Long-term Mortality Research Articles

Difference in long-term mortality after takotsubo syndrome. The role of gender, socioeconomic profile, and psychological distress

Abstract Background While Takotsubo Syndrome is less common in men, their mortality rates surpass those of women. The influence of socioeconomic factors and psychological distress, remains unexplored in this context. The aim of the study was: 1) to investigate gender differences in socioeconomic profile, and psychological distress in patients with incident Takotsubo Syndrome. And 2) to investigate gender differences in survival in patients discharged alive after incident takotsubo syndrome when taking into account differences in socioeconomic profile and psychological distress. Method A nationwide cohort study using the Danish national registers was performed. All patients discharged alive from Danish hospitals with an incident Takotsubo Syndrome diagnosis between 2008 and 2018 were eligible. Socioeconomic factors covering marital status, cohabitation status, labour market attachment, highest formal education and family income, and psychological distress was explored, and compared. Multivariable Cox-regression models were performed to assess the mortality risk. Results A total of 662 patients with Takotsubo Syndrome were discharged alive from Danish hospitals. Of those, 79 (11.9%) were men with a median age of 67 years (IQR 62-77). Men with Takotsubo Syndrome were socioeconomically disadvantaged compared to their women counterparts, and this disparity was also reflected in mortality rates. Secondly, mortality within three years after an incident Takotsubo Syndrome diagnose was higher among men than women, HR 2.19, 95%CI 1.04-4.61, most pronounced among men with a low family income, HR 2.08, 95% CI 1.03-4.18, and increase in comorbidity score, HR 1.23, 95% CI 1.06-1.43. Conclusion Results unveiled notable gender differences in the socioeconomic profile of individuals diagnosed with TS. Furthermore, the identified gender disparities in mortality can be attributed to socioeconomic and sociodemographic factors, the use of psychiatric medication as an indicator of psychological distress, and a greater comorbidity burden.Survival according to socioeconomy

Clinical characteristics and outcomes of patients with takotsubo syndrome and dynamic left ventricular outflow tract obstruction

Abstract Background Left ventricular outflow tract obstruction (LVOTO) is recognized as a serious complication of Takotsubo syndrome (TTS). However, its impact on patient prognosis remains insufficiently investigated. Purpose This study aimed to assess clinical characteristics and short- and long-term outcomes of patients with TTS complicated by LVOTO. Methods Patients with TTS were enrolled from the Takotsubo Italian Network (TIN). The primary outcome was the composite of acute heart failure, cardiogenic shock, and mortality during hospitalization. Secondary outcomes included the single components of the primary outcome and the occurrence of death or TTS recurrence during follow-up. Results Overall, 881 patients were included in the study [median age 72.0 (63.0–78.0) years; 91.3% female], with LVOTO detected in 59 patients (6.7%). Low diastolic blood pressure, ST-segment elevation, and moderate-to-severe mitral regurgitation were independently associated with occurrence of LVOTO. Propensity score weighting regression analysis revealed a significant higher risk of the primary outcome (OR, 2.99; 95% CI, 2.22–4.02), acute heart failure (OR, 2.19; 95% CI, 1.59–3.02), cardiogenic shock (OR, 4.56; 95% CI, 3.07–6.78), and in-hospital mortality (OR, 2.42; 95% CI, 1.13–5.21) in patients with TTS complicated by LVOTO. No significant association between LVOTO and long-term mortality or TTS recurrence was observed during follow-up. Conclusions In this real-world evidence study, LVOTO was detected in about 7% of TTS patients and was associated with a significantly higher risk of adverse events during hospitalization, including mortality. Early detection of LVOTO can aid in prognostic assessment and guide therapeutic management in patients with TTS.

Prognostic significance of the estimated pulse wave velocity in critically ill patients with coronary heart disease

Abstract Background The estimated pulse wave velocity (ePWV) has emerged as an alternative measurement of arterial stiffness which has been suggested as a potential marker for mortality and cardiovascular risk. Nonetheless, its prognostic significance in critically ill patients with coronary heart disease (CHD) remains uncertain. Methods Patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) were grouped into quartiles according to the ePWV levels. We conducted logistic and Cox regression analyses to examine the association between ePWV and both in-hospital and 1-year all-cause mortality among critically ill patients with CHD. Additionally, we employed restricted cubic spline (RCS) analysis to explore the relationship between ePWV as a continuous variable and mortality. Results A total of 11001 patients (men: 63.6%, age: 71.94 [IQR: 62.69-81.31]) were included in this study. In-hospital mortality and 1-year mortality rates were 9.1% and 25.1%, respectively. Multivariable logistic regression models demonstrated that ePWV was independently associated with an elevated risk of in-hospital mortality (OR 1.27; 95%CI [1.14-1.41]; p<0.001) and 1-year mortality (OR 1.49; 95% CI [1.38-1.60]; p<0.001]. The restricted cubic splines regression model revealed a linear relationship between ePWV and both in-hospital and 1-year mortality (p for non-linearity = 0.098 and p for non-linearity = 0.156, respectively). Conclusion Our findings indicate a linear association between ePWV levels and short- and long-term mortality in critically ill patients with CHD.

