Cardiovascular Rehospitalization Research Articles

Highlights From the Circulation Family of Journals.

Highlights From the Circulation Family of Journals.

Effect of Angiotensin Receptor-Neprilysin Inhibitor versus Valsartan on Cardiac Status in Patients with Chronic Heart Failure with Reduced Ejection Fraction: A Randomized Clinical Trial in Rangpur Medical College Hospital, Bangladesh

Background: Heart failure with reduced ejection fraction has a significant association with considerable morbidity and mortality, but there is still inadequacy in appropriate treatment to prevent this condition. We observed the effect of angiotensin receptor neprilysin inhibitor (ARNi) with such disorder compared to valsartan. Methods: In this single-blind trial, the patients were enrolled with chronic HF aged on or above 40 years, symptomatic NYHA class II - IV, an elevated NT-proBNP above 400 pg/ml level and a reduced LVEF of 40% or less. The patients were randomly assigned 1:1 to the treatment arms either ARNi (50 mg titrated to 100 mg twice a day) or valsartan (40 mg titrated to 80 mg twice a day) and followed for a median of 88 days. The primary outcome was mode of cardiovascular death and re-hospitalization for heart failure. Changes in the level of NT-proBNP and rate of ejection fraction were also measured. Results: Cardiovascular deaths occurred 4 (8%) in the ARNi treatment arm, while 11 (22%) in the valsartan treatment arm with significant hazard ratio in the ARNi group [Hazard Ratio = 0.37; 95% CI: 0.34, 0.64; p = 0.042] during a median of 88 days of follow up period and 2 (4%) of the patients from the ARNi treatment arm were hospitalized due to HF, while in the valsartan treatment arm, 10 (20%) patients were hospitalized due to HF followed by receiving treatment respectively with hazard ratio in the ARNi group [Hazard Ratio = 0.80; 95% CI: 0.57, 0.92; p < 0.037]. Furthermore, a significant effect was found to have in LVEF and NT-proBNP at 95% level of significance (p < 0.05). These effects resulted from somewhat increased in LVEF (30.4% ± 6.7% to 38.8% ± 8.1%) and intensely decreased in NT-proBNP (3066.5 ± 1882.1 pg/ml to 808.2 ± 592.5 pg/ml) in the ARNi group, as compared to valsartan group in LVEF (30.6% ± 6.0% to 35% ± 7.9%) and in NT-proBNP (3488.2 ± 2912.2 pg/ml to 1886.4 ± 1017.8 pg/ml). Conclusion: Chronic treatment with the angiotensin receptor neprilysin inhibitor (ARNi) strongly decreases the NT-proBNP as well as morbidity and mortality and increases LVEF in patients with heart failure compared to valsartan.

Impact of incomplete coronary revascularization on late ischemic and bleeding events after transcatheter aortic-valve Replacement

The respective influences of coronary artery disease (CAD) and revascularization by percutaneous coronary intervention (PCI) on prognosis in patients undergoing Transcatheter aortic-valve replacement (TAVR) remain highly controversial. The residual SYNTAX Score (rSS) has been developed to assess the impact of residual CAD after PCI. Both baseline SYNTAX Score (bSS) and rSS have been associated with dismal prognosis in patients undergoing PCI. To assess whether the degree of bSS and rSS impact ischemic and bleeding events after TAVR. Three hundred and eleven patients were admitted for TAVR. Severe CAD was defined by bSS > 22. Incomplete revascularization was defined by rSS > 8. The primary outcome was the occurrence of a composite endpoint of either cardiovascular death, myocardial infarction, stroke or rehospitalization for heart failure (MACE). Secondary endpoints included each primary endpoint individually and the occurrence of late major/life threatening bleeding complications (MLBCs). After a median follow-up of 830 days, bSS > 22 was associated with higher occurrence of MACE ( P = 0.013). However, bSS > 22 and rSS > 8 had no impact on overall cardiovascular mortality. By contrast, they were associated with higher rates of periprocedural major bleeding ( P = 0.002), myocardial infarction ( P = 0.001) and late occurrence of MLBCs and transfusion rate ( P = 0.005). Results of multivariate analysis showed that bSS > 22 (HR 2.43 95% CI (1.01–5.85); P = 0.048) and rSS > 8 (HR 2.39 95% CI (1.2–4.7); P = 0.013) remained predictors of MLBCs but not of myocardial infarction ( Table 1 , Fig. 1 ). In unselected TAVR patients, initial CAD burden and incomplete coronary revascularization did not impact overall and cardiac mortality but constitute reliable predictors of late MLBCs.

Exercise and Coronary Heart Disease.

