Multivariate Cox Proportional Hazards Analysis Research Articles

Clinical impact of permanent pacemaker implantation following surgical ablation of atrial fibrillation concomitant to mitral valve surgery: a multicenter study

Abstract Background Permanent pacemaker (PPM) implantation is a common adverse event following arrhythmia surgery. However, the epidemiology and clinical impact of PPM has been shown in only few studies in heterogeneous population, and the results are controversial. Purpose The present study aimed to investigate the clinical impact of PPM implantation following surgical ablation of atrial fibrillation (AF) concomitant to mitral valve (MV) surgery. Methods We identified 721 patients (aged 60.2±11.0 years, 437 females) who underwent surgical ablation of AF along with MV repair or replacement at five representative institutions in Korea between 2005 and 2017. Of these, 56 had PPM implanted (PPM group) and the remainder (n=665) did not receive a PPM (No-PPM group). The clinical outcomes were compared between the groups, and multivariable Cox proportional hazard analysis with time-varying covariate was conducted to determine the impact of PPM implantation on mortality and stroke. Results The patients in the PPM group were older, and had a higher CHAD2S2-VASc score than those in the No-PPM group (Table). During follow-up of 68.3 months (interquartile range 44.5-105.4 months), no significant survival difference was evident between the groups, however, the PPM group presented a significantly higher incidence of stroke than No-PPM group (p<0.001) (Figure). On time-varying multivariable analysis, the PPM was not a risk factor for mortality (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.18-1.08; p=0.072), however, old age (HR, 1.10; 95% CI, 1.07-1.13; p<0.001), chronic kidney disease (HR, 1.61; 95% CI, 1.01-2.58; p=0.046) and previous cardiac surgery (HR, 1.86; 95% CI, 1.01-3.21; p=0.027) were independent predictors of mortality in this subset of patients. The only significant risk factor for stroke was CHAD2S2-VASc score (HR, 1.27; 95% CI, 1.01-1.61; p=0.044), and PPM was not associated with risk of stroke (HR, 1.87; 95% CI, 0.71-4.90; p=0.202). Conclusion PPM implantation following surgical ablation of AF concomitant to MV surgery was not associated with an increased risk of mortality or stroke. This study result provides a supporting evidence for an active attempt in surgical ablation despite of inherent risk of PPM implantation.

The incremental value of non-necrosis biomarkers to risk stratification in acute chest pain, with MI excluded: the first prospective long term cohort study in the high sensitive troponin era

Abstract Background Approximately 90% of patients presenting to ED (Emergency Department) with suspected Acute Coronary Syndrome (ACS) have Myocardial Infarction (MI) excluded. Long term outcome and risk stratification for this cohort has rarely been studied. Purpose To study long term cardiovascular outcomes in patients with acute Chest Pain (CP) in whom MI is excluded, and to investigate the incremental value of biomarkers of inflammation, myocardial ischaemia and stress, for risk stratification, to that of existing methods of stratifying risk including absolute values of two high sensitive troponins below the 99th percentile. Methods A prospective observational study in a large university teaching hospital with a median follow-up of 5.8-year. Cardiovascular outcomes studied included adjudicated type 1 MI (to 4th universal definition), unstable angina requiring urgent revascularisation and cardiovascular death. Inclusion criteria included CP with features of ischaemia but with MI excluded (High sensitive cardiac troponin [hs-cTn] T ≤99th percentile). Exclusion criteria included non-cardiac chest pain, chronic atrial fibrillation, heart failure and recent ACS. The biomarkers HFABP, GDF-15, NT-proBNP, Galectin-3, HS-CRP taken on first venepuncture for high sensitive cardiac troponins were investigated using univariable and multivariable backward stepwise elimination logistic modelling, receiver operator characteristic (ROC) analysis, and Net Reclassification Indices (NRI). They were compared to absolute values of both sub-99th percentile hs-cTnT (Roche Elecsys) and hs-cTnI (Abbot Architect) both as a single entity or when the troponin values were incorporated with HEART and TIMI scores. Results 487 consented patients were enrolled. The mean age of the population was 56 years (SD 11.8), 44% were female, 16.2% were diabetic, 20.9% had a previous MI, 13.8% previous PCI and 5.1% coronary artery bypass grafting. 100% follow-up was achieved. There were 48 events in follow-up. (event rate 9.9%). Multivariable Cox Proportional Hazards analysis including hs-cTnT or hs-cTnI (below 99th percentile) demonstrated incremental improvement in risk stratification with absolute values of either hs-cTn below the 99th percentile when added to either TIMI or HEART risk score. The results were consistent with NRI analysis. Only GDF-15 demonstrated significance in multivariable analysis when analysed with the HEART score regardless of troponin assay and the TIMI score with HS-cTnI but not with HS-cTnT. Conclusion Absolute values of hs-cTnT or I, below 99th percentiles, significantly improve risk modelling for cardiovascular outcomes in acute CP patients, presenting to ED, who have MI excluded. No other biomarker retains independent risk with the exception of GDF-15. Effective dichotomisation of sub99th percentile hstnT or I, used alone or incorporated into risk scores, could allow improved targeting of resources for investigation and management for this large pool of patients.

