Independent Predictor Of Death Research Articles

Echocardiographic predictors of mid-term outcome after transcatheter aortic valve implantation in patients with severe aortic stenosis

Abstract Background Transcatheter aortic valve implantation (TAVI) has become a standard treatment option in severe symptomatic aortic stenosis (AS). Extra-valvular cardiac damage affects prognosis after aortic valve replacement (AVR). Knowledge of cardiac remodeling factors that predict a poor outcome after TAVI is scarce. Purpose The study aim was to assess if echographic cardiac remodeling parameters could predict mid-term outcome after transfemoral TAVI with balloon expandable valves. Methods This study included 157 consecutive patients (76.4±7.3 yrs., 82 men) with severe AS at increased risk for surgical AVR, undergoing TAVI between October 2017 and December 2019. Patients underwent echocardiography before and 30 days after the procedure and clinical follow-up 3 years after inclusion. Pulmonary hypertension (PH) was defined as systolic pulmonary artery pressure (sPAP) >35 mmHg. Longitudinal LA strain was assessed in apical views. Peak values of global longitudinal LA strain (LAε), systolic strain rate (SSr) and early diastolic strain rate (ESr) were measured in all patients. Contractile LA function (late diastolic strain rate, ASr) was assessed in patients in sinus rhythm. Primary outcome was all-cause mortality. Results Three-year follow-up was available for all patients. Mean follow-up was 52±9 months (39-73). During follow-up 45 pts (76.8±7.3 yrs., 24 men) died, mid-term mortality was 29%. Between survivors and non-survivors, we found no differences in age and sex (p=0.3 and 0.8), LV ejection fraction, global longitudinal strain and AS severity. The presence of syncope, angina and significant coronary lesions before TAVI was similar between survivors and non-survivors. There was a significant reduction in sPAP after TAVI (33±11 vs 40±14, p<0.001), still PH was present 30 days after the procedure in 51 pts (32%). Patients with persistent PH at 30 days after TAVI had a significantly higher mid-term mortality (41.6% vs 22.4%, p=0.02), worse global LA strain (-9.2±4.8 vs -13.7±7.1%, p<0.001) and worse LA contractile function (ASr: -1.0±0.6 vs -1.3±0.6, p=0.002). Using binary logistic regression, atrial fibrillation (p=0.004), increased indexed LA volume (baseline and 30 days after TAVI, p=0.006 and p=0.021), impaired peak global LA strain after TAVI (p=0.04), baseline sPAP (p=0.03) and persistent PH (p=0.02) were significant univariate correlates of all-cause mortality. In the multivariable regression model, increased LA volume at baseline (OR 1.01, p=0.012) emerged as an independent predictor of death. Conclusions The mid-term follow-up revealed a mortality of 29% in high-risk patients with severe AS. No echocardiographic parameters of LV or RV systolic function or AS severity were associated with an increased risk of death. PH (at baseline and persistent), LA dilation and impaired LA strain after TAVI were associated with mortality. Increased LA volume before the procedure was an independent predictor of mid-term mortality after TAVI.

Mechanical dispersion predicts long-term survival of dialysis-dependent patients with preserved ejection fraction

Abstract Background Since cardiovascular disease is a major cause of death in patients with chronic kidney disease (CKD), echocardiographic risk stratification of CKD patients may be clinically important, especially if left ventricular (LV) systolic function is still preserved. Purpose To investigate the prognostic implications of conventional (LV mass) and advanced echocardiographic parameters [global longitudinal strain (GLS) and mechanical dispersion] in dialysis-dependent patients with preserved left ventricular ejection fraction (LVEF). Methods A total of 78 patients with LVEF≥50% were prospectively enrolled and followed for 60 months for all-cause death. LV mass was calculated using the ASE/EACVI recommended formula for estimating LV mass from LV linear dimensions and indexed to body surface area (LVMI). Longitudinal myocardial strain was measured by speckle-tracking echocardiography. The duration of mechanical contraction was determined as the time from the ECG R-wave to peak longitudinal strain in each of 18 LV segments. Mechanical dispersion was defined as the difference between the longest and shortest time intervals. Results In univariable analysis, age [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01-1.07, p=0.014], diabetes mellitus (HR 2.16, 95%CI 1.03-4.52, p=0.042), LVMI (HR 1.02, 95%CI 1.01-1.03, p=0.001), GLS (HR 0.77, 95%CI 0.66-0.88) and mechanical dispersion (HR 1.01, 95%CI 1.01-1.02, p<0.001) were all predictive of all-cause mortality. The results of the multivariable Cox regression model are shown in the Figure: in addition to age, mechanical dispersion, LVM and GLS were found to be independent predictors of death from any cause. Patients with mechanical dispersion ≥260 ms had worse survival (HR 3.74, 95% 1.51-9.27) than those with a lesser degree of dispersion (p=0.004). Conclusions In dialysis-dependent patients with preserved LVEF, higher extent of mechanical dispersion is associated with worse long-term survival. Higher LV mass and reduced GLS were also identified as independent predictors of survival. Echocardiography-derived parameters may be useful for risk stratification in this vulnerable patient population.

