Clinical and echocardiographic characteristics associated with the development of infective endocarditis in patients with significant mitral stenosis.

BACKGROUND: Infective endocarditis (IE) confers significant mortality and morbidity in patients with underlying mitral stenosis (MS), with both diseased native valves and after valvular procedures. PURPOSE: We examined the clinical and echocardiographic parameters in association with the development of IE on patients with significant MS. METHODS: A total of 478 consecutive patients with index echocardiographic diagnosis of significant mitral stenosis (mitral valve area <1.5 cm2 ) were included. Patients were grouped into those with or without IE on at least 5 years of follow-up. Baseline clinical, echocardiographic profile and clinical outcomes were compared. RESULTS: IE was observed in 4.4% (n = 21) of the cohort. These patients were younger (45.3 ± 14.6 vs. 53.2 ± 15.5 years, p = 0.022) at the time of MS diagnosis. NT-proBNP was higher in patients who developed IE (13529 ± 12230 vs. 4381 ± 5875 pg/ml, p < 0.001), with larger left atrial diameter (54.4 ± 10.1 vs. 49.9 ± 9.5 mm, p = 0.040) and elevated pulmonary artery systolic pressure (PASP, 62.3 ± 17.2 vs. 47.2 ± 16.5 mmHg, p = 0.026). There was no significant difference in terms of MS severity, other concomitant valvulopathies, or etiology (rheumatic or degenerative) of MS. Patients who smoked had higher incidence of IE (33.3% vs. 14.2%, log-rank 7.27, p = 0.007). After adjusting for age, valve procedure and PASP, patients who smoked remained at elevated risk of IE (adjusted hazards ratio 2.99, 95% confidence interval 1.18-7.56, p = 0.021). CONCLUSION: IE occurs in a proportion of patients with MS. Smoking, younger age of diagnosis of MS as well as dilated left atria with elevated PASP may be associated with an elevated risk of this complication.

Effects of Sodium/Glucose Cotransporter Inhibitors on Atrial Fibrillation and Stroke: A Meta-Analysis.

OBJECTIVES: Recent clinical trials have shown the potential of sodium glucose cotransporter (SGLT) 2 inhibitors to reduce the risk of atrial fibrillation but not stroke. We conducted a systematic review and meta-analysis to clarify if SGLT2 or combined SGLT1/2 inhibitors affect the risk of atrial fibrillation and stroke in patients regardless of diabetic status. MATERIALS AND METHODS: Four electronic databases were searched on 21st November 2020 for studies evaluating outcomes of stroke and atrial fibrillation with SGLT2 or combined SGLT1/2 inhibitors in both diabetic and non-diabetic patients. Both random and fixed effect, pair-wise meta-analysis models were used to summarize the results of the studies. RESULTS: A total of 13 placebo-controlled, randomized-controlled trials were included. Eight trials comprising 35,702 patients were included in the analysis of atrial fibrillation outcomes and eight trials comprising 47,910 patients were included in the analysis of stroke outcomes. Patients on SGLT inhibitors, particularly SGLT2 inhibitors, had lower odds of atrial fibrillation (Peto odds ratio [95% confidence interval] = 0.76 [0.63-0.92]) compared to placebo. This effect remained significant with a follow-up duration longer than 1 year, in studies utilizing dapagliflozin, patients with type 2 diabetes mellitus, and patients with cardiovascular disease. No difference was observed in the odds of atrial fibrillation in patients with baseline heart failure. No effect was seen on the risk of stroke in patients taking SGLT inhibitors. CONCLUSIONS: SGLT2 inhibitors significantly reduced the odds of atrial fibrillation in diabetic patients. However, SGLT inhibitors did not significantly affect the risk of stroke.

Effects of sex on clinical outcomes of hypertrophic cardiomyopathy in Singapore.