Impact of intravascular imaging on mortality in patients undergoing left main coronary artery PCI. Propensity score matching analysis of the high-volume single centre registry

Abstract Background Recent guidelines endorsed use of intravascular imaging in left main coronary artery (LMCA) percutaneous coronary intervention (PCI). However, impact of adjunctive percutaneous imaging tools on mortality is ambiguous. Purpose The purpose was to investigate impact of intravascular imaging (IVI) on all-cause mortality in patients with LMCA disease. Methods Group of 998 individuals undergoing LMCA PCI was selected from medical records of patients hospitalized in years 2008-2022. Data on mortality were obtained from the Ministry of Digital Affairs. Overall observation time was 14 years (mean 4.3 years). Survival analysis was performed using Cox proportional hazard regression in the overall and propensity-score matched (PSM) population. Results The median age was 71 y.o. (IQR 16), 265 (41.0%) of patients presented with acute myocardial infarction and 183 (20.7%) had history of previous coronary artery bypass grafting (CABG). IVI-guided PCI was performed in 353 (35.4%) patients. In the overall unmatched population, IVI reduced one-year and long-term mortality by 70% (HR 0.3, 95% 0.19-0.47, P<0.001) and 57% (HR 0.43, 95% CI 0.34-0.55, P<0.001). In the subgroup analysis stratified on the history of previous CABG, in patients with unprotected LMCA, IVI resulted in 74% and 63% mortality reduction in the one-year and long-term follow-up (HR 0.26, 95% CI 0.16-0.42, P<0.001; HR 0.37, 95% CI 0.28-0.47, P<0.001; respectively). No influence of IVI on patients with previous CABG was observed. After PSM adjustment for baseline and angiographical characteristics, in the overall population IVI was still associated with significant one-year (HR 0.49, 95% CI 0.25-0.99, P=0.045) and long-term mortality reduction (HR 0.65, 95% CI 0.44-0.97, P=0.03). In patients with unprotected LMCA disease, IVI reduced mortality in two-year observation (HR 0.49, 95% CI 0.26-0.91, P=0.02) and long-term follow-up (HR 0.62, 95% CI 0.41-0.93, P=0.02), with no significant effect in one-year observation. No effect of IVI was observed in the PS-matched cohort of patients with previous CABG. Conclusions Intravascular imaging is associated with significantly better survival in patients undergoing LMCA PCI. The greatest benefit may be obtained in patients with no previous history of CABG. Further studies should investigate subgroups that benefit the most from adjunctive percutaneous tools.PS-matching detailsKaplan-Meier curves in subgroups

Acute kidney injury (AKI) in cardiac intensive care unit patients: a real challenge to overcome

Abstract Introduction Acute kidney injury (AKI) is a major cause of morbidity and mortality in intensive care units (ICUs), but in cardiac intensive care unit (CICU), despite the evidence of a causal link between cardiac illness and AKI, few data are available (1). Purpose We analyzed the predictive factors of AKI in CICU, as well as the impact of AKI on the long-term prognosis of patients admitted to CICU. Methods We reviewed the medical data of patients admitted to our CICU over a 2-year period. We excluded patients with chronic kidney disease prior to admission. We defined AKI according to the KDIGO (Kidney Disease Improving Global Outcomes) classification based on serum creatinine and urine output. To determine the predictive factors, we performed a logistic regression analysis, and to determine the prognostic impact of AKI, we performed a Cox proportional hazards regression, taking all-cause mortality at 30 months as the main study outcome. p-values less than 0.05 were considered statistically significant Results We included in our study 1581 patients hospitalized in our unit over a 2-year period, 70.4% of whom were men and 29.6% women. Among these patients, 291 presented with AKI (18.4%), 35.5% classified as KDIGO 1, 42% as KDIGO 2, and 22.5% as KDIGO 3. For the admission diagnosis of patients with AKI, STEMI came first at 56.3%, followed by NSTEMI at 17.3%, acute heart failure at 9.3%, pulmonary embolism at 2.1%, severe arrhythmias at 7.9%, and valvular disease at 1.1%. Among patients in the KDIGO 3 group, 54% benefited from a renal replacement strategy. La morta For factors predictive of AKI, and after adjustment for variables significant in univariate analysis, we objectified the following factors: arterial hypertension (OR=1.92, p<0.001), Diabetes (OR=1.50, p=0.007), KILLIP>2 at admission (OR=1.75, p=0.003), Ejection fraction<40% at admission (OR=1. 93, p<0.001), right ventricular systolic dysfunction (OR=2.95, p<0.001), anemia with Hb<10g/dl (OR=2.95, p<0.001), cardiogenic shock (OR=3.02, p<0.001), high-grade conduction disorder (OR=2.7, p=0.003) and bleeding events (OR=5.93, p<0.001) (Table 1-figure 1). For all-cause mortality at 30 months, 204 events were observed, 104 in the AKI group (35%), and 100 in the non-AKI group (7.75%) (p<0.001), and AKI was independently associated with the outcome studied for all KDIGO classes with for stage 1 (HR = 1.33; p=0.03), stage 2 (HR = 2.28; p<0. 001), and stage 3 (HR = 5.71; p<0.001), adding to this diabetes (HR = 1.96; p<0.001), cardiogenic shock (HR = 2.27; p<0.001) and finally EF<35% at discharge (HR = 1.53; p=0.001) (Table 2-figure 1). The Kaplein-Meier survival analysis showed a significant difference between the rates of mortality between the different KDIGO at 30-months, with a log-rank test p<0.001 (Figure 2). Conclusion We can conclude that AKI remains a real challenge for admitted patients, since long-term mortality in this group is very high.Figure 1.Figure 2.