The Effect of Rehabilitation Therapy in Children with Intervened Congenital Heart Disease: A Study Protocol of Randomized Controlled Trial Comparing Hospital and Home-Based Rehabilitation

Background/Objectives: Children who suffer from congenital heart defects (CHDs) have a decreased ability to perform physical exercise and consequently have a decrease in their functional capacity. The main causes of this decrease in functional capacity have been related on the one hand to residual hemodynamic defects and, at the same time, to a situation of physical deconditioning due to inactivity, as well as problems in lung function, especially the presence of restrictive patterns that influence the amount of O2 insufflated (decreased maximum VO2), consequently generating a deficient maximum O2 consumption and maximum work rate. This represents an important prognostic value, since it constitutes an independent predictor of death and hospitalization. This study aims to determine the benefits obtained regarding respiratory function, exercise capacity, and quality of life after implementing a hospital-based cardio-respiratory rehabilitation program compared to a home-based Cardio-respiratory Physical Activity Program in patients with intervened CHDs. Methods: This is a randomized controlled trial on the effectiveness of two different rehabilitation programs on respiratory function, exercise capacity, and quality of life in patients with CHDs conducted at the Child Cardiology and Congenital Heart Disease Unit of the University Hospital Complex of A Coruña (CHUAC). There will be two groups: Cardio-respiratory rehabilitation group program conducted in a face-to-face format at the hospital (n = 26) and a study group that follows a home-based Cardio-respiratory Physical Activity Program (TELEA) (n = 26). The measurement variables will be respiratory function, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), maximum expiratory flow (PEF), the Tiffeneau index (FEV1 /FVC), forced expiratory flow (FEF25%, FEF50%, FEF75%, FEF25–75%), exercise capacity (peak VO2), and the quality of life of these children and their families. Conclusions: The implementation of cardiac and pulmonary rehabilitation programs in children with CHDs is essential to improve their quality of life, exercise tolerance, and socialization. These programs optimize life expectancy and promote integration, being crucial for their physical and emotional well-being

One-Year Prognosis for Patients Diagnosed with Acute Coronary Syndrome Compared to Those with Chronic Coronary Syndrome Following Complex Coronary Procedures

Background: Acute coronary syndrome (ACS) remains the primary cause of mortality worldwide. Performing complex coronary intervention in patients with ACS is considered a significant factor for worsening prognosis. This study aimed to evaluate the prognosis of patients with ACS treated with complex procedures compared to patients with chronic coronary syndrome (CCS). Methods: Among 980 patients from the Polish Complex Registry, we enrolled 829 consecutive patients who underwent complex percutaneous coronary intervention (PCI) for acute or chronic coronary syndrome with a completed one-year follow-up. The primary endpoint is defined as the major adverse cardiac event (MACE) at 12 months, a composite endpoint including all-cause death, target lesion revascularization, target vessel revascularization, and non-fatal myocardial infarction. Results: The incidence of the composite endpoint of MACE at one-year follow-up was comparable between the patients with acute and chronic coronary syndrome who underwent complex PCI (12.4% vs. 7.6%, LogRank p = 0.035). Cox multivariate analysis indicated that ACS is an independent risk factor for death at one-year follow-up. Additionally, age and comorbidities, such as heart failure and chronic kidney disease, along with procedural factors, including lesion length and pre-procedural diameter stenosis, are independent predictors of death in patients with complex lesions. Independent risk factors for MACE at one-year follow-up include age, heart failure, previous PCI, in-stent restenosis, and pre-procedural diameter stenosis. Conclusions: The prognosis of patients with acute and chronic coronary syndrome in the annual follow-up is comparable in the context of cardiovascular events. The clinical presentation of ACS is an independent risk factor for all-cause death.

Predictors and Impact of Cardiogenic Shock in Oldest-Old ST-Elevation Myocardial Infarction Patients.

Background: Cardiogenic shock (CS) is the most frequent cause of in-hospital mortality after ST-elevation myocardial infarction (STEMI). Data about CS in very elderly (age ≥ 85 years) STEMI patients are scarce. We sought to assess the prognostic factors and the short- and mid-term impact of CS in this population. Methods: Consecutive very elderly STEMI patients undergoing invasive treatment were included in a retrospective multicenter registry. Results: Among 608 patients, 72 (11.8%) fulfilled experienced CS. Peripheral artery disease (PAD) (OR: 2.25, 95% CI: 1.29-3.92, p < 0.01) and cardiac arrest at presentation (OR: 4.36, 95% CI: 2.32-8.21, p < 0.01) were the major independent predictors of CS. Age (HR: 1.07, 95% CI: 1.03-1.11, p < 0.001), PAD (HR: 1.29, 95% CI: 1.01-1.66, p = 0.045), previous MI (HR: 2.16, 95% CI: 1.32-3.55, p = 0.002), and cardiac arrest at presentation (HR: 1.59, 95% CI: 1.29-1.96, p < 0.001) were the major independent predictors of death. CS was associated with a higher risk of mortality at 30 days (adjusted HR: 4.21, 95% CI: 2.19 to 7.78, p < 0.01) mostly driven by higher intraprocedural and in-hospital mortality. Among patients who survived the acute phase and hospitalization, CS at presentation was not associated with a higher mortality risk during the remaining follow-up period (log-rank p = 0.78). Conclusions: At short-term follow-up, very elderly STEMI patients presenting with CS had a higher risk of mortality when compared to non-CS patients. Interestingly, CS patients surviving the acute phase showed a similar survival rate to non-CS patients after discharge.

