Endpoint Of Heart Failure Research Articles

Sex differences in treatment strategy for coronary artery aneurysms: Insights from the international Coronary Artery Aneurysm Registry.

IntroductionSex disparities exist in coronary artery disease (CAD) in terms of risk profile, clinical management and outcome. It is unclear if differences are also present in coronary aneurysms, a rare variant of CAD.MethodsPatients were selected from the international Coronary Artery Aneurysm Registry (CAAR; ClinicalTrials.gov: NCT02563626), and differences between groups were analysed according to sex. The CAAR database is a prospective multicentre registry of 1565 patients with coronary aneurysms (336 females). Kaplan-Meier method was used for event-free survival analysis for death, major adverse cardiac events (MACE: composite endpoint of death, heart failure and acute coronary syndrome) and bleeding.ResultsFemale patients were older, were more often hypertensive and less frequently smoker. They were treated conservatively more often compared to male patients and received significantly less frequently aspirin (92% vs 88%, p = 0.002) or dual antiplatelet therapy (DAPT) (67% vs 58%, p = 0.001) at discharge. Median DAPT duration was also shorter (3 vs 9 months, p = 0.001). Kaplan-Meier analysis revealed no sex differences in death, MACE or bleeding during a median follow-up duration of 37 months, although male patients did experience acute coronary syndrome (ACS) more often during follow-up (15% vs 10%, p = 0.015).ConclusionsThese CAAR findings showed a comparable high-risk cardiovascular risk profile for both sexes. Female patients were treated conservatively more often and received DAPT less often at discharge, with a shorter DAPT duration. ACS was more prevalent among male patients; however, overall clinical outcome was not different between male and female patients during follow-up.

Sacubitril/valsartan versus angiotensin inhibitors and arrhythmia endpoints in heart failure with reduced ejection fraction.

BackgroundAngiotensin receptor–neprilysin inhibitor (ARNI) therapy has been associated with improved survival for patients with symptomatic heart failure and reduced ejection fraction (HFrEF).ObjectivesWe performed a meta-analysis of arrhythmia endpoints from studies comparing ARNI with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with HFrEF to assess for incremental benefit.MethodsWe searched PubMed, Embase, and ClinicalTrials.gov. Baseline study characteristics were collected and outcomes were sustained ventricular arrhythmias, atrial arrhythmias, appropriate implantable cardioverter-defibrillator (ICD) therapy, sudden cardiac death (SCD), and biventricular (BiV) pacing rate.ResultsWe included 9 studies, 4 randomized trials, and 5 observational studies (5589 patients on ARNI vs 5615 on ACEIs/ARBs). Follow-up ranged from 2 to 51 months. The mean age was 65.4 ± 9.8 years, with 77.3% male patients and a mean ejection fraction of 29.0% ± 7.6%. Ischemic cardiomyopathy was present in 62% of patients. In the ARNI group, there were less SCD (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.63–0.96; P = .02), ventricular arrhythmias (OR 0.45, 95% CI 0.25–0.79; P = .005), and appropriate ICD therapy (OR 0.39, 95% CI 0.21–0.74; P = .004). Higher rates of BiV pacing were seen (mean difference 3.13, 95% CI 2.58–3.68; P < .00001) when compared with ACEIs/ARBs. No difference in atrial arrhythmias was seen.ConclusionARNI therapy provides incremental benefit with respect to ventricular tachyarrhythmias/SCD, which may, in part, explain improved outcomes in patients with HFrEF compared to ACEIs/ARBs. There was increased BiV pacing and decreased ICD therapy in the ARNI group.

Outpatient diuretic intensification as endpoint in heart failure with preserved ejection fraction trials: an analysis from TOPCAT.

Outpatient treatment for the worsening of signs and symptoms of heart failure (HF) is usually not incorporated in the main outcomes of HF trials. Patients with HF and a preserved ejection fraction (HFpEF) may experience frequent episodes of outpatient worsening HF. The aim of this study was to evaluate the frequency, prognostic impact, and the effect of spironolactone on outpatient diuretic intensification (ODI), among 1767 patients enrolled in TOPCAT-Americas. Time-updated Cox models and win ratio analysis. ODI was defined by a post-randomization loop diuretic dose increase or new initiation. The median follow-up was 2.9 years. At baseline, 1362 (77%) patients were taking loop diuretics. During the follow-up, 685 (38.8%) patients experienced ODI, which was associated with a higher risk of subsequent cardiovascular events and death [adjusted hazard ratio (HR) for HF hospitalization or cardiovascular death 1.67, 95% confidence interval (CI) 1.36-2.04; HR for cardiovascular death 2.17, 95% CI 1.64-2.87); and HR for all-cause mortality 1.75, 95% CI 1.41-2.16] (p< 0.001 for all outcomes). Adding ODI to the composite of HF hospitalization or cardiovascular death increased the event rate by three-fold in the placebo group (from 10.4 to 29.9 events per 100 person-years). Spironolactone treatment led to a 26% relative reduction of the extended composite of ODI or HF hospitalization or cardiovascular death (HR 0.74, 95% CI 0.65-0.85; p< 0.001) compared with a 16% relative reduction of HF hospitalization or cardiovascular death (HR 0.84, 95% CI 0.70-0.99; p= 0.044). Using win ratio provided similar estimates. In HFpEF, ODI was frequent and independently associated with subsequent cardiovascular events. Spironolactone significantly reduced an extended composite outcome incorporating ODI.