Coronary artery disease (CAD) can be obstructive or nonobstructive. Patients with nonobstructive and stable angina pectoris are usually women. Nonobstructive CAD is caused by endothelial dysfunction at the microvascular level, such as cardiac syndrome X and coronary slow flow syndrome. Even if coronary anatomy is nonobstructive, the presence of myocardial ischemia is a major determinant for the exercise program. CAD is a chronic inflammatory disease, and the progression of the disease can lead to a rapid change in the functional capacity of CAD patients. Exercise training is a major component of cardiac rehabilitation and reduces cardiovascular mortality, morbidity, and rehospitalization as well as improves psychological stress and controls risk factors of CAD, such as diabetes mellitus, hypertension, and obesity. It is possible that the quality of life of patients with CAD can be improved by using appropriate exercise therapy. However, the exercise programs among CAD patients are highly underutilized. This chapter will summarize the research progress of exercise in the prevention and treatment of CAD as well as how to create safe exercise programs and the importance of exercise for patients with CAD. In addition, exercise training has fundamental beneficial effects on ischemic and nonischemic heart failure.

Long-term Clinical Outcomes of Radiofrequency Catheter Ablation versus Permanent Pacemaker Implantation in Patients with Tachycardia-Bradycardia Syndrome.

Background and ObjectivesPacemaker (PM) implantation is a well-accepted treatment option for patients with paroxysmal atrial fibrillation (AF) and related tachycardia-bradycardia syndrome (TBS). Data on the long-term clinical outcomes after radiofrequency catheter ablation (RFCA) or PM implantation are sparse.MethodsThe medical records of 217 patients with TBS were retrospectively assessed. Outcomes in patients who underwent RFCA (n=108, 49.8%) were compared to those with PM implantation (n=109, 50.2%). The clinical outcomes were sinus rhythm maintenance, conversion to persistent AF, additional procedure or crossover, and the composite of cardiovascular hospitalization and death.ResultsDuring the follow-up period (mean 3.5±2.0 years), the RFCA group, compared to the PM group, showed better sinus rhythm maintenance (adjusted hazard ratio [aHR], 0.27; 95% confidence interval [CI], 0.15–0.46; p=0.002) and less progression to persistent AF (aHR, 0.20; 95% CI, 0.06–0.63; p=0.006). Additional procedure or crossover did not differ significantly between the groups (aHR, 2.07; 95% CI, 0.71–6.06; p=0.185 and aHR, 0.69; 95% CI, 10.8–2.67; p=0.590, respectively). Most RFCA patients (92.6%) did not require pacemaker implantation during long term follow-up period (>3.5 years). The composite endpoint of cardiovascular rehospitalization and death was not significantly different between the groups (aHR, 0.92; 95% CI, 0.50–1.66; p=0.769).ConclusionsRFCA is an effective alternative to PM implantation in patients with TBS. In these patients, successful RF ablation of AF is related to a higher rate of sinus rhythm maintenance compared to PM implantation, and the composite outcome of cardiovascular rehospitalization and death is similar.

Outcomes of Takotsubo Syndrome at 15 Years: A Matched Cohort Study

BackgroundThe association of takotsubo syndrome with future risk of cardiovascular and noncardiovascular morbidity and mortality is unclear. We assessed the long-term risk of morbidity and mortality in patients with takotsubo syndrome. MethodsWe performed a matched cohort study of 174 patients with takotsubo syndrome between 1989 and 2006 in Quebec, Canada, with 15 years of follow-up on future hospitalization outcomes. We matched takotsubo patients to 2 comparison groups, including 1736 patients with acute myocardial infarction and 1740 population controls. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of takotsubo syndrome with subsequent in-hospital mortality, cardiovascular morbidity, and other hospitalization outcomes. ResultsDuring 15 years of follow-up, patients with takotsubo syndrome had a risk of in-hospital mortality similar to patients with myocardial infarction (HR 1.06; 95% CI, 0.81-1.38), but a lower risk of cardiovascular rehospitalization (HR 0.79; 95% CI, 0.66-0.95). Compared with population controls, however, takotsubo was associated with 1.59 times the risk of in-hospital mortality (95% CI, 1.21-2.09), 2.71 times the risk of cardiovascular rehospitalization (95% CI, 2.24-3.28), and 1.86 times the risk of hospitalization for stress and anxiety disorders (95% CI, 1.21-2.85). Associations were significantly stronger the first few years after the initial admission for takotsubo, and weakened over time. ConclusionsTakotsubo syndrome is associated with a risk of mortality similar to that of myocardial infarction after 15 years, but a lower risk of cardiovascular rehospitalization. Patients with takotsubo syndrome nonetheless have more in-hospital mortality and cardiovascular morbidity than population controls.