Relationship between pre-procedural non-ischemic ST-segment depression and the clinical outcomes after catheter ablation in persistent atrial fibrillation patients

Abstract Background ST-segment depression suggests the presence of coronary artery disease (CAD) during sinus rhythm, but the clinical significance, including the outcomes after catheter ablation (CA), in atrial fibrillation (AF) patients remains unknown. Purpose The aim of this study was to investigate the relationship between non-ischemic ST-segment depression during AF rhythm before CA and late arrhythmia recurrence in persistent AF (PerAF) patients. Methods The present study included PerAF patients from the Osaka Rosai Atrial Fibrillation ablation (ORAF) registry who underwent an initial ablation and had no history of CAD. We assigned the patients based on the presence of ST-segment depression before CA and evaluated the impact of relevant factors on ST-segment depression and the relationship between ST-segment depression, including leads locations (anterior leads, inferior leads, and lateral leads) or depression type (upsloping, horizontal and downsloping) or the degree of ST-segment depression and late recurrence of AF (LRAF). Results This study population included a total of 551 patients of which 189 had ST-segment depression. The median follow-up duration was 397 days and LRAF occurred in 195 patients. By multiple regression analysis, diabetes mellitus, hemoglobin, brain natriuretic peptide, left ventricular ejection fraction and left atrial diameter were significant determinants of ST-segment depression before CA. Kaplan-Meier analysis demonstrated that the patients with ST-segment depression had a significantly greater risk of LRAF than those without (p<0.001). Multivariate Cox proportional hazards analysis showed ST-segment depression was independently and significantly associated with a higher risk of LRAF (p<0.001). The patients with ST-segment depression≥0.15mV had a significantly higher risk of LRAF than those with ST-segment depression≥0.15mV (p<0.001). No significant differences among the ST-segment depression leads locations and ST-segment depression type were observed. Conclusion Non-ischemic ST-segment depression during AF rhythm was significantly associated with LRAF post CA in PerAF patients.

Comprehensive simulation training for E-CPR improves the 1-year mortality of patients with refractory cardiac arrest

Abstract Background Extracorporeal cardiopulmonary resuscitation (E-CPR) has been utilized as a rescue strategy for patients with refractory cardiac arrest (CA). The collapse to ECMO initiation time (CTET) has a strong correlation with survival, but decisions of initiating E-CPR are sometimes difficult to make and the opportunities for developing teamwork skills are limited. Therefore, to improve the outcome of E-CPR, we developed a comprehensive simulation-based E-CPR training program. Purpose In the present study we assessed whether the E-CPR training improved the mortality and the neurological outcome. Methods E-CPR simulation training program was carried out twice a year to the medical team using a mock vascular model since October 2017. We enrolled 177 consecutive patients who underwent E-CPR from January 2012 to January 2022. The patients were divided into two groups: the pre-simulation and the post-simulation. The outcome was CTET, 1-year mortality and favorable neurological outcomes defined as cerebral performance categories (CPC) of 1 or 2 at hospital discharge. Results There were 86 patients in the Pre-simulation group and 91 patients in the Post-simulation group. No differences were found in age, rates of witnessed CA and bystander-CPR, shockable rhythms, or acute coronary syndrome (ACS). The frequency of use of the intra-aortic balloon pump was significantly higher in the Pre-simulation group compared to the Post-simulation group (74% vs. 23%; p <0.001), while the Impella device was only used in the Post-simulation group (46%), due to its availability in our institution since October 2017. Compared to Pre-simulation group, the CTET was significantly shorter (44 minutes vs. 33 minutes; p = 0.001), and the Kaplan-Meier analysis for 1-year survival was significantly higher with the Post-simulation group (12% vs. 23%; p = 0.02 by log-rank test). The rate of favorable neurological outcome was not significantly different between the two groups. However, when patients were analyzed separately by in-hospital CA (IHCA) and out-of-hospital CA (OHCA), no significant difference was observed in IHCA, whereas OHCA demonstrated a significant reduction in both door to ECMO initiation time and CTET, leading to a significant improvement in neurological outcome (3% vs. 20%; p = 0.04). Multivariate cox proportional hazard analysis revealed that age (hazard ratio [HR], 1.22 [10 years increase]; 95% confidence interval [CI], 1.07-1.41, p = 0.004), initial shockable rhythm (HR, 0.61; 95%CI 0.41-0.91, p = 0.01), combined use of Impella (HR, 0.59; 95% CI, 0.37–0.98, p = 0.02), and CTET (HR, 1.02, 95%CI, 1.01-1.03, p <0.0001) were significantly associated with the 1-year mortality. Conclusions The E-CPR training significantly improved the collapse to ECMO time. The faster deployment of ECMO increased the 1-year survival rate in patients with refractory CA. Additionally, the use of Impella (ECPELLA) may have improved the survival rate.The effect of simulation trainingKaplan-Meier analysis

Temporal changes in stroke and heart failure following first-time atrial fibrillation/flutter in patients under 65 years of age: A Danish nationwide study