The association between elevated systemic inflammation response index and long-term mortality in patients with triple-vessel coronary disease

Abstract Background Inflammation is a critical factor in the development of coronary artery disease. The systemic inflammatory response index (SIRI) is a novel biomarker of inflammation. Studies have shown that SIRI is associated with the severity of coronary artery disease. However, there is currently a lack of research on the relationship between SIRI and adverse outcomes in patients with multivessel coronary artery disease. Our study aimed to investigate the correlation between SIRI and long-term mortality risk in patients with triple-vessel coronary disease (TVD) and explore the interaction between SIRI and treatment strategies. Methods After excluding patients with missing data or loss to follow-up, a total of 8559 patients with TVD were included in our study. Based on their SIRI levels during hospitalization, patients were evenly divided into three groups (SIRI-L, SIRI-M, and SIRI-H). All patients received appropriate treatment, including medical therapy alone (MT), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG). The primary endpoint was all-cause death. SIRI was calculated by the formula: neutrophil counts × monocyte counts / lymphocyte counts. Results During a median follow-up of 6.58 years, a total of 1264 all-cause deaths (14.8%) were recorded. Elevated SIRI was significantly associated with increased mortality rates (11.1%, 14.6%, and 18.6% in the SIRI-L, SIRI-M, and SIRI-H groups, respectively). The risk of all-cause mortality was significantly higher in the SIRI-M and SIRI-H groups compared to the SIRI-L group (adjusted HR: 1.203, 95% CI: 1.037-1.395, p=0.015; adjusted HR: 1.400, 95% CI: 1.212-1.617, p<0.001; respectively). In elderly patients, the relationship between elevated SIRI and the risk of all-cause mortality was more pronounced, while it attenuated in younger patients. Additionally, it is noteworthy that there was an interaction between SIRI and treatment strategy (p=0.037). In patients of the SIRI-L group, there was no significant difference between PCI and CABG treatment. However, in patients of the SIRI-M and SIRI-H groups, CABG shows a significant survival advantage over PCI. Conclusion Evaluating SIRI may help identify high-risk groups among patients with triple-vessel coronary disease and guide the selection of treatment strategies.Kaplan-Meier curves

Impact of Phase III cardiac telerehabilitation on cardiorrespiratory fitness, safety and adherence in patients with ischemic heart disease

Abstract Background and Purpose Cardiac rehabilitation program (CRP) is an interdisciplinary intervention aimed to improve exercise tolerance, promote the reintegration of patients with heart disease into their normal lives, and reduce the rate of long-term complications and mortality. Of the three phases, Phase II is responsible for achieving sufficient and safe gains to guarantee adaptation, but it is in Phase III where the long-term beneficial effects and self-management will be achieved. Nevertheless, only 30% - 60% of patients report continuing regular exercise during this stage, adherence rates are heterogeneous, and the diversity of results sustained over time is wide. Therefore, cardiac telerehabilitation (CTR) emerged as an affordable tool to achieve closer and safer surveillance at Phase III. The aim of the study is to evaluate the impact of CTR on exercise tolerance, safety and phase III adherence in patients with ischemic heart disease (IHD) Methods Quasi-experimental study that follows Phase II, in which patients with IHD were assigned to virtual sessions at 1st, 3rd, 6th and 12th months, In each session, they were questioned about adherence to training, exercise tolerance, symptoms, outcomes and control of cardiovascular risk factors (CVRF). The percentage of moderate in relation to vigorous physical activity was also evaluated. After one year they underwent a cardiopulmonary exercise test to analyze comparisons in cardiorespiratory fitness (CRFit) and control of CRF between the end of Phase II and the annual follow-up of Phase III. Results At one year of Phase III follow-up, a significant gain in VO2p and maintenance of the other variables associated with fitness such as oxygen pulse (OP2) and VE/VCO2 slope were evident, with a reduction in weight and diastolic blood pressure. There was a significant gain in CRF measured by VO2p and METs-load in those patients who maintained adherence to CTR Phase III (p=0.0001, see figure), with more improvement in those with attendance>50% (2 or more virtual sessions; p=0.008 and p=0.004 , respectively). A directly proportional correlation was observed between the percentage of attendance and the percentage of vigorous physical activity (p<0.01, Pearson r=0.46, CI 0.16-0.68). A positive and significant correlation was observed between the percentage of attendance at CTR Phase III and the number of METs-load (p<0.05, Pearson r=0.36, CI 0.05-0.61), as well as positive and significant correlation with the amount of VO2p (p<0.01, Pearson r=0.50, CI 0.21-0.70) at the end of Phase III. No cardiovascular adverse events were reported. Conclusion CTR strategy in Phase III is safe, effective and has high adherence rates among patients in our population, achieving control of CVRF, maintaining levels of METs-load and obtaining even greater increases in VO2p at one year of follow-up compared to those obtained at the end of Phase II.