Abstract 11473: Renal and Cardiac Effects of Remote Ischemic Preconditioning in Children Undergoing Cardiopulmonary Bypass Surgery

Introduction: Children undergoing cardiac surgery are at risk for AKI and cardiac dysfunction affecting outcome. Improved surgical techniques and post-operative care allow better outcomes in complex repairs and at-risk patients. Opportunity exists in further protecting multiple end organ function with remote ischemic preconditioning (RIPC) given promising but mixed data in adults and children. Hypothesis: A non-invasive technique of inducing reversible lower extremity ischemia with inflation of pressure cuff lessens renal and myocardial injury. Methods: A single center randomized, placebo controlled, double blinded trial of RIPC in children undergoing cardiac surgery of RACHS-1 category 2 or greater. RIPC was performed in the operating room after anesthesia and before sternotomy. Pre-specified end points are change in creatinine, eGFR, development of AKI, B-type natriuretic peptide and Troponin I at 6, 12, 24, 48, 72 hours post separation from bypass. Secondary end points included select clinical outcomes. Results: There were 45 in the RIPC and 39 patients in the control group: age was 3.5 and 3.8 years, respectively; 57 patients below 1 year of age; 35 patients below 1 month of age. There was no difference between groups in creatinine, cystatin C, eGFR at each time points. There was a trend for a larger rate of decrease, especially for cystatin C (p=0.042) in the RIPC group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of RIPC group (p=0.094). Adjusting for baseline creatinine, the odds ratio for AKI in in RIPC compared to control group was 0.31 (p=0.037). Adjusted for clinical characteristics, the odds ratio was 0.34 (p=0.056). Peak troponin occurred at 6 hrs. Compared to control, the RIPC group had a lower troponin at 6 hrs (p=0.140). However, no difference in other analyses of troponin and B-type natriuretic peptides between the groups. Length of stay, all-cause mortality, systolic function by echocardiography and composite clinical end points of advanced renal and heart failure were not different between groups. Conclusions: There is suggestion of RIPC delivering renal protection in an at-risk pediatric population. Additional larger, higher risk population studies will be required to fully determine its efficacy.

Abstract 13932: Association Between Layer-Specific Global Longitudinal Strain and Cardiovascular Events After Coronary Artery Bypass Grafting

Introduction: Sectionalized quantification of layer-specific global longitudinal strain (GLS) has recently become available with new technological advancements. We sought to investigate the prognostic value of layer-specific strain in patients undergoing coronary artery bypass grafting (CABG). Methods: This retrospective cohort study comprised patients undergoing isolated CABG between 2006 and 2011. The patients were followed through nation-wide registries for the composite endpoint of heart failure (HF) or cardiovascular death (CVD) (HF/CVD). Multivariable Cox regression models adjusted for clinical and echocardiographic baseline characteristics, as well as European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) were used to assess the association between layer-specific GLS and the endpoint. Results: Of 641 patients included (mean age 67 years, 84% male), 62 experienced the composite of outcome (HF: n=30, CVD: n=38) during a median follow-up of 3.8 years. Patients who developed the outcome during follow-up had reduced layer-specific GLS in all layers (GLSendo: -14.3% vs. -16.3; GLSww: -12.2 vs. -13.9; GLSepi: -10.7 vs. -12.2). Additionally, all layer-specific GLS parameters were predictors of outcome in unadjusted models (GLSendo: HR=1.11 (1.05-1.17); GLSww: HR=1.13 (1.06-1.21); GLSepi: HR=1.15 (1.07-1.24), per 1% absolute decrease). The risk of the endpoint increased linearly with decreasing absolute GLS for all layers ( Figure 1 ). These findings were unchanged in multivariable models. Patients with reduced GLS in any layer had a higher risk of HF/CVD, however, the risk was highest for those with reduced epicardial GLS (HR=2.60 (1.46-4.66), p=0.001). Conclusions: Layer-specific GLS is an independent prognosticator of cardiovascular events after CABG. Reduced epicardial GLS poses the highest risk of HF/CVD.