Introduction: Despite the growing recognition that sex can affect the presentation and outcomes in hypertrophic cardiomyopathy (HCM), this relationship is understudied in Asians. Therefore, we aimed to explore sex differences in Asian patients with HCM. Method: A total of 295 consecutive patients diagnosed with HCM were recruited from a tertiary cardiology centre from 2010 to 2017 over a mean of 3.9±2.7 years. We evaluated the effects of sex on the outcomes of HCM in Asian patients. Results: HCM patients were more commonly men (72%). Women were older and had more comorbidities, including hypertension and atrial fibrillation. On transthoracic echocardiography, the indexed left ventricular end-systolic and end-diastolic volumes were similar, but more women had more-than-moderate mitral regurgitation and had a smaller left ventricular outflow tract (LVOT). Women more commonly had findings of obstructive physiology with significant LVOT obstruction, defined as >30 mmHg at rest. The use of implantable cardioverter defibrillators was similar across sexes. On multivariable analysis, women were found to be more likely to develop progressive heart failure requiring admission (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.05-4.71, P=0.021) but had a lower rate of all-cause mortality (HR 0.36, 95% CI 0.19-0.70, P=0.003). Conclusion: Women diagnosed with HCM were older, had more comorbidities and were more likely to develop heart failure while men had a higher risk of all-cause mortality.

Incidence of acute cerebrovascular events in patients with rheumatic or calcific mitral stenosis: A systematic review and meta-analysis.

BACKGROUND: Patients with mitral stenosis (MS) may be predisposed to acute cerebrovascular events (ACE) and peripheral thromboembolic events (TEE). Concomitant atrial fibrillation (AF), mitral annular calcification (MAC) and rheumatic heart disease (RHD) are independent risk factors. Our aim was to evaluate the incidence of ACEs in MS patients and the implications of AF, MAC and RHD on thromboembolic risks. METHODS: This systematic review was registered on PROSPERO (CRD42021291316). Six databases were searched from inception to 19th December 2021. The clinical outcomes were composite ACE, ischaemic stroke/transient ischaemic attack (TIA) and peripheral TEE. RESULTS: We included 16 and 9 papers, respectively, in our qualitative and quantitative analyses. The MS cohort with AF had the highest incidence of composite ACE (31.55%; 95% CI 3.60-85.03; I2 = 99%), followed by the MAC (14.85%; 95% CI 7.21-28.11; I2 = 98%), overall MS (8.30%; 95% CI 3.45-18.63; I2 = 96%) and rheumatic MS population (4.92%; 95% CI 3.53-6.83; I2 = 38%). Stroke/TIA were reported in 29.62% of the concomitant AF subgroup (95% CI 2.91-85.51; I2 = 99%) and in 7.11% of the overall MS patients (95% CI 1.91-23.16; I2 = 97%). However, the heterogeneity of the pooled incidence of clinical outcomes in all groups, except the rheumatic MS group, was substantial and significant. The logit-transformed proportion of composite ACE increased by 0.0141 (95% CI 0.0111-0.0171; p < 0.01) per year of follow-up. CONCLUSION: In the MS population, MAC and concomitant AF are risk factors for the development of ACE. The scarcity of data in our systematic review reflects the need for further studies to explore thromboembolic risks in all MS subtypes.

Prognostically Distinct Phenotypes of Metabolic Health Beyond Obesity in Aortic Stenosis.

Although current evidence is in favor of metabolic health and nonobesity in the reduction of incident cardiovascular disease, little is known regarding the prognosis across the metabolic phenotypes once cardiovascular disease occurs. This study examined the prognosis of patients with significant aortic stenosis (AS) on the basis of the presence of metabolic health and obesity. This a retrospective cohort study on consecutive patients who presented with moderate-to-severe AS to a tertiary hospital between 2010 and 2015. Patients were allocated into 4 groups on the basis of obesity and metabolic health: metabolically healthy obese (MHO), metabolically healthy nonobese (MHNO), metabolically unhealthy obese (MUO), and metabolically unhealthy nonobese (MUNO). Metabolic health was defined in accordance to the Adult Treatment Panel III criteria. The primary outcome was all-cause mortality. Cox regression examined independent associations between mortality and metabolic phenotypes, adjusting for aortic valve area, ejection fraction, age, gender, chronic kidney disease, and aortic valve replacement as a time-dependent covariate. Of 727 patients, the majority (51.6%) were MUNO, followed by MUO (32.7%), MHNO (11.4%), and MHO (4.3%). MHNO had the highest mortality (43.0%), followed by the MUNO (37.5%), MUO (30.0%), and MHO (6.9%) groups (p = 0.001). Compared with MHNO, MHO (hazard ratio 0.159, 95% confidence interval 0.038 to 0.668, p = 0.012) and MUO (hazard ratio 0.614, 95% confidence interval 0.403 to 0.937, p = 0.024) were independently associated with lower all-cause mortality rates after adjusting for confounders. In patients who are obese, metabolic health had favorable survival compared with metabolically unhealthy (p = 0.015), but this protective impact of metabolic health was not observed in patients with overweight or normal weight. Obesity had favorable survival compared with overweight and normal weight in both patients who are metabolically healthy (p = 0.002) and unhealthy (p = 0.007). In conclusion, patients who are MHO with AS have the most favorable prognosis, whereas the seemingly healthy MHNO group had the worst survival. There should be a paradigm shift toward prioritizing metabolic health rather than weight reduction in patients with significant AS.

