Cardiac Outcomes Research Articles

Clinical presentation, management and outcomes of myocardial infarction in the Heart Center, Al-Thawra Hospital, Sana'a City, Yemen: Stemi cardiac arrest management outcomes

Background and aim: Acute ST-segment elevation myocardial infarction (STEMI) is a critical medical emergency requiring emergency evaluation, diagnosis, and intervention. The aim of the study was to evaluate the clinical presentation, type of treatment, and outcomes of patients with acute ST-segment elevation myocardial infarction at the Heart Center of Al-Thawra Hospital, Sana'a. Methods: prospective study. We enrolled all patients with a final diagnosis of STEMI who have been admitted to the cardiac CCU in the cardiac center in AL-Thawrah Hospital during one year, January to December 2023. Results: A total of 358 patients with STEMI were analyzed. The mean age was 55 ± 8 years old, with male patients representing 80% (286)). The traditional risk factors among these patients were: hypertension 28.23% (101), smoking represents 26.05% (93), diabetes mellitus represents 19% (68), BMI > 30 kg/m2 represents 16.34% (57), and khat chewing represents 78.2% (279). STEMI patients who managed by primary PCI were 14% (50). Patients who have been managed by thrombolytic therapy were 28% (101) and the conventional medical treatment was managed for those who arrived after 12 hours and represent 58%% (204). The most commonly used thrombolytic was streptokinase in 96% (97) of patients who received thrombolytics. Primary PCI within 24 hours has been done in 14% (50) of cases. Heart failure (EF < 50%) represented (26%) (93), cardiovascular shock was 13% (46 cases), and mortality rate was 11% (39 cases))

Comparative Influences of Beta blockers and Verapamil on Cardiac Outcomes in Hypertrophic Cardiomyopathy

Guidelines recommend β blockers (BBs) as first-line therapy in symptomatic patients with hypertrophic cardiomyopathy (HCM) and nondihydropyridine calcium channel blockers, particularly, verapamil, as the second-line therapy, despite the absence of comparison trials between those 2 drugs. Because deleterious effects of verapamil have been reported in this setting, the present analysis aimed to evaluate the prognostic impact of BBs and verapamil in a cohort of patients with HCM. From a nationwide cohort of 1,434 patients with a diagnosis of HCM included in the French prospective observational REgistry of hypertrophic cardioMYopathy (REMY), we retrospectively analyzed patients with sarcomeric HCM included in the 3 largest centers and treated either with BBs or verapamil. Patients with a cardiac defibrillator or a pacemaker or who underwent a procedure of atrial fibrillation or septal ablation were excluded. The primary end point was the composite of cardiovascular death, hospitalization for heart failure, and hospitalization for atrial fibrillation. Of 600 patients with HCM, 544 (91%) were treated with BBs and 56 (9%) with verapamil. At inclusion, the 2 groups were comparable concerning the presence/amplitude of obstruction and sudden cardiac death risk factors. At up to 8 years of follow-up (median 3.9 years, interquartile range 2.1 to 5.8), no significant differences were observed in the primary end point (132 [24%] vs 10 [18%] under BBs or verapamil, respectively, hazard ratio 1.84, 95% confidence interval 0.94 to 3.63). In conclusion, in a real-world cohort of low-risk patients with HCM, verapamil therapy was not associated with a higher incidence of adverse events than β-blocker therapy.

Contemporary outcomes of catheter ablation of the structural ventricular tachycardias in severe ischemic and non‐ischemic cardiomyopathies in Turkish population

AbstractIntroductionCurrently, there are no data regarding outcomes of the catheter ablation for structural ventricular tachycardia (VT) in Türkiye. In this observational study, we aim to investigate cardiac outcomes of patients undergoing catheter VT ablation at a tertiary center in Türkiye.MethodsThis was a retrospective observational study performed at a single university center. Patients with a confirmed ischemic or non‐ischemic cardiomyopathy, undergoing structural VT ablation were included. Procedural and mid‐term outcomes were analyzed.ResultsA total of 124 patients were enrolled in the study. 54(43.5%) patients presented with an electrical storm. During the mean follow‐up of 351 ± 232 days 10(8.1%) patients experienced a recurrence. There was only one peri‐procedural death and cardiac tamponade occurred in two patients.14(11.3%) patients died during the follow‐up, most commonly due to a cardiovascular death. In the multivariate analysis only age >70 was found to be correlated with death during follow‐up, with p =.008, HR = 4.923.ConclusionA good acute success with low complications was observed in patients undergoing VT ablation for structural heart disease in a tertiary center in Türkiye. Mid‐term outcomes are comparable with international studies with no difference in VT recurrence in ischemic and non‐ischemic patients. Similar to international studies, significant mid‐term mortality was observed.