Abstract 10091: Fine Fibrillatory Wave as a Risk Factor for Heart Failure Event in Atrial Fibrillation Patients: The Fushimi Af Registry

Introduction: The clinical significance of fibrillatory (F) wave on electrocardiogram during atrial fibrillation (AF) is poorly understood. Hypothesis: We assessed the hypothesis that fine F wave was associated with heart failure (HF) event in AF patients. Methods: The current study enrolled 2442 AF patients whose baseline electrocardiogram during AF rhythm was available from a Japanese community-based prospective survey, the Fushimi AF Registry. The impact of fine F wave, defined as the amplitude of F waves less than 0.1mV, on the primary composite HF endpoint (a composite of hospitalization due to HF and cardiac death) was examined. Results: Fine F wave was observed in 589 patients (24.1%). Patients with fine F wave were older, and had higher prevalence of sustained AF, pre-existing HF and larger left atrial diameter than those with coarse F wave. During the median follow-up duration of 5.9 years, the cumulative incidence of a composite of hospitalization due to HF and cardiac death was significantly higher in patients with fine F wave than in those with coarse F wave (33.3%, and 23.9% at 8 years, log-rank P&lt;0.001: Figure). The higher risk associated with fine F wave was consistent even for individual components of the primary composite HF endpoint. By multivariable analysis with 11 clinically relevant variables, fine F wave became an independent predictor for the primary composite HF endpoint (hazard ratio 1.31, 95% confidence interval 1.07-1.61, P=0.01). Conclusions: Compared with coarse F wave, fine F wave was more prevalent in patients with larger left atrial diameter or those with sustained AF, and was independently associated with higher risk for HF events.

Abstract 11820: Physician-Adjudicated Heart Failure Phenotypes Among Patients With Chronic Inflammatory Diseases

Objective: To characterize clinical phenotypes of incident heart failure (HF) among patients with various chronic inflammatory diseases (CIDs). Background: Several CIDs are associated with increased HF risk, but differences in HF phenotypes across CIDs are incompletely understood. No prior studies to our knowledge have adjudicated HF phenotypes with physician chart review across a spectrum of CIDs. Methods: We screened for patients with CIDs (and controls without CIDs) who had possible HF in a large urban medical system, then performed physician adjudication of HF endpoints. Possible HF was based on the intentionally sensitive criterion of a single inpatient or outpatient administrative code for HF; we then determined if HF was definite/probable vs. not present using standardized, validated criteria. Charts of patients with adjudicated HF were queried to define specific HF phenotypes. We then compared clinical, demographic, and HF phenotypic characteristics for HF patients with specific CIDs vs. non-CID controls using Fisher’s exact test. Results: Out of 415 patients with at least one code for HF, 192 had definite/probable HF. We observed significant differences in HF phenotypes across CIDs (Table 1). Isolated right-sided HF was more than twice as common in patients with scleroderma (27.8%) than in any other CID. Left ventricular systolic dysfunction was most common in patients with HIV and lupus (SLE); mean LVEF was 45.0% ± 18.6% for HIV and 41.3% ± 17.1% for SLE, while it was 57.7% ± 10.7% for scleroderma. Those with HIV and multiple CIDs were most likely to have coronary artery disease. Conclusions: Different CIDs are associated with different phenotypic presentations of physician-adjudicated HF, which may reflect different underlying inflammatory pathophysiologies. Future studies in larger, multi-center cohorts are needed to confirm these findings, as are mechanistic studies focused on understanding specific immunoregulatory contributors to HF.

Remote Ischaemic Conditioning in STEMI Patients in Sub-Saharan AFRICA: Rationale and Study Design for the RIC-AFRICA Trial

PurposeDespite evidence of myocardial infarct size reduction in animal studies, remote ischaemic conditioning (RIC) failed to improve clinical outcomes in the large CONDI-2/ERIC-PPCI trial. Potential reasons include that the predominantly low-risk study participants all received timely optimal reperfusion therapy by primary percutaneous coronary intervention (PPCI). Whether RIC can improve clinical outcomes in higher-risk STEMI patients in environments with poor access to early reperfusion or PPCI will be investigated in the RIC-AFRICA trial.MethodsThe RIC-AFRICA study is a sub-Saharan African multi-centre, randomized, double-blind, sham-controlled clinical trial designed to test the impact of RIC on the composite endpoint of 30-day mortality and heart failure in 1200 adult STEMI patients without access to PPCI. Randomized participants will be stratified by whether or not they receive thrombolytic therapy within 12 h or arrive outside the thrombolytic window (12–24 h). Participants will receive either RIC (four 5-min cycles of inflation [20 mmHg above systolic blood pressure] and deflation of an automated blood pressure cuff placed on the upper arm) or sham control (similar protocol but with low-pressure inflation of 20 mmHg and deflation) within 1 h of thrombolysis and applied daily for the next 2 days. STEMI patients arriving greater than 24 h after chest pain but within 72 h will be recruited to participate in a concurrently running independent observational arm.ConclusionThe RIC-AFRICA trial will determine whether RIC can reduce rates of death and heart failure in higher-risk sub-optimally reperfused STEMI patients, thereby providing a low-cost, non-invasive therapy for improving health outcomes.

