Predictors of Mortality in Acute Myocardial Infarction Complicated by Cardiogenic Shock despite Intra-Aortic Balloon Pump: Opportunities for Advanced Mechanical Circulatory Support in Asia.

Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify predictors of mortality in AMI-CS implanted with IABP and the proportion eligible for advanced MCS in an Asian population. Methods: We retrospectively analyzed a cohort of Society for Cardiovascular Angiography and Intervention (SCAI) stage C and above AMI-CS patients with IABP implanted from 2017-2019. We excluded patients who had IABP implanted for indications other than AMI-CS. Primary outcome was 30-day mortality. Binary logistic regression was used to calculate adjusted odds ratios (aOR) for patient characteristics. Results: Over the 3-year period, 242 patients (mean age 64.1 ± 12.4 years, 88% males) with AMI-CS had IABP implanted. 30-day mortality was 55%. On univariate analysis, cardiac arrest (p < 0.001), inotrope/vasopressor use prior to IABP (p = 0.004) was more common in non-survivors. Non-survivors were less likely to be smokers (p = 0.001), had lower ejection fraction, higher creatinine/ lactate and lower pH (all p < 0.001). On multi-variate analysis, predictors of mortality were cardiac arrest prior to IABP (aOR 4.00, CI 2.28-7.03), inotrope/vasopressor prior to IABP (aOR 2.41, CI 1.18-4.96), lower arterial pH (aOR 0.02, CI 0.00-0.31), higher lactate (aOR 2.42, CI 1.00-1.19), and lower hemoglobin (aOR 0.83, CI 0.71-0.98). Using institutional MCS criteria, 106 patients (44%) would have qualified for advanced MCS. Conclusions: Early mortality in AMI-CS remains high despite IABP. Many patients would have qualified for higher degrees of MCS.

Prognostic performance of soluble urokinase plasminogen activator receptor for heart failure or mortality in Western and Asian patients with acute breathlessness.

AIMS: The performance of circulating soluble urokinase plasminogen activator receptor (suPAR) for predicting the composite endpoint of subsequent heart failure (HF) hospitalisation and/or death at 1 year was assessed in (i) patients with undifferentiated breathlessness, and generalisability was compared in (ii) disparate Western versus Asian sub-cohorts, and in (iii) the sub-cohort adjudicated with HF. METHODS AND RESULTS: Patients with acute breathlessness were recruited from the emergency departments in New Zealand (NZ, n = 612) and Singapore (n = 483). suPAR measured in the presentation samples was higher in patients incurring the endpoint (n = 281) compared with survivors (5.2 ng/mL vs 3.1 ng/mL, P < 0.0001). The discriminative power of suPAR for endpoint prediction was c-statistic of 0.77 in the combined population, but was superior in Singapore than NZ (c-statistic: 0.83 vs 0.71, P < 0.0001). Although the highest suPAR tertile (>4.37 ng/mL) was associated with risks of >4-fold in NZ, >20-fold in Singapore, and ≥3-fold in HF for incurring the outcome, there was no interaction between country and suPAR levels after adjustment. Multivariable analysis indicated suPAR to be robust in predicting HF/death at 1-year [hazard ratio: 1.9 (95% CI:1.7 to 2.0) per SD increase] and improved risk discrimination for outcome prediction in HF (∆0.06) and for those with NT-proBNP >1000 pg/mL (∆0.02). CONCLUSION: suPAR is a strong independent predictor of HF and/or death at 1 year in acutely breathless patients, in both Asian and Western cohorts, and in HF. suPAR may improve stratification of acutely breathless patients, and in acute HF, for risk of later onset of heart failure or mortality.

The Role of Exercise-based Cardiac Rehabilitation in Heart Failure.

Exercise-based cardiac rehabilitation (EBCR) is a treatment modality for patients with heart failure (HF) that has withstood the test of time. It has continued to show benefits even in the current era of pharmacotherapeutics for HF. Participation in a multidisciplinary comprehensive EBCR programme reduces mortality and morbidity, has a multitude of physiological benefits, and improves cardiovascular risk factor control and quality of life. Despite this, historical barriers to enrolment and uptake remain. Strategies to overcome these, as well as alternative delivery methods of EBCR in HF patients, are emerging and include telerehabilitation, focus on special groups and emphasis on behavioural change. This review provides oversight on the modalities of exercise training in HF as well as their benefits and gives an overview of barriers to the utilisation of EBCR along with future progress in the field.

