Prognostic significance of echocardiographic deformation imaging in adult congenital heart disease.

BACKGROUND: Due to medical and surgical advancements, the population of adult patients with congenital heart disease (ACHD) is growing. Despite successful therapy, ACHD patients face structural sequalae, placing them at increased risk for heart failure and arrhythmias. Left and right ventricular function are important predictors for adverse clinical outcomes. In acquired heart disease it has been shown that echocardiographic deformation imaging is of superior prognostic value as compared to conventional parameters as ejection fraction. However, in adult congenital heart disease, the clinical significance of deformation imaging has not been systematically assessed and remains unclear. METHODS: According to the Preferred Reporting Items for Systematic Reviews checklist, this systematic review included studies that reported on the prognostic value of echocardiographic left and/or right ventricular strain by 2-dimensional speckle tracking for hard clinical end-points (death, heart failure hospitalization, arrhythmias) in the most frequent forms of adult congenital heart disease. RESULTS: In total, 19 contemporary studies were included. Current data shows that left ventricular and right ventricular global longitudinal strain (GLS) predict heart failure, transplantation, ventricular arrhythmias and mortality in patients with Ebstein's disease and tetralogy of Fallot, and that GLS of the systemic right ventricle predicts heart failure and mortality in patients post atrial switch operation or with a congenitally corrected transposition of the great arteries. CONCLUSIONS: Deformation imaging can potentially impact the clinical decision making in ACHD patients. Further studies are needed to establish disease-specific reference strain values and ranges of impaired strain that would indicate the need for medical or structural intervention.

Non-Invasive Assessment of Multivalvular Heart Disease: A Comprehensive Review.

Multivalvular heart disease (MVD) implies the presence of concomitant valvular lesions on two or more heart valves. This condition has become common in the few last years, mostly due to population aging. Every combination of valvular lesions uniquely redefines the hemodynamics of a patient. Over time, this may lead to alterations in left ventricle (LV) dimensions, shape and, eventually, function. Since most of the echocardiographic parameters routinely used in the valvular assessment have been developed in the context of single valve disease and are frequently flow- and load-dependent, their indiscriminate use in the context of MVD can potentially lead to errors in judging lesion severity. Moreover, the combination of non-severe lesions may still cause severe hemodynamic consequences, and thereby systolic dysfunction. This review aims to discuss the most frequent combinations of MVD and their echocardiographic caveats, while addressing the opportunities for a multimodality assessment to achieve a better understanding and treatment of these patients.

Diagnostic value of late gadolinium enhancement at cardiovascular magnetic resonance to distinguish arrhythmogenic right ventricular cardiomyopathy from differentials.

BACKGROUND: While late gadolinium enhancement (LGE) is proposed as a diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC), the potential of LGE to distinguish ARVC from differentials remains unknown. We aimed to assess the diagnostic value of LGE for ARVC diagnosis. METHODS: We included 132 subjects (60% male, 47 ± 11 years) who had undergone cardiac magnetic resonance imaging with LGE assessment for ARVC or ARVC differentials. ARVC was diagnosed as per 2010 Task Force Criteria (n = 55). ARVC differentials consisted of familial/genetic dilated cardiomyopathy (n = 25), myocarditis (n = 13), sarcoidosis (n = 20), and amyloidosis (n = 19). The diagnosis of all differentials was based on the most current standard of reference. The presence of LGE was evaluated using a 7-segment right ventricle (RV) and 17-segment left ventricle (LV) model. Subsequently, we assessed LGE patterns for every patient individually for fulfilling LV- and/or RV-LGE per Padua criteria, independent of their clinical diagnosis (i.e. phenotype). Diagnostic values were analyzed using sensitivity and specificity for any RV-LGE, any LV-LGE, RV-LGE per Padua criteria, and prevalence graphs for LV-LGE per Padua criteria. The optimal integration of LGE for ARVC diagnosis was determined using classification and regression tree analysis. RESULTS: One-third (38%) of ARVC patients had RV-LGE, while half (51%) had LV-LGE. RV-LGE was less frequently observed in ARVC vs non-ARVC patients (38% vs 58%, p = 0.034) leading to a poor discriminatory potential (any RV-LGE: sensitivity 38%, specificity 42%; RV-LGE per Padua criteria: sensitivity 36%, specificity 44%). Compared to ARVC patients, non-ARVC patients more often had LV-LGE (91% vs 51%, p < 0.001) which was also more globally distributed (median 9 [interquartile range (IQR): 3-13] vs 0 [IQR: 0-3] segments, p < 0.001). The absence of anteroseptal and absence of extensive (≥5 segments) mid-myocardial LV-LGE, and absence of moderate (≥2 segments) mid-myocardial LV-LGE predicted ARVC with good diagnostic performance (sensitivity 93%, specificity 78%). CONCLUSION: LGE is often present in ARVC differentials and may lead to false positive diagnoses when used without knowledge of LGE patterns. Moderate RV-LGE without anteroseptal and mid-myocardial LV-LGE is typically observed in ARVC.