Rate of Heart Failure Following Atrial Fibrillation According to Presence of Family History of Dilated Cardiomyopathy or Heart Failure: A Nationwide Study.

BackgroundIt is poorly understood why some patients with atrial fibrillation develop heart failure (HF) and others do not. We examined the rate of developing HF in patients with atrial fibrillation with and without first‐degree family members with HF or dilated cardiomyopathy (DCM).Methods and ResultsUsing Danish nationwide registries, patients born after 1942 diagnosed with atrial fibrillation in the period 2005 to 2015 were identified and followed for up to 5 years. Patients with pre‐existing HF, DCM, and/or ischemic heart disease diagnoses were excluded. Exposure was defined as a first‐degree relative with HF or DCM. The rate of developing the composite end point of HF or death, and the components, was estimated with multivariable Cox proportional hazard regression models. We included 10 605 patients. A total of 17% had a family member with DCM/HF. Having a family member with HF/DCM was associated with an increased 5‐year risk of the composite of HF/death (cumulative incidence, 9.2% [95% CI, 7.8–10.7] versus 5.6% [95% CI, 5.0–6.1]; adjusted hazard ratio [HR] 1.36 [95% CI, 1.13–1.64]). (HF 8.4% [95% CI, 7.0–9.8] versus 4.5% [95% CI, 4.1–5.0]); (adjusted HR, 1.49 [95% CI, 1.22–1.82]). However, familial HF/DCM was not significantly associated with an increased 5‐year risk and rate of death (0.8% [95% CI, 0.4–1.2] versus 1.1% [95% CI, 0.8–1.3]); (adjusted HR, 0.80 [95% CI, 0.46–1.39]).ConclusionsIn patients with incident atrial fibrillation without prior ischemic heart disease or HF diagnoses, 1 of 6 had a first‐degree relative with HF, and having such a family history of HF/DCM was associated with an 87% increase in 5‐year incidence of HF compared with those without.

Acute myocardial infarction in the Covid-19 era: incidence, clinical characteristics and in-hospital outcomes – a multicenter registry

Abstract Background A reduction in acute myocardial infarction (AMI) hospitalizations during the coronavirus pandemic has been previously documented. We aimed to describe the characteristics and in-hospital outcomes of AMI patients during the Covid-19 era compared to a recent previous registry. Methods We conducted a prospective, multicenter, observational study involving 13 intensive cardiac care units (ICCUs) to evaluate consecutive AMI patients admitted throughout an 8-week period during the Covid-19 outbreak. Data were compared to the corresponding period in 2018 using an acute coronary syndrome survey conducted in all ICCUs in Israel. The primary end-point was defined as a composite of sustained ventricular arrhythmia, pulmonary congestion, and/or in-hospital mortality. Results The study cohort comprised 1466 patients, of whom 774 (53%) were hospitalized during the Covid-19 outbreak. Overall, 841 patients were diagnosed with ST-elevation MI (STEMI): 424 (50.4%) during the Covid-19 era and 417 (49.6%) during the parallel period in 2018. No differences were detected in the admission rate of patients between the two study periods. STEMI patients admitted during the Covid-19 period tended to have fewer co-morbidities, but a higher Killip class (p value = 0.03). The median time from symptom onset to reperfusion was extended from 180 minutes (IQR 122–292) in 2018 to 290 minutes (IQR 161–1080, p&amp;lt;0.001) in 2020. Hospitalization during the Covid-19 era was independently associated with an increased risk of the combined endpoint of heart failure, malignant arrhythmia, or death in the multivariable logistic regression model (OR 1.63, 95% CI 1.02–2.65, p value = 0.05). Conclusion While the admission rate of AMI and STEMI in Israel remained similar during both the Covid-19 era and the corresponding period in 2018, total ischemic time extended significantly during the Covid-19 period, which translated into a more severe disease status upon hospital admission, and a higher rate of in-hospital adverse events. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by a grant from a Fefer foundation for medical research

Clinical risk score for individualized risk stratification of patients with clinically suspected myocardial inflammation