P6508Percutaneous versus surgical paravalvular leak: a ten-year tertiary centre experience

Abstract Aims Paravalvular leak (PVL) presents an incidence ranging from 2–17%. Open heart surgery is considered the standard treatment and there is no consensus regarding the role of percutaneous closure of non-endocarditis PVL. Methods Single-centre retrospective study including consecutive patients that had their PVL closed percutaneously or by surgery, after heart team agreement, between 2007 and 2018. The primary goal was to assess mortality and rehospitalizations. The secondary goals were: a) the technical success, defined as reduction in regurgitation [≥1 degree] and b) clinic and laboratorial improvement. Results Forty-eight patients were included (mean age of 66±13 years, 56% male), 12 submitted to percutaneous closure and 36 to surgery (74 vs 65 years, p=0,026, respectively), with similar gender distribution. 56% had an aortic PVL, with the remainder having a mitral leak, with no difference between groups. The indications were heart failure in 91% and haemolytic anaemia in 42%. A combination of both indications and NYHA heart failure functional class ≥ III were higher in percutaneous group. The severity of leak was comparable in both groups. Patients treated percutaneously had a significant higher rate of atrial fibrillation (92% vs 42%), COPD (33% vs 3%), peripheral artery disease (58% vs 22%) and higher EuroScore II (13,1% [7,1 - 19,0 CI 95%] vs 4,1 [2,9 - 6,5 CI 95%], p=0,003). There was no significant difference between groups with respect to all- cause mortality at 6 months, and to cardiovascular (CV) mortality and CV rehospitalization at 1-year follow-up. The technical success was lower in percutaneous group, but clinic and laboratorial results did not differ (table). Primary and secondary [(a) tecnical success (b) clinical and laboratorial improvements] endpoints of percutaneous vs surgery paravalvular leak closure Percutaneous PVL closure Surgical PVL Closure p-value Mortality @ 6 M 17% 25% p=1.000 CV Mortality @ 12 M 25% 31% p=1.000 Rehospitalization @ 12 M 18% 21% p=0.694 Technical success (a) 75% 97% p=0.043 NYHA improvement (b) 70% 71% p=0.171 Hb improvement (b) mean Δ: 1.2±1.1 g/dl mean Δ: 1.3±2.5 g/dl p=0.737 LDH reduction (b) mean Δ: −682±828 U/L mean Δ: −473±1215 U/L p=0.577 Conclusions In this high-risk population, clinical and laboratorial improvement was achieved by both methods. The percutaneous technique seems more appropriate for patients with higher risk, despite a lower technical success in the reduction of the severity of the leak.

3036Identifying low-risk patients eligible for early discharge after ST-segment elevation myocardial infarction

Abstract Introduction Early discharge after ST-segment elevation myocardial infarction (STEMI) should be considered in low-risk patients after successful percutaneous coronary intervention (PCI) to reduce healthcare costs and improve resource utilization. The Zwolle criteria is recommended by current guidelines for the identification of low-risk patients but a new score, the FASTEST score, has recently demonstrated to add prognostic value over Zwolle score in small and unicentric studies. Purpose Assess if FASTEST score could better identify low-risk patients compared to Zwolle in a contemporary nationwide cohort of patients with STEMI who underwent primary PCI and complete revascularization. Methods Multicentric observational study of consecutive patients with ACS recorded in the Portuguese Registry of Acute Coronary Syndromes (ProACS) between October 2010 and January 2019. Patients who underwent primary PCI and received complete revascularization were included, and those with missing data for score calculation were excluded. The FASTEST score awards 1 point for each: femoral access, age&gt;65, LVEF&lt;50, TIMI&lt;3; creatinine &gt;1.5 mg/dl; stenosis of the left main coronary artery; and Killip≥2. The Zwolle score was calculated for comparison. The rate of hospital mortality and a composite of serious adverse events (heart failure, cardiogenic shock, re-infarction, mechanical complication, ventricular arrhythmia and major hemorrhage) was compared between low-risk patients as classified by FASTEST (score=0) or Zwolle (score≤3). One-year mortality and cardiovascular rehospitalization was compared between the two groups. Results We included 3322 patients (77.4% male, mean age 62±13 years, 49.5% with anterior STEMI). The FASTEST score identified 855 (25.8%) and Zwolle 2353 (70.7%) low-risk patients. Discrimination by AUC for hospital mortality was 0.92 (95% CI 0.91–0.93) for FASTEST score, significantly higher than Zwolle (0.83 (95% CI 0.82–0.84), p&lt;0.001 for comparison) (Fig.1). Overall hospital mortality was 2.8%. 1 patient died in low-risk FASTEST compared to 24 (1%) in low-risk Zwolle (p=0.01). Low-risk Zwolle patients were more likely to suffer serious hospital adverse events compared with FASTEST score low-risk (19.5% vs 8.5%, p&lt;0.001). At one-year, 1384 patients had follow-up data. Mortality was significantly lower in low-risk FASTEST than Zwolle (1.5% vs 4.6%, p&lt;0.001) and a tendency for less cardiovascular rehospitalization was also noted (5.4% vs 7.5%, p=0.08). Figure 1. ROC-AUC for hospital mortality Conclusion Approximately one in every four patients were classified as low-risk according to FASTEST score, in contrast with 70% for Zwolle score. Low-risk FASTEST score patients exhibited significantly less hospital mortality (1 patient), hospital serious adverse events and 1-year mortality compared with low-risk Zwolle patients. FASTEST score demonstrated better discriminatory capacity for hospital mortality than Zwolle score and its use for risk stratification should be preferred.