Abstract Background The incidence of atrial fibrillation/flutter (AF) has increased throughout the past two decades - also for patients under 65 years of age. Whether this increment in patients with AF under 65 years of age also influences the subsequent incidence of ischaemic stroke (stroke) and heart failure (HF) is yet to be elucidated. This patient group are of special interest as this population often is considered at low risk of stroke. Methods Using Danish nationwide registries, we identified all patients from 18–65 years with a first-time AF-diagnosis in 2000-2018. The cohort was categorised according to calendar periods into five groups: 2000-200, 2003-2006, 2007-2010, 2011-2014, and 2015-2018. Crude incidence rate (IR) of stroke and HF per 1,000 person years (PY) were calculated. The cumulative incidence (CI) of stroke and HF during one year of follow-up was computed accounting for death as a competing risk. The reverse Kaplan-Meier estimator was used to examine mortality during one year follow-up. Multivariable Cox proportional hazard analysis was used to compare outcomes between calendar periods with 2000-2002 as comparative reference. Hazard ratios (HR) were reported with 95% confidence intervals (95% CI). Results In this study 51,137 patients were included; 6,911 (median age 56, 64.5% males, 22.0% on OAC) in 2000-2002, 9,964 (median age 58, 65.5% males, 26.4% on OAC) in 2003-2006, 11,538 (median age 58, 64.7% males, 23.9% on OAC) in 2007-2010, 11,764 (median age 58, 63.6% males, in 29.2% on OAC) in 2011-2014, and 10,960 (median age 56, 65.9% males, 39.5% on OAC) in 2015-2018. For stroke, crude IR/1,000 PY [95% CI] declined through calendar time as seen in the Figure. The crude IR were 10.4 [8.0;13.5] in 2000-2002 and 6.3 [4.9;8.0] in 2015-2018 with corresponding CIs of 1.0%, 0.9%, 0.9%, 0.8%, and 0.6%, respectively (p-value for difference=0.08). The corresponding adjusted HRs [95% CI] were 0.94 [0.66;1.35] for calendar period 2003-2006, 0.87 [0.61;1.24] for 2007-2010, 0.86 [0.61;1.23] for 2011-2014, and 0.61 [0.41;0.91] for 2015-2018 as compared with 2000-2002. As seen in the Figure crude IR [95% CI] for HF were stagnant over time with 37.2 [32.4;42.8] in 2000-2002 and 38.3 [34.7;42.3] in 2015-2018 with corresponding CIs of 3.4%, 3.3%, 3.5%, 3.4%, and 3.3%, respectively (p-value for difference=0.89). The corresponding adjusted HRs [95% CI] were 0.93 [0.79;1.10] for calendar period 2003-2006, 0.99 [0.84;1.17] for 2007-2010, 0.99 [0.84;1.16] for 2011-2014, and 1.02 [0.86;1.20] for 2015-2018 as compared with 2000-2002. Mortality with one year of follow-up was 3.8%, 4.4%, 4.4%, 4.5%, and 3.7% in calendar period 1-5 respectively (p-value for difference=0.38). Conclusion From nationwide registries in patients with atrial fibrillation/flutter under 65 years of age, we found a stepwise decline in one-year rates of ischaemic stroke with more recent calendar periods. Heart failure and mortality incidence were stable across calendar time.Incidence rates of ischemic stroke

Patient characteristics and long-term outcomes in patients undergoing transcatheter aortic valve implantation in a failed surgical prosthesis versus in a native valve

Abstract Background Valve-in-valve transcatheter aortic valve implantation (TAVI) is an increasingly used treatment for failed surgical aortic prosthesis, but data from clinical practice are limited. Purpose We examined patient characteristics and outcomes of patients undergoing TAVI in a surgical valve compared with patients undergoing TAVI in a native valve. Methods Patients undergoing TAVI from January 1, 2008, to December 31, 2020, were identified using Danish nationwide registries. Results In total, 6070 patients undergoing TAVI were identified; 247 (4%) patients had a history of SAVR (The valve-in-valve cohort). Patients with valve-in-valve-TAVI were younger but had a greater burden of cardiovascular comorbidities compared with patients with native-valve-TAVI. The cumulative 30-day risk of death was 2.4% (95% CI: 1.0% to 5.0%) in patients with valve-in-valve-TAVI and 2.7% (95% CI: 2.3% to 3.1%) in patients with native-valve-TAVI (Figure 1A). Correspondingly, the cumulative 5-year risk of death was 42.5% (95% CI: 34.2% to 50.6%) and 44.8% (95% CI: 43.2% to 46.4%), respectively. Within 30 days post-procedure, 11 (0.2%) patients with valve-in-valve-TAVI and 748 (13.8%) patients with native-valve-TAVI, had a pacemaker implantation. In multivariable Cox proportional hazard analysis, patients with valve-in-valve TAVI did not have a significantly different risk of rehospitalization from any cause compared to patients with native valve TAVI at 30 days (HR 0.80 [95% CI 0.58-1.10]) and at 5 years (HR 0.85 [95% CI 0.73-1.00]) (Figure 1B). Furthermore, in adjusted analysis, valve-in-valve-TAVI was not associated with significantly different risk of death at 30 days (Hazard ratio (HR)= 0.98, 95% CI 0.43-2.22) and 5 years (HR=0.81, 95% CI 0.64-1.03) compared with native-valve-TAVI. Conclusions TAVI in a failed surgical aortic prosthesis as compared to TAVI in a native valve, was not associated with significantly different short- and long-term mortality. Although these findings to some extent reflect thorough patient selection, valve-in-valve-TAVI appears to be a safe procedure.

Clinical and Prognostic Value of Non-Fasting Lipoproteins and Apolipoproteins in Chinese Patients with Coronary Heart Disease.

Lipid profiles differ naturally between individuals and between populations. So far, the data relating to non-fasting lipid profiles has been derived predominantly from studies on Western population. The characteristics and clinical significance of non-fasting lipids in Chinese patients with coronary heart disease (CHD) in response to traditional Chinese diets remain poorly understood. A total of 1022 Chinese CHD patients with coronary artery luminal stenosis 40% as diagnosed by coronary artery angiography were enrolled in the study. All patients received standard treatment for CHD, including statins. They were divided into an intermediate stenosis group (luminal stenosis 40-70%, n = 486) or a severe stenosis group (luminal stenosis 70%, n = 536). Their blood lipid profiles were measured in the fasting state, and 4 hours after normal breakfast. All participants were followed up for five years. Major adverse cardiovascular events (MACE) including all-cause death, cardiac death, myocardial infarction, unscheduled coronary revascularization and stroke were recorded. After normal breakfast intake, patients with intermediate or severe stenosis showed an apparent increase in the levels of triglyceride (TG), remnant cholesterol (RC) and Apo (apolipoprotein) A1 compared to the fasting state, but a significant reduction in the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), Apo B and Apo E. In addition to the traditional risk factors (older age, male, diabetes and smoking) and coronary artery stenosis, the fasting levels of LDL-C and Apo B, as well as non-fasting levels of HDL-C and Apo A1, were identified as independent predictors of 5-year MACE occurrence by multivariate Cox proportional hazards analysis. Patients in the 1st tertile of the non-fasting HDL-C group ( 0.86 mmol/L) showed a significantly higher risk of MACE than 3rd tertile ( 1.07 mmol/L) (1st tertile: 2.786, 95% CI (confidence intervals) [1.808, 4.293], p 0.001). This prospective observational study found that lipid profiles in either the fasting or non-fasting states were associated with the long-term risk of MACE in Chinese CHD patients. In addition to the fasting LDL-C level, a low non-fasting HDL-C level may also be an independent risk factors for cardiovascular events. Measurement of lipid profiles during the non-fasting state may be feasible for the management of CHD patients in routine clinical practice in China.