The Role of Oxygenation Index as an Outcome Predictor in Mechanically Ventilated Acute Respiratory Distress Syndrome Patients

Background: Acute respiratory distress syndrome (ARDS) is associated with a significant mortality rate and a high likelihood of failing to wean from mechanical ventilation. Predicting such outcomes in such patients is crucial for the modification of appropriate treatment approaches and for facilitating family communication. Several studies have found that the oxygenation index is an early predictor of outcomes. This study aimed to assess the role of OI assessed on day 1 for predicting weaning outcomes and mortality within 28 days. Methods: This prospective observational study was done at Dhaka Medical College Hospital (DMCH) over a year. A total of 122 patients with ARDS admitted to the non-COVID intensive care unit (ICU) at the Department of Anesthesia, Pain, Palliative &amp; Intensive Care were included in the study based on selection criteria, using a non-probability sampling technique after receiving informed written consent from the patient’s attendants. On day one, the oxygenation index (OI) was measured, and the outcomes were recorded. Results: An oxygenation index of ≥16.01 cm of H2O substantially increased the risk of mortality by 295.211 (95% confidence interval (CI): 28.163-3094.528) times and predicted mortality with 88.06% sensitivity and 87.27% specificity. The oxygenation index (≥11.11 cm of H2O) was found to independently and significantly increase the chance of weaning outcome (failure) by 35.094 (95% CI: 4.041-304.762) times and weaning failure was predicted with 95.45% sensitivity and 70.27% specificity. Conclusion: In ARDS patients on mechanical ventilation, the OI measure at day one can be used as a highly accurate, and independent predictor of death and weaning failure.

Prognostic value of the fibrinogen-to-albumin ratio (FAR) in patients with chronic heart failure across the different ejection fraction spectrum

ABSTRACT The ratio of fibrinogen to albumin (FAR) is considered a new inflammatory biomarker and a predictor of cardiovascular disease risk. However, its prognostic value for patients with chronic heart failure (CHF) with different ejection fractions (EFs) remains unclear. A total of 916 hospitalized patients with CHF from January 2017 to October 2021 in the First Affiliated Hospital of Kunming Medical University were included in the study. Death occurred in 417 (45.5%) patients out of 916 patients during a median follow-up time of 750 days. Among these patients, 381 patients suffered from HFrEF (LVEF <40%) and 535 patients suffered from HFpEF or HFmrEF (HFpEF plus HFmrEF, LVEF ≥ 40%). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR (9.06) obtained from receiver operating characteristic (ROC) curve analysis. Upon analysing the Kaplan – Meier plots, the incidence of death was significantly higher in all patients with FAR-H and patients in both HF subgroups (p < 0.001). The multivariate Cox proportional hazard analyses indicated that the FAR was an independent predictor of all-cause mortality, regardless of heart failure subtype. (HR 1.115, 95% CI 1.089–1.142, p < 0.001; HFpEF plus HFmrEF, HR 1.109, 95% CI 1.074–1.146, p < 0.0001; HFrEF, HR 1.138, 95% CI 1.094–1.183, p < 0.0001) The optimal cut-off value of FAR in predicting all-cause mortality was 9.06 with an area under the curve value of 0.720 (95% CI: 0.687–0.753, p < 0.001), a sensitivity of 68.8% and a specificity of 65.6%. After adjusting for the traditional indicators (LVEF, Lg BNP, etc.), the new model with the FAR had better prediction ability in patients with CHF. Elevated FAR is an independent predictor of death in CHF and is not related to the HF subtype.

Predictors of long-term all-cause mortality after carotid artery stenting: evaluation of the Naples prognostic score

Background Mortality in patients after carotid artery stenting (CAS), a treatment approach for atherosclerotic carotid artery stenosis, is influenced by numerous factors. This study aimed to investigate the prognostic value of the Naples prognostic score (NPS), which reflects nutritional and inflammatory status, in CAS patients. Methods We retrospectively included 697 patients who underwent CAS from January 2016 to December 2020 at our institute. The primary endpoint of the study was long-term all-cause mortality. The study population was divided into two groups based on the NPS value: Low NPS (NPS 0–2) and high NPS (NPS 3-4). Univariable and multivariable Cox regression analysis was used to identify independent predictors of death. Results The median follow-up time was 60.8 (46.36-75.36) months. During the follow-up period, all-cause mortality was higher in the high-NPS group compared to the low-NPS group [54% (n = 88) vs. 24% (n = 128) p < 0.001]. Advanced age (p = 0.003), diabetes (p = 0.023), and NPS (hazard ratio: 1.83, confidence interval: 1.58-2.12, p < 0.001) were found to be independent predictors of all-cause mortality at long-term follow-up. Conclusion Consequently, NPS as a marker of malnutrition and inflammation, was found to be associated with long-term mortality and serves as an independent predictor of long-term mortality in patients undergoing CAS.