Cost-Effectiveness of Empagliflozin on Top of Standard of Care for Heart Failure With Reduced Ejection Fraction in Singapore.

OBJECTIVES: The prevalence of heart failure (HF) and its risk factors are high in Singapore. The EMPEROR-Reduced trial demonstrated that add-on empagliflozin resulted in a reduction in the risk of cardiovascular death or hospitalization for HF compared with standard of care (SoC). This study aimed to estimate the cost-effectiveness of empagliflozin+SoC versus SoC in patients with HF with reduced ejection fraction from a Singaporean healthcare perspective. METHODS: A Markov cohort model simulated progression through health states based on New York Heart Association classes over a lifetime horizon using a cycle length of 1 month. Transition probabilities, and the risk of transient events (hospitalization for HF and cardiovascular/all-cause death) were modeled based on the EMPEROR-Reduced trial. Costs for HF-related events, adverse events, and for monitoring were estimated from a combination of published literature and publicly available fees for public hospitals/polyclinics. RESULTS: Empagliflozin+SoC was estimated to be very cost-effective versus SoC alone with an incremental cost-effectiveness ratio of<8000 Singapore Dollars/quality-adjusted life-year gained. The base-case results were robust as evidenced from the consistency of various scenario and sensitivity analyses performed. When using Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score quartiles as the health states, the incremental cost-effectiveness ratio reduced significantly to 4625 Singapore Dollars/quality-adjusted life-year. CONCLUSION: The use of empagliflozin on top of SoC represents a highly cost-effective solution for the treatment of patients with HF with reduced ejection fraction in Singapore when considering its efficacy, relative affordability, and the growing economic burden of HF in Singapore.

Natural Progression of Left Ventricular Function following Anthracyclines without Cardioprotective Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Anthracyclines form the backbone of many systemic chemotherapy regimens but are accompanied by dose-limiting cardiotoxicity. We elucidate the progression and severity of cardiac function over time, in the absence of cardioprotection, which less is known about. METHODS: This PRISMA-guideline-adherent review was registered on PROSPERO (CRD42022373496). RESULTS: 26 studies met the eligibility criteria including a total of 910 patients. The overall reduction in post-anthracycline pooled mean left ventricular ejection fraction (LVEF) in placebo arms of the included randomised-controlled trials was 4.5% (95% CI, 2.6 to 6.4). The trend in LVEF showed a progressive decline until approximately 180 days, after which there was no significant change. Those receiving a cumulative anthracycline dose of 300 mg/m2 experienced a more profound reduction. The overall pooled risk of a 10% absolute decline in LVEF from baseline, or a decline to an LVEF below 50%, was 17% (95% CI: 11 to 24; I2 = 71%). Sensitivity analyses of baseline LVEF and trastuzumab treatment status did not yield significant differences. CONCLUSION: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines is required.

Ischaemic events in hypertrophic cardiomyopathy patients with and without atrial fibrillation: a systematic review and meta-analysis.

Hypertrophic cardiomyopathy predisposes to acute cerebrovascular events including ischaemic stroke, transient ischaemic attack and systemic thromboembolism. Atrial fibrillation confers even higher risk. We aim to report the incidence of these complications and to investigate the impact of atrial fibrillation on the ischaemic risk in patients with hypertrophic cardiomyopathy. A literature search was performed on PubMed, Scopus, Embase/Ovid and Cochrane library from inception to 20th March 2021. We compared the incidence of ischaemic strokes, transient ischaemic attack, non-specified thromboembolism events and systemic thromboembolism in hypertrophic cardiomyopathy patients with or without atrial fibrillation. Non-specified thromboembolism events in our paper referred to thromboembolic events whereby types were not specified in the studies. Meta-analysis was performed using StataSE 16 software, and heterogeneity was assessed using I2 test. A total of 713 studies were identified. Thirty-five articles with 42,570 patients were included. The pooled incidence of stroke/ transient ischaemic attack was 7.45% (95% confidence interval [CI] 5.80-9.52, p < 0.001) across 24 studies with a total of 37,643 hypertrophic cardiomyopathy patients. Atrial fibrillation significantly increased the risk of total stroke/ transient ischaemic attack (Risk Ratio 3.26, 95% CI 1.75-6.08, p < 0.001, I2 = 76.0). The incidence of stroke/ transient ischaemic attack was 9.30% (95% CI 6.64-12.87, p = 0.316) in the apical hypertrophic cardiomyopathy subgroup. Concomitant atrial fibrillation in hypertrophic cardiomyopathy increases the risk of thromboembolic events including ischaemic stroke and transient ischaemic attack. The apical subgroup shows a similar risk of acute cerebrovascular events as the overall hypertrophic cardiomyopathy population.