Life beyond 5 Years after TAVI: Patients' Perceived Health Status and Long-Term Outcome after Transcatheter Aortic Valve Implantation.

Background Transcatheter aortic valve implantation (TAVI) is currently recommended for patients with severe aortic stenosis at intermediate or high surgical risk. The decision process during TAVI evaluation includes a thorough benefit-risk assessment, and knowledge about long-term benefits and outcomes may improve patients' expectation management. Objective To evaluate patients' perceived health status and self-reported long-term outcome more than 5 years after TAVI. Methods and Results Demographic and procedure data were obtained from all patients treated with TAVI at our institution from 2006 to 2012. A cross-sectional survey was conducted on the patients alive, measuring health status, including the EQ-5D-5L questionnaire, and clinical outcomes. 103 patients (22.8%) were alive at a median follow-up period of 7 years (5.4–9.8). 99 (96%) of the 103 patients were included in the final analysis. The mean age at follow-up was 86.5 years ± 8.0 years, and 56.6% were female. Almost all patients (93.9%) described an improvement of their quality of life after receiving TAVI. At late follow-up, the mean utility index and EQ-VAS score were 0.80 ± 0.20 and 58.49 ± 11.49, respectively. Mobility was found to be the most frequently reported limitation (85.4%), while anxiety/depression was the least frequently reported limitation (19.8%). With respect to functional class, 64.7% were in New York Heart Association (NYHA) class III or IV, compared to 67.0% prior to TAVI (p=0.51). Self-reported long-term outcomes revealed mainly low long-term complication rates. 74 total hospitalizations were reported after TAVI, and among those 43% for cardiovascular reasons. Within cardiovascular rehospitalizations, new pacemaker implantations were the most frequently reported (18.9%), followed by cardiac decompensation and coronary heart disease (15.6%). Conclusion The majority of the patients described an improvement of health status after TAVI. More than five years after TAVI, the patients' perceived health status was satisfactory, and the incidence of clinical events and hospitalizations was very low.

P1633Age, creatinine, and ejection fraction (ACEF) score continues to predictive prognosis in patients with ischemic cardiomyopathy

Abstract Purpose ACEF (Age, Creatinine, and Ejection Fraction) andACEFMDRD (Modification of Diet in Renal Disease) score have been validated as effective predictors for prognosis in patients undergoing elective cardiac surgery or PCI. However, the predictive value for ICM (Ischemic Cardiomyopathy)was not clear. This study sought to investigate their predictive value in patients with ICM. Methods 862 ICM patients hospitalized in the Department of Cardiology were prospectively enrolled during November 2014 and December 2017.Inclusion criteria: previous definite diagnosis of myocardial infarction, previous PCI, CABG, or coronary angiographic findings of one or more vessel stenosis &gt;70%; Simpson echocardiography showed LVEF &lt;45%. Exclusion criteria: malignant tumors of any organ or once had a history of malignancies; and other serious diseases with estimated survival time less than one year.The ACEF score was calculated by the formula: age/ejection fraction + 1 (if creatinine &gt;176 μmol/L). As for ACEFMDRD score, estimated glomerular filtration rate (eGFR) was calculated using the MDRD formula. Then using the formula: age/EF +1 point for every 10 mL/min reduction in eGFRMDRD below 60 ml/min per 1.73 m2 (up to a maximum of 6 points). Patients were divided into low, middle and high ACEF, ACEFMDRD tertiles. The median duration of follow-up was 13 months (IQR: 7–23 months). The clinical endpoints were all-cause mortality, cardiac mortality, major adverse cardiovascular and cerebrovascular events (MACCEs) and re-hospitalization for heart failure (HF). Results The mean original ACEF and ACEFMDRD score were 1.99±0.63 and 2.53±1.42. Patients in high ACEF and ACEFMDRD tertile were associated with significantly higher all-cause and cardiac mortality, MACCEs and re-hospitalization for HF. Compared with ACEFMDRD score, original ACEF exhibited similar discrimination and predictive ability on all-cause mortality (AUC: 0.739 vs. 0.724, P=0.567), cardiac mortality (AUC: 0.733 vs. 0.717, P=0.525), MACCEs (AUC: 0.635 vs. 0.624, P=0.587) and rehospitalizaiotn (AUC: 0.642 vs. 0.632, P=0.757). In multivariate Cox analysis, the original ACEF or ACEFMDRD score were related with increasing risks of all-cause mortality (HR: 2.00 vs. 1.32, 95% CI: 1.46–2.73 vs. 1.13–1.53, P&lt;0.001), cardiac mortality (HR: 1.97 vs. 1.28, 95% CI: 1.43–2.70 vs. 1.10–1.50, P&lt;0.001 vs. P=0.002), MACCEs and re-hospitalization for HF, respectively. ROC curves of cardiac mortality Conclusions In patients with ICM, the original ACEF and ACEFMDRD score are independent predictors of adverse outcomes during 13-month follow-up, respectively. Acknowledgement/Funding None