Cardiac troponin and increased mortality risk among individuals with restrictive spirometric pattern on lung function testing

ABSTRACT Background Individuals with a restrictive spirometric pattern have a high burden of cardiovascular and metabolic morbidity. Objective To assess prevalence of elevated cardiac biomarkers among individuals with a restrictive spirometric pattern compared to those with a normal lung function and to evaluate the association between cardiac biomarkers and mortality. Methods In 2002–04, individuals with airway obstruction were identified from population-based cohorts, together with age- and sex-matched non-obstructive referents. The analysis population consisted of the non-obstructive referents stratified according to whether they had a restrictive spirometric pattern or normal lung function in whom cardiac biomarkers were measured. Deaths were recorded until 31 December 2010. Results Participants with a restrictive spirometric pattern were older and more likely to be obese with a higher burden of cardiovascular risk factors than those with normal function. Elevated cardiac troponin but not natriuretic peptide levels were more common in those with a restrictive spirometric pattern independent of age, sex, BMI, or risk factors (adjusted OR 1.8, 95% CI 1.29–2.74). At 5 years, death occurred more frequently in participants with restrictive spirometric pattern compared to those with normal function (15.7% [31/197] versus 7.6% [57/751]), with highest mortality rate in those with restriction and elevated cardiac troponin (28.7% [27/94]). Cardiac troponin was independently associated with death among those with a restrictive spirometric pattern (HR 4.91, 95% CI 1.58–15.26) but not in those with normal lung function. Conclusion Cardiac troponin was elevated more often in people with a restrictive spirometric pattern in whom it was a strong independent predictor of death.

Impact of polypharmacy on patients undergoing revascularisation for peripheral arterial disease.

Background: To evaluate the impact of polypharmacy, defined as the concurrent use of five or more medications, on the clinical outcomes of patients undergoing revascularisation for symptomatic peripheral arterial disease (PAD). Patients and methods: This is a retrospective analysis of consecutive PAD patients treated by surgical, endovascular or hybrid therapy in a tertiary center between January 2017 and December 2017. The composite of amputation and/or death (amputation-free survival; AFS) was the primary endpoint. Mortality, major limb amputation, risk for Major Cardio-Cerobro-vascular Events (MACCE) and re-intervention during follow-up were additionally analyzed. Results: A total of 560 patients (369 male, 66%) were included. Mean age was 72.43 ± 38.67, while the main indication for treatment was lifestyle limiting claudication (330 patients, 59%). Most patients (434, 78%) were treated with endovascular means, and the commonest anatomical site of intervention was the femoropopliteal arterial segment (449 patients, 80%). A total of 409 (73%) met the criteria for polypharmacy. Cox regression analysis showed that polypharmacy was an independent predictor of death (exp: 4.72, p=0.008), MACCE (exp: 2.82, p=0.001), re-intervention (exp 1.51, p=0.0016) and of the composite outcome of AFS (exp: 3.46, p=0.021) but not of major amputation (exp: 1.26, p=0.686). Propensity-score matching analysis showed that even when controlling for comorbidity and procedural characteristics, polypharmacy is associated with a higher risk of cardiovascular death (p<0.001), MACCE (p<0.001), and re-intervention (p=0.001). Conclusions: In this study, polypharmacy was associated with unfavourable clinical outcomes for patients undergoing revascularisation for symptomatic PAD, without influencing the risk for major limb amputation.

Abstract 4145876: Prognostic significance of somatic mutations in myeloid cells of men with chronic heart failure – interaction between loss of Y chromosome and clonal hematopoiesis

Introduction: Age-associated clonal hematopoiesis of indeterminate potential (CHIP) has been associated with increased incidence and worse prognosis of chronic heart failure. CHIP is driven by somatic mutations in hematopoietic stem and progenitor cells (HSPC). Mosaic loss of the Y chromosome (LOY), the most common somatic mutation in blood cells of men, also correlates with clonal expansion of myeloid cells, increases with age and was experimentally shown to lead to diffuse cardiac fibrosis and subsequent heart failure in mice. However, the prognostic significance of LOY as well as its potential interaction with CHIP in patients with chronic heart failure is unknown. Aims/Methods: We investigated the prevalence and prognostic significance of the extent of LOY and the two most common CHIP-driver mutations DNMT3A and TET2 in 705 male patients with established chronic heart failure across the entire spectrum of left ventricular ejection fraction. Results: Both, LOY and DNMT3A/TET2 mutations, increased with age, and LOY co-occurred with DNMT3A/TET2 mutations in 27.1% of men at age &gt; 70 years. LOY was an independent predictor of death during 3-years of follow-up across the entire spectrum of left ventricular ejection fraction. The co-occurrence of harboring LOY and DNMT3A/TET2 mutations significantly contributed to the observed increased mortality observed in carriers of DNMT3A/TET2 mutations. The detrimental effect of LOY on prognosis was confirmed in a validation cohort of patients with ischemic heart disease.scRNA sequencing of peripheral blood cells in patients with chronic ischemic heart failure showed increased profibrotic signaling in LOY monocytes with elevated markers of monocyte mediated inflammation and profibrotic cardiac remodeling (S100A8, TLR2, CLEC4D) and reduced expression of TGF-b inhibiting genes (SMAD7, TGIF2). The proinflammatory phenotype of LOY monocytes was further amplified in LOY monocytes of patients simultaneously harboring DNMT3A mutations, who displayed heightened expression of alarmins (S100A8, HMGB2) and interferon signaling related genes (IFNGR1, TRIM56, CD84) compared to patients without CHIP mutations. Conclusion: The age-associated acquisition of somatic mutations in blood cells of men with chronic heart failure is associated with increased mortality, with loss of Y chromosome emerging as an independent predictor of all-cause death across the entire spectrum of left ventricular function.

Diagnosis and Prognosis of Isolated Cardiac Sarcoidosis: Multidisciplinary Diagnosis vs Japanese Circulation Society Criteria.