Microaxial Left Ventricular Assist Device in Cardiogenic Shock: A Systematic Review and Meta-Analysis.

Microaxial left ventricular assist devices (LVAD) are increasingly used to support patients with cardiogenic shock; however, outcome results are limited to single-center studies, registry data and select reviews. We conducted a systematic review and meta-analysis, searching three databases for relevant studies reporting on microaxial LVAD use in adults with cardiogenic shock. We conducted a random-effects meta-analysis (DerSimonian and Laird) based on short-term mortality (primary outcome), long-term mortality and device complications (secondary outcomes). We assessed the risk of bias and certainty of evidence using the Joanna Briggs Institute and the GRADE approaches, respectively. A total of 63 observational studies (3896 patients), 6 propensity-score matched (PSM) studies and 2 randomized controlled trials (RCTs) were included (384 patients). The pooled short-term mortality from observational studies was 46.5% (95%-CI: 42.7-50.3%); this was 48.9% (95%-CI: 43.8-54.1%) amongst PSM studies and RCTs. The pooled mortality at 90 days, 6 months and 1 year was 41.8%, 51.1% and 54.3%, respectively. Hemolysis and access-site bleeding were the most common complications, each with a pooled incidence of around 20%. The reported mortality rate of microaxial LVADs was not significantly lower than extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pumps (IABP). Current evidence does not suggest any mortality benefit when compared to ECMO or IABP.

Prevalence and incidence of stroke, white matter hyperintensities, and silent brain infarcts in patients with chronic heart failure: A systematic review, meta-analysis, and meta-regression.

Introduction: Heart failure (HF) is associated with ischemic stroke (IS). However, there are limited studies on the prevalence of IS, white matter hyperintensities (WMHs), and silent brain infarcts (SBIs). Furthermore, interaction with ejection fraction (EF) is unclear. Methods: We searched three databases (viz., PubMed, Embase, and Cochrane) for studies reporting the incidence or prevalence of IS, WMHs, and SBIs in HF. A total of two authors independently selected included studies. We used random-effects models, and heterogeneity was evaluated with I2 statistic. Meta-regression was used for subgroup analysis. Results: In total, 41 articles involving 870,002 patients were retrieved from 15,267 records. Among patients with HF, the pooled proportion of IS was 4.06% (95% CI: 2.94-5.59), and that of WMHs and SBIs was higher at 15.67% (95% CI: 4.11-44.63) and 23.45% (95% CI: 14.53-35.58), respectively. Subgroup analysis of HFpEF and HFrEF revealed a pooled prevalence of 2.97% (95% CI: 2.01-4.39) and 3.69% (95% CI: 2.34-5.77), respectively. Subgroup analysis of WMH Fazekas scores 1, 2, and 3 revealed a decreasing trend from 60.57 % (95% CI: 35.13-81.33) to 11.57% (95% CI: 10.40-12.85) to 3.07% (95% CI: 0.95-9.47). The relative risk and hazard ratio of patients with HF developing IS were 2.29 (95% CI: 1.43-3.68) and 1.63 (95% CI: 1.22-2.18), respectively. Meta-regression showed IS prevalence was positively correlated with decreasing anticoagulant usage. Conclusion: We obtained estimates for the prevalence of IS, WMH, and SBI in HF from systematic review of the literature. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=255126, PROSPERO [CRD42021255126].

Prevalence and Risk Factors of Cardiac Amyloidosis in Heart Failure: A Systematic Review and Meta-Analysis.