Abstract Objective To develop a clinical risk score for individualized risk stratification of patients with clinically suspected myocardial inflammation. Background Myocardial inflammation is a prominent cause of non-ischaemic dilated cardiomyopathy, heart failure (HF) and sudden cardiac death. Methods This is a prospective multicentre longitudinal study of consecutive patients referred to cardiac magnetic resonance (CMR) with clinically suspected myocardial inflammation between October 2011 and December 2019 as a part of standard diagnostic pathway. Patients were followed up from the date of CMR. The outcome endpoints included major adverse cardiovascular event (MACE, cardiovascular mortality, sudden cardiac death, appropriate device discharge); or death or hospitalisation due to HF). A prognostic model was developed using Cox proportional hazards analysis and validated internally and externally. Results The final dataset included 722 subjects (50 years (40–61); males 422 (58%)). During a follow-up period of median 19 (15–23) months, there were 64 (9%) MACE and 130 (18%) HF events. Ten predictor variables qualified for entry into the prognostic model: age, sex, hematocrit, C-reactive protein, high-sensitive troponin-T (TNT), left and right ventricular ejection fraction, native T1 and T2, and late gadolinium enhancement (LGE). The final multivariable Cox regression model included native T2 (Figure 1A), TNT and LGE (Figure 1B) for the primary (Chi-square: 102.0, p&amp;lt;0.001) and secondary endpoint (Chi-square: 166.9, p&amp;lt;0.001), respectively. Cross-validation as well as external validation of the secondary models revealed good performance and no healthcare system effect. Based on the MyoRISK Score, patients were classified into three risk groups with respective event rates for MACE of 0%, 6.3% and 25.1%, and HF endpoint of 1.8%, 17.3% and 44.2%. TNT≥7 pg/ml allowed to efficiently preselect patients prior to CMR. Conclusions This is the first systematic assessment of outcomes in patients with clinically suspected myocardial inflammation, providing a non-invasive estimation of the probability of adverse events based on a score using readily available clinical parameters. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): DZHK

Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes in over 200,000 adults

Abstract Background Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population. Purpose To determine the population prevalence of HCM-associated sarcomeric variants, characterise their phenotypic manifestations, estimate penetrance, and identify associations between sarcomeric variants and clinical outcomes, we performed an observational study of 218,813 adults in the UK Biobank (UKBB), of whom 200,584 have whole exome sequencing (WES). Methods We carried out an integrated analysis of WES and cardiac magnetic resonance (CMR) imaging in UK Biobank participants stratified by sarcomere-encoding variant status. Computer vision techniques were used to automatically segment the four chambers of the heart (Figure 1). Cardiac motion analysis was used to derive strain and strain rates. Regional analysis of left ventricular wall thickness was performed using three-dimensional modelling of these segmentations. Results Median age at recruitment was 58 (IQR 50–63 years), and participants were followed up for a median of 10.8 years (IQR 9.9–11.6 years) with a total of 19,507 primary clinical events reported. The prevalence of rare variants (allele frequency &amp;lt;0.ehab724.17314) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n=5,727; 1 in 35), and the prevalence of pathogenic or likely pathogenic variants (SARC-P/LP) was 0.24% (n=474, 1 in 423). SARC-P/LP variants were associated with increased risk of death or major adverse cardiac events (MACE) compared to controls (HR 1.68, 95% CI 1.37–2.06, p&amp;lt;0.001), mainly due to heart failure endpoints (Figure 2: cumulative hazard curves with zoomed plots for lifetime risk of A) death and MACE or B) heart failure, stratified by genotype; genotype negative (SARC-NEG), carriers of indeterminate sarcomeric variants (SARC-IND) or SARC-P/LP; C) Forest plot of comparative lifetime risk of clinical endpoints by genotype). While males had a higher overall risk of adverse outcomes, the incremental genetic risk from SARC-P/LP mutations was greater in females (HR for females: 2.18 CI 1.65–2.89, p&amp;lt;0.001; HR for males: 1.42 CI 1.05–1.9, p=0.02). In 21,322 participants with CMR, SARC-P/LP were associated with asymmetric increase in left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p&amp;lt;0.001) but hypertrophy (≥13mm) was only present in 16% (n=7/43, 95% CI 7–31%). Other rare sarcomere-encoding variants had a weak effect on wall thickness (9.5±1.7 vs 9.4±1.6 mm, p=0.002) with no combined excess cardiovascular risk. Conclusions In the general population, SARC-P/LP variants have low aggregate penetrance for overt HCM but are associated with increased risk of adverse cardiovascular outcomes and a sub-clinical cardiomyopathic phenotype. Although absolute event rates are low, identification of these variants may enhance risk stratification beyond familial disease. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The study was supported by the Medical Research Council, UK (MC-A651-53301); National Institute for Health Research (NIHR) Imperial College Biomedical Research Centre; NIHR Royal Brompton Cardiovascular Biomedical Research Unit; British Heart Foundation (NH/17/1/32725, RG/19/6/34387, RE/18/4/34215).