1135Angiotensin receptor-neprilysin inhibition in patients with de novo acute decompensated heart failure: a prespecified subgroup analysis of the PIONEER-HF trial

Abstract Background The efficacy, safety, and tolerability of an angiotensin receptor-neprilysin inhibitor (ARNi) in patients presenting with de novo heart failure (HF) has not been previously well-defined. Methods The PIONEER-HF trial was a prospective, multicenter, double-blind, active-controlled, randomized clinical trial which enrolled 887 patients (pts) at 129 sites in the United States. Pts with or without a history of prior HF and an ejection fraction (EF) &lt;40% and a NT-proBNP &gt;1600 pg/mL or BNP &gt;400 pg/mL were eligible for participation no earlier than 24 hours while still hospitalized for acute decompensated HF (ADHF). Pts were randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan (S/V) titrated to 97/103 mg vs. enalapril titrated to 10 mg both by mouth twice daily for 8 weeks. We performed a pre-specified analysis in pts with de novo HF (i.e., defined as pts without a history of HF prior to the qualifying ADHF event). Results At the time of enrollment, 34% (N=303) had de novo HF. These pts experienced a similar improvement in NT-proBNP with S/V vs. enalapril (Ratio of geometric means 0.65, 95% Confidence Interval [CI] 0.53–0.81; p-value = 0.0002) compared to pts with worsening chronic HF (ratio 0.72 (0.63–0.83, p-value &lt;0.0001) (Figure). In addition, the incidence of worsening renal function, hyperkalemia, and hypotension was comparable with S/V vs. enalapril regardless of whether they were hospitalized for de novo or worsening chronic HF. Finally, there was no interaction (p-value = 0.350) between previous HF status and the effect of S/V on the composite of cardiovascular death or rehospitalization for HF (de novo HF: Hazard Ratio [HR] 0.34, 95% CI 0.11–1.05 vs. worsening chronic HF: HR 0.60, 95% CI 0.39–0.93). Conclusion Among patients admitted for ADHF, irrespective of prior HF history, in-hospital initiation of an ARNi led to a greater reduction in natriuretic peptide levels, a comparable safety profile, and a significant improvement in clinical outcomes. Acknowledgement/Funding Novartis

4331Safety and efficacy of sacubitril/valsartan by dose level in patients hospitalized with acute heart failure: Observations from PIONEER-HF

Abstract Background In hemodynamically stabilized patients with acute decompensated heart failure (ADHF) enrolled in the PIONEER-HF trial, compared with enalapril, sacubitril/valsartan started in-hospital and continued for 8 weeks was well tolerated, achieved a greater reduction in NT-proBNP, and reduced cardiovascular death or rehospitalization for HF. Nearly 1/2 of patients achieved the target dose of blinded study drug. We performed an exploratory analysis of the safety and efficacy of sacubitril/valsartan according to the dose level dispensed at 4 weeks in PIONEER-HF Methods PIONEER-HF was a randomized, double-blind, active-controlled trial of sacubitril/valsartan vs. enalapril in 881 hospitalized ADHF pts following hemodynamic stabilization. Blinded study medication was administered for 8-weeks, with initial dosing selected based on the systolic blood pressure (SBP) at randomization (starting dose 24/26 or 49/51 mg twice daily vs 2.5 or 5 mg twice daily) and titrated toward a target of sacubitril/valsartan 97 mg/103 mg twice daily, or enalapril 10 mg twice daily with an algorithm using SBP along w/ the investigator's assessment of tolerability. Results At the week 4 visit, 199 patients (45.2%) in the sacubitril/valsartan group and 210 (47.6%) in the enalapril group were dispensed the target dose. Baseline characteristics were similar in the 2 treatment groups within each dose level. The prespecified adverse events of special interest were similar between sacubitril/valsartan and enalapril irrespective of dose level (Table) with no significant heterogeneity. In addition, there was no heterogeneity across dose levels in the favorable effect of sacubitril/valsartan on the change in NTproBNP by week 8 (Table, p-interaction=0.54) or the serious composite endpoint (p-interaction=0.71). Efficacy and Safety by Dose-Tier Conclusion In hemodynamically stabilized patients with ADHF, the safety and efficacy of sacubitril/valsartan appears generally consistent among patients at various dose levels. Acknowledgement/Funding Novartis Pharmaceuticals