The prognosis of isolated cardiac sarcoidosis (ICS) has not been fully elucidated. The only diagnostic criteria available for ICS, the Japanese Circulation Society (JCS) criteria, have not been validated. Our objective was to study the prognosis of ICS, according to 2 different diagnostic strategies. We prospectively included patients with high suspicion for cardiac sarcoidosis (CS) by a multidisciplinary sarcoidosis team from November 2016 to June 2021. We included only incident cases. We applied the JCS ICS criteria and our multidisciplinary diagnosis (MDD) ICS criteria. We included 198 incident patients who had a final diagnosis of cardiac sarcoidosis. Median follow up time was 2.4 years (p25-p75 1.2-3.7). The prevalence of ICS was 7% (14/198) per the JCS criteria, and 29% (57/198) per our MDD criteria. Compared to non-isolated CS, patients with ICS per either criteria had similar rates of major cardiovascular outcomes (progression of atrioventricular block, worsening EF ≥ 10%, appropriate implantable cardioverter defibrillator [ICD] therapies, heart transplant, and death). Kaplan-Meier analyses showed similar prognosis for ICS and non-isolated CS in all outcomes, except for an association between ICS by MDD criteria and a shorter time to cardiac hospitalization. Multivariable Cox regression analyses showed that ICS was not an independent predictor of death, heart transplant, or clinical worsening. In conclusion, our MDD ICS criteria were more inclusive than the JCS ICS criteria. The prognosis was similar between ICS and non-isolated CS patients, regardless of which criteria were used.

A prediction nomogram for mortality in patients following wasp stings: a retrospective study

Numerous studies have shown that wasp stings can lead to serious, sometimes fatal, health outcomes. Predicting deaths associated with wasp stings remains challenging yet is of critical importance. This study was conducted to identify predictors and develop a visual model for predicting mortality following wasp stings. Clinical data from 486 patients were analyzed, dividing them into two groups: survival group (N = 435) and death group (N = 51). Various statistical methods were used to create a prognostic model, including one-way analysis, the least absolute shrinkage and selection operator (LASSO) regression, and binary logistic regression. The model’s accuracy was evaluated through ROC curves, calibration plots, and decision curve analysis (DCA). The study identified four key predictors of mortality: receiving more than 50 stings, having serum lactate dehydrogenase (LDH) levels of ≥ 2200 U/L, activated partial thromboplastin time (APTT) of ≥ 90 s, and the requirement for invasive mechanical ventilation within 24 h. These factors contributed to a model with an area under the ROC curve of 0.980 (95% CI: [0.968–0.992]), indicating high calibration and applicability. The decision curve analysis confirmed the model’s substantial net clinical benefit. Thus, the number of stings, serum LDH, APTT, and the need for early invasive mechanical ventilation are reliable, independent predictors of death among patients experiencing wasp stings. The developed predictive model exhibits high levels of accuracy, sensitivity, consistency, and practical use.

Periprocedural complications during transvenous lead extraction. Lessons learned from the GermAn Laser Lead Extraction RegistrY (GALLERY)

Abstract Background Transvenous lead extraction (TLE) has become an established therapy for patients with cardiac device-related complications such as infection or lead dysfunction. Although safe and effective, periprocedural complications such as vascular or cardiac lacerations with the need for major surgical intervention occur and lead to morbidity and mortality. Objective &amp; Methods The aim of this study was to conduct a retrospective analysis of the incidence, management and outcome of all major complications suffered by patients undergoing TLE in the GALLERY and to compare patient characteristics, procedural data and outcome against patients who suffered minor or no periprocedural complications. We performed multivariate regression analysis to identify independent predictors for death in patients with major complications. Results We identified 52 patients with major (Group A), 57 patients with minor (Groups B) and 2415 patients with no periprocedural complications (Group C) undergoing TLE in the GALLERY (2.1%, 2.3% and 95.7% of total patients, respectively). There were no differences in age (67.4±14.0 vs. 66.6±13.5 vs. 68.1±13.8 years; p=0.612), body mass index (BMI – 26.5±5.4 vs. 26.1±4.2 vs. 27.1±4.7 kg/m2; p=0.140) or other comorbidities, such as arterial hypertension or chronic kidney disease (CKD), except for more patients with diabetes mellitus (15.4 vs. 42.1 vs. 31.3%; p=0.01) in Group B and a trend towards less patients with previous cardiac surgery (15.4 vs. 35.1 vs. 24.2%; p=0.053) in Group A. Mean number of leads per patient were 2.5±1.1, 2.4±1.0 and 2.4±1.0 (p=0.645). Most common minor complication was pocket hematoma in 82.6% of cases. Laceration of the superior vena cava (SVC – 40.4%) was the most common major complication, followed by perforation of the right atrium (RA – 23.1%). Emergent median sternotomy was necessary in 80.8% of cases in Group A, of which 67.4% required cardiopulmonary bypass. Clinical success for TLE could only be achieved in 63.5% of cases in Group A, whereas Groups B and C achieved 100.0 and 98.5% (p&amp;lt;0.001), respectively. The mortality rate in Group A was 28.9%, in contrast to 5.3% and 3.0% in Groups B and C (p&amp;lt;0.001), which translates into a procedure-related mortality of 0.6% for the entire GALLERY. Septic shock was the most common cause of death in all groups (7.7 vs. 3.5 vs. 1.9%, p=0.013). Multivariate regression analysis revealed CKD (OR:4.7, 95%CI: 1.06-20.7, p=0.04) and previous cardiac surgery (OR:6.3, 95%CI: 1.2-33.6, p=0.03) as independent predictors for death in patients who suffered a major complication during TLE. Conclusion Although rare, TLE remains a procedure with potential for major complications such as lacerations of the SVC or perforation of the RA. Immediate availability of emergent surgical intervention ensures a survival rate of 71,1%. Previous cardiac surgery and CKD seem to be independent predictors for death in such patients.