Incident Heart Failure in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

Background: The contemporary incidence of heart failure (HF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This prospective cohort study was designed to study the incidence and predictors of new-onset HF in CAD patients after PCI (ChiCTR1900023033).Methods: From January 2014 to December 2018, 3,910 CAD patients without HF history undergoing PCI were prospectively enrolled. Demographics, medical history, cardiovascular risk factors, cardiac parameters, and medication data were collected at baseline. Multivariable adjusted competing-risk regression analysis was performed to examine the predictors of incident HF.Results: After a median follow-up of 63 months, 497 patients (12.7%) reached the primary endpoint of new-onset HF, of which 179, 110, and 208 patients (36.0, 22.1, and 41.9%) were diagnosed as having HF with reduced ejection fraction (EF) (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF), respectively. Higher B-type natriuretic peptide (BNP) or E/e′ level, lower estimated glomerular filtration rate (eGFR) level, and atrial fibrillation were the independent risk factors of new-onset HF. Gender (male) and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) prescription were the negative predictors of new-onset HF. Moreover, it was indicated that long-term ACEI/ARB therapy, instead of beta-blocker use, was linked to lower risks of development of all three HF subtypes (HFrEF, HFmrEF and HFpEF).Conclusions: This prospective longitudinal cohort study shows that the predominant subtype of HF after PCI is HFpEF and ACEI/ARB therapy is accompanied with reduced risks of incident HF across three subtypes.

Prevalence and Significance of Patient Prosthesis Mismatch Following Edwards SAPIEN XT and SAPIEN 3 Transcatheter Aortic Valve Replacement.

BackgroundSevere patient prosthesis mismatch (sPPM) after surgical aortic valve replacement is associated with worse outcomes. Limited data exists on the impact of sPPM on outcomes after transcatheter aortic valve replacement (TAVR), especially regarding the newer generation valves. The aim of this study was to evaluate the incidence, determinants, and outcomes of sPPM in patients undergoing TAVR with Edwards SAPIEN XT (ES XT) and Edwards SAPIEN 3 (ES3) valves (Edwards Lifesciences, Irvine, CA, USA).MethodsWe retrospectively reviewed 366 patients who underwent TAVR with ES XT (n = 114) or ES3 (n = 252) valves between July 2012 and June 2018. sPPM was defined as indexed effective orifice area (iEOA) <0.65 cm2/m2. Kaplan-Meier survival estimates were used to determine outcomes.ResultsMultivariate linear regression analysis was utilized to determine potential independent effects of PPM on outcomes. sPPM was present in 40 (11%) of the patients [8 (7%) ES XT and 32 (13%) ES3] and was associated with female sex, smaller left ventricular outflow tract (LVOT) diameter and aortic valve annular area, absence of prior coronary artery bypass graft (CABG) surgery, shorter height, higher body mass index, and smaller pre-TAVR valve area (all p < 0.05). Among those with ES3 valves, the incidence of sPPM was inversely proportional to the valve size (50%, 25%, 5% and 3% for 20-, 23-, 26- and 29-mm valve sizes, respectively; p < 0.001). At a mean follow-up period of 3.5 ± 1.5 years, there was no difference in all-cause mortality (22.5% vs. 25.6%, p = 0.89) or a composite endpoint of heart failure, arrhythmias, stroke, and myocardial infarction (30% vs. 34%, p = 0.24) in those with or without sPPM.ConclusionES3 was associated with a higher incidence of sPPM, particularly with smaller valve sizes. However, the presence of sPPM as defined by iEOA was not an independent predictor of adverse outcomes in patients undergoing TAVR within an intermediate follow-up period.

The effect of sodium-glucose link transporter 2 inhibitors on heart failure end points in people with type 2 diabetes mellitus: a systematic review and meta-analysis

Sodium-glucose linked transporter 2 inhibitors (SGLT2i) have been demonstrated to improve cardiovascular outcomes. In particular, SGLT2i appear to be beneficial in improving heart failure outcomes in people with and without diabetes. The aim of this review was to synthesis current evidence from randomised controlled trials (RCTs) comparing SGLT2i to placebo in adults with type 2 diabetes mellitus. The outcomes of interest were rate hospitalisation due to heart failure (primary), death due to heart failure (secondary) and incidence rates of heart failure (secondary).Methods: Searches were performed using recognised terms in MedLine, EMBASE, Pubmed and CINAHL. Studies were included if they compared an SGLT2i to inhibitor in an RCT and contained data for an outcome of interest. Studies were reviewed for inclusion by two people (TSJC and REJR) and data extraction and bias assessment were performed using a modified Cochrane’s data extraction tool and bias assessment tool. Meta-analysis of hazard ratios was performed in RevMan 5.4 using generic inverse variance and a fixed effects model where possible.Results: 2,850 records were identified of which 11 were eventually included, covering 9 clinical studies. Eight of these were suitable for meta-analysis for the outcome of hospitalisation due to heart failure – the pooled hazard ratio was found to be 0.69 (95% CI 0.63, 0.75). Interstudy heterogeneity was minimal (I2 0%) Only one study contained outcomes for death specifically due to heart failure, but its results were not significant. No current studies report incidence rates of new heart failure diagnosis.Conclusion: SGLT2is reduce the rates of hospitalisation due to heart failure in people with type 2 diabetes. This may help mediate the improvements seen in all cardiovascular outcomes, especially when assessed as a composite. More evidence is needed to support their use in reduce mortality due to heart failure and incidence rates of new heart failure in this high-risk cohort.