Drug-use-associated infective endocarditis in Denmark

Abstract Introduction Infective endocarditis (IE) has high mortality and the incidence is rising. Intravenous drug use is a risk factor for IE and poses challenges in clinical care. Amid the opioid crisis in many countries, rates of drug-use-associated IE (DU-IE) are increasing. While drug use in Denmark has remained stable the last decade, little is understood about the features and prognostic impact of DU-IE in developed nations not facing a current opioid crisis. Further, with multiple preventive measures deployed in local Danish regions, data on the evolution of DU-IE are warranted. Purpose To examine the temporal evolution, baseline characteristics, and long-term rates of all-cause mortality and IE recurrence in patients with DU-IE compared with patients with non-DU-IE. Methods This nationwide cohort study identified all first-time IE-patients (1999-2018) and categorized them in 1) patients with DU-IE, and 2) patients with non-DU-IE. Drug use was defined using ICD-8/10 codes or treatment for opioid use disorder. Patients were followed from the date of discharge, and absolute one-year rates of mortality and IE recurrence were examined with Kaplan-Meier estimates and the cumulative incidence function, respectively. Outcomes were compared with a multivariable adjusted Cox model. Results We identified 8,843 patients with IE: 407 (4.6%) with DU-IE (61% male, median age 44 years) and 8,436 (95.4%) with non-DU-IE (66% male, median age 72 years). While the absolute number of DU-IE increased, the proportion of DU-IE decreased from 5.9% in 1999-2003 (n=87) to 3.8% in 2014-2018 (n=114). Patients with DU-IE had a higher proportion of bloodstream infection with Staphylococcus aureus (49.4% vs 26.7%, p<0.001); conversely, they had a lower proportion of bloodstream infections with Streptococcusspecies (14.4% vs. 26.2%, p<0.011). Patient with DU-IE had lower in-hospital mortality compared with non-DU-IE (15.5% vs. 20.9%, p<0.001). Among those surviving admission, the one-year cumulative incidence of all-cause mortality was 16.9% in DU-IE and 17.3% in non-DU-IE (p=0.82), yet in adjusted analysis, DU-IE was associated with a higher one-year mortality rate (HR 1.64 [95% CI:1.23-2.21]) (Figure). The one-year cumulative incidence of IE recurrence was 12.8% in DU-IE and 4.3% in non-DU-IE, which corresponded to an adjusted HR of 3.39 (95% CI:2.35-4.88) in DU-IE. Conclusion While an increase in the absolute number of patients with DU-IE was observed, the proportion among all IE-patients was on the decline in Denmark until 2018—which contrasts with other countries where physicians currently battle collateral damage of the opioid crisis. Although drug use was associated with lower in-hospital mortality, it was striking that even though patient with DU-IE was almost 30 years younger, they still had higher rates of all-cause mortality and a more than three-fold increase in IE recurrence one year following discharge.

Clinical impact of helicopter transport with a physician in cardiogenic shock complicating acute coronary syndrome

Abstract Introduction Cardiogenic shock (CS) remains the leading cause of death in patients with acute coronary syndrome (ACS). Helicopter transport with a physician may improve the prognosis through reduction of the ischemic time and an early critical care. However, the impact of transfer of a physician-staffed helicopter and outcomes of CS complicating ACS is uncertain. Purpose The aim of the present study was to evaluate compare the clinical characteristics and long-term outcome between helicopter transport with a physician and ground transport in CS complicating ACS patients. Methods We retrospectively investigated 2324 consecutive patients with ACS who underwent primary percutaneous coronary intervention (pPCI) in our institution from January 2004 to December 2017. The primary outcome was cardiovascular (CV) death. Results Among the 2324 eligible patients, 273 ACS patients (11.7%) were complicated by CS. Of 273 CS complicating ACS, a total of 81 (29.7%) patients were transported by helicopter, 166 (60.8%) patients were transported by ambulance, and 26 (9.5%) patients did not use emergency medical service. The mean age was 71 years, 75% of patients were male, STEMI was seen in 87%, and mechanical circulatory support was used in 64%. Kaplan-Meier analysis showed that CV mortality up to 30 days was significantly lower with helicopter transport group compared those with ground transport (P = 0.0407). The rate of long-term CV death was comparable between groups (P = 0.19). Multivariate Cox regression analysis showed helicopter transport was significantly associated with lower 30-day CV mortality (adjusted HR 0.56, 95%CI 0.32-0.99, P = 0.0447). Conclusions Helicopter transport with a physician may improve cardiovascular outcomes of CS complicating ACS.Figure 1.Figure 2.

Serial troponin sampling over 60-minutes allows early distinction between myocardial infarction and chronic myocardial injury in patients presenting to emergency departments

Abstract Background High-sensitivity cardiac troponins (hs-cTn) are key clinical biomarkers in the assessment and diagnosis of patients with suspected acute coronary syndromes presenting to Emergency Departments (ED). These tests facilitate rapid triage through 0h/1h blood sampling regimens. Most patients will not have myocardial infarction (MI) diagnosed, having either hs-cTn levels below the upper reference limit (URL) or stable elevations. The latter group of complex, often multimorbid, patients is termed chronic myocardial injury (CMI) according to the 4th Universal Definition of MI (4thUDMI). These patients have long-term morbidity and mortality rates higher than those with type 1 MI. Early distinction of CMI from MI remains challenging with debate regarding optimal hs-cTnT delta cut-offs; both 3ng/L and 5ng/L over one-hour have been proposed. Methods and Results We prospectively collected 0-, 30- and 60-minutes (+/- 5 min) hs-cTnT samples from 185 patients presenting to Liverpool Hospital ED (Sydney, Australia) between March and August 2023. Diagnoses were adjudicated according to the 4thUDMI as follows: 16 (8.6%) MI ruled-in, 66 (35.7%) CMI and 103 (55.7%) MI ruled-out. Linear regression was used to calculate individual hs-cTnT slopes for each patient. Between CMI and MI, each 1 ng/L/hour increase in the slope of hs-cTnT resulted in a two-fold (95% CI: 1.5 to 2.9) greater likelihood of MI being diagnosed (P < 0.001). A stable hs-cTnT trajectory was observed in CMI, which ranged between 0 and 3 ng/L/hour in all patients with an initial hs-cTnT level ≤ 50 ng/L. Chronic myocardial injury patients with an initial hs-cTnT level > 50ng/L (n=12), exhibited more kinetic slopes ranging up to 8ng/L/hour (P <0.001). Unexpectedly, three MI patients had a non-linear slope, of whom two patients would not have displayed a significant rise had the additional 30-minute sample not been collected. These outlying patients presented at 9-12 hours and over 12 hours from symptom onset. Conclusion This study offers a novel characterisation of CMI, which has not previously been investigated in an unselected ED cohort using three serial samples over one hour. It validates a hs-cTnT delta of 3ng/L/hour in the recent ESC guidelines. However, there is a need for greater characterisation of short-term hs-cTn variability for more personalised MI risk stratification and to guide more targeted observation and further investigation of CMI patients.