Clinical impacts of changes of renal function during hospitalization depend on grades of renal dysfunction in acute decompensated heart failure.

Clinical impact of changes of renal function (RF) in heart failure (HF) hospitalization is controversial. This study aimed to clarify whether clinical impact of changes of RF during HF hospitalization depends on the intrinsic RF. In 786 hospitalized HF patients, RF were classified into 3 grades based on estimated glomerular filtration rate (eGFR, mL/min/1.73m2) at discharge; ≥ 60 (n = 243), < 60 and ≥ 30 (n = 400), and < 30 (n = 143). Increase and decrease of serum creatinine over 0.3mg/dL during HF hospitalization were defined as worsening renal function (WRF) and improved renal function (IRF), respectively, and remaining subjects were defined as stable RF. The primary endpoint was a composite of cardiovascular death and rehospitalization for HF. In all patients, WRF was not associated with clinical outcomes, although eGFR has a significant association with prognosis. Clinical outcomes did not differ between changes of RF patterns in both preserved and severely impaired RF groups. In contrast, IRF, not WRF, was an independent predictor of clinical outcomes in the moderately impaired RF group (HR 1.965, 95% CI 1.09-3.18, p = 0.01). Only in patients with moderately impaired RF, changes of RF were associated with clinical outcome, and IRF was an independent predictor of clinical outcomes.

Effects of Serelaxin in Patients with Acute Heart Failure

BackgroundSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure.MethodsIn this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days.ResultsA total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups.ConclusionsIn this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.)

The Relationship between LVEF and Cardiovascular Outcomes Following Hospitalization for Heart failure: Insights from the RELAX-AHF-2 Trial

Background Although left ventricular ejection fraction (LVEF) is routinely used to categorize heart failure (HF) patients, whether this variable predicts outcomes across the full spectrum of patients with acute heart failure (AHF) is uncertain. We assessed the relationship between LVEF and cardiovascular outcomes in a large cohort of patients hospitalized with AHF. Methods 6128 AHF patients from the RELAX-AHF-2 trial who had LVEF measured during AHF hospitalization were separated into quartiles: Q1, LVEF 7-29%; Q2, LVEF >29-38%; Q3, LVEF >38-50% and Q4, LVEF >50-87% in order to determine the relationship between LVEF and a composite of cardiovascular (CV) mortality and rehospitalization for HF or renal failure (RF) through 180 days, the individual components of this composite and all-cause mortality. Results Patients in the lowest LVEF quartile had the highest risk for the composite of CV mortality and HF or RF hospitalization. When LVEF was assessed as a continuous variable, risk for the composite outcome, its components and all-cause mortality became progressively lower as EF increased (HR 0.95, 95% CI 0.93-0.98 per 5% LVEF increase for composite endpoint, P Conclusions In patients hospitalized with AHF, cardiovascular events occurred more frequently at 180 days in patients in the lowest LVEF quartile, especially in patients with an ischemic etiology and pre-existing HF.

Leveraging Machine Learning Techniques to Forecast Patient Prognosis After Percutaneous Coronary Intervention