PET Myocardial Perfusion Imaging: Trends, Challenges, and Opportunities.

Various non-invasive images are used in clinical practice for the diagnosis and prognostication of chronic coronary syndromes. Notably, quantitative myocardial perfusion imaging (MPI) through positron emission tomography (PET) has seen significant technical advancements and a substantial increase in its use over the past two decades. This progress has generated an unprecedented wealth of clinical information, which, when properly applied, can diagnose and fine-tune the management of patients with different types of ischemic syndromes. This state-of-art review focuses on quantitative PET MPI, its integration into clinical practice, and how it holds up at the eyes of modern cardiac imaging and revascularization clinical trials, along with future perspectives.

Parameter subset reduction for imaging-based digital twin generation of patients with left ventricular mechanical discoordination.

BACKGROUND: Integration of a patient's non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019-10-07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013-11-12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient ( ICC ) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error ( χ 2 ) of LV myocardial strain, strain rate, and cavity volume. RESULTS: A subset of 270 parameters remained after MSM which produced high-quality DTs of all patients ( χ 2 < 1.6), but minimum parameter reproducibility was poor ( ICC min = 0.01). Iterative reduction yielded a reproducible ( ICC min = 0.83) subset of 75 parameters, including cardiac output, global LV activation duration, regional mechanical activation delay, and regional LV myocardial constitutive properties. This reduced subset produced patient-resembling DTs ( χ 2 < 2.2), while septal-to-lateral wall workload imbalance was higher for the LBBB-only DTs than for the MI-only DTs (p < 0.05). CONCLUSIONS: By applying sensitivity and identifiability analysis, we successfully determined a parameter subset of the CircAdapt model which can be used to generate imaging-based DTs of patients with LV mechanical discoordination. Parameters were reproducibly estimated using particle swarm optimization, and derived LV myocardial work distribution was representative for the patient's underlying disease substrate. This DT technology enables patient-specific substrate characterization and can potentially be used to support clinical decision making.

In-hospital mortality of patients with acute coronary syndrome (ACS) after implementation of national health insurance (NHI) in Indonesia.

BACKGROUND: The National Health Insurance (NHI) was implemented in Indonesia in 2014, and cardiovascular diseases are one of the diseases that have overburdened the healthcare system. However, data concerning the relationship between NHI and cardiovascular healthcare in Indonesia are scarce. We aimed to describe changes in cardiovascular healthcare after the implementation of the NHI while determining whether the implementation of the NHI is related to the in-hospital mortality of patients with acute coronary syndrome (ACS). METHODS: This is a retrospective comparative study of two cohorts in which we compared the data of 364 patients with ACS from 2013 to 2014 (Cohort 1), before and early after NHI implementation, with those of 1142 patients with ACS from 2018 to 2020 (Cohort 2), four years after NHI initiation, at a tertiary cardiac center in Makassar, Indonesia. We analyzed the differences between both cohorts using chi-square test and Mann-Whitney U test. To determine the association between NHI and in-hospital mortality, we conducted multivariable logistic regression analysis. RESULTS: We observed an increase in NHI users (20.1% to 95.6%, p < 0.001) accompanied by a more than threefold increase in patients with ACS admitted to the hospital in Cohort 2 (from 364 to 1142, p < 0.001). More patients with ACS received invasive treatment in Cohort 2, with both thrombolysis and percutaneous coronary intervention (PCI) rates increasing more than twofold (9.2% to 19.2%; p < 0.001). There was a 50.8% decrease in overall in-hospital mortality between Cohort 1 and Cohort 2 (p < 0.001). CONCLUSIONS: This study indicated the potential beneficial effect of universal health coverage (UHC) in improving cardiovascular healthcare by providing more accessible treatment. It can provide evidence to urge the Indonesian government and other low- and middle-income nations dealing with cardiovascular health challenges to adopt and prioritize UHC.

Virtual pacing of a patient's digital twin to predict left ventricular reverse remodelling after cardiac resynchronization therapy.