Association of P2Y12 inhibitor pretreatment strategy with short and long term ischemic and bleeding outcomes in NSTE-ACS patients

Abstract Background and Aims Oral P2Y12 inhibitors form the basis of both short and long term antiplatelet therapy in NSTE-ACS patients. While reducing thrombogenic activity and ischemic risk is the basis of routine P2Y12 inhibitor pretreatment in NSTE-ACS patients, timing of treatment became controversial as a result of studies showing routine P2Y12 inhibitor pretreatment is associated with an increased risk of bleeding. Even though routine pretreatment is no longer recommended in the ESC guidelines, the inadequacies in RCTs combining all treatment modalities have been noted. Our study aims to determine the relationship between P2Y12 inhibitor pretreatment strategy and short and long-term ischemic and bleeding events. Methods The study was designed as a single-center, prospective and observational study. 2602 patients, aged between 18 and 85, diagnosed with NSTE-ACS in accordance with ESC guidelines were included in the study. 2189 patients were administered with P2Y12 inhibitor pretreatment while 413 patients weren't. Demographic data, CVD risk factors, ECG, echocardiography and laboratory findings at the time of admission, interventional procedural details, type of antiplatelet and anticoagulant treatment and application time were recorded. Patients were divided into two groups as pretreatment and no-pretreatment according to the time of administration of P2Y12 inhibitor loading dose. In the no-pretreatment group choice of P2Y12 inhibitor was left to operator in the cath lab before proceeding to PCI. Post-procedural in-hospital and long term follow up (1 year) were obtained through hospital and national registry systems and patient survey. Results In the no-pretreatment group 91.3% of patients underwent coronary angiography and PCI was performed in 51.8%. In patients proceeding to PCI, 58.5% were given clopidogrel and 41.5% were given a potent P2Y12 inhibitor. In the pretreatment group, clopidogrel was the drug of choice in 93.8% of patients. In the pretreatment group, the primary composite endpoint (MACE and bleeding events) were more common during in-hospital follow-up and this difference was due to a significant increase in both BARC class I & II and class III, IV & V bleedings (Table 1). In the long-term follow up, statistically significant difference was only seen in BARC class I & II bleedings in the pretreatment group. There were no difference in MACE rates in neither in-hospital or long-term follow up (Table 2). Also in multivariate regression analysis, pretreatment with a P2Y12 inhibitor was found to be an independent predictor of short term primary composite endpoints and long-term all-cause mortality. Conclusion The results of our study investigating the effects of the P2Y12 inhibitor pretreatment strategy on ischemic and bleeding endpoints in NSTE-ACS patients showed that the pretreatment strategy did not lead to an improvement in MACE rates in in-hospital and long-term follow-up but caused on overall increase in bleeding events.Kaplan-Meier Survival Analysis

Circadian heart rate fluctuations predict 21-year cardiovascular and all-cause mortality in type 2 and type 1 diabetes

Abstract Background Alterations in circadian heart rate (HR) fluctuations have been associated with cardiovascular events in the general population. This study aimed at defining their long-term prognostic value for cardiovascular and all-cause mortality in patients with diabetes. Methods We examined a cohort of 349 patients with type 2 or type 1 diabetes (52% women, age 57.1±11.9 years, BMI 29.4±5.9 kg/m2, HbA1c 8.6±2.1%, 81% type 2 diabetes) who underwent 24h ambulatory blood pressure and HR monitoring (ABPM) and assessment of diabetic microvascular complications. The median standard deviation (SD) value of ABPM-derived HR measurements was used to define patients with low daily HR fluctuations (low 24h-HR SD), while a <10% decline in average night-time vs day-time HR identified patients with blunted nocturnal HR dip (n=107, 31%). The clinical features and time-dependent prognostic impact of these conditions were evaluated over a 21-year observational follow-up. Results Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and high prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years of follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. After adjustment for potential confounders, the low 24h-HR SD group had a higher risk for both cardiovascular (hazard ratio 1.99, 95% CI 1.29–3.06, p=0.002) and all-cause mortality (hazard ratio 1.50, 95% CI 1.03–2.18, p=0.033), compared with high 24h-HR SD. Consistently, patients with blunted nocturnal HR dip had a higher adjusted risk for cardiovascular (1.61, 95% CI 1.07–2.43, p=0.023) and all-cause mortality (1.61, 95% CI 1.11–2.34, p=0.012), compared with those with preserved nocturnal HR dip. Conclusions Impaired circadian HR fluctuations are frequent in patients with long-standing diabetes and are associated with microvascular disease and increased long-term cardiovascular and all-cause mortality. Identifying these conditions via 24h-ABPM may provide a cost-effective risk stratification tool in this high-risk population.Kaplan-Meier curves

Correlation between short-term quality of life improvement and clinical outcomes - a post-hoc ISCHEMIA trial analysis