Prevalence, types and treatment of bradycardia in obstructive sleep apnea - A systematic review and meta-analysis.

BACKGROUND: The association of obstructive sleep apnea (OSA) with bradycardia is not well-characterized, which may confer significant morbidity and mortality if left untreated. We sought to clarify the prevalence of comorbid OSA and bradycardia, and the effect of continuous positive airway pressure (CPAP) therapy on bradycardia outcomes. METHODS: We systematically searched four electronic databases (PubMed, Embase, Cochrane Library, Scopus) for randomized or observational studies reporting the co-prevalence of sleep apnea and bradycardia or evaluated the use of CPAP on the incidence of bradycardias. We used random-effects models in all meta-analyses and evaluated heterogeneity using I2. RESULTS: We included 34 articles from 7204 records, comprising 4852 patients. Among patients with OSA, the pooled prevalence of daytime and nocturnal bradycardia were 25% (95% CI: 18.6 to 32.7) and 69.8% (95% CI: 41.7 to 88.2) respectively. Among patients with bradycardia, the pooled prevalence of OSA was 56.8% (95% CI: 21.5 to 86.3). CPAP treatment, compared to those without, did not significantly reduce the risk of daytime (two randomized trials; RR: 0.50; 95% CI: 0.11 to 2.21) or nocturnal bradycardia (one randomized-controlled trial and one cohort study; RR: 0.76; 95% CI: 0.48 to 1.20). CONCLUSIONS: This meta-analysis demonstrates a high comorbid disease burden between OSA and bradycardia. Future research should explore the treatment effect of CPAP on bradycardia incidence, as compared to placebo.

Prevalence and outcomes of concomitant cardiac amyloidosis and aortic stenosis: A systematic review and meta-analysis.

OBJECTIVE: Cardiac amyloidosis (CA) is an increasingly recognised condition in patients with aortic stenosis (AS). However, there is a large variation in the reported prevalence figures, due to differences in populations and diagnostic methods. We aimed to investigate the prevalence, risk factors and outcomes of concomitant CA and AS. METHODS: We performed a systematic review and meta-analysis of the literature searched on MEDLINE, Embase, Scopus and CENTRAL. We analysed the prevalence of CA in patients with AS grouped according to the diagnostic techniques, and the risk factors and outcomes of concomitant CA and AS were analysed in AS patients referred for surgical or transcatheter aortic valve replacement (AVR). RESULTS: A total of 21 studies were included, involving 4,243 patients. The pooled prevalence of CA in patients with AS was 14.4%, with substantial heterogeneity. The pooled prevalence of AS in patients CA was 8.7%, with substantial heterogeneity. Patients with both AS and CA had higher all-cause mortality than those with AS or CA alone. In AS patients requiring AVR, CA was associated with increasing age, male sex, higher NT-proBNP levels, increased interventricular septal end diastole (IVSd) thickness and lower left ventricular ejection fraction. Concomitant AS and CA was associated with increased all-cause mortality and pacemaker implantation post-procedure. Study limitations included heterogeneity of the results and the fair to good quality of the studies published. CONCLUSION: Overall, a substantial proportion of patients with AS may have CA, and they have poorer prognosis. A high degree of clinical suspicion is needed to identify the "red flags" and perform appropriate diagnostic imaging.