Location-specific prognostic significance of plaque burden, stenosis, and plaque morphology in coronary artery disease

Abstract Background The prognostic significance of coronary plaque localization, percentage atheroma volume (PAV), stenosis, and plaque morphology has been underexplored. Purpose To investigate the prognostic significance of plaque localization beyond plaque burden, presence of stenosis and plaque morphology. Methods Patients with no cardiac history who underwent coronary CTA were included. PAV, maximum diameter stenosis, and plaque morphology were assessed and classified into proximal, mid, or distal segments of the coronary tree. Major adverse cardiac events (MACE) were defined as death or non-fatal myocardial infarction. Results Among 2819 patients 267 events (9.5%) occurred during a median follow-up of 6.9 years. PAV of the proximal segments was strongly correlated to PAV localized at of the mid (R= 0.76) and distal segments (R = 0.74, p &amp;lt; 0.01 for both). When adjusted for traditional risk factors and presence of plaque on other locations, only proximal PAV was independently associated with MACE (3rd quartile HR 2.08, 95% 1.17–3.71, p=0.01 and 4th quartile HR 2.29, 95% CI 1.21–4.34, p=0.01). Similar results were seen for presence of stenosis. Proximal, mid, and distal PAV as a solitary metric (unadjusted) had similar predictive value for MACE with an AUC of 0.73 (95% CI 0.69-0.76) for proximal PAV and 0.72 (95% CI 0.68-0.76) for both mid and distal localized plaque). Similar results were obtained using diameter stenosis instead of PAV. The presence of low-attenuation plaque (LAP) in the proximal segments had additional prognostic value. Calcified or noncalcified PAV did not provide additional value beyond total location-specific PAV and presence of low-attenuation plaque. Conclusions Proximal located PAV is an independent predictor of death and non-fatal MI, while there was no incremental prognostic value of plaque localized at the mid or distal coronary segments. The presence of LAP in the proximal segments provided additional prognostic value for prediction of MACE.

Influence of persistent atrial fibrillation on the prognosis of heart failure with preserved, mildly reduced, and reduced ejection fraction in women and men

Abstract Introduction Heart failure (HF) is one of the leading causes of death from cardiovascular disease. Persistent atrial fibrillation (PAF) is associated with a worse prognosis in HF. However, little is known about the influence of AF on mortality in women and men with heart failure with preserved (HFpEF ≥50%), mildly reduced (HFmrEF 41% to 49%), and reduced ejection fraction (HFrEF ≤40%). Purpose to analyze the characteristics and influence of PAF on the prognosis of different HF phenotypes. Methods From February 2017 to September 2020, we analyzed hospitalizations, emergency admissions, and mortality of different HF phenotypes with and without PAF. Baseline data included clinical features and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) and Cox proportional hazards methods to analyze mortality rates. Results We studied 11,543 patients, with a mean of 64.1±14.0 years: 55.1% male, 42% with HFrEF, 12.8% with HFmrEF, and 45.1% with HFpEF. PAF was associated with higher mean age (67.6±14.3 vs. 62.8±13.4 years, p&amp;lt;0.001) and more prevalent in men (21% vs. 19%; p=0.019) and in patients with valvular and Chagas etiologies, chronic kidney disease (CKD), stroke, and anemia. The prevalence of PAF in women and men was, respectively, 12.4% vs. 18.3% (p&amp;lt;0.001) in HFrEF, 18.1% vs. 22.2% (p=0.029) in HFmrEF, and 23.3% vs. 23.9 (p=NS) in HFpEF. The overall mortality was 21.6%, with mortality being 2.4 times higher in patients with PAF (40.9% vs. 16.7%, p&amp;lt;0.001) compared to sinus rhythm but similar in women and men with PAF (39.5% vs. 41.9%; p=NS), respectively. The hospitalization (30.3% vs 19.4%, p&amp;lt;0.001) and emergency admissions (38.4% vs 25.7%, p&amp;lt;0.001) were higher in patients with AF. Cumulative mortality was higher in patients with PAF in all HF phenotypes: HFrEF (36.6%), HFmrEF (16.8%), HFpEF (46.6%; p&amp;lt;0.001). Men had higher cumulative mortality in HFrEF (18.3% vs. 12.4%; p&amp;lt;0.001) and in HFmrEF (22.2% vs. 18.09%; p=0.029), but not for HFpEF (23.9% vs. 23.3%; p=NS). In the multivariate analysis, adjusted for age, sex, previous myocardial infarction and stroke, diabetes, CKD, PAF, Cardiac surgery, and electronic device implantation, PAF was an independent predictor of death in all HF phenotypes: HFrEF [HR=1.78(95%CI:1.57-2.02); p&amp;lt;0.001], HFmrEF [HR=2.14(95%CI:1.74-2.65); p&amp;lt;0.001], HFpEF [HR=2.08(95%CI:1.82-2.37); p&amp;lt;0.001]. Conclusion PAF is a frequent comorbidity in HF and is associated with a worse prognosis in all HF phenotypes. Women with PAF had a better prognosis than men with AF in HFrEF and HFmrEF. Sex-specific strategies to maintain sinus rhythm in HF patients on the overall risk of death are needed.

