (ADHF). We analyzed 3943 patients (age 77 years; 40.1% female) registered from 2006 to 2017. According to LVEF the patients were divided into the 3 groups: HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) and preserved EF. The primary endpoint was defined as the composite of cardiac death and ADHF rehospitalization after discharge. ResultsIn HFmrEF, implementation of guideline-directed medical therapy (GDMT) such as the combination of renin-angiotensin-system inhibitor (RASi) and β-blocker at discharge was significantly lower in women than men even after adjustment for covariates (p = 0.007). There were no such sex-related differences in HFrEF. Female sex was associated with higher incidence of the primary endpoint and ADHF rehospitalization after adjustment for covariates exclusively in HFmrEF. Restricted cubic spline analysis demonstrated a U-shaped relationship between LVEF and the hazard ratio of the primary endpoint showing higher event rate in HFmrEF and HFsnEF in women, but such relationship was not observed in men (p for interaction = 0.037). ConclusionsIn women, mrEF and snEF were associated with worse long-term outcomes. Additionally, sex-related differences in the GDMT implementation for HFmrEF highlight the need for further exploration, which might lead to creation of sex-specific guidelines to optimize HF management.

Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial.

The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

Catheter ablation for atrial fibrillation in heart failure with reduced ejection fraction patients: A meta-analysis

The optimal treatment for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (HFrEF) remains unsettled. To assess the efficacy of catheter ablation (CA) and medical therapy compared to medical therapy alone in patients with AF and HFrEF. We performed a systematic review of randomized controlled trials (RCTs) comparing CA versus guideline-directed medical therapy for AF in patients with HFrEF (left ventricular ejection fraction (LVEF) ≤40%). We systematically searched PubMed, Embase, and Cochrane for eligible trials. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). Six RCTs comprising 1,055 patients were included, of whom 530 (50.2%) were randomized to CA. Compared with medical therapy, CA was associated with a significant reduction in heart failure (HF) hospitalization (RR 0.57; 95% CI 0.45-0.72; p<0.01), cardiovascular mortality (RR 0.46; 95% CI 0.31-0.70; p<0.01), all-cause mortality (RR 0.53; 95% CI 0.36-0.78; p<0.01), and AF burden (MD -29.8%; 95% CI -43.73,-15.90; p<0.01). Also, there was a significant improvement in LVEF (MD 3.8%; 95% CI 1.6,6.0; p<0.01) and quality of life (Minnesota living with HF questionnaire; MD -4.92 points; 95% CI -8.61,-1.22; p<0.01) in the ablation group. In this meta-analysis of RCTs of patients with AF and HFrEF, CA was associated with a reduction in HF hospitalization and cardiovascular and all-cause mortality, as well as a significant improvement of LVEF and quality of life.

Management of Heart Failure in a Resource-Limited Setting: Expert Opinion from India.

Heart failure poses a global health challenge affecting millions of individuals, and access to guideline-directed medical therapy is often limited. This limitation is frequently attributed to factors such as drug availability, slow adoption, clinical inertia, and delayed diagnosis. Despite international recommendations promoting the use of guideline-directed medical therapy for heart failure management, personalized approaches are essential in settings with resource constraints. In India, crucial treatments like angiotensin II receptor blocker neprilysin inhibitors and sodium-glucose co-transporter 2 inhibitors are not fully utilized despite their established safety and efficacy. To address this issue, an expert consensus involving 150 specialists, including cardiologists, nephrologists, and endocrinologists, was convened. They deliberated on patient profiles, monitoring, and adverse side effects and provided tailored recommendations for guideline-directed medical therapy in heart failure management. Stressing the significance of early initiation of guideline-directed medical therapy in patientswith heart failure, especially with sodium-glucose co-transporter 2 inhibitors, the consensus also explored innovative therapies like vericiguat. To improve heart failure outcomes in resource-limited settings, the experts proposed several measures, including enhanced patient education, cardiac rehabilitation, improved drug access, and reforms in healthcare policies.

Evaluating haemodynamic changes: vericiguat in patients with heart failure with reduced ejection fraction.