Endometriosis, a prevalent disease, is associated with significant cardiac disease

Abstract Background Endometriosis, a chronic systemic gynecological disease affecting 10% of women in the reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiac outcomes are scarce. Further research is needed to address this gap in knowledge as highlighted by recent calls from the European Heart Journal. Purpose To examine the incidence of the following outcomes both as a composite and individually: 1) ischemic events, 2) arrhythmias, and 3) heart failure among women with endometriosis compared with the background population. Methods Using Danish nationwide registries, all women with a diagnosis of endometriosis (1977-2021) were identified and matched with women from the background population in a 1:4 ratio based on year of birth. The incidence of 1) ischemic heart disease and ischemic stroke, 2) arrhythmias (including atrial flutter/fibrillation), and 3) heart failure were examined and compared between women with and without endometriosis. Results After exclusion of women with ischemic events/arrhythmias/heart failure prior to index, 59,194 women with endometriosis and 238,352 matched controls were included (median age 37.1 years [IQR 29.8-44.4 years]). The women were followed for a median of 17 years and a maximum of 45 years. Overall, women with endometriosis were more comorbid and used more medications than their matched controls. The 40-year cumulative incidences of the composite outcome were 36.2% (95%CI 35.4-37.1%) and 30.2% (95%CI 29.8-30.7%) among women with and without endometriosis, whereas it were 23.8% (95%CI 23.0%-24.5%) and 18.8% (95%CI 18.5%-19.1%) for ischemic events, 20.1% (95%CI 19.4%-20.9%) and 17.2% (95%CI 16.8%-17.5%) for arrhythmias, and 7.5% (95%CI 7.0-8.0%) and 6.6% (95%CI 6.3-6.8%) for heart failure, respectively (Figure 1). The most common arrhythmia was atrial fibrillation/flutter constituting more than half of the events in both groups. In both unadjusted and adjusted analyses, women with endometriosis compared with controls had a significantly higher associated risks of the composite outcome (unadjusted HR 1.30 [95%CI 1.27-1.34], adjusted HR 1.29 [95%CI 1.25-1.32]), ischemic events (unadjusted HR 1.32 [95%CI 1.28-1.37], adjusted HR 1.31 [95%CI 1.26-1.35]), arrhythmias (unadjusted HR 1.25 [95%CI 1.20-1.30], adjusted HR 1.24 [95%CI 1.19-1.29]), and heart failure (unadjusted HR 1.07 [95%CI 1.01-1.14]), adjusted analysis (HR 1.05 [95%CI 0.98-1.12]). Conclusions Women with endometriosis have a higher associated long-term risk of significant cardiac outcomes compared with the background population. Despite the small relative differences, the high prevalence of endometriosis underscores the importance of these findings and emphasizes the need for enhanced understanding and prevention of its long-term cardiac outcomes.

The prognostic value of contrast stress echocardiography in a real-world population of symptomatic patients without known coronary artery disease

Abstract Background Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. In addition to diagnosis, non-invasive tests may also provide prognostic information useful in the risk stratification and management of CAD patients. Stress echocardiography (SE) is an accurate, non-invasive method for the detection of obstructive CAD. However, in real-world clinical practice the test performance may vary among different centres, depending on availability, local protocols, and operator expertise. Purpose To evaluate the prognostic value of contrast SE in a real-world population of symptomatic patients without known CAD. Methods This was a cohort follow-up study of patients without known CAD and symptoms of atypical chest pain, unexplained dyspnoea or palpitations who were referred to the echocardiography lab of a tertiary hospital for SE between January 2020 and December 2021. Patients with resting regional wall motion abnormalities were excluded. All patients underwent treadmill exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) if unable to exercise. Contrast agents were used in almost all patients (99%). The study population was followed-up for at least 2 years after SE by phone and/or electronic hospital records. Cardiac outcome was defined as anatomically or functionally significant stenosis on angiography, revascularization, acute coronary syndrome (ACS), or cardiac-related death. Results The study comprised 266 patients (mean age 58±12 years, 63% male) who underwent either ESE (58%) or DSE (42%). The patients' details are reported in Table 1. The most common indication for the exam was atypical chest pain, with a prevalence of 73%. SE exams were positive for inducible ischaemia in 14 (5%) patients. Symptoms during the exam were present in 3 (21%) patients with positive SE and 4 patients (2%) with negative SE (p=0.004). No serious complications (sustained ventricular tachycardia, myocardial infarction, or death) were recorded. During the follow-up (median 30, IQR 23–38 months), 264 patients (99%) were successfully contacted. Cardiac outcome occurred in 10 patients. Among 14 patients with positive SE, 8 underwent revascularization due to significant coronary artery stenosis. Among 250 patients with negative SE, 1 underwent revascularization due to significant coronary artery stenosis and 1 presented with ACS 13 months after the test (both patients underwent DSE). Negative predictive value was 99% over a median follow-up of 30 months, corresponding to an annualized event rate of 0.32% per year. A positive SE was significantly associated with cardiac outcome (log-rank test p<0.0001, Figure 1). Conclusion Contrast SE carries significant prognostic implications in symptomatic patients without known CAD. A positive test is strongly associated with the need for revascularization, while a normal test result has an excellent negative predictive value regarding cardiovascular morbidity and mortality.Figure 1

Comparative analysis of the 2016 diastolic guidelines and left atrial stiffness in predicting exercise tolerance and cardiac events