Abstract Background Patients with symptomatic coronary artery disease (CAD) exhibit improvement in quality of life (QoL) after invasive management (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]). However, it is not clear how QoL improvements after intervention are related to clinical outcomes. Purpose Using the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) population, we sought to assess the relationship between short-term QoL improvement and long-term clinical outcomes. Methods All participants in the ISCHEMIA trial who were randomized to the invasive arm and who had QoL scores available were included in the analysis. QoL improvement was calculated using the difference between the Seattle Angina Questionnaire (SAQ) score at baseline and at six months regarding randomization. The primary outcome was the trial-defined composite outcome (cardiovascular death, myocardial infarction, cardiac arrest or hospitalization for unstable angina/heart failure) and all-cause death. The secondary outcome was all-cause mortality. Median follow-up was 3.3 years. Cox proportional hazards models included clinically relevant demographic and angiographic covariates. Results After the exclusion of the conservative treatment arm and patients without QoL follow-up or covariate data, 1,577 patients were selected for the final analysis (Fig.1). The median baseline SAQ score was 74 (interquartile range, IQR: 60-88), the change in score at six months was 14 (IQR: 2-26), and 76.1% of patients experienced improvement in QoL. Six-month QoL improvement was not associated with a lower risk of the primary outcome (hazard ratio [HR]: 0.961, 95% confidence interval [CI], 0.920-1.005, p=0.081 – Table 1), but was associated with all-cause mortality (HR: 0.919, 95% CI, 0.859-0.982, p=0.013 – Table 1). In this population, increased age (HR: 2.370, 95% CI, 1.710-3.287, p<0.001, per 10 years) was also associated with higher risk of all-cause mortality. Conclusions Among invasive treated patients in ISCHEMIA trial, six-month QoL improvement was associated with a lower risk of long-term all-cause mortality, but not with a lower risk of major adverse events.Figure 1.Study population.

Epidemiology and temporal trends of infective endocarditis between 2006 and 2018 at a tertiary referral center

Abstract Introduction Despite modern diagnostics, targeted antibiotic therapy and surgical treatment the mortality rate of infective endocarditis (IE) remains high. In developed countries both the risk factors and pathogens have changed. Objective and methods In our retrospective study we analyzed the clinical and microbiological characteristics, short- and long-term all-cause mortality, and temporal trends of consecutive patients admitted with IE between 2006 and 2018. Results We included 537 cases in our study, the mean age was 55.9 ± 16.5 years (72.2% male). 325 (60.5%) cases were native left-sided IE, 14 (3%) cases were right-sided IE, 130 (24%) cases were prosthetic valve IE, 62 (11.5%) cases were intracardiac device-related IE and 6 (1%) other cases. The most common microorganisms were Staphylococci (n=175; 33%), including 104 cases of methicillin-sensitive Staphylococcus aureus (MSSA), 27 cases of methicillin-resistant Staphylococcus aureus (MRSA) and 44 cases of coagulase-negative Staphylococci. Streptococcus species were identified in 141 cases (26%), Enterococcus species in 88 cases (16%) and 72 cases (13%) were classified as blood culture-negative IE. In-hospital all-cause mortality was 14%, mortality at six months was 27%, at one-year was 31%, and at five-year was 45%. The incidence of MSSA infections increased over time (p=0.024), while coagulase-negative Staphylococci (p<0.001), and Streptococci (p=0.047) infections decreased. None of the observed mortality rates showed significant change over the study period. Predictors of mortality were advanced age (HR 1.37; p<0.001), impaired renal function (HR: 1.03; p<0.001), reduced ejection fraction on admission (HR 1.38; p<0.001), stroke (HR 1.74; p=0.001), and MRSA infection compared to Streptococci (HR 2.56; p=0.002). Conclusion During the observed 13-year period Staphylococci were the most common pathogens, with an increasing incidence of MSSA infection in our tertiary center. The mortality rate of IE remained high and showed no improvement over time.

Statin use before acute coronary syndrome and coronary risk factors, clinical presentation, interventions, and outcomes: ACC-NCDR-CathPCI Registry in India

Abstract Background Statins are used for coronary artery disease (CAD) primary and secondary prevention. Limited studies on the association of statin use before acute coronary syndrome (ACS) with clinical presentation and outcomes are available. Purpose We compared statin-user and statin-naïve ACS patients for clinical and angiographic findings and in-hospital and 3-year outcomes following percutaneous coronary intervention (PCI). Methods Successive patients with ACS who underwent PCI from Sep’17 to Dec’23 were enrolled in the ACC-NCDR-CathPCI registry in India. Details of risk factors, clinical presentation, coronary angiography, interventions and in-hospital were recorded. Follow-up data in a sub-cohort recruited from Apr’19 to Mar’22 were obtained for incident major cardiovascular events (MCE) (cardiovascular deaths, recurrent ACS, PCI and bypass surgery). Results 8296 ACS patients were enrolled; prior statin use was in 3149 (38%) and statin naïve were 5147 (62%). Statin-user vs statin-naïve patients were older (61.6+10 vs 59.7+11y), with more hypertension (60.1 vs 48.6%), diabetes (35.8 vs 31.8%), pre-existing CAD (PCI 20.9 vs 9.1%; CABG 5.0 vs 2.3%) and lower mean total, LDL, and NHDL cholesterol (p<0.001). Statin users had less ST-elevation myocardial infarction (STEMI) (28.4% vs 45.2%), more non-STEMI (65.2 vs 50.8%), better LVEF (46.3+10 vs 44.5+10%), >2 coronary stents (35.5 vs 29.5%), lower mechanical circulatory support (2.2 vs 3.9%) and lower median hospitalization (66.1 vs 68.5h) (p<0.001). In statin-users incidence of in-hospital CAD deaths was 29 (0.92%) vs 78 (1.52%) (odds ratio, OR 0.61, 95% confidence intervals 0.39-0.93) and all-cause deaths 33 (1.05) vs 91(1.77%) (OR 0.59, 95%CI 0.39-0.88) (p<0.01). ORs attenuated following multivariate adjustments for risk factors, clinical presentation and interventions. In the follow up cohort (n=3813, high-intensity statins 99.6%), among baseline statin-users incident MCE was 98 (6.9%) vs 214 (8.9%) (hazard ratio, HR 0.76, 95%CI 0.59-0.97) and CVD deaths were in 46 (3.2%) vs 113 (4.7%) (HR 0.68, 95%CI 0.48-0.96) with attenuation following adjustment for baseline clinical variables and interventions. Conclusions Acute coronary syndrome patients taking pre-admission statins have significantly lower in-hospital and long-term cardiovascular and all-cause mortality following PCI.