Left ventricular longitudinal myocardial function in heart failure patients with transition to preserved ejection fraction from reduced ejection fraction and those with preserved ejection fraction

Abstract Background Left ventricular (LV) longitudinal myocardial dysfunction is considered the first marker of a preclinical form of heart failure (HF) with preserved ejection fraction (HFpEF), and is strongly associated with poor outcomes. LV ejection fraction (LVEF) may improve over time during treatment or follow-up in some patients with HF with reduced ejection fraction (HFrEF). Furthermore, it has been reported that patients with HF with improved EF, known as HFimpEF, which was defined as current LVEF > 40% but any previously documented LVEF ≤ 40%, had favorable outcomes compared to those with HFpEF. However, LV longitudinal myocardial function in patients with previously reduced LVEF who had improved LVEF to normal range (≥ 50%), and its association with cardiovascular events remains unclear. Purpose The purpose of this study was the comparison of LV longitudinal myocardial function in patients with HFpEF and those with previously reduced LVEF who had improved LVEF to normal range (reduced LVEF-HFpEF), and to investigate whether LV longitudinal myocardial function was associated with cardiovascular events. Methods We retrospectively studied 70 patients with HFpEF and 45 patients with reduced LVEF-HFpEF. Reduced LVEF-HFpEF was defined as current LVEF ≥ 50% but any previously documented reduced LVEF < 50% (mean: 34 ± 10%). HFpEF was defined as current and all previous LVEF reports ≥ 50%, and met the HFA-PEFF diagnostic algorithm criteria. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS) by means of two-dimensional speckle-tracking strain. The primary endpoint was defined as cardiovascular death over a median follow-up period of 5.0 (0.5-9.0) years. Results As expected, the Kaplan-Meier curve indicated that patients with reduced LVEF-HFpEF experienced fewer cardiovascular death than those with HFpEF (Figure A). GLS in patients with HFpEF was significantly lower than that in patients with reduced LVEF-HFpEF (13.6 ± 3.5% vs. 14.8 ± 2.2%, P = 0.03) regardless of similar LVEF (55.7 ± 3.3% vs 56.8 ± 5.0%, P = 0.15). An important finding of the multivariate Cox proportional hazards analysis showed that GLS was an independently associated with cardiovascular death (Figure B). Conclusion Impaired LV longitudinal myocardial function was observed in patients with HFpEF compared to those with reduced LVEF-HFpEF regardless of similar LVEF. Moreover, LV longitudinal myocardial function was independently associated with cardiovascular death HF patients with current LVEF ≥ 50%. Our findings may provide new insights for the management of HF patients.FigureAFigureB

Combined use of VA-ECMO and Impella (ECPELLA) improves short- and long-term mortality in patients with cardiogenic shock who received VA-ECMO

Abstract Introduction Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is beneficial for patients with refractory cardiac arrest and cardiogenic shock. Despite its benefits, VA-ECMO increases left ventricular (LV) afterload and causes pulmonary edema and LV distension. Recently, a transcatheter left ventricular assist device, Impella has been introduced and potential benefits of the concomitant use of VA-ECMO and Impella (ECPELLA) are expected. However, with the concomitant increase in complications, the utility of ECPELLA remains controversial and unsettled. Objective This single-site cohort study aimed to assess the impact of ECPELLA compared to VA-ECMO with or without intra-aortic balloon pump (IABP) in patients with refractory cardiogenic shock, including cardiac arrest, who received VA-ECMO treatment. Methods We retrospectively reviewed 245 consecutive patients, who underwent VA-ECMO treatment between January 2012 and December 2021 at our institute. Seventeen patients for difficult weaning from cardiopulmonary bypass (n = 15) and as a backup during high-risk transcatheter aortic valve implantation (n = 2) were excluded. The patients were divided into two groups, ECEPLLA (n = 64) and VA-ECMO with or without IABP (n = 164). We performed propensity score analysis with 1:1 score matching using dependent variables of age, the rate of male gender, acute coronary syndrome, out-of-hospital and in-hospital cardiac arrest, and extracorporeal cardiopulmonary resuscitation. We evaluated hemodynamic data, safety profiles, and mortality. Results Following matching, 58 ECPELLA and 58 VA-ECMO patients were included for analysis. No significant differences in the adjusted factors and comorbidities were found between the two groups, except for a significantly higher prevalence of chronic kidney disease in the VA-ECMO group compared to the ECPELLA group. Seventy-one percent of patients received concomitant use of IABP in the VA-ECMO group. During the first 72 hours following the initiation of VA-ECMO, the ECPELLA group received a significantly higher total mechanical circulatory support flow and correspondingly less administration of catecholamines compared with the VA-ECMO group. There were no statistical differences in safety profiles, except for hemolysis and embolic cerebral infarction, between the treatment groups. Kaplan-Meier analysis demonstrated that the 30-day and 1-year survival rates were significantly higher in the ECPELLA group than in the VA-ECMO group. Multivariate cox proportional hazard analysis revealed that age (hazard ratio [HR], 1.36 [10 years increase]; 95% confidence interval [CI], 1.15–1.62, p < 0.001), lactate level at ER (HR 1.07; 95% CI 1.03–1.12, p = 0.001), and ECPELLA (HR, 0.47, 95% CI, 0.30–0.73, p = 0.008) were significantly associated with the 1-year mortality. Conclusion ECPELLA was associated with improvement of short- and long-term mortality in patients with refractory cardiogenic shock who received VA-ECMO.Total MCS flow index and VISKaplan-Meier for 1-year mortality

Hepatic venous stasis index reflects hepatic congestion and predicts adverse outcomes in patients with heart failure