Abstract Background While the 2016 ASE/EACVI guideline for diastolic dysfunction is a robust tool for prognostication, their complexity and 20% rate of indeterminate limit their routine clinical practice. Purpose Left atrial (LA) stiffness, calculated as the E/e' ratio divided by LA strain, provides a simpler measure that indirectly reflects LA pressure. This study aims to evaluate whether LA stiffness can be better than the 2016 guidelines in predicting poor exercise tolerance and cardiac events (cardiac death or heart failure hospitalization) in patients with dyspnea. Methods In this retrospective single-center cohort study, 404 patients who underwent echocardiography and cardiopulmonary exercise test simultaneously were reviewed. Poor exercise tolerance was defined by a peak oxygen uptake (VO2) of <14 ml/kg/min or a minute ventilation-carbon dioxide production (VE/VCO2) slope of ≥ 40. The predictive abilities of LA stiffness for peak VO2, VE/VCO2 slope, and cardiac outcomes (cardiac death or heart failure hospitalization) were compared to those of the 2016 guidelines using ROC curve analysis. Results The mean left ventricular ejection fraction was 50% (IQR 58.58-66.70). Of the 404 patients (mean age 58.51, male 50.74%), peak VO2 < 14 and VE/VCO2 ≥ 40 were observed in 38 and 24 patients, and cardiac events occurred in 37 patients during median follow up of 85.45 months. ROC analysis showed that LA stiffness had AUC values of 0.697 (95% CI: 0.604-0.789) for peak VO2 < 14, 0.645 (95% CI: 0.529-0.760) for VE/VCO2 slope ≥ 40, and 0.628 (95% CI: 0.541-0.715) for cardiac events. The 2016 guidelines achieved AUCs of 0.685 (95% CI: 0.604-0.766), 0.586 (95% CI: 0.481-0.690), and 0.589 (95% CI: 0.505-0.674). Statistical comparison revealed no significant difference between the predictive capabilities of LA stiffness and the 2016 guidelines (p-values: 0.735, 0.165, and 0.439, respectively). (Figure) Conclusion LA stiffness offers comparable diagnostic accuracy to the 2016 ASE/EACVI guidelines in assessing poor exercise tolerance and cardiac events in patients with dyspnea. Given its simplicity and ease of measurement, LA stiffness represents a viable alternative for evaluating diastolic dysfunction.ROC curve

Prediction of incident major adverse cardiac events in patients starting haemodialysis for end stage kidney disease, using clinical laboratory cardiac biomarkers - a real world analysis.

Abstract Background and Aims Despite its many advantages, haemodialysis (HD) is associated with increased cardiovascular mortality and morbidity, with some studies reporting 48% higher mortality within 2 years of starting HD. Cardiac biomarkers provide insight into cardiac structure and function, including myocyte stress, inflammation and fibrosis. We aimed to investigate the prognostic significance of routine cardiac biomarkers (troponin and natriuretic peptides) in the prediction of incident major adverse cardiac events (MACE) within 5 years if commencing HD. Methods A retrospective cohort study was performed using electronic medical records from a global federated research network from the US. The network was searched on 26th February 2023. The cohorts commenced HD post-diagnosis of end-stage kidney disease. Data censoring for MACE was invoked prior to the index event of HD. Cardiac biomarkers were the first reported result within 3 months of starting HD. Cohorts were grouped according to biomarker-specific thresholds and 1:1 propensity-score matched for age, gender and co-morbidities (hypertension, diabetes mellitus and smoking status). Logistical regression produced odds ratios with 95%CI for 5-year incident MACE. MACE was defined, a priori, as a composite of ischaemic heart disease, angina pectoris, acute myocardial infarction, heart failure, AF, stroke and all-cause mortality. All statistical analysis was performed on the online platform. Results The results are shown Tables 1(Troponin I and BNP alone) and 2 (Combined Troponin I and BNP). Results that reached statistical significance (p<0.05) are shown. Conclusion Routinely available cardiac biomarkers can predict MACE and cardiac outcomes in incident HD, although results differ between markers of myocyte injury (troponin) and stress (BNP). A combined approach may prove most beneficial. The results suggest the clinical need for CV mortality and morbidity risk profiling in incident dialysis using a combination of clinical and laboratory variables and the need for prospective validation.Table 1Table 2

Machine learning methods for diagnostic disease prediction and treatment decisions in parvovirus B19 positive viral cardiomyopathy

Abstract Background Parvovirus B19 (B19V) is the most common type of virus found in endomyocardial biopsies (EMB) from patients with inflammatory heart disease. However, the detection of genomic B19V-DNA appears to have little clinical significance and is often considered an incidental finding. Recent analyses of a large cohort of B19V-positive patients revealed that the detection of RNA transcripts rather than DNA is of clinical importance, as B19V-RNA-positive patients have a significantly worse cardiovascular outcome. Here, we applied machine learning (ML) methods to assess the impact of B19V transcriptional activity on cardiac inflammation and patient clinical outcome. Methods and results A total of 305 patients with a known clinical course and a positive endomyocardial B19V-DNA test were included in this study. Follow-up measurements of the B19V-specific transcripts VP1/2 and NS1 revealed significantly worse clinical courses than in patients without B19V-RNA detection (P=0.019, hazard ratio (95% CI)=1.62 (1.10-2.57)). LVEF at follow-up was significantly lower in patients with detected B19V-RNA (P=0.007), and adverse events such as worsening LV function (P=0.003) or stable systolic dysfunction (P=0.013) were more frequent in this group. Importantly, analysis of inflammatory markers in EMB showed no difference in patients with and without RNA detection (P=0.432), suggesting that the deterioration in clinical outcome was related to B19V transcriptional activity rather than an increase in inflammation. The analysis of area under the receiver operating characteristic curve (AUROC) of B19V-RNA-negative patients revealed that the macrophage marker MAC-1 (AUROC=0.66, P=0.002) was the single most prognostically relevant parameter, while the T cell marker CD3 (AUROC=0.73, P<0.001) was identified as the most prognostically relevant marker in B19V-RNA-positive patients. The linear combination of several inflammatory markers increased the AUROC value to 0.67 in B19V-RNA-negative patients and to 0.74 in B19V-RNA-positive patients. To further increase prognostic accuracy, we trained ML models on features derived from EMB inflammatory markers. For the prediction of major adverse cardiac events within 60 months, the best ML-models achieved an AUROC of 0.87 in B19V-RNA-positive and of 0.86 in B19V-RNA-negative patients, while models that neglect the differentiation of patients with regard to the presence of B19V RNA transcripts only achieved an AUROC of up to 0.76. Conclusions These results show that B19V transcriptional activity is an independent risk marker for adverse cardiac events in patients with viral cardiomyopathy and thus confirm the clinical-therapeutic importance of myocardial biopsy. Furthermore, we present an ML-based algorithm that accurately indicates disease progression in B19V-positive cardiomyopathy patients and is thus helpful for appropriate therapy recommendation.