AIMS: Heart failure (HF) is one of the leading causes of mortality worldwide. Heart failure is also one of the most common presentations of cardiac amyloidosis (CA). Contemporary epidemiological data of CA in HF patients is lacking. Hence, this systematic review and meta-analysis was conducted to determine the prevalence of amyloidosis in HF patients, and to clarify the risk factors of concomitant CA and HF. METHODS: A systematic review and meta-analysis was performed. Studies were retrieved from Medline, EMBASE, Scopus and Cochrane library. The search was not restricted in time, type or language of publication. The prevalence of CA in HF grouped according to diagnostic techniques and risk factors of CA with HF was analysed. RESULTS: Eleven (11) studies were included, involving 3,303 patients. The pooled prevalence of CA in HF was 13.7%. The overall prevalence of CA in HF with preserved ejection fraction was 15.1%, and that of HF with reduced ejection fraction was 11.3%. The main factors associated with the diagnosis of CA in HF included older age, males, raised NT pro-BNP, increased interventricular septal thickness in diastole, apical sparing, and reduced left ventricular systolic function. CONCLUSION: A high index of clinical suspicion is required to identify HF patients with CA. Supportive investigations may be helpful when clinically correlated. A considerable proportion of HF patients have CA and certain risk factors may be helpful in increasing suspicion of CA in HF.

Clinical recommendations to diagnose and monitor patients with transthyretin amyloid cardiomyopathy in Asia.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a debilitating and life-threatening condition with a heterogeneous clinical presentation. Recent guidelines from the United States and Europe have been published to guide clinical practice and to facilitate management conformity by covering current diagnostic and treatment strategies for patients with ATTR-CM. These guidelines highlight the importance of an early diagnosis to optimize therapeutic outcomes, specifying the use of tests and imaging techniques to allow accurate, noninvasive diagnosis of ATTR-CM. However, as regional practice variations across Asia may limit access to healthcare, availability of specific tests, and expertise in assessing diagnostic images, there is an ongoing need to provide an Asian perspective on these clinical guidelines. This review article provides practical recommendations for the diagnosis and monitoring of patients with ATTR-CM in Asia, highlighting the need for additional guidelines to support a broad and diverse population, consider differing healthcare systems and diagnostic testing availability, and provide a flexible yet robust algorithm.

Prevalence and incidence of cognitive impairment and dementia in heart failure - A systematic review, meta-analysis and meta-regression.

INTRODUCTION: The burden of cognitive impairment in heart failure (HF) patients is significant and leads to longer hospital stay, higher readmission rates, and increased mortality. This review seeks to synthesize the available studies to determine the prevalence and incidence of cognitive impairment and dementia in HF patients. METHODS: PubMed, Embase, PsychoINFO, and Cochrane databases were systematically searched from their inception through to May 3, 2021. Study and population characteristics, total patients with HF, prevalence of cognitive impairment and dementia in HF patients, and cognitive assessment tool were abstracted by two reviewers. RESULTS: In HF patients, the overall prevalence for cognitive impairment and dementia was 41.42% (CI) and 19.79% (dementia), respectively. We performed a meta-regression analysis, which demonstrated that the risk of cognitive impairment and dementia increased with age. DISCUSSION: Further research should investigate whether HF accelerates the rate of cognitive decline and the progression of dementia.

Utility and pitfalls of the electrocardiogram in the evaluation of cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis is a protein misfolding disorder involving deposition of amyloid fibril proteins in the heart. The associated fibrosis of the conduction tissue results in conduction abnormalities and arrhythmias. "Classical" electrocardiogram (ECG) findings in cardiac amyloidosis include that of low voltage complexes with increased left ventricular wall thickness on echocardiography. However, this "classical" finding is neither sensitive nor specific. As cardiac amyloidosis is associated with a generally poor prognosis, the need for early recognition of this disease is important given the availability of new treatment options. In this review, we highlight 3 cases of patients with cardiac amyloidosis. Although presenting with typical clinical signs and symptoms, ECG for all 3 patients was not consistent with the classical findings described. They underwent further diagnostic tests which clinched the diagnosis of cardiac amyloidosis, allowing patients to receive targeted treatment. Through the review of the literature, we will highlight the different ECG patterns in patients with different types of cardiac amyloidosis and clinical scenarios, as well as the pitfalls of using ECG to identify the condition. Lastly, we also emphasize the current paradigms in diagnosing cardiac amyloidosis through the non-invasive methods of echocardiography, cardiac magnetic resonance imaging, and nuclear technetium-pyrophosphate imaging. CONCLUSIONS: Electrocardiogram is often the first investigation used in evaluating many cardiac disorders, including cardiac amyloidosis. However, classical features of cardiac amyloidosis on ECG are often not present. A keen understanding on the ECG features of cardiac amyloidosis and knowledge of the diagnostic workflow is important to diagnose this condition.