Abstract Background It has been reported that the hepatic vein waveforms determined by abdominal ultrasonography can assess hepatic congestion in heart failure (HF) patients. However, the parameter which quantifies hepatic vein waveforms has not been established. We suggest hepatic venous stasis index (HVSI) as the novel indicator to evaluate hepatic congestion quantitatively. To examine the clinical significance of HVSI in HF patients, we aimed to clarify the associations of HVSI with parameters of cardiac function and right heart catheterization (RHC), as well as that with prognosis, in patients with HF. Methods We performed abdominal ultrasonography, echocardiography and RHC in patients with HF (N = 513). The patients were divided into three groups based on HVSI as follows; HVSI 0 (HVSI = 0, N = 253), low HVSI (HVSI 0.01–0.20, N = 132) and high HVSI (HVSI > 0.20, N = 128) as shown in Figure 1. We examined the associations of HVSI with parameters of cardiac function and RHC, and followed up for cardiac events defined as cardiac death or worsening HF. Results There were significant correlations between HVSI and mean right atrial pressure (R = 0.244, P < 0.001), right ventricular fractional area change (R = -0.195, P < 0.001) and inferior vena cava diameter (R = 0.318, P < 0.001). During the follow-up period, cardiac events occurred in 87 patients. In the Kaplan–Meier analysis, cardiac event rate increased across increasing HVSI (log-lank, P = 0.002, Figure 2). In the multivariate Cox proportional hazard analysis, high HVSI was independently associated with cardiac events (high HVSI group vs. HVSI 0 group: hazard ratio, 1.746; 95% confidence interval, 1.053–2.894, P = 0.031). Conclusions HVSI assessed by abdominal ultrasonography reflects hepatic congestion and right-sided HF, and is associated with adverse prognosis in HF patients.Figure 1Figure 2

Prognostic impact of cardiovascular polypharmacy on octogenarians with heart failure with preserved ejection fraction

Abstract Backgrounds Drug treatments of heart failure with preserved ejection fraction (HFpEF) have a little clinical benefit, but cardiovascular polypharmacy (CP) trend is observed in elderly HFpEF. We investigated the impact of CP on octogenarian with HFpEF. Methods We examined 783 consecutive octogenarians (≥80 years) enrolled in the PURSUIT-HFpEF registry. We defined medications for hypertension, dyslipidemia, heart failure (HF), coronary artery disease, stroke, peripheral artery disease, and atrial fibrillation as cardiovascular medications (CM). In this study, we defined CP as ≥5 CM. We investigated whether CP was correlated with the composite end point (CE) of all-cause mortality and HF rehospitalization. Results The proportion with CP was 51.9% (n=406). Background characteristics correlated with CP were frailty, history of coronary artery disease, atrial fibrillation and left atrial dimension. Multivariable Cox proportional hazards analysis showed CP was significantly and independently correlated with CE (hazard ratio (HR): 1.31; 95% confidence Interval (CI): 1.01-1.70) in addition to age, clinical frailty scale, history of HF admission and N-terminal pro brain natriuretic peptide (Table). Kaplan-Meier curve analysis showed that, compared with the non-CP group, the CP group had significantly higher risk of CE and HF (HR: 1.27; 95%CI: 1.04-1.56; P=0.02 and HR: 1.46; 95%CI: 1.13-1.88; P<0.01, respectively), but not any-cause death (Figure). In addition, diuretics were correlated with CE (HR: 1.61; 95%CI: 1.17-2.22; P<0.01), but antithrombotic drugs and HFpEF medications were not. Conclusions CP at discharge is a prognostic factor driven by HF rehospitalization in octogenarians with HFpEF. In these patients, diuretics may be correlated with the prognosis.

Prognostic impact of thyroid dysfunction in patients with incident heart failure: a nationwide study

Abstract Background Thyroid hormones directly affect the cardiovascular system. Thyroid dysfunction can cause a variety of haemodynamic alterations and has been associated with an increased risk of atrial fibrillation (AF), heart failure (HF), and all-cause mortality. However, a paucity remains regarding knowledge on the prognostic impact of thyroid dysfunction in patients with HF. Purpose To examine the impact of the whole spectrum of thyroid dysfunction in patients with HF on the associated risk of AF, HF admissions, and all-cause mortality. Methods This Danish cohort study included patients with a first-time HF diagnosis from 2000–2021. According to blood samples within 6 months prior to the HF diagnosis, the study population was categorized based on thyroid function in 1) overt hypothyroidism, 2) subclinical hypothyroidism, 3) euthyroidism, 4) subclinical hyperthyroidism, and 5) overt hyperthyroidism. With up to one year of follow-up from the date of HF diagnosis, we used Aalen-Johansen estimator to examine the cumulative incidence frequency (CIF) of AF and HF admissions and Kaplan-Meier estimates to assess all-cause mortality. Multivariable Cox proportional hazard analysis was performed to investigate differences in outcomes among groups. Results Of the 7,380 individuals included in this study (56.6% female, median age 76.5 years [p25-p75: 67.9-84.1]), 102 (1.4%) had overt hypothyroidism, 1,706 (23.1%) had subclinical hypothyroidism, 4,374 (59.3%) were euthyroid, 691 (9.4%) had subclinical hyperthyroidism, and 507 (6.9%) had overt hyperthyroidism. Compared with euthyroid patients, the adjusted one-year hazard ratio (HR) for AF was 0.77 (95% CI, 0.49-1.20) for overt hypothyroidism, 1.01 (95% CI, 0.90-1.13) for subclinical hypothyroidism, 1.18 (95% CI, 1.01-1.38) for subclinical hyperthyroidism, and 1.19 (95% CI, 1.01-1.39) for overt hyperthyroidism (Figure). The adjusted one-year HR for HF hospitalizations was 1.51 (95% CI, 1.06-2.14) in patients with overt hypothyroidism, 1.07 (95% CI, 0.96-1.20) in patients with subclinical hypothyroidism, 0.99 (95% CI, 0.84-1.16) in patients with subclinical hyperthyroidism, and 1.26 (95% CI, 1.06-1.50) in patients with overt hyperthyroidism. The adjusted one-year HR for mortality was 1.81 (95% CI, 1.25-2.63) in patients with overt hypothyroidism, 1.25 (95% CI, 1.10-1.42) in patients with subclinical hypothyroidism, 1.15 (95% CI, 0.96-1.37) in patients with subclinical hyperthyroidism, and 1.46 (95% CI, 1.20-1.78) in patients with overt hyperthyroidism. Conclusion In patients with HF, overt and subclinical hyperthyroidism was associated with an increased rate of AF. Both hypo and hyperthyroid states were associated with increased risk of HF admission and mortality. Increased awareness regarding thyroid status in patients with HF is warranted.