Clinical outcome based on functional complete revascularization in patients with three-vessel coronary artery disease: The FAME 3 Trial

Abstract Background Anatomic complete revascularization after angiography-guided percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. The impact of functional complete revascularization (PCI of all fractional flow reserve (FFR) positive lesions) in patients with 3-vessel coronary artery disease (3VD) amenable to PCI or coronary artery bypass grafting (CABG) is unknown. Purpose To investigate the clinical impact of functional complete revascularization after FFR-guided PCI in the FAME 3 trial Methods The FAME 3 trial is a multicenter, international, randomized study comparing FFR-guided PCI with CABG in patients with angiographic 3VD. This pre-specified sub-study evaluated the impact of functional complete revascularization after PCI on the primary endpoint of death, myocardial infarction (MI), or stroke at 3 years. The degree of functional complete revascularization was quantified by calculating the residual functional SYNTAX score (rFSS), defined as the residual anatomic SYNTAX score based on post-PCI angiography minus any FFR-negative deferred lesions. Results Of the 757 patients treated with FFR-guided PCI, the rFSS could be calculated by the core laboratory in 81% (n=601). Among the angiographically significant lesions, PCI was deferred based on FFR in 17% (51 % of patients had deferral of at least one lesion). The patients were divided into two groups according to acceptable functional complete revascularization: rFSS 0-8 (63%) and functional incomplete revascularization: rFSS&amp;gt;8 (37%). The cumulative incidence of death, MI, or stroke at 3 years was significantly lower in patients with rFSS 0-8 (9% vs. 17%, Hazard ratio[HR]:0.5, 95% confidence interval[CI]:0.3-0.8, p=0.006) compared with rFSS&amp;gt;8. In comparison with the CABG arm, the patients with rFSS 0-8 had similar outcome (HR:0.97, 95%CI:0.6-1.5, p=0.87), while in those with rFSS &amp;gt;8 outcome was worse (HR:1.9, 95%CI: 1.3-2.8, p=0.002) (Figure). There was no difference in death, MI or stroke in CABG patients with or without anatomic complete revascularization. In a multivariate-adjusted model, rFSS&amp;gt;8 showed a significant association with death, MI or stroke at three years (adjusted HR: 1.83, 95% CI: 1.09-3.09, p=0.02). Conclusions Acceptable functional complete revascularization with FFR-guided PCI in patients with 3VD is an independent predictor of death, MI or stroke at three years and can be achieved in 63% of patients resulting in similar outcomes compared with CABG.

Long-term prognostic impact of fasting plasma glucose and myocardial flow reserve beyond other risk factors and heart disease phenotypes

Abstract Background Cardiometabolic risk factors, including high fasting plasma glucose (hFPG), are emerging determinants of residual mortality risk in patients with coronary artery disease (CAD) or heart failure (HF). Coronary microvascular dysfunction, encompassing a broad spectrum of traditional and emerging risk factors, might be a comprehensive risk predictor in these patients. Purpose To assess whether hFPG and global myocardial blood flow (MBF) reserve measured by positron emission tomography (PET), expressing global coronary function, may predict long-term prognosis beyond other risk factors and the presence of obstructive CAD or left ventricular (LV) dysfunction associated with HF. Methods Among 281 consecutive patients undergoing cardiac PET/CT because of stable chest pain or dyspnea we retrospectively collected long-term follow-up data in 103 patients (mean age 61±10 years, 74 males) in whom MBF measurements, coronary angiography and clinical data were available. Disease phenotypes included obstructive CAD (35%), LV dysfunction without obstructive CAD (43%) or none (22%). Results The mean age was 61±10 years (74 males, 72%). Among CVD risk factors, high LDL-cholesterol (hypercholesterolemia under treatment or LDL-C&amp;gt; 130 mg/dL) was present in 72%, high systemic blood pressure (hypertension under treatment or SBP&amp;gt;130/85 mmHg) in 51%, smoking habits in 49%, obesity (BMI&amp;gt;30 Kg/m2) in 22%, type 2 diabetes under treatment in 17%, low HDL-cholesterol (HDL-C&amp;lt; 40 mg/dL in males and &amp;lt;50 mg/dL in females) in 51%, high triglycerides (TG&amp;gt;150 mg/dL) in 27% and high fasting plasma glucose (FPG&amp;gt;100 mg/dL) in 33%. Global MBF reserve was &amp;lt;2 in 68% of patients. In a median follow-up of 10.9 years (7.8-13.9 IQR), 39 patients (37.8%) died (13.6% cardiac death). At multivariable Cox analyses including all risk factors and MBF reserve, age (HR 1.06, 95% CI 1.02-1.11), high FPG (HR 2.28, 95% CI 1.09-4.79) and depressed MBF reserve (HR 4.79, 95% CI 2.14-10.69) were the only independent predictors of death (Global χ2 36.74, P=0.0001). When disease phenotypes were added to the model, age (HR 1.07, 95% CI 1.02-1.12), high FPG (HR 2.18, 95% CI 1.02-4.63) and depressed MBF reserve (HR 4.47, 95% CI 1.96-10.18) remained independent predictors of death (Global χ2 37.41, P=0.0004) (Figure 1). Figure 2 plots the observed all cause death rate in patients with different disease phenotypes stratified for absence/presence of high FPG or MBF reserve &amp;lt;2. Death rate progressively increases according to disease phenotypes and is significantly associated with high FPG (P=0.049) or impaired MBF reserve (P=0.012) in each patient group. Conclusions These results suggest a strong long-term prognostic role of high FPG and depressed MBF reserve in a selected high-risk population of patients with high prevalence of obstructive CAD or HF.Figure 1 Figure 2