Association between cardiac consultation and outcomes in patients with perioperative myocardial infarction/injury

Abstract Introduction Perioperative cardiac complications are a frequent occurrence and can lead to high short- and long-term mortality rates after major noncardiac surgery. No single intervention has yet demonstrated its effectiveness in treating perioperative myocardial infarction/injury (PMI). In this large prospective multicentre study, we aimed to evaluate the association between postoperative cardiac consultation and major adverse cardiac event (MACE) and all-cause death within 365 days in patients with PMI after undergoing major noncardiac surgery. Methods We prospectively included consecutive patients undergoing major inpatient noncardiac surgery at two hospitals who were eligible for the institutional active PMI surveillance and response programme. For this analysis, only patients with PMI who were directly transferred to the regular ward following surgery were included. In the case of a PMI, the standardised structured institutional response included assessing the patient for possible symptoms, recording a 12-lead ECG and a cardiac consultation. The specific scope of the PMI workup and management was determined by the attending clinical cardiologist following an institutional flowchart. Our primary endpoint was the occurrence of MACE (defined as a composite of cardiovascular death, MI, AHF, and life-threatening arrhythmia) within 365 days, excluding the initial PMI. All-cause death after 365 days was the secondary endpoint. Multivariable Cox proportional hazard models were used to evaluate the association of cardiac consultation with MACE and all-cause death after 365 days. Results During the period between October 2014 and September 2019, the BASEL-PMI study programme enrolled 14294 patients. After the exclusion of patients without PMI, with a postoperative ICU stay, multiple inclusion, or palliative setting 1048 patients remained. Among those, 434 patients received postoperative cardiac consultation (41.4%). Patients had a median age of 77 years and 44.8% were female. After adjustment, patients who received a postoperative cardiac consultation had a lower risk of having MACE after 365 days (adjusted hazard ratio [aHR] = 0.54, 95% confidence interval [CI] 0.37 - 0.79, p-value = 0.001) and a lower risk of death of any cause after 365 days (aHR = 0.66, 95%CI 0.44 - 1.00, p-value = 0.048). Conclusion In a large multicentre prospective cohort study, postoperative cardiac consultation in patients with PMI was associated with a reduced risk of MACE and all-cause death after 365 days.Kaplan-Meier curve for MACE

Cardiac rehabilitation attendance and outcomes 3 years after acute coronary syndrome (ACS): Linked national data of the SNAPSHOT ACS audit

Abstract Background In international guidelines, cardiac rehabilitation is recommended to reduce readmissions, mortality and improve disease management. However, evidence from a long-term follow-up in a representative cohort is scarce. Purpose To compare 3-year outcomes among acute coronary syndrome (ACS) survivors who attended cardiac rehabilitation programs and those who did not. Methods This was a follow-up of the SNAPSHOT ACS cohort in 1,920 Australians. Clinical data of those presenting with suspected ACS, hospitalised, discharged alive and followed for 18 months were linked to jurisdictional/national regulatory hospitalisation, mortality and pharmacotherapy records. Outcomes were all-cause and cardiovascular mortality, myocardial infarction (MI) and cardiovascular readmissions. Cox regression was used to analyse all-cause mortality, and Fine and Gray competing risk model for cardiovascular mortality, MI and cardiovascular readmissions, where non-cardiovascular mortality or all-cause mortality were competing events. The models were adjusted for age, sex, discharge diagnosis and coronary revascularisation. Results The cohort was aged 66±13.5 years; 60% were male, 31% had a discharge diagnosis of MI, and 490 (26%) attended cardiac rehabilitation. Cardiac rehabilitation attendees more frequently received coronary revascularisation and had a discharge diagnosis of MI during index admission. Attendees were more likely to be men (70% vs 57%, p<0.001) with a family history of coronary disease (43% vs 36%, p=0.008). The prescription of ≥3 guideline-indicated medications was higher in cardiac rehabilitation attendees. Compared to those who did not attend cardiac rehabilitation, the hazard of all-cause mortality was lower for the attendees (4.3% vs 8.6%, HR: 0.55, 95% CI: 0.34-0.91), but the hazard of MI and cardiovascular readmissions significantly greater in the attendees (17% vs 8.5%, HR: 1.99, 95% CI: 1.41-2.82; 42% vs 33%, HR: 1.34, 95% CI: 1.10-1.63; respectively) (Figure). There was insufficient cardiovascular mortality between groups to fit a statistical model (n=7 (1.4%) vs n=24 (1.7%), p=0.705). Conclusions Survivors of ACS attending cardiac rehabilitation were associated with reduced all-cause mortality and increased readmissions related to MI and cardiovascular disease at 3 years follow-up. These findings support secondary prevention strategies to mitigate mortality risk after ACS.