Is frailty associated with greater symptom burden following catheter ablation for atrial fibrillation?

Abstract Background Previous, small studies have found that the effectiveness of catheter ablation among patients with atrial fibrillation (AF) is affected by frailty. However, whether the symptom burden after catheter ablation varies according to frailty remains uncertain. Purpose We aimed to assess whether severity of patient frailty modified the recurrence of AF in the year after first-time catheter ablation for AF including proportion of hospital admissions with AF. Methods We identified patients with a first-time catheter ablation for AF (Jan. 1st 2010-Dec. 31st 2018) from the Danish National Ablation Registry, and eligible for one year of follow-up. Patient comorbidities and concomitant pharmacotherapy were identified using Danish nationwide registries. The patients’ Hospital Frailty Risk Score was calculated using diagnosis codes, and patients were grouped according to cut points of low (<5), intermediate (5-10), and high-risk (>10) frailty. Multivariable Cox proportional-hazards analyses were performed for comparison of associated factors for the risk of recurrence of AF during one year of follow-up after a 3-month blanking period. McNemars test was used for comparison of AF hospital admission rates before and after catheter ablation. Results Among 3,638 patients treated with first-time catheter ablation for AF (median age 62.4 years [Q1,Q3=55.1,68.5 years], 72.8% male), 89.0% had low-risk frailty, 9.4% had intermediate-risk frailty and 1.6% had high-risk frailty. At one year follow-up, 546 (15.0%) patients had recurrence of AF (hospital admission with AF or treatment with electrical cardioversion). Both intermediate-risk frailty patients (HR 1.56, CI: 1.22-2.00, p<0.001) and high-risk frailty patients (HR 2.13, CI: 1.30-3.49, p=0.003) had a significantly increased risk of recurrence of AF during one year of follow-up compared with patients with a low-risk frailty score. All patients across frailty groups had a 5-fold decrease in AF hospital admissions in the year after catheter ablation (15%) compared with the year before (68%) (p<0.001). Patients with high-risk frailty had a more than 3-fold reduction of AF hospital admissions in the year after catheter ablation (28%) compared with the year before (88%) (p<0.001) (Figure 1). During one year follow-up, 35 patients (1.0%) died. Conclusion Patients with high-risk frailty had a 3-fold decrease while all patients across frailty groups had a 5-fold decrease in AF hospital admissions in the year after catheter ablation compared with the year before. Thus, indicating a lower symptom burden after catheter ablation. Nevertheless, intermediate-risk and high-risk frailty was associated with significantly higher recurrence rates of AF one year after first-time catheter ablation for AF compared with low-risk frailty patients. Patient frailty should be considered when selecting patients eligible for ablation in order to improve patient outcomes.

Atrial fibrillation in patients with hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is associated with complications such as heart failure, atrial fibrillation (AF) and sudden cardiac death. The treatment of AF in HCM patients can be challenging since AF often aggravates symptoms and increases the risk of stroke. Little is known on which factors contribute to the development of AF in these patients. Purpose To determine the incidence of AF in Danish HCM patients and identify risk factors that increase risk of AF. Methods Using Danish national registers all patients without previous AF, aged 16 or older diagnosed with HCM between the 1st of January 2005, and the 31st of December 2018 were included in the analysis. The association between HCM and incident AF was investigated using multivariable Cox proportional-hazard analysis. Cumulative incidence of AF was calculated using the Aalen-Johansen estimator, taking death as a competing risk into account. Results A total of 3,200 HCM patients without prevalent AF were included, median age was 66 years (IQR 55-77) and 48% were female. During the study period, 477 (15%) patients were diagnosed with incident AF. The risk of developing AF was equal between genders and average time from HCM diagnosis to debut of AF was 1260 days. Risk of AF development was increased for patients with prevalent ischemic heart disease (HR 1.33, CI [1.08 – 1. 63]) and hypertension (HR 1.34, CI [1.11 – 1. 63]) as well as for patients classifies as obstructive HCM at diagnosis (HR 1.27, CI [1.06 – 1. 53]). Following AF diagnosis, prescription with oral anticoagulants and antiarrhythmic medication increased markedly. Conclusion AF is a common complication in HCM. Patients with obstructive HCM, hypertension and ischemic heart disease were at increased risk of developing AF.Figure 1:CI of AF by genderFigure 2:HR for AF developement

TDE-derived impaired post-PCI Coronary flow velocity reserve predicts MACE in patients who underwent LAD PCI