Evaluating the Initiation of Sodium/Glucose Cotransporter 2 Inhibitors within 2 Weeks of an Acute Hospital Admission: A Systematic Review and Meta-Analysis of Nine Clinical Trials.

OBJECTIVE: Recent studies have increasingly shown the benefits of using sodium/glucose cotransporter 2 inhibitor (SGLT2i). However, there are concerns regarding the initiation of SGLT2i during acute hospital admissions due to the potential increased risk of complications. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of SGLT2i initiation within 2 weeks of an acute hospital admission. METHODS: Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched for articles published from inception up to 27 March 2021 that evaluated the efficacy and/or safety of SGLT2i initiation within 2 weeks of an acute hospital admission. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. The protocol was registered with PROSPERO (CRD42021245492). RESULTS: Nine clinical trials were included with a combined cohort of 1,758 patients. Patients receiving SGLT2i had a mean increase in 24-h urine volume of +487.55 mL (95% CI 126.86-848.25; p = 0.008) compared to those not started on SGLT2i. Patients with heart failure treated with SGLT2i had a 27% relative risk reduction in rehospitalizations for heart failure, compared to controls (risk ratio 0.73; p = 0.005). There were no differences in other efficacy and safety outcomes examined. CONCLUSION: There was no increased harm with initiation of SGLT2i within 2 weeks of an acute hospital admission, and its use reduced the relative risk of rehospitalizations for heart failure in patients with heart failure. It was also associated with increased urine output. However, current evidence pool is limited, especially in specific population subtypes.

Non-alcoholic fatty liver disease association with structural heart, systolic and diastolic dysfunction: a meta-analysis.

OBJECTIVE: Several studies have documented a relationship between non-alcoholic fatty liver disease (NAFLD) and structural heart disease, particularly diastolic function. This meta-analysis will be the first to examine the echocardiographic-derived cardiac function and structural characteristics in NAFLD patients, and its association with liver disease severity and metabolic profile. METHODS: Medline and Embase were searched and pairwise meta-analysis was conducted in DerSimonian and Laird to obtain the odds ratio (OR) and mean difference (MD) for dichotomous and continuous variables, respectively, to compare the effects of NAFLD on the echocardiography parameters. RESULTS: Forty-one articles involving 33,891 patients underwent echocardiography. NAFLD patients had worse systolic indices with lower ejection fraction (EF, MD: - 0.693; 95% CI: - 1.112 to - 0.274; p = 0.001), and worse diastolic indices with higher E/e' (MD: 1.575; 95% CI: 0.924 to 2.227; p < 0.001) compared to non-NAFLD patients. NAFLD patients displayed increased left ventricular mass (LVM, MD: 34.484; 95% CI: 26.236 to 42.732; p < 0.001) and epicardial adipose thickness (EAT, MD: 0.1343; 95% CI: 0.055 to 0.214; p = 0.001). An increased severity of NAFLD was associated with worse diastolic indices (decreased E/A ratio, p = 0.007), but not with systolic indices. CONCLUSIONS: NAFLD is associated with impaired systolic and diastolic function with changes in cardiac structure. Concomitant metabolic risk factors and liver disease severity are independently associated with worsening systolic and diastolic function.

Ventricular tachycardia from myocarditis following COVID-19 vaccination with tozinameran (BNT162b2, Pfizer-BioNTech).

To combat the coronavirus disease 2019 (COVID-19) pandemic, many countries have started population vaccination programs using messenger ribonucleic acid (mRNA) vaccines. With the widespread use of such vaccines, reports are emerging worldwide, of the vaccine's association with the development of myocarditis. Younger men are more likely to develop postvaccine myocarditis, which usually presents as self-limiting chest pain within a week after the second dose. We present a case of myocarditis following vaccination with tozinameran (BNT162b2, Pfizer-BioNTech), which presented late, with ventricular tachycardia (VT) reduced left ventricular ejection fraction (LVEF).