AIMS: Identifying heart failure (HF) patients who will benefit from cardiac resynchronization therapy (CRT) remains challenging. We evaluated whether virtual pacing in a digital twin (DT) of the patient's heart could be used to predict the degree of left ventricular (LV) reverse remodelling post-CRT. METHODS AND RESULTS: Forty-five HF patients with wide QRS complex (≥130 ms) and reduced LV ejection fraction (≤35%) receiving CRT were retrospectively enrolled. Echocardiography was performed before (baseline) and 6 months after CRT implantation to obtain LV volumes and 18-segment longitudinal strain. A previously developed algorithm was used to generate 45 DTs by personalizing the CircAdapt model to each patient's baseline measurements. From each DT, baseline septal-to-lateral myocardial work difference (MWLW-S,DT) and maximum rate of LV systolic pressure rise (dP/dtmax,DT) were derived. Biventricular pacing was then simulated using patient-specific atrioventricular delay and lead location. Virtual pacing-induced changes ΔMWLW-S,DT and ΔdP/dtmax,DT were correlated with real-world LV end-systolic volume change at 6-month follow-up (ΔLVESV). The DT's baseline MWLW-S,DT and virtual pacing-induced ΔMWLW-S,DT were both significantly associated with the real patient's reverse remodelling ΔLVESV (r = -0.60, P < 0.001 and r = 0.62, P < 0.001, respectively), while correlation between ΔdP/dtmax,DT and ΔLVESV was considerably weaker (r = -0.34, P = 0.02). CONCLUSION: Our results suggest that the reduction of septal-to-lateral work imbalance by virtual pacing in the DT can predict real-world post-CRT LV reverse remodelling. This DT approach could prove to be an additional tool in selecting HF patients for CRT and has the potential to provide valuable insights in optimization of CRT delivery.

Stress hyperglycemia and poor outcomes in patients with ST-elevation myocardial infarction: a systematic review and meta-analysis.

Background: Hyperglycemia, characterized by elevated blood glucose levels, is frequently observed in patients with acute coronary syndrome, including ST-elevation myocardial infarction (STEMI). There are conflicting sources regarding the relationship between hyperglycemia and outcomes in STEMI patients. We aimed to compile evidence to assess the association between hyperglycemia and adverse outcomes. Methods: We conducted a comprehensive search for articles on PubMed and Embase using search strategies which yielded 4,061 articles. After full-text screening, 66 articles were included for systematic review, and 62 articles were further selected for meta-analysis. Results: The 66 included articles spanned the years 2005-2023. Of these, 45 articles reported admission blood glucose, 13 articles used HbA1c, and 7 articles studied fasting blood glucose. Most studies defined STEMI with primary PCI as their inclusion criteria. Mortality was the most often outcome reported related to hyperglycemia. Overall, 55 (83.3%) studies were at low risk of bias. Both admission and fasting blood glucose were significantly related to short- and long-term mortality after STEMI, with a pooled risk ratio (RR) of 3.02 (95%CI: 2.65-3.45) and 4.47 (95% CI: 2.54-7.87), respectively. HbA1c showed substantial association with long-term mortality (HR 1.69, 95% CI: 1.31-2.18)) with a pooled RR of 1.58 (95% CI 1.26-1.97). In subsequent analyses, admission hyperglycemia was associated with an increased risk of reinfarction (pooled RR 1.69, 95% CI 1.31-2.17), heart failure (pooled RR 1.56, 95% CI: 1.37-1.77), cardiogenic shock (pooled RR 3.68, 95% CI 2.65-5.11), repeat PCI or stent thrombosis (pooled RR 1.99, 95% CI 1.21-3.28), and composite major adverse cardiac and cerebrovascular events (MACCE) (pooled RR 1.99, 95% CI: 1.54-2.58). Conclusions: Our study demonstrated that hyperglycemia has a strong association with poor outcomes after STEMI. Admission and fasting blood glucose are predictors for short-term outcomes, while HbA1c is more appropriate for predicting longer-term outcomes in STEMI patients. Systematic Review Registration: PROSPERO 2021 (CRD42021292985).

Left Ventricle Myocardial Work Correlated with Functional Capacity in Severe Rheumatic Mitral Stenosis with Preserved Left Ventricular Ejection Fraction.