ObjectivesThis study sought to determine whether machine learning can be used to better identify patients at risk for death or congestive heart failure (CHF) rehospitalization after percutaneous coronary intervention (PCI). BackgroundContemporary risk models for event prediction after PCI have limited predictive ability. Machine learning has the potential to identify complex nonlinear patterns within datasets, improving the predictive power of models. MethodsWe evaluated 11,709 distinct patients who underwent 14,349 PCIs between January 2004 and December 2013 in the Mayo Clinic PCI registry. Fifty-two demographic and clinical parameters known at the time of admission were used to predict in-hospital mortality and 358 additional variables available at discharge were examined to identify patients at risk for CHF readmission. For each event, we trained a random forest regression model (i.e., machine learning) to estimate the time-to-event. Eight-fold cross-validation was used to estimate model performance. We used the predicted time-to-event as a score, generated a receiver-operating characteristic curve, and calculated the area under the curve (AUC). Model performance was then compared with a logistic regression model using pairwise comparisons of AUCs and calculation of net reclassification indices. ResultsThe predictive algorithm identified a high-risk cohort representing 2% of all patients who had an in-hospital mortality of 45.5% (95% confidence interval: 43.5% to 47.5%) compared with a risk of 2.1% for the general population (AUC: 0.925; 95% confidence interval: 0.92 to 0.93). Advancing age, CHF, and shock on presentation were the leading predictors for the outcome. A high-risk group representing 1% of all patients was identified with 30-day CHF rehospitalization of 8.1% (95% confidence interval: 6.3% to 10.2%). Random forest regression outperformed logistic regression for predicting 30-day CHF readmission (AUC: 0.90 vs. 0.85; p = 0.003; net reclassification improvement: 5.14%) and 180-day cardiovascular death (AUC: 0.88 vs. 0.81; p = 0.02; net reclassification improvement: 0.02%). ConclusionsRandom forest regression models (machine learning) were more predictive and discriminative than standard regression methods at identifying patients at risk for 180-day cardiovascular mortality and 30-day CHF rehospitalization, but not in-hospital mortality. Machine learning was effective at identifying subgroups at high risk for post-procedure mortality and readmission.

Update on the clinical impact of mild aortic regurgitation after transcatheter aortic valve implantation: Insights from the Japanese multicenter OCEAN‐TAVI registry

This study aimed to compare the clinical impact of mild postprocedural aortic regurgitation (post-AR) to that of none-trivial post-AR after transcatheter aortic valve implantation (TAVI) and to identify the vulnerability factors to mild post-AR. Moderate-severe post-AR, associated with increased mortality, is an important issue. However, the clinical impact of mild post-AR remains controversial. We analyzed data from 1,572 consecutive patients (1,026 of none-trivial post-AR and 546 of mild post-AR) obtained from the Optimized transCathEter vAlvular Intervention (OCEAN-TAVI) Japanese multicenter registry. We evaluated the 1-year cumulative cardiovascular death and re-hospitalization rates for heart failure (HF) after TAVI according to the degree of post-AR. Kaplan-Meier curves showed no significant difference between "none-trivial post-AR" and "mild post-AR" in terms of cardiovascular death, but a significant difference was noted in the cumulative incidence of re-hospitalization for HF between the two groups (hazard ratio 1.57, 95% confidence interval 1.02-2.41, p = .04). In the stratified analysis, only in patients with not more than 50% of left ventricular ejection fraction (LVEF), concentric left ventricular hypertrophy (LVH), and none-trivial pre-procedural aortic regurgitation (pre-AR), mild post-AR resulted in a higher incidence of re-hospitalization for HF. In this study, the clinical impact of mild post-AR compared to none-trivial post-AR tended to be augmented in the presence of reduced LVEF, concentric LVH, and none-trivial pre-AR. Pre-procedure echocardiographic findings including LVEF, left ventricular geometry, and pre-AR may help to judge the necessity of postdilatation in case of mild post-AR just after the bioprosthesis deployment.

Pan-Asia United States PrEvention of Sudden Cardiac Death Catheter Ablation Trial (PAUSE-SCD): rationale and study design.

The role of catheter ablation as an adjunct and alternative to ICD implantation is not known in patients at risk for recurrent ventricular tachycardia (VT) and sudden cardiac death (SCD) across Asia. Patients with nonischemic etiologies of cardiomyopathy, which are highly prevalent in Asia, have not been previously enrolled in randomized trials of VT ablation. To evaluate whether preemptive catheter ablation in patients with monomorphic VT and an indication for ICD implantation results in improved clinical outcomes compared to ICD implantation with standard medical therapy alone. To examine the natural history of ablation outcomes in the absence of background ICD therapy in patients that refuse randomization. The PAUSE-SCD study (NCT02848781) is a prospective, multi-center, randomized controlled trial enrolling patients with structural heart disease (EF < 50%) with an indication for ICD implantation. Patients are randomized in a 1:1 fashion to two treatment arms: ICD with ablation and ICD with standard medical therapy alone. A prospective registry cohort was designed to follow the outcomes of patients who refuse ICD and randomization but elect to receive catheter ablation as primary therapy. The primary endpoint is defined as a composite of recurrent VT, cardiovascular rehospitalization, and death. Pre-specified secondary endpoints include each of the individual components of the primary endpoint in addition to comparison between randomized and registry patients. The PAUSE-SCD study is a prospective, multi-center, randomized, and controlled trial examining the impact of preemptive catheter ablation on cardiovascular outcomes in patients with an indication for ICD at risk for recurrent VT and SCD. It represents the first multi-center VT ablation study in Asia, with a design intended to provide insights into the role of both ICD and ablation therapy in a predominantly nonischemic population.