Clinical characteristics, treatment and long-term outcomes of patients with right-sided cardiac thrombus.

OBJECTIVE: Right-sided cardiac thrombus is rare and may be caused by venous thromboembolism, in association with medical devices or stasis of blood in atrial fibrillation (AF) and cardiomyopathies. Complications include pulmonary embolism (PE) and paradoxical stroke. Current data are limited and mostly from case series and PE registries. We aimed to describe the clinical characteristics, echocardiographic features, treatments, and outcomes of right-sided cardiac thrombus patients. METHODS: This was a retrospective observational study of 97 consecutive patients with right-sided cardiac thrombus detected on echocardiography. We studied co-morbidities, predisposing factors, thrombus characteristics, and therapeutic interventions and assessed their associations with the development of PE, paradoxical stroke, circulatory collapse, and all-cause mortality. RESULTS: The mean age was 58.7 years, and 55/97 (56.7%) of the participants were female. Ischemic heart disease (IHD), heart failure, chronic kidney disease, and malignancy were common co-morbidities. Right atrial (RA) thrombus was often associated with medical devices, while right ventricular (RV) thrombus was more commonly associated with cardiomyopathy. Thrombus mobility did not affect embolic events but was associated with greater short-term mortality. On multivariable analysis, anticoagulation (HR 0.25, 95% CI 0.09-0.68) and thrombus resolution (HR 0.28, 95% CI 0.13-0.62) were associated with greater survival. CONCLUSION: Right-sided cardiac thrombus is rare but may have potentially life-threatening complications such as PE and paradoxical stroke. Further research is needed to determine the optimal therapeutic strategies for this poorly studied population.

Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors on Cardiac Imaging Parameters: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Recent studies have shown that sodium/glucose cotransporter 2 (SGLT2) inhibitors might exert favourable changes on cardiac parameters as observed on cardiovascular imaging. We conducted a systematic review and meta-analysis to determine the effects of SGLT2 inhibitors on cardiac imaging parameters. Four electronic databases (PubMed, Embase, Cochrane, Scopus) were searched for studies in which the effects of SGLT2 inhibitors on cardiac imaging parameters were examined. Studies in which a population was administered SGLT2 inhibitors and analysed by echocardiography and/or cardiac magnetic resonance (CMR) imaging were included. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. A total of 11 randomized controlled trials was included with a combined cohort of 910 patients. Comparing patients receiving SGLT2 inhibitors with subjects receiving placebo, the mean change in CMR-measured left ventricular mass (LVM) was -3.87 g (95% confidence interval [CI], -7.77 to 0.04), that in left ventricular end-systolic volume (LVESV) was -5.96 mL (95% CI, -10.52 to -1.41) for combined LVESV outcomes, that in left atrial volume index (LAVi) was -1.78 mL/m² (95% CI, -3.01 to -0.55) for combined LAVi outcomes, and that in echocardiography-measured E/e' was -0.73 (95% CI, -1.43 to -0.03). Between-group differences were not observed in LVM and LVESV after indexation. The only between-group difference that persisted was for LAVi. Treatment with SGLT2 inhibitors resulted in reduction in LAVi and E/e' on imaging, indicating they might have an effect on outcomes associated with LV diastolic function.

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.

Obstructive sleep apnea during acute coronary syndrome is related to myocardial necrosis and wall stress.