Pharmacologic therapy for engraftment arrhythmia induced by transplantation of human cardiomyocytes.

SummaryHeart failure remains a significant cause of morbidity and mortality following myocardial infarction. Cardiac remuscularization with transplantation of human pluripotent stem cell-derived cardiomyocytes is a promising preclinical therapy to restore function. Recent large animal data, however, have revealed a significant risk of engraftment arrhythmia (EA). Although transient, the risk posed by EA presents a barrier to clinical translation. We hypothesized that clinically approved antiarrhythmic drugs can prevent EA-related mortality as well as suppress tachycardia and arrhythmia burden. This study uses a porcine model to provide proof-of-concept evidence that a combination of amiodarone and ivabradine can effectively suppress EA. None of the nine treated subjects experienced the primary endpoint of cardiac death, unstable EA, or heart failure compared with five out of eight (62.5%) in the control cohort (hazard ratio = 0.00; 95% confidence interval: 0–0.297; p = 0.002). Pharmacologic treatment of EA may be a viable strategy to improve safety and allow further clinical development of cardiac remuscularization therapy.

Phenotypic Expression and Outcomes in Individuals With Rare Genetic Variants of Hypertrophic Cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population. ObjectivesThe goal of this study was to compare lifetime outcomes and cardiovascular phenotypes according to the presence of rare variants in sarcomere-encoding genes among middle-aged adults. MethodsThis study analyzed whole exome sequencing and cardiac magnetic resonance imaging in UK Biobank participants stratified according to sarcomere-encoding variant status. ResultsThe prevalence of rare variants (allele frequency <0.00004) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n = 5,712; 1 in 35), and the prevalence of variants pathogenic or likely pathogenic for HCM (SARC-HCM-P/LP) was 0.25% (n = 493; 1 in 407). SARC-HCM-P/LP variants were associated with an increased risk of death or major adverse cardiac events compared with controls (hazard ratio: 1.69; 95% confidence interval [CI]: 1.38-2.07; P < 0.001), mainly due to heart failure endpoints (hazard ratio: 4.23; 95% CI: 3.07-5.83; P < 0.001). In 21,322 participants with both cardiac magnetic resonance imaging and whole exome sequencing, SARC-HCM-P/LP variants were associated with an asymmetric increase in left ventricular maximum wall thickness (10.9 ± 2.7 mm vs 9.4 ± 1.6 mm; P < 0.001), but hypertrophy (≥13 mm) was only present in 18.4% (n = 9 of 49; 95% CI: 9%-32%). SARC-HCM-P/LP variants were still associated with heart failure after adjustment for wall thickness (hazard ratio: 6.74; 95% CI: 2.43-18.7; P < 0.001). ConclusionsIn this population of middle-aged adults, SARC-HCM-P/LP variants have low aggregate penetrance for overt HCM but are associated with an increased risk of adverse cardiovascular outcomes and an attenuated cardiomyopathic phenotype. Although absolute event rates are low, identification of these variants may enhance risk stratification beyond familial disease.

Problems with the outcome measures in randomized controlled trials of traditional Chinese medicine in treating chronic heart failure caused by coronary heart disease: a systematic review