Prognostic value of follow-up hemodynamics after initial treatment in pulmonary arterial hypertension

Abstract Background Hemodynamic variables such as right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2) have consistently been associated with survival in pulmonary arterial hypertension (PAH). The prognostic importance of hemodynamics after treatment initiation seems to be superior to baseline evaluation and stroke volume index (SVI) emerged as an independent prognostic parameter. New PAH treatments are, however, able to improve exercise capacity without increasing CI or SVI. Purpose The aim of this work was to define the prognostic role of follow-up hemodynamic parameters in a population of patients with idiopathic, hereditary, drug-induced PAH (I/H/D-PAH) and PAH associated with connective tissue disease (CTD-PAH) and congenital heart disease (CHD-PAH). Methods Treatment naïve PAH patients were assessed at baseline and at 1st follow-up (3-4 months after starting PAH-specific therapy; 1st F-UP) with 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC) and right heart catheterization (RHC). Collected hemodynamic parameters were: RAP, systolic, diastolic and mean pulmonary artery pressure (s/d/mPAP), CI, SVI, SvO2, pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), cardiac efficiency (CE), pulmonary arterial elastance (Ea), resistance–compliance product (RC), right ventricular (RV) power, and RV stroke work index (RVSWI). The primary outcome was all cause death. We used stepwise Cox regression to assess variables obtained at baseline and at 1st F-UP. Results 794 patients with PAH were enrolled (54% I/H/D, 28% CTD, 18% CHD). A primary outcome occurred in 54% of patients over a median follow-up duration of 5.8 (2.4–11) years. In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis but RAP. At first follow-up RHC (n=706), WHO-FC, 6-minute walk distance, RAP, and Ea were independently associated with death, adjusted for age, gender, and etiology of PAH. Because hemodynamic variables were highly correlated, we compared multivariable Cox regression models adding only variables with a correlation coefficient &amp;lt;0.6. In these models, RAP, Ea, PAC, CE, PVR, SvO2, CI, and SVI at follow-up RHC were independent predictors of death (Table). Conclusions Ea and right atrial pressure were the hemodynamic variables independently associated with death at 1st F-UP RHC after initial PAH treatment. These findings suggest that beyond improving RV function, RV afterload reduction can be considered a further treatment target.Table

Long-term prognosis and predictors of death in chronic Chagas cardiomyopathy in women and men

Abstract Background Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of heart failure (HF) in Latin America and carries high morbidity and mortality. Previous studies showed conflicting results in epidemiological and clinical evidence of a gender-associated risk of death in patients with HF due to CCC. Purpose This study analysed the long-term prognosis and the main predictors of death in women and men with HF due to CCC. Methods From March 2009 to January 2023, we followed a cohort of outpatients with HF due to CCC. Specific serological tests diagnosed Chagas disease. Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) method to analyse time-to-event data and Cox proportional hazards methods to search for predictors of death. Results We studied 739 patients, with a mean age of 57.0 ± 12.1 years, 387 (52%) male. Women had a higher mean age (58.4 ± 11.7 vs. 55.8 ± 12.3 years; p=0.001), had a higher mean baseline left ventricular ejection fraction (LVEF) (44.3±14.5 % vs. 37.0±14.5%; p&amp;lt;0.001) and a smaller left ventricular diastolic diameter (LVDD) (56.8±8.9 vs. 62.5±9.4 mm; p&amp;lt;0.001). Over a median follow-up period of 10 years, 213 (56%) men and 169 (44%) women died (K-M: log-rank p=0.043; Figure). Men received more beta-blocker therapy (52.4% vs. 47.6%; p=0.040) and had a higher prevalence of chronic kidney disease (CKD) (p=0.003) and stroke (p=0.007). HFpEF was more prevalent in women and HFrEF in men (p&amp;lt;0.001). Device implantation and transplant were similar between women and men. Cox regression analysis for death adjusted for age, sex, myocardial infarction, diabetes, CKD, stroke, atrial fibrillation (AF), and LVEF showed LVEF (HR= 0.98;95%CL:0.97-0.98), age (HR=1.03;95%CL1.02-1.04) and CKD (HR= 1.32;95%CL:1.10-1.64) as the main predictors of death. In men, the main predictors were age (HR=1.02;95%CL:1.01-1.04), CKD (HR=1.409;95%CL:1.07-1.86), and LVEF (HR=0.98;95%CL:0.97-0.99), and in women AF (HR=1.41;95%CL:1.03-1.91), age (HR=1.03;95%CL:1.01-1.04), and LVEF (HR=0.97;95%CL:0.96 -0.98). Conclusion women had a better prognosis than men, but gender was not an independent predictor of death. Prevention of comorbidities, especially CKD in men and AF in women, and higher beta-blocker therapy can significantly reduce the death rate in women and men with HF from CCC.