Background and Aims: Functional capacity is reduced in mitral stenosis (MS) patients. Previous studies showed a correlation between left atrial strain and functional capacity in this population. However, currently, no left ventricle (LV) echocardiographic parameters were associated with functional capacity in patients with MS. Noninvasive LV pressure-strain loop analysis is a new echocardiographic method for evaluating LV function, integrating longitudinal strain from speckle-tracking analysis and noninvasively measured blood pressure to estimate myocardial work (MW) that overcomes the preload-dependent characteristics conventional parameters by integrating afterload. This study aimed to evaluate the association between MW and functional capacity measured using exercise tests in patients with severe MS and preserved LV ejection fraction (LVEF). Methods: Adult patients with symptomatic severe rheumatic MS (mitral valve area <1.5 cm2), and preserved LVEF (>50%) and sinus rhythm who underwent echocardiography and exercise stress test in our hospital from 2019 to 2021 were included. Exclusion criteria were suboptimal image quality for myocardial deformation analysis, significant mitral regurgitation or aortic valve lesions, coronary artery disease, intracardiac shunt, and atrial fibrillation. Standard echocardiographic parameters were measured, and all MW parameters were included. Exercise treadmill testing was performed using the modified Bruce protocol. Results: A total of 33 individuals with isolated severe rheumatic MS in sinus rhythm (age 39.8 ± 9.8 years) were included in the study. Patients with severe isolated MS showed significantly impaired LV-global longitudinal strain values compared to normal reference values. Furthermore, patients with severe MS showed significantly lower values of global work index, global constructive work, and efficiency compared to normal values and higher wasted work. Global work efficiency was significantly correlated to the duration of exercise (P = 0.025, Pearson's r = 0.389). Conclusions: In stable patients with isolated severe mitral stenosis, MW efficiency significantly correlated with functional capacity measured objectively through exercise testing.

Adherence to penicillin treatment is essential for effective secondary prevention of rheumatic heart disease: a systematic review and meta-analysis.

Background: Penicillin is essential for secondary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). However, the incidences of ARF recurrence and RHD progression remain high, particularly in endemic countries. This meta-analysis evaluated the effectiveness of penicillin adherence in secondary prevention of ARF recurrence and RHD progression. Methods: The authors included original articles employing an observational study design in which the study population included patients with ARF or RHD and documented adherence to secondary prophylaxis with penicillin for secondary prevention. Systematic searches of the PubMed, Scopus, and Cochrane databases were performed. Moreover, the authors also conducted a snowballing literature search from Europe PMC to expand the included studies. The quality of each study was assessed using the National Institute of Health Quality Assessment Tool. The statistical analyses were conducted using Review Manager 5.4.1 software developed by Cochrane. In addition, the authors utilized pooled odds ratios (ORs) to compare the adherence techniques. Results: A total of 310 studies were identified, of which 57 full-text articles were assessed for eligibility. The authors included six studies with 1364 patients for the qualitative synthesis and meta-analysis. Good adherence to penicillin for the secondary prophylaxis of ARF and RHD, significantly reduced the odds of ARF recurrence or RHD progression by up to 71% compared to that associated with poor adherence [pooled OR 0.29 (0.21-0.40); I²=0% (p=0.56); Z=7.64 (p <0.00001)]. Conclusion: Good adherence to penicillin for secondary prophylaxis in patients with ARF or RHD is essential for reducing the risk of ARF recurrence or RHD progression.

Diagnostic yield of a proactive strategy for early detection of cardiovascular disease versus usual care in adults with type 2 diabetes or chronic obstructive pulmonary disease in primary care in the Netherlands (RED-CVD): a multicentre, pragmatic, cluster-randomised, controlled trial.

BACKGROUND: Progressive cardiovascular diseases (eg, heart failure, atrial fibrillation, and coronary artery disease) are often diagnosed late in high-risk individuals with common comorbidities that might mimic or mask symptoms, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes. We aimed to assess whether a proactive diagnostic strategy consisting of a symptom and risk factor questionnaire and low-cost and accessible tests could increase diagnosis of progressive cardiovascular diseases in patients with COPD or type 2 diabetes in primary care. METHODS: In this multicentre, pragmatic, cluster-randomised, controlled trial (RED-CVD), 25 primary care practices in the Netherlands were randomly assigned to usual care or a proactive diagnostic strategy conducted during routine consultations and consisting of a validated symptom questionnaire, followed by physical examination, N-terminal-pro-B-type natriuretic peptide measurement, and electrocardiography. We included adults (≥18 years) with type 2 diabetes, COPD, or both, who participated in a disease management programme. Patients with an established triple diagnosis of heart failure, atrial fibrillation, and coronary artery disease were excluded. In the case of abnormal findings, further work-up or treatment was done at the discretion of the general practitioner. The primary endpoint was the number of newly diagnosed cases of heart failure, atrial fibrillation, and coronary artery disease, adjudicated by an expert clinical outcome committee using international guidelines, at 1-year follow-up, in the intention-to-treat population. FINDINGS: Between Jan 31, 2019, and Oct 7, 2021, we randomly assigned 25 primary care centres: 11 to usual care and 14 to the intervention. We included patients between June 21, 2019, and Jan 31, 2022. Following exclusion of ineligible patients and those who did not give informed consent, 1216 participants were included: 624 (51%) in the intervention group and 592 (49%) in the usual care group. The mean age of participants was 68·4 years (SD 9·4), 482 (40%) participants were female, and 734 (60%) were male. During 1 year of follow-up, 50 (8%) of 624 participants in the intervention group and 18 (3%) of 592 in the control group were newly diagnosed with heart failure, atrial fibrillation, or coronary artery disease (adjusted odds ratio 2·97 [95% CI 1·66-5·33]). This trial is registered with the Netherlands Trial Registry, NTR7360, and was completed on Jan 31, 2023. INTERPRETATION: An easy-to-use, proactive, diagnostic strategy more than doubled the number of new diagnoses of heart failure, atrial fibrillation, and coronary artery disease in patients with type 2 diabetes or COPD in primary care compared with usual care. Although the effect on patient outcomes remains to be studied, our diagnostic strategy might contribute to improved early detection and timely initiation of treatment in individuals with cardiovascular disease. FUNDING: Dutch Heart Foundation.