Cardioprotection with transcoronary saline infusion during primary angioplasty for ST-elevation myocardial infarction: design and rationale of the STEMI-Cool pilot study

Abstract Background Prompt restoration of blood flow in ST-segment elevation myocardial infarction (STEMI) with primary percutaneous coronary intervention (pPCI) improves outcomes, but is associated with myocardial stunning, increased infarct size, and microvascular dysfunction. To date, there is no effective therapy to reduce this ischaemia-reperfusion injury (IRI). Mild systemic hypothermia has demonstrated potential but is difficult to achieve and poorly tolerated. Transcoronary hypothermia delivers rapid and effective myocardial cooling, is well tolerated, but not effective when commenced after flow restoration. Coronary haemodilution during reperfusion has shown cardioprotective effects in preclinical studies but has not been fully assessed. Purpose STEMI-Cool is a pragmatic, registry-based randomised clinical trial to assess recruitment rate, feasibility, and safety of a simple protocol which we have reported in a proof-of-concept study. The study has commenced recruitment and aims to overcome the limitations of previous negative studies by combining the beneficial effects of transcoronary cooling and dilution, initiating the infusion prior to wire insertion - therefore avoiding initial unprotected reperfusion (likely to be the critical time for IRI), and avoiding significant delays in reperfusion. Moreover, we will explore mechanistic endpoints and an original method to quantify the intracoronary dilution (with a thermodilution-derived "haemodilution constant ratio"). Lastly, we will investigate ways to "engineer out" the thermistor wire so that the method could be applied to routine pPCI with conventional equipment. Methods Pragmatic broad eligibility criteria allow potential recruitment of all STEMI cases clinically eligible for pPCI. Sixty patients will be randomised 1:1 to standard of care or protected reperfusion with continuous infusion of room temperature saline through the guiding catheter, to achieve intracoronary temperature reduction of 6-8°C. The infusion commences prior to crossing the occlusion with a thermistor wire, which is used as guidewire, and continues for 10 minutes after flow restoration (i.e., TIMI flow≥2). Invasive coronary physiology studies are undertaken after pPCI. Novel and established biomarkers of myocardial damage and inflammation (including dipeptidyl peptidase 3, tumor necrosis factor α, and interleukins 1β, 6, 10) are measured in the preprocedural arterial blood. Cardiac imaging and clinical outcomes are assessed at 48h and 6-12 months. Nesting STEMI-Cool in our local registry Heart-ACS facilitates blood sampling and follow-up. Conclusions STEMI-Cool will primarily investigate recruitment rate, feasibility and safety of an innovative, simple cooling and diluting strategy for cardioprotection during pPCI. Mechanistic outcomes will explore inflammatory, microvascular, structural and functional changes. Finally, we will aim to simplify further the protocol for future research and potential clinical use.STEMI-Cool method schematicSTEMI-Cool protocol timeline

Associations between cardiac rehabilitation and clinical outcomes in patients with heart failure and cognitive frailty

Abstract Introduction Patients with heart failure (HF) often contend with various comorbidities, including cognitive impairment. Cognitive impairment has been increasingly recognised as cognitive frailty, which is reportedly associated with poor outcomes. On the other hand, cardiac rehabilitation (CR) for HF contributes to improved clinical outcomes. However, very few reports have examined whether CR is effective in patients with HF who have cognitive frailty. Purpose The present study aimed to investigate whether CR is associated with clinical outcomes in patients with HF, even in the presence of cognitive frailty. Methods This observational study analysed 1404 consecutive patients who admitted to a university hospital for the treatment of HF and received CR during hospitalisation. Patients who had dementia, did not perform the cognitive function evaluation, or died during hospitalisation were excluded from this study. All patients were encouraged to continue outpatient CR after hospital discharge. Cognitive function was assessed using the Mini-Cog© and a score ≤2 points was defined as the cognitive frailty. As physical function, quadriceps isometric strength (QIS) and 6-min walking distance (6MWD) were measured at the discharge and at the end of outpatient CR. The primary outcome was composite events, comprising all-cause death and re-admission due to HF. The secondary outcome was the change in physical function (ΔQIS and Δ6MWD) following outpatient CR. The association between participation in outpatient CR and composite events was assessed using the multivariate Cox proportional hazard models. We also compared the physical function changes between the presence or absence of cognitive frailty using analysis of covariance. Results The median age of the patients was 75 (interquartile range [IQR]: 66–81) years and 62.3% were males. Among them, 23.4% were identified as cognitive frailty. While 45.1% of overall population participated in outpatient CR, the cognitive frailty was relevant to a lower participation rate (P <0.001). Over a median follow-up period of 1.0 years (IQR: 0.3–2.4 years), a total of 544 composite events occurred. Participation in outpatient CR was associated with a reduced incidence of composite events in both the cognitive frailty and non-cognitive frailty, as well as in the overall patient population (Figure 1). Additionally, ΔQIS and Δ6MWD did not significantly differ between the cognitive frailty status (P = 0.655 and 0.573, respectively). Conclusions Participating in outpatient CR was linked to reduced rates of composite events and improved physical function in patients with HF, regardless of the presence or absence of cognitive frailty. Encouraging active participation in outpatient CR, even among patients with cognitive frailty, is essential as it is associated with favourable clinical outcomes.Survival analysisANCOVA

Angiotensin receptor-neprilysin inhibitor (Sacubitril/Valsartan) in cancer therapy-related cardiac dysfunction: real-world experience from a nurse-led cardio-oncology clinic