Vericiguat has been used to treat patients with heart failure with reduced ejection fraction (HFrEF) who demonstrated worsening heart failure despite treatment with other guideline-directed medical therapies. The haemodynamic effects of vericiguat remain unclear. This study enrolled 12 patients (median age, 63 [quartiles 53.5, 70] years; 16.7%(N=2) women) with symptomatic HFrEF (New York Heart Association functional class II-IV) who demonstrated worsening heart failure despite treatment with the four foundational guideline-recommended therapies between March and December 2022, with follow-ups completed in June 2023. A balloon-tipped pulmonary artery thermodilution catheter was placed in the right internal jugular vein to perform right heart catheterisation (RHC) on day 1. Haemodynamic data were acquired before and after vericiguat intake (2.5mg) on days 2 and 3. The data on days 2 and 3 were averaged. RHC was repeated on day 105 (37, 168). Oral intake of vericiguat 2.5mg decreased mean pulmonary artery pressure (19.3 [14.3, 26.8] mmHg) and pulmonary artery wedge pressure (PAWP) (11 [7.5, 15] mmHg) before the intake to mean pulmonary artery pressure (17.5 [12.5, 24] mmHg) and PAWP (9.3 [6.8, 14] mmHg) at 30min after (both P<0.05). Reduction in PAWP was also found from 14.5 [9.5, 19.5] mmHg on day 1 to 9.5 [6.5, 12.5] mmHg on day 105 (37, 168) (P<0.05), when vericiguat was titrated to 2.5mg 25% (N=3), 5mg 50% (N=6), and 10mg 25% (N=3). The consistent reduction in PAWP underscores the well-tolerated nature of vericiguat and its potential to enhance cardiac performance in patients with HFrEF.

Association Between Coronary Assessment in Heart Failure and Clinical Outcomes Within a Safety-Net Setting Using a Target Trial Emulation Observational Design.

Ischemic cardiomyopathy is the leading cause of heart failure (HF). Most patients do not undergo coronary assessment after HF diagnosis. There are no randomized clinical trials of coronary assessment after HF diagnosis. Using an electronic health record cohort of all individuals with HF within the San Francisco Health Network from 2001 to 2019, we identified factors associated with coronary assessment. Then, we studied the association of coronary assessment within 30 days of HF diagnosis with all-cause mortality and a composite of mortality and emergent angiography using a target trial emulation observational comparative-effectiveness approach. Target trial emulation is an approach to causal inference based on creating a hypothetical randomized clinical trial protocol and using observational data to emulate the protocol. We used propensity scores for covariate adjustment. We used national death records to improve the ascertainment of mortality and included falsification end points for the cause of death. Among 14 829 individuals with HF (median, 62 years old; 5855 [40%] women), 3987 (26.9%) ever completed coronary assessment, with 2467/13 301 (18.5%) with unknown coronary artery disease status at HF diagnosis assessed. Women, older individuals, and people without stable housing were less likely to complete coronary assessment. Among 5972 eligible persons of whom 627 underwent early elective coronary assessment, coronary assessment was associated with lower mortality (hazard ratio, 0.84 [95% CI, 0.72-0.97]; P=0.025), reduced risk of the composite outcome (hazard ratio, 0.86 [95% CI, 0.73-1.00]), higher rates of revascularization (odds ratio, 7.6 [95% CI, 5.4-10.6]), and higher use of medical therapy (odds ratio, 2.5 [95% CI, 1.7-3.6]), but not the falsification end points. In a safety-net population, disparities in coronary assessment after HF diagnosis are not fully explained by coronary artery disease risk factors. Early coronary assessment is associated with improved HF outcomes possibly related to higher rates of revascularization and guideline-directed medical therapy but with low certainty that this finding is not attributable to unmeasured confounding.

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Cardiology: What You May Have Missed in 2023.

Cardiology and all its subspecialties continue to push the envelope in developing new treatment strategies for a wide variety of diseases. After screening more than 1300 articles, we highlight a selection of important cardiology articles published in 2023. Starting with prevention, we note articles that look at the effect of semaglutide in patients with obesity as well as a first-in-class drug, bempedoic acid, on cardiovascular outcomes. We have also examined new evidence comparing conservative management with invasive management of frail, older patients with non-ST-segment elevation myocardial infarction (NSTEMI). In patients with cardiac arrest secondary to NSTEMI, another article examines the rationale for expedited transfer to a cardiac arrest center. The STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) trial builds on looking at half-dose thrombolysis in older populations with STEMI. Emphasis is placed on guideline-directed medical therapy before hospital discharge in those with heart failure. In addition, in patients with stable symptomatic coronary artery disease, initial noninvasive testing using coronary computed tomography angiography may be a viable option compared with invasive strategies. More details have emerged on anticoagulation strategies in those with device-detected atrial fibrillation. Finally, transcatheter approaches to treat both mitral and tricuspid regurgitation have also been included.