Location-Specific Prognostic Significance of Plaque Burden, Stenosis, and Plaque Morphology in Coronary Artery Disease.

AIMS: To investigate the location-specific prognostic significance of plaque burden, diameter stenosis and plaque morphology. METHODS AND RESULTS: Patients without a documented cardiac history who underwent coronary computed tomography angiography (CCTA) for suspected coronary artery disease were included. Percentage atheroma volume (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. Among 2819 patients 267 events (9.5%) occurred during a median follow-up of 6.9 years. When adjusted for traditional risk factors and presence of PAV on other locations, only proximal PAV was independently associated with MACE. However, PAV of the proximal segments was strongly correlated to PAV localized at the mid (R= 0.76) and distal segments (R=0.74, p<0.01 for both). When only adjusted for cardiovascular risk factors, the area under the curve (AUC) to predict MACE for proximal PAV was 0.73 (95%CI 0.69-0.76), which was similar compared to mid PAV (AUC 0.72, 95%CI 0.68-0.76) and distal PAV (AUC 0.72, 95%CI 0.68-0.76). Similar results were obtained using diameter stenosis instead of PAV. The presence of proximal low-attenuation plaque had borderline additional prognostic value. CONCLUSIONS: Proximal PAV was the strongest predictor of MACE when adjusted for cardiovascular risk factors and plaque at other locations. However, when presence of plaque was only adjusted for cardiovascular risk factors, proximal, mid, and distal plaque localization showed a similar predictive ability for MACE.

Prognostic implications of invasive hemodynamics during cardiac resynchronization therapy: Stroke work outperforms dP/dtmax.

Background: Invasive measurements of left ventricular (LV) hemodynamic performance can evaluate acute response to cardiac resynchronization therapy (CRT). Objective: The study sought to determine which metric, maximum rate of LV pressure rise (LV dP/dtmax) or LV stroke work (LVSW), is more strongly associated with long-term prognosis. Methods: CRT patients were prospectively included from 3 academic centers. Invasive pressure-volume loop measurements during implantation were performed, and LV dP/dtmax and LVSW were determined at baseline and during biventricular pacing (BVP) as well as their relative increase (%Δ). Hazard ratios (HRs) for the primary outcome of 8-year all-cause mortality were derived using Cox proportional hazards. The secondary endpoint was echocardiographic response, defined as 6-month LV end-systolic volume reduction ≥15%. Results: Paired data from 82 patients were analyzed (67% male; age 66 ± 9 years; QRS duration 158 ± 22 ms, median survival time 72 months). Survival was better when LVSW during BVP was ≥4400 mL∙mm Hg (HR 0.21, 95% CI 0.08-0.58, P < .003) or when ΔLVSW% was ≥10% (HR 0.22, 95% CI 0.08-0.65, P = .006). In multivariate analysis, following direct comparison of continuous measures of acute ΔLV dP/dtmax% and ΔLVSW%, only ΔLVSW% remained associated with the primary endpoint (HR 0.982 per percentage point, P = .028). In contrast to LV dP/dtmax (all P > .05), significant associations with echocardiographic response were found for stroke work during BVP (area under the receiver-operating characteristic curve 0.745, P = .001) and ΔLVSW% (area under the receiver-operating characteristic curve 0.803, P < .001). Conclusion: Stroke work, but not LV dP/dtmax, is consistently associated with long-term prognosis and response after CRT. Our results therefore favor the use of stroke work as the hemodynamic parameter to predict long-term outcome after CRT.