Abstract Introduction Cancer therapy-related cardiac dysfunction (CTRCD) is a common toxicity amongst patients receiving anti-cancer treatment1. Angiotensin receptor-neprilysin inhibitor (ARNI) Sacubitril/Valsartan is recommended to reduce Heart Failure (HF) admissions and cardiovascular mortality2. However, patients with active cancer were excluded from the key trials of ARNI. This study aims to provide a real-world experience of ARNI prescription and management from the perspective of a nurse-led Cardio-Oncology clinic. Methods This is a single centre, retrospective, observational cohort study performed at a Cardio-Oncology specialist centre between the period of 2021 to 2024. Adult cancer patients receiving anti-cancer therapy were included if they had symptomatic HF or asymptomatic CTRCD, were initiated on ARNI and followed up in the nurse-led Cardio-Oncology clinic. Results Twenty-nine patients were started on ARNI (see Figure 1). The mean age of the patients was 66+11 years and 17 (59%) were male. Cardiovascular risk factors were common: hypertension (45%), hyperlipidaemia (35%), diabetes mellitus (21%), and smoking (17%). Haematological and breast malignancies were most common (31% and 21% respectively), followed by gynaecological malignancies (14%). Twenty-one (72%) were treated with cytotoxic chemotherapy including 10 (35%) received anthracyclines. Five (17%) patients received human epidermal growth factor receptor 2 (HER2) targeted therapies, 3 (10%) were on tyrosine kinase inhibitors, and 2 (7%) received immunotherapy. Twenty-five (86%) patients presented with symptomatic HF while 4 (14%) had asymptomatic CTRCD. The median N-terminal-pro B-type natriuretic peptide (NTproBNP) level was elevated at 1325(806-4330)ng/L. Thirteen (45%) patients tolerated the maximum dose of 200mg twice daily, while 16 (56%) could only tolerate middle and lowest dosages. ARNI dose up titration to the maximum tolerated dose took 26 (15-79) days. Twenty-eight (97%) patients were on beta blockers, 26 (90%) received SGLT2 inhibitors, 25 (86%) on mineralocorticoid receptor antagonists, and 10 (35%) patients required diuretics. The most common side effect was symptomatic hypotension in 11 (38%) patients. Two (7%) had hyperkalemia, 1 (3%) acute kidney injury following initiation, and 1 (3%) had dizziness without significant hypotension. Nine (31%) required dose reduction allowing ARNI to be continued, while 3 (10%) patients had to permanently discontinue ARNI. There were no cardiovascular deaths, cancer deaths or HF admissions. Conclusion The Cardio-Oncology nurse-led clinic permits rapid up-titration of ARNI to target dosages in patients with CTRCD, resulting in significant improvements in cardiac function. The nurse lead clinic education, support and side effect management allowed uninterrupted continuation of cancer treatment. Whether this approach translates into be better cardiac and cancer outcomes requires further study.

Risk assessment using DEVI and CARPREG -1 score to predict maternal adverse cardiac cvents in pregnancies with valvular heart disease: external validation study from MPAC registry

Abstract Background Even though many risk assessment tools in pregnant women with valvular heart disease (VHD) are available, validation studies are few that assess their performance in diverse settings, which is needed prior to the application of routine clinical practice. Objectives To validate and establish the clinical utility of two risk stratification tools – DEVI (VHD-specific tool) and CARPREG-I in predicting adverse cardiac events in pregnant patients with VHD. Methods This cohort study involved consecutive pregnancies complicated with VHD enrolled in the prospective MPAC registry from July 2016 to December 2019(1). The ability to discriminate those with and without adverse cardiac outcomes was assessed using the area under the curve for both the DEVI and CARPREG-1 scores. Performance was assessed through discrimination and calibration characteristics. Clinical utility was evaluated with Decision Curve Analysis. Results Among 1029 pregnancies complicated with heart disease in the MPAC registry cohort, 604(52.3%) with valvular heart disease were included in this analysis. One or more composite adverse cardiac events occurred in 70 (11.6%) pregnancies during antenatal or the early postpartum period. Mitral regurgitation was the most common lesion (67.7%). In assessing the pregnancy outcomes, those who continued past 20 weeks were included, with the majority (92.0%) delivered at term, and the cesarean rates were 33.6% (n=203). The most common adverse event was heart failure (n=32, 5.3%), most of which (68.6%) occurred in the postnatal period. There were 11 maternal deaths (1.8%) during the study period, six among those with mechanical heart valves (four prosthetic valve thrombosis), two among those with severe mitral stenosis and pulmonary hypertension and two with severe mitral regurgitation and infective endocarditis. The area under the receiver operating characteristic curve (AUC) was 0.766, with 95% confidence intervals (CI) 0.703- 0.828 for DEVI and 0.703 (95%CI 0.644- 0.763) for CARPREG-I models. Calibration plots suggested that the DEVI score overestimates risk at higher probabilities, whereas the CARPREG-I score underestimates the risk at most probabilities. Decision curve analysis demonstrated that both models were useful across predicted probability thresholds between 10% and 60%. Conclusion In this external validation study in pregnant women with primary rheumatic VHD, DEVI and CARPREG-I scores showed good discrimination ability and clinical utility across various probabilities. Both can be used to classify those who develop adverse cardiac outcomes during pregnancy and childbirth. However, both models need recalibration to improve the agreement between the predicted and observed events prior to routine application in diverse clinical settings.Figure 1.a and b ROC and Decision Curves

Performance and safety of complex percutaneous coronary intervention in centres without on-site cardiac surgery: a multi-centre australian registry study.