Multi-modal artificial intelligence-based prediction for cardiovascular mortality after transcatheter aortic valve implantation: a time-to-event survival prediction

Abstract Background Predicting long-term outcomes following Transcatheter Aortic Valve Implantation (TAVI) presents a significant challenge. Objective We aimed to predict post-TAVI long-term cardiovascular mortality using multimodal data and employing time-to-event artificial intelligence (AI) algorithms. Methods This study enrolled 3,973 consecutive patients from the prospective TAVI registry (between August 2007 and June 2023). Multimodal information was collected and extracted as numerical data for each patient, encompassing clinical history, medication, laboratory, procedural characteristics, ECG, angiography, echocardiography (TTE and TEE), and CT. Clinical outcomes were adjudicated by an independent clinical event committee. From the multimodal information, 147 features were extracted at baseline before the TAVI procedure. The datasets were divided into a training/validation set (80%) and a hold-out test set (20%) for model development and evaluation, respectively. Cox-LASSO feature selection was employed to identify the most relevant features, followed by the implementation of Random Survival Forest (RSF), Gradient Boosting Survival Analysis (GBSA), and Survival Support Vector Machine (SSVM) to predict the timing and occurrence of cardiac death events in patients. Feature selection, model parameters, and hyperparameters selection were performed using 10-fold cross-validation on the training set. Model performance was evaluated using different metrics, such as the concordance index (c-index) and cumulative Area Under the Curve (C-AUC) on a 20% untouched test set. Results In the patient cohort, 28.4% experienced cardiovascular death. Features were selected from various modalities, including 22 from clinical history, two from medication, eight from laboratory tests, one from ECG, eight from CT scans, and five from echocardiography and angiography. In the univariate Cox-PH model, all features exhibited a C-index ranging from 0.50 to 0.57. In the test set, the conventional Multivariate Cox-PH model achieves a c-index of 0.59 (C-AUC: 0.56). RSF, GBSA, and SSVM achieve a C-index of 0.70 (C-AUC: 0.69), 0.66 (C-AUC: 0.64), and 0.69 (C-AUC: 0.68), respectively, in the holdout test set. Conclusion Integrating multimodal information, encompassing imaging, signal, laboratory data, and clinical history, with AI algorithms has markedly enhanced the prediction of long-term cardiac outcomes following the TAVI procedure. The initially developed model can predict the probability of cardiac death up to 10 years. Furthermore, the RFS model significantly outperformed the conventional Cox model in predicting time-to-event outcomes.

An international comparison of Long-term Care Facility outcomes during the COVID-19 pandemic

Abstract Background The COVID-19 pandemic has had huge repercussions for public health internationally and different countries had different outcomes based on preconceived policy interventions. Lessons influencing future policy have been learned, notably how best to manage vulnerable populations, particularly those living in long-term care facilities (LTCFs). In Ireland LTCF residents accounted for 56% of deaths during the first wave of the pandemic and it is imperative to establish the causes of this. International research has highlighted how factors including county incidence rate, facility size, occupancy, LTCF ownership and compliance with health inspection regulations influenced LTCF COVID-19 outcomes. The aim of this research is to explore the impact of these factors in an Irish context and compare to best international standards. Methods The main outcome considered was deaths per 100 beds. Data on crude mortality were available for 580 Irish LTCFs up to 28 May 2020. Data regarding occupancy, ownership, facility size and compliance with regulations were obtained for these LTCFs from a novel dataset of 1130 available LTCF regulatory inspection reports between 2018- 2022. Regression analysis was carried out to show how LTCF mortality was predicted by examined variables. Results The most significant predictor of deaths from COVID-19 in Irish LTCFs resulting from this research was LTCF occupancy (Odds ratio:1.029, significance <0.001). Regional community incidence, in concordance with international literature was also an important factor. Other stated predictors in this model were either non-significant or only marginally significant. These results are analysed in conversation with international research of the same variables. Conclusions To protect LTCF residents for potential future pandemics, attention should be paid to monitoring and suppressing local incidence rates and moves should be implemented towards designing smaller facilities with individual rooms for vulnerable residents. Key messages • Irish long-term care pandemic mortality was predicted by high occupancy of facilities and high regional COVID-19 incidence. • Comparing International COVID-19 outcomes in long-term care facilities can provide guidelines for the future.