Hospital Care of Older Patients With COPD: Adherence to International Guidelines for Use of Inhaled Bronchodilators and Corticosteroids

ObjectivesWe aimed to analyze the prevalence and impact of COPD in older patients hospitalized in internal medicine or geriatric wards, and to investigate adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, associated clinical factors, and outcomes. DesignData were obtained from REgistro POliterapie SIMI (REPOSI), a prospective multicenter observational registry that enrolls inpatients aged ≥65 years. Setting and ParticipantsOlder hospitalized patients enrolled from 2008 to 2016 with a diagnosis of COPD. MeasuresWe evaluated adherence to the 2018 GOLD guidelines at admission and discharge, by examining the prescription of inhaled bronchodilators and corticosteroids in COPD patients. We also evaluated the occurrence of outcomes and its association with COPD and guideline adherence. ResultsAt hospital admission, COPD was diagnosed in 1302 (21.5%) of 6046 registered patients. COPD patients were older, with more impaired clinical and functional status and multiple comorbidities. Overall, 34.3% of COPD patients at admission and 35.6% at discharge were adherent to the GOLD guidelines. Polypharmacy (≥5 drugs) at admission [odds ratio (OR): 3.28, 95% confidence interval (CI): 2.24-4.81], a history of acute COPD exacerbation (OR: 2.65, 95% CI: 1.44-4.88) at admission, smoking habit (OR: 1.45, 95% CI: 1.08-1.94), and polypharmacy at discharge (OR: 6.76, 95% CI: 4.15-11.0) were associated with adherence to guidelines. COPD was independently associated with the risk of cardiovascular and respiratory death and rehospitalization occurrence compared to patients without COPD during follow-up. Adherence to guidelines was inversely associated with the occurrence of death from all causes (OR: 0.12, 95% CI: 0.02-0.90). Conclusions/ImplicationsCOPD was common in older patients acutely hospitalized, showing an impaired functional and clinical status. Prescriptions for older COPD patients were often not adherent to GOLD guidelines. Poor adherence to guidelines was associated with a worse clinical status. There is a need to improve adherence to guidelines in treating COPD patients, with the ultimate goal of reducing clinical events.

Clinical success of cryoballoon pulmonary vein isolation in patients with atrial fibrillation

Aim. To estimate the clinical success of cryoballoon pulmonary vein isolation (PVI).Methods.230 patients (males: 49.6%, mean age 57 (53; 62) with symptomatic paroxysmal and persistent atrial fibrillation (AF) resistant to antiarrhythmic therapy were included in a single-center prospective study. The patients were randomized into 2 groups to undergo either cryoballoon ablation (n = 122) or radiofrequency (RF) (n = 108) ablation. Both groups were comparable in baseline parameters. The follow-up period was 12 months. Clinical outcomes were estimated with the use of a three-stage scale. The rates of cardiovascular rehospitalizations, direct-current cardioversions and repeated ablations during were estimated within the follow-up. The quality of life (QoL) in the cryoablation group was measured using the AFEQT scale.Results.77% (n = 94) of patients in the cryoballoon ablation group and 71.3% (n = 77) of patients in the RF group (р = 0.71) demonstrated reported the optimal clinical effects. Both groups, cryo ablation and RF ablation, had similar rates of cardiovascular hospitalizations (23.8 vs 28.7%, OR 0.8, 95% CI 0.4–1.4; р = 0.39), direct-current cardioversions (12.3 vs 17.6%, OR 0.7, 95% CI 0.3–1.4; р = 0.26) and repeated ablations (9.8–11.1%, OR 0.9, 95% CI 0.4–2.0; р = 0.75). The patients treated with cryoballoon as opposed to RF ablation had significantly more successful usage of “pill-in-pocket” strategy – 14.8 vs 6.5% (OR 2.5, 95% CI 1.01–6.2; р = 0.04). Significant improvements of the QoL parameters with strong size effect have been found in the cryoablation group, i.e. global score (GS) increased by 8.9±6.9 (95% CI 6.6–10.1; dCohen 1.2; р&lt;0.001), symptoms (S) – by 8.3±7.9 (95% CI 4.2–8.8; dCohen 1.5; р&lt;0.001), daily activities (DA) – by 10.0±6.9 (95% CI = 6.4–10.6; dCohen 0.9; р&lt;0.001), treatment concerns (TC) – by 5.5±6.0 (95% CI 6.3–9.2; dCohen 1.2; р&lt;0.001) and treatment satisfaction (TS) – by 5.5±6.0 (95% CI 5.4–9.8; dCohen 0.9; р&lt;0.001).Conclusion.The both catheter-based technologies had comparable clinical success. Cryoablation was characterized by improvement in all QoL parameters based on the AFEQT score.