Abstract Background Performing complex percutaneous coronary intervention (PCI) procedures in hospitals with no on-site cardiac surgery (NOSCS) remains controversial due to a lack of contemporary data and guideline support. Methods Victorian Cardiac Outcomes Registry data was analysed including all PCI cases in the state of Victoria, Australia, from 2014 to 2022. Patients were stratified by PCI at sites with on-site cardiac surgery (OSCS) or NOSCS. Complex PCI was defined as PCI to unprotected left main, bifurcation lesions, rotational atherectomy or intravascular lithotripsy use, severe left ventricular systolic dysfunction, chronic total occlusion, or vein graft PCI. The primary outcome was composite MACCE comprising all-cause mortality, stroke, non-fatal MI, emergency CABG, unplanned revascularisation, definite stent thrombosis and major bleeding (BARC 3 & 5) at 30-days. Risk ratio for average treatment effect in the NOSCS cohort was estimated using inverse probability treatment weighting. Results 94,268 total PCI procedures (32.6% NOSCS) were analysed, including 12,459 complex PCI cases (28.7% NOSCS). Patients from NOSCS were younger (65.0 vs 67.4, p<0.001), less likely to have had previous PCI (29.5% vs 34.5%, p<0.001) or CABG (4.6% vs 8.0% p<0.001) and presented more frequently with acute coronary syndromes (NSTEMI [32.0% vs 28.0%, p<0.001; STEMI [23.3% vs 15.2%], p<0.001). A propensity weighted sample of 30,850 OSCS patients and 30,692 NOSCS patients demonstrated no difference in adjusted 30-day MACCE (risk ratio 0.93, 95% CI 0.87-1.01, p=0.051) for all PCI procedures. In a propensity-weighted subgroup of 3,638 OSCS and 3,576 NOSCS patients who underwent complex PCI, there was also no difference in adjusted 30-day MACCE (risk ratio 0.97, 95%CI 0.86-1.09, p=0.60). Unadjusted rates of CABG at 30-days were very low (0.1 vs 0.1%, p=1.00). Conclusion Patients undergoing PCI and complex PCI at NOSCS centres had comparable 30-day outcomes to those treated at OSCS centres. Newer percutaneous therapies such as intravascular lithotripsy and percutaneous left ventricular assist devices may further improve safety and efficacy of high-risk PCI in NOSCS centres as operator experience increases. Increasing PCI and complex PCI capabilities at NOSCS is likely to increase equitable treatment access for more patients.

Prognostic parameters predict cardiac events in Brugada syndrome: a meta-analysis

Abstract Background Brugada syndrome (BrS) is recognized as a cause of sudden cardiac death (SCD), ventricular tachycardia or ventricular fibrillation (VT/VF). However, the prognosis varies among the patients with Brugada electrocardiograph (ECG) pattern. Furthermore, there is no prognostic tool to predict the worsening cardiac outcomes in BrS. Objectives Primary outcome was to assess the association between risks including patient history, ECG pattern, electrophysiology study (EPS) findings and cardiac events which is identified as VT/VF or SCD. Method We performed a meta-analysis of prospective and retrospective cohort studies which assessed the risks and cardiac events in patients with BrS. Pooled hazard ratios (HRs) was analyzed by using Random-effect model. Result A total of 27 studies involving 15,990 BrS patients. Of these, 17 were retrospective studies and 10 were prospective studies. In univariate analysis, the risks including male, aborted SCD, QRS duration≥120 msec, fragmented QRS (multiple spikes within the QRS complex in lead V1-V3), late potential (positive terminal filtered QRS complex of signal-averaged ECG), sinus node dysfunction or inducibility of ventricular tachyarrhythmias during EPS associated with a higher risk of cardiac events in BrS. In multivariate analysis, higher risks of cardiac events were associated in BrS patients with history of syncope (HR 2.65, 95% confidence interval (CI): 1.68-4.19, I2 = 54 %, p-value <0.001), family history of SCD (HR 2.64, 95%CI:1.39-5.01, I2 = 0%, p-value = 0.003), prior VF (HR 14.52, 95%CI: 3.36-62.84, I2 = 62%, p-value <0.001), type 1 Brugada ECG pattern (HR 2.07, 95%CI: 1.13-3.79, I2 = 0%, p-value = 0.018), spontaneous type 1 ECG pattern (HR 1.91, 95%CI: 1.01-3.61, I2 = 58%, p-value = 0.046), early repolarization pattern (HR 2.78, 95%CI: 1.9-4.07, I2 = 0%, p-value < 0.001) and history of atrial fibrillation before BrS diagnosis (HR 1.82, 95%CI: 1.03-3.23, I2 = 49%, p-value = 0.039) (Table 1). Conclusion Our findings suggest that patient history, ECG pattern, EPS findings can predict the cardiac events. Introducing a risk prediction model could aid in early management of BrS.

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.

Association between GDF-15 levels and cardiac morphology and function in cardiac magnetic resonance imaging: insights from UK Biobank data analysis