BackgroundTraditional Chinese medicine (TCM) has gained widespread application in treating chronic heart failure (CHF) secondary to coronary heart disease (CHD). However, the sound clinical evidence is still lacking. Corresponding clinical trials vary considerably in the outcome measures assessing the efficacy of TCM, some that showed the improvement of clinical symptoms are not universally acknowledged. Rational outcome measures are the key to evaluate efficacy and safety of each treatment and significant elements of a convincing clinical trial. We aimed to summarize and analyze outcome measures in randomized controlled trials (RCTs) of TCM in treating CHF caused by CHD, subsequently identify the present problems and try to put forward solutions.MethodsWe systematically searched databases including Embase, PubMed, Cochrane Library, CBM, CNKI, VIP and Wanfang from inception to October 8, 2018, to identify eligible RCTs using TCM interventions for treating CHF patients caused by CHD. Cochrane Database of Systematic Reviews (CDSR) was searched to include Cochrane systematic reviews (CSRs) of CHF. Two authors independently assessed the risk of bias of the included RCTs according to the Cochrane Handbook. Outcome measures of each trial were extracted and analyzed those compared with the CSRs. We also evaluated the reporting quality of the outcome measures.ResultsA total of 31 RCTs were included and the methodology quality of the studies was generally low. Outcome measures in these RCTs were mortality, rehospitalization, efficacy of cardiac function, left ventricular ejection fraction (LVEF), 6 min’ walk distance (6MWD) and Brain natriuretic peptide (BNP), of which mortality and rehospitalization are clinical end points while the others are surrogate outcomes. The reporting rate of mortality and rehospitalization was 12.90% (4/31), the other included studies reported surrogate outcomes. As safety measure, 54.84% of the studies reported adverse drug reactions. Two trials were evaluated as high in reporting quality of outcomes and that of the other 29 studies was poor due to lack of necessary information for reporting.ConclusionsThe present RCTs of TCM in treating CHF secondary to CHD did not concentrate on the clinical end points of heart failure, which were generally small in size and short in duration. Moreover, these trials lacked adequate safety evaluation, had low quality in reporting outcomes and certain risk of bias in methodology. For objective assessment of the efficacy and safety of TCM in treating CHF secondary to CHD, future research should be rigorous designed, set end points as primary outcome measures and pay more attention to safety evaluation throughout the trial.

Racial Disparities in Adverse Cardiovascular Outcomes After a Myocardial Infarction in Young or Middle-Aged Patients.

BackgroundBlack patients tend to develop coronary artery disease at a younger age than other groups. Previous data on racial disparities in outcomes of myocardial infarction (MI) have been inconsistent and limited to older populations. Our objective was to investigate racial differences in the outcome of MI among young and middle‐aged patients and the role played by socioeconomic, psychosocial, and clinical differences.Methods and ResultsWe studied 313 participants (65% non‐Hispanic Black) <61 years old hospitalized for confirmed type 1 MI at Emory‐affiliated hospitals and followed them for 5 years. We used Cox proportional‐hazard models to estimate the association of race with a composite end point of recurrent MI, stroke, heart failure, or cardiovascular death after adjusting for demographic, socioeceonomic status, psychological, and clinical risk factors. The mean age was 50 years, and 50% were women. Compared with non‐Black patients, Black patients had lower socioeconomic status and more clinical and psychosocial risk factors but less angiographic coronary artery disease. The 5‐year incidence of cardiovascular events was higher in Black (35%) compared to non‐Black patients (19%): hazard ratio (HR) 2.1, 95% CI, 1.3 to 3.6. Adjustment for socioeconomic status weakened the association (HR 1.3, 95% CI, 0.8–2.4) more than adjustment for clinical and psychological risk factors. A lower income explained 46% of the race‐related disparity in outcome.ConclusionsAmong young and middle‐aged adult survivors of an MI, Black patients have a 2‐fold higher risk of adverse outcomes, which is largely driven by upstream socioeconomic factors rather than downstream psychological and clinical risk factors.

Layer-specific global longitudinal strain and the risk of heart failure and cardiovascular mortality in the general population: the Copenhagen City Heart Study.

Layer-specific global longitudinal strain (GLS) has been demonstrated to predict outcome in various patient cohorts. However, little is known regarding the prognostic value of layer-specific GLS in the general population and whether different layers entail differential prognostic information. The aim of the present study was to investigate the prognostic value of whole wall (GLSWW ), endomyocardial (GLSEndo ), and epimyocardial (GLSEpi ) GLS in the general population. A total of 4013 citizens were included in the present study. All 4013 had two-dimensional speckle tracking echocardiography performed and analysed. Outcome was a composite endpoint of incident heart failure and/or cardiovascular death. Mean age was 56 years and 57% were female. During a median follow-up time of 3.5 years, 133 participants (3.3%) reached the composite outcome. Sex modified the relationship between all GLS parameters and outcome. In sex-stratified analysis, no GLS parameter remained significant predictors of outcome in females. In contrast, GLSWW [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.02-1.31, per 1% decrease] and GLSEpi (HR 1.19, 95% CI 1.04-1.38, per 1% decrease) remained as significant predictors of outcome in males after multivariable adjustment (including demographic, clinical, biochemistry, and echocardiographic parameters). Lastly, only in males did GLS parameters provide incremental prognostic information to general population risk models. In the general population, sex modifies the prognostic value of GLS resulting in GLSEpi being the only layer-specific prognosticator in males, while no GLS parameter provides independent prognostic information in females.