Abstract Background Coronary flow velocity reserve (CFVR) can be obtained noninvasively by stress transthoracic Doppler echocardiography (S-TDE). However, prognostic significance of S-TDE-derived CFVR after percutaneous coronary intervention (PCI) remains unknown. Purpose This study aimed to investigate the relationship between post-PCI CFVR and major adverse cardiac event (MACE). Methods This study prospectively included 200 patients with stable coronary artery disease who were scheduled for elective PCI of de novo, single, functionally significant left anterior descending (LAD) lesions at a single tertiary-care center between April 2019 and November 2022. All patients underwent fractional flow reserve (FFR)-guided elective PCI. Exclusion criteria were patients with previous coronary artery bypass graft surgery, left main coronary artery disease and periprocedural myocardial infarction as defined by the fourth universal definition of myocardial infarction. Eligible patients underwent pre- (1 day before) and post-procedural (3 days after) LAD coronary flow assessments by stress-TDE. CFVR was calculated as the ratio of the hyperemic peak diastolic flow velocity to the basal peak diastolic flow velocity. We also excluded the patients with suboptimal S-TDE imaging. Association between post-PCI physiological parameters and MACE (composite of cardiac death, myocardial infarction, heart failure and target vessel revascularization) were evaluated. Results A total of 174 patients were included in the final analysis after successful LAD PCI. MACE occurred in twenty-one (12.0%) patients during the follow-up (1.9 [0.9-2.5] years). Clinical demographics were similar in patients with versus without MACE. Post-PCI S-TDE-derived CFVR was lower in patients with versus without MACE (P = 0.023), while post-PCI FFR values tended to be lower in patients with versus without MACE, albeit not significant (P = 0.077). Receiver-operating characteristic curve analysis revealed that the optimal cut-off values of post-PCI FFR and post-PCI CFVR values to predict MACE were 0.83 and 1.70, respectively. Significant differences in the MACE were detected according to post-PCI FFR (≤ 0.83 versus > 0,83: 17.9 % versus 6.7 %, P = 0.035) and post-PCI CFVR (< 1.70 versus ≥ 1.70: 33.3% versus 8.2%, P = 0.001). On a multivariable Cox-proportional hazard analysis, patients with post-PCI CFVR < 1.70 had an increased risk for MACE (adjusted hazard ratio [HR] 4.75, 95% confidence interval [CI] 1.98-11.38, P < 0.001), along with post-PCI FFR ≤ 0.83 (adjusted HR 2.78, 95% CI 1.07-7.20, P=0.035). Conclusions In patients who underwent successful elective PCI for LAD, S-TDE-derived impaired post-PCI CFVR and post-PCI FFR were independently associated with MACE.

A long-term prognostic factor for cardiovascular risk in patients with chest pain without diabetes mellitus and significant coronary stenosis

Abstract Background Chest pain is the most common symptom of coronary artery disease (CAD); diabetes mellitus (DM) is a well-known single largest risk factor for cardiovascular diseases and survival worldwide. So, the impact of CAD and DM on long-term clinical effects is reported widely. This study aimed to evaluate the long-term prognostic factor for major adverse cardiac and clinical events (MACCE) in patients with chest pain without DM and CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation test. Methods A total of 1,046 patients with chest pain without DM and significant CAD who underwent CAG and ACH tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. All subjects were followed clinically for up to 5 years. Results Coronary spasm (CAS) seems the most common cause of chest pain. However, long-term MACCE of CAS is not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a repeated chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year follows, MACCE has occurred 7.3%, including recurrent angina of 6.9%. Dyslipidemia, mild to moderate CAD, and the use of aspirin/nitrates are associated with long-term MACCE. Conclusions Among the patients with chest pain without DM and significant CAD, the occurring major adverse cardiac events, including death, MI, and de novo CAD, are rare, but recurrent angina is still a challenging problem who had the treatment by anti-anginal medications.

Synergistic adverse impact of diabetes and chronic kidney disease on cardiovascular mortality in patients underwent percutaneous coronary intervention

Abstract Background Diabetes and chronic kidney disease (CKD) are frequently complicated each other. While approximately 40% of patients have diabetes among those with CKD, it is the most major (40-50%) and clinically important complication of diabetic patients which critically effects on their quality of life and outcomes. Moreover, numerous previous evidence has indicated the adverse prognostic impact by each of diabetes and CKD particularly in the secondary prevention of patients with established coronary artery disease (CAD). Nevertheless, to date, limited data is available regarding the synergistic impact of these two major risk factors on outcomes of patients with CAD. Purpose We studied the synergistic adverse effects of diabetes and chronic kidney disease on cardiovascular mortality in patients undergoing percutaneous coronary intervention (PCI). Methods This study is a part of a single-center prospective registry database of patients underwent PCI, which launched at 1984. A total of 4880 patients who underwent their first PCI (index PCI) at our university hospital between 2000 and 2018 were enrolled for the study. Participants were divided into 4 groups by the presence or absence of CKD and DM: DM−/CKD− (n=2028, 41.6%), DM+/CKD− (n=1411, 28.9%), DM−/CKD+ (n=754, 15.5%), and DM+/CKD+ (n=687, 14.1%). The endpoint was set as cardiovascular-related death (CV death). The median follow-up duration was 5.2 years since PCI procedure. Results During follow-up, 288 (5.9%) CV deaths were identified, in which 79.1% had DM or CKD. Unadjusted Kaplan-Meier curves showed patients with DM+/CKD+ had a significantly higher cumulative incidence of CV death compared to those with DM-/CKD- (log-rank p<0.0001) and DM-/CKD+ (p=0.03) (Figure 1). Moreover, multivariate Cox-proportional hazard analysis set DM-/CKD- as a reference and adjusted by age, gender, body mass index, hemoglobin, ejection fraction, acute coronary syndrome, statin and smoking history showed significantly increased risk of having both of diabetes and CKD (Hazard ratio (HR) and 95% confidence interval (CI) of DM and CKD: 3.1,: 1.9-5.1, p<0.0001) than having each of these (HR and 95% CI of DM alone: 1.2, 0.7-2.0, p=0.5, and of CKD alone: 1.8, 1.1-3.0, p=0.02 (Figure 2). Conclusions Findings in the present study indicated that CKD is a significant risk for CV death in patients following PCI, while only DM without CKD was not a significant risk factor in this population. Moreover, the risk for CV death was synergistically increased, when a patient had both of DM and CKD, compared to having each of these.Kaplan-Meier curves in CV deathAdjusted Cox hazard model in CV death