Ankle brachial index,a non invasive tool predicts cardiovascular events after acute myocardial infarction:a 3 year follow -up study

Abstract Background / Introduction The ankle-brachial index (ABI) is a non-invasive tool that was initially used for the diagnosis of lower-extremity peripheral artery disease (PAD). It has been proven that ABI is a marker of atherosclerosis in other vascular sites and can therefore be used to predict cardiovascular events regardless the presence or not of PAD symptoms. Purpose This study aims to examine the prognostic value of ABI in the setting of acute myocardial infarction (MI), as up till now there is not enough relevant evidence. Method We followed up 441 patients [79% male;mean age 62 years;67% hypertnesive; 30% with diabetes mellitus (DM); 52% current smokers] who were hospitalized because of MI for a period of three years. All patients underwent baseline estimation of clinical and laboratory parameters during theri hospitalization.The ABI was measured according to established methodology using a certified automated device and abnormal ABI defined as a value ≤ 0.9. The primary endpoint was a composite of all-cause and cardiovascular death, as well as major cardiovascular events including decompensated heart failure, new acute coronary syndrome, cerebrovascular event, malignant arrhythmia, PAD event and new onset renal dysfunction. All events were assessed both in-hospital and within 3 years of follow-up. Results Our study population had a mean ABI of 1.1 (IQR: 1.00 to 1.18). With the use of reduced multivariate regression models ABI was proven to be a prognostic indicator for the in-hospital composite endpoint. Patients with an abnormal ABI had a threefold risk of in-hospital events [HR 2.93, 95% CI: 1.48-5.81, p=0.002]. After conducting multivariate analysis ABI maintained its predictive power of all-cause mortality [HR 2.88, 95% CI: 1.53 – 5.42, p=0.001], regardless of hypertension DM, LDL levels and smoking status of the study population in 3 years follow-up. Conclusion An impaired ABI is associated with greater risk of in-hospital events in patients with acute MI. Moreover, ABI emerges as an independent predictor of long-term all-cause mortality in those patients.The findings of this study suggest that subclinical and clinical PAD are associated with poor outcomes among patients with acute MI; thus, routine ABI tests enhance risk stratification and might carry important prognostic significance in these patients regardless of PAD symptoms.

Association between all-cause mortality and diabetic avoidable hospitalization among older patients

Abstract Background In South Korea, the prognosis of avoidable hospitalization in diabetes has not been evaluated, even though the incidence rate is considerably high compared to the Organization for Economic Co-operation and Development average. This study investigated the association between diabetic avoidable hospitalization after the diagnosis of type 2 diabetes mellitus and short- and long-term all-cause mortality. Methods Participants were type 2 diabetes mellitus patients aged 60 years and older and gathered through the National Health Insurance Services Senior cohort data from 2008 to 2019. The outcome measures included five-year and overall period all-cause mortality. The main independent variable was the first-year experience of diabetic avoidable hospitalization after type 2 diabetes mellitus diagnosis. Regression analysis was performed using the Cox proportional hazard model. To enhance the robustness of the study results, a sensitivity analysis and inverse probability of treatment weighting method were conducted. Results Among 31 222 participants, 2343 (7.5%) died within 5 years of type 2 diabetes mellitus diagnosis and 5314 (17.0%) died in the overall study period after type 2 diabetes mellitus diagnosis. Participants who experienced diabetic avoidable hospitalization one year after being diagnosed with type 2 diabetes mellitus had a higher risk of all-cause mortality compared to those who did not (Five-year: hazard ratio 1.84, 95% confidence interval 1.54-2.21; Overall period: hazard ratio 1.81, 95% confidence interval 1.60-2.06). Conclusions Enhancing accessibility and quality of primary care to prevent avoidable hospitalization in older patients with type 2 diabetes mellitus is necessary. Key messages • Older patients with T2DM who experienced avoidable hospitalization exhibited higher all-cause mortality rates in both the short and long terms. • Enhancing the accessibility and quality of primary care to prevent avoidable hospitalization in older patients with type 2 diabetes mellitus is necessary.

Expression of cardiomyopathy-related genes in mononuclear blood cells predicts all-cause mortality in patients presenting with acute versus chronic coronary syndrome requiring revascularisation

Abstract Objective Despite advances in the revascularisation techniques their net clinical benefit differs substantially between patients presenting with myocardial infarction (ACS) and chronic coronary syndrome (CCS) due to obstructive coronary atherosclerosis. Considering that leukocytes represents a key pathophysiological component of myocardial ischaemia, exploration of mononuclear blood cell (PBMC) gene expression profile in CCS and ACS setting could reveal clinically relevant transcriptomic signals. The aim of the present study was to identify differences in PBMC transcriptome between ACS and CCS patients which are linked to mortality after revascularisation. Methods and Results We analysed PBMC transcriptomes from719 ACS and 486 CCS patients creating discovery cohort. The results of transcriptomic analysis were verified in replication cohort (ACS: N=682 for CCS: N=489) generated based on propensity score matching. Median time from revascularisation to blood collection (IQR) was 15.68 (-4.52, 23.23) hrs. Patients with ACS showed consistent differential expression of 8173 genes (4544 upregulated, 3629 downregulated) when compared with CCS patients. The subsequent pathway analysis also showed significant enrichment of several canonical pathways involved in major cardiovascular pathologies i.e. atherosclerosis (p = 1.22-06, enrichment = 3.39), vascular endothelial growth factor production (p = 1.16-06, enrichment = 16.73), positive regulation of vascular development (p = 2.78-06, enrichment = 5.30) and heterotopic cell adhesion including gene desmocollin 2 (DSC2, p = 3.64-04, enrichment = 6.30). In der multivariate survival analysis with differentially expressed genes, increased expression of DCS2, lamin A/C (LMNA), and UGGT2, and decreased expression of SNRNP70 predicted poor survival over the median follow-up 11.35 yrs. Consistently, controlling the false discovery rate at ≤ 5% these genes enriched pathways involved in cardiomyopathies such as arrhythmogenic right-ventricular cardiomyopathy (p = 4.19x10-4, enrichment = 58.9) and collagen disease (p = 2.29x10-3, enrichment = 23.8). Conclusion We found altered PBMC expression of multiple genes in patients requiring revascularisation for ACS versus CCS. Several differentially expressed genes included in cardiomyopathy pathways predicted long-term all-cause mortality in these patients.