Abstract Background/Introduction Growth Differentiation Factor-15 (GDF-15) has emerged as a biomarker associated with cardiovascular disease and adverse cardiac outcomes. Cardiac morphology and function, assessed through cardiac magnetic resonance imaging (CMR), are critical indicators of cardiovascular pathology. Understanding the relationship between GDF-15 levels and LV characteristics could provide valuable insights into cardiac pathophysiology and disease progression. Purpose This study aims to investigate the association between GDF-15 levels and cardiac morphology and function, utilizing data from the UK Biobank and CMR. By analyzing various CMR-derived parameters, including LV strain, myocardial mass, LV mass-to-volume ratio, ventricular and atrial volumes, we seek to elucidate the impact of GDF-15 on cardiac structure and function. Methods Data from the UK Biobank, including 2,264 participants, were analyzed. The median age of the analyzed participants was 55 years, with a median BMI of 26.0. Among the participants, 53% were females and 47% were males. CMR-derived variables related to cardiac morphology and function, along with GDF-15 levels, were examined. Multiple linear regression models were constructed to assess the association between GDF-15 levels and cardiac parameters, adjusting for age, sex, and other relevant covariates. Confidence intervals (CI) and p-values were calculated to determine the significance of observed associations. Results Analysis of the UK Biobank data revealed significant associations between GDF-15 levels and specific cardiac parameters (table1). Notably, GDF-15 levels were negatively associated with LV myocardial mass (LVM)(coefficient = -1.146, p = 0.0071), LV end-diastolic volume LVEDV)(coefficient = -3.321, p < 0.0001), LV end-systolic volume (coefficient = -1.876, p < 0.0001), as well as right atrial maximum volume (coefficient = -3.025, p < 0.0001) and minimum volume (coefficient = -1.858, p = 0.0003). In addition, LVM/LVEDV was positively associated with GDF-15 level (p<0.03). However, no significant associations were observed between GDF-15 levels and LV strain parameters, ejection fraction, or left atrial volumes. Conclusion This study provides evidence of a significant association between GDF-15 levels and selected parameters of cardiac morphology and function, as assessed by CMR in the UK Biobank population. These findings suggest a potential role of GDF-15 in modulating specific aspects of cardiac structure, function and left ventricle concentric remodeling warranting further investigation.GDF 15

Renal Semaphorin 3C mediates cardiac adaptive response

Abstract Cardiorenal syndrome, characterized by reciprocal heart-kidney interactions that progressively promote dysfunction in both organs, is associated with a high mortality rate. However, the mechanisms linking the two organs are insufficiently understood. Here we report that semaphorin 3C (SEMA3C) is a novel cardioprotective mediator secreted from the kidney. SEMA3C was highly expressed in the renal proximal tubules in mice. Renal Sema3c expression and circulating SEM3C were reduced by the left ventricular pressure overload that induced renal remodeling. Proximal tubule-specific secretory Sema3c deletion exacerbated cardiac hypertrophy, fibrosis and dysfunction after the pressure overload, suggesting renal SEMA3C is important for the proper cardiac adaptive response. Mechanistically, SEMA3C inhibits pathological cardiac remodeling at least partly by inhibiting Akt, ERK and Wnt/β-catenin signaling in cardiomyocytes. In heart failure patients, the plasma SEMA3C level was decreased and the low plasma SEMA3C was associated with poor cardiac outcomes. Collectively, our results show that SEMA3C produced by the kidney pivotally contributes to the cardiac stress response and its reduction contributes to the progression of heart failure. SEMA3C signaling appears to be an attractive therapeutic and diagnostic target for cardiorenal syndrome.

1-year outcomes of patients presenting with acute coronary syndromes in Western Cape, South Africa: findings from the PERFUSION ACS registry

Abstract Background Cardiovascular disease(CVD), particularly acute myocardial infarction(MI), has emerged as a public health challenge in South Africa(SA), however, there is a paucity of data regarding long-term clinical outcomes such as CVD mortality, heart failure, stroke and recurrence of MI in this region. Purpose To determine 1-year major adverse cardiac outcomes among individuals discharged alive following admission for troponin-positive Acute Coronary Syndromes(ACS) in Western Cape, SA. Methods Between February 2021 and May 2022, 838 adults(≥18 years) with a diagnosis of ACS were prospectively enrolled into the investigator-initiated, multi-center PrEsentation, Rationale, and impact of reperFUSION for Acute Coronary Syndromes (PERFUSION ACS) registry. Participants were enrolled at a tertiary-care referral center and four secondary-level healthcare facilities. Key data elements were measured at index admission, including baseline demographics, risk factors, clinical presentation, complications, laboratory tests, revascularization strategies, and discharge medication. Survivors at discharge provided consent for 30-day and 12-month telephonic evaluations for major adverse cardiovascular events(MACE), which were captured on a web-based system that was centrally managed and analyzed. Results Of 838 participants, 39% were female, one-third were <55 years of age, 76% had a history of smoking, 74% had hypertension, 58% had dyslipidemia, and 56% were obese. STEMI accounted for 51% of cases, with NSTEMI in 49%. Baseline data for the cohort, stratified into two categories of MI, are provided in Table 1. Median duration from symptom onset to hospital presentation was 10.42 (±15.26) hours, with a majority(80%) presenting first to a non-PCI-capable facility. Among STEMI cases, two-thirds received thrombolysis(65%), primarily with Streptokinase; 49% underwent angiography via a pharmacoinvasive strategy, and 3% received primary percutaneous coronary intervention(PCI). Overall, 57% of patients with NSTEMI were treated with an invasive approach. The one-year all-cause mortality was 21%, with 88% attributable to cardiovascular disease-related death. Cumulative MACE rate at one year was 57%. Event rates for the individual MACE components were 32% for heart failure, 19% for non-fatal MI, and 6% for non-fatal stroke. 6% of participants died in-hospital, while 30-day mortality was 9%. There were no significant differences in all-cause mortality between STEMI and NSTEMI at 1 year. Conclusion Troponin-positive ACS are associated with a high rate of 12-month mortality and non-fatal major adverse cardiac events in Western Cape, SA. The concerning registry findings emphasize the need to prioritize ischemic heart disease prevention and management, and highlight important gaps in care which can serve as targets for improvement throughout the country.PERFUSION: Table 1PERFUSION: All-cause mortality and MACE