Association between triglyceride glucose-body mass and one-year all-cause mortality of patients with heart failure: a retrospective study utilizing the MIMIC-IV database

BackgroundThe triglyceride glucose-body mass (TyG-BMI) index is acknowledged as both a reliable indicator of the risk of cardiovascular disease and an accurate surrogate biomarker for evaluating insulin resistance (IR). The importance of the TyG-BMI index among people with heart failure (HF), however, requires more investigation. The objective of this study was to inquire about the relationship between HF patients’ TyG-BMI index and their risk of 360-day mortality.MethodsThe Medical Information Mart for Intensive Care (MIMIC-IV) database provided the study’s patient data, which were divided into quartiles according to their TyG-BMI index. The endpoint was mortality from all causes within 360 days. Kaplan-Meier analysis was used to compare this primary endpoint amongst the four groups indicated above. The association between the TyG-BMI index and the endpoint was investigated using restricted cubic splines and Cox proportional hazards analysis.ResultsThe study enrolled a total of 423 patients with HF (59.2% male), of whom 70 patients (16.9%) died within 360 days. Patients with higher TyG-BMI indexes had significantly lower mortality risks, according to the Kaplan-Meier analysis (log-rank P = 0.003). Furthermore, the restricted cubic spline analysis illustrated a decrease in the risk of all-cause mortality with an increasing TyG-BMI index. Additionally, multivariable Cox proportional hazards analyses showed that the risk of 360-day death from all causes was considerably higher in the lowest quartile of TyG-BMI. In comparison to the lowest TyG-BMI group, the fully adjusted Cox model yielded a hazard ratio (HR) of 0.24 (95% CI: 0.10, 0.59; p = 0.002) for 360-day mortality.ConclusionsIn patients diagnosed with HF, a lower TyG-BMI index is strongly related to a higher risk of 360-day mortality. This index can be employed to categorize the risk levels of patients with HF and predict their one-year all-cause mortality .

Abstract 13555: Effect of Calcium Channel Blockers on Clinical Outcomes in Patients After Percutaneous Coronary Intervention With Left Ventricular Dysfunction

Although calcium channel blockers (CCBs) are effective in hypertension and IHD, short-acting CCBs are not recommended for heart failure due to have negative inotropic effects. On the other hand, long-acting CCBs have been reported to be safe for use in patients with cardiac dysfunction, but details are still unclear. In this study, we investigated the relationship between the effects of CCBs on CAD patients and left LV function. Methods: We enrolled 7173 consecutive CAD patients (Age; 69 [61-76] years and male; 78%) who underwent successful PCI for AP or ACS between April 2008 and March 2020 from prospective, multicenter registry (FUJISUN registry). Of the enrolled patients, 5307 analyzable patients were divided by LVEF <40 or ≥40%. Patients were prospectively followed for a maximum of 8 years or until the occurrence of the cardiac events (CEs): cardiac death, nonfatal MI. Results: During the follow-up period (3.6 [1.4-6.7] years), 230 (4%) CEs occurred (109 Cardiac death, 121 MI). Both patients with LVEF <40% and ≥40% had higher prevalence of HT and lower levels of BNP in CCB group than in non-CCB group. Propensity match analysis was performed to reduced selection bias for CCB use in each group. In patients with LVEF <40%, Kaplan-Meier analysis showed that CCB group had significantly lower probability of CEs than non-CCB group, whereas in those with LVEF ≥40%, the probability of CE was similar in both groups. Multivariate Cox proportional hazards analysis showed that CCB group had significantly lower probabilities of CEs compared with non-CCB group in patients with LVEF<40%, (HR 0.25; 95% CI 0.09-0.71, p <0.01), but not in those with LVEF≥40% (HR 1.13; 95% CI 0.80-1.60, p = 0.50). Conclusions: Long-acting CCBs may improve clinical outcomes in post-PCI CAD patients with LV dysfunction.

Abstract 12984: Impact of Cardio-Ankle Vascular Index on New Cancer Diagnosis in Patients With Coronary Artery Disease

Introduction: Cardiovascular risk factors are associated with increased risk of future cancer. However, the relationship between quantitative parameters of atherosclerosis and the risk of future cancer is unclear. Here we investigated the association between cardio-ankle vascular index (CAVI), an indicator of arterial stiffness, and future new cancer diagnosis in patients with coronary artery disease. Methods: This was a prospective observational study which enrolled consecutive 1122 patients with coronary artery disease, excluding patients with atrial fibrillation or dialysis. According to the receiver operating characteristic curve analysis, the cut-off value of CAVI in predicting new cancer diagnosis was 8.70. We divided patients into two groups: the high-CAVI group (CAVI ≥ 8.70, n = 578, 51.6%) and the low-CAVI group (CAVI < 8.70, n = 544, 48.4%). We compared the patients’ characteristics and followed the incidence of new cancer diagnosis. Results: The high-CAVI group, as compared with the low-CAVI group, were older (72.3 vs. 64.0 years, P < 0.001) and had higher prevalence of diabetes mellitus (53.8 vs. 45.6%, P = 0.006), chronic kidney disease (47.1 vs. 32.5%, P < 0.001) and anemia (46.0 vs. 32.9%, P < 0.001). In contrast, there was no difference in the prevalence of smoking, hypertension, dyslipidemia, heart failure and history of malignancies between two groups. In the follow up period (mean of 2182 days), there were 141 new cancer diagnosis. The cumulative incidence of new cancer diagnosis was significantly higher in the high-CAVI group than in the low-CAVI group ( P = 0.007). In the multivariable Cox proportional hazard analysis after adjusting for confounding factors, CAVI was found to be an independent predictor of new cancer diagnosis (hazard ratio 1.51, 95% confidence interval 1.05-2.17, P = 0.022). Conclusions: High CAVI is associated with the risk of future cancer in patients with coronary artery disease.