BACKGROUND: The relative contribution of pathophysiological mechanisms in acute coronary syndrome (ACS) towards obstructive sleep apnea (OSA) is not well-studied. We examined the correlation between severity of OSA and inflammation, myocardial necrosis, wall stress, and fibrosis. METHODS: A total of 89 patients admitted with ACS underwent a sleep study during index admission. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), troponin I, N-terminal pro-brain natriuretic peptide (NT-proBNP), and suppression of tumorigenicity 2 (ST2) were prospectively analyzed. Two patients diagnosed with central sleep apnea were excluded. RESULTS: The recruited patients were divided into no (AHI <5 events/hour, 9.2%), mild (5-<15, 27.6%), moderate (15-<30, 21.8%), and severe (≥30, 41.4%) OSA. Compared to the no, mild and moderate OSA groups, the severe OSA group had a higher body mass index (p = 0.005). They were also more likely to present with ST-segment elevation ACS (versus non-ST-segment elevation ACS) (p = 0.041), have undergone previous coronary artery bypass grafting (p = 0.013), demonstrate complete coronary occlusion during baseline coronary angiography (p = 0.049), and have a larger left atrial diameter measured on echocardiography (p = 0.029). Likewise, the severe OSA group had higher plasma levels of hs-CRP (p = 0.004), troponin I (p = 0.017), and NT-proBNP (p = 0.004), but not ST2 (p = 0.10). After adjustment for the effects of confounding variables, OSA was independently associated with troponin I (ie, myocardial necrosis; p = 0.001) and NT-proBNP (ie, myocardial wall stress; p = 0.008). CONCLUSION: Severe OSA during the acute phase of ACS was associated with extensive myocardial necrosis and high myocardial wall stress, but not with inflammation and myocardial fibrosis.

Coronavirus-induced myocarditis: A meta-summary of cases.

BACKGROUND: Myocarditis caused by SARS-CoV-2 infection was proposed to account for a proportion of cardiac injury in patients with COVID-19. However, reports of coronavirus-induced myocarditis were scarce. The aim of this review was to summarise the published cases of myocarditis and describe their presentations, diagnostic processes, clinical characteristics and outcomes. METHODS: A literature search of MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL and OpenGrey on was performed on 3 June 2020. Studies of myocarditis in patients with COVID-19 were included, and those only reporting cardiac injury or heart failure were excluded. Cases were "confirmed" myocarditis if diagnosed on cardiac magnetic resonance imaging (CMR) or histopathology. Those without were grouped as "possible" myocarditis. RESULTS: A total of 31 studies on 51 patients were included; 12 cases were confirmed myocarditis while 39 had possible myocarditis. The median age was 55 and 69% were male. The most common presenting symptoms were fever, shortness of breath, cough and chest pain. Electrocardiogram changes included non-specific ST-segment and T-wave changes and ventricular tachycardia. Most patients had elevated cardiac and inflammatory biomarkers. Left ventricular dysfunction and hypokinesis was common. CMR established the diagnosis in 10 patients, with features of cardiac oedema and cardiac injury. Five patients had histopathological examination. Some cases required mechanical ventilation and extracoporeal membrane oxygenation, and 30% of patients recovered but 27% died. CONCLUSIONS: COVID-19 myocarditis was associated with ECG, cardiac biomarker and echocardiographic changes, and the manifestation could be severe leading to mortality. Endomyocardial biopsy was not available in most cases but CMR was valuable.

Home-based advance care programme is effective in reducing hospitalisations of advanced heart failure patients: a clinical and healthcare cost study.

INTRODUCTION: In end-stage heart failure (HF) that is not eligible for mechanical assist device or heart transplant, palliative care serves to maximise symptom control and quality of life. We sought to evaluate the impact of home-based advance care programme (ACP) on healthcare utilisation in end-stage HF patients. MATERIALS AND METHODS: Prospectively collected registry data on all end-stage HF recruited into ACP between July 2008 and July 2010 were analysed. Chart reviews were conducted on HF database and hospital electronic records. Phone interview and home visit details by ACP team were extracted to complete data entry. HF and all-cause hospitalisations 1 year before, and any time after ACP inception were defined as events. For the latter analysis, follow-up duration adjustment to event episodes was performed to account for death less than a year. RESULTS: Forty-four patients (mean age 79 years, 39% men) were followed up for 15±8 months. Fifty-seven percent had diabetes, 80% ischaemic heart disease, and 60% chronic kidney disease. All reported functional class III/IV at enrolment. Mean serum sodium was 136±6 mmol/L, and creatinine 186±126 mmol/L. Thirty (68%) died within the programme. Mean time to death was 5.5 months. Mean all-cause and HF hospitalisations were 3.6 and 2.0 per patient before enrolment, but improved to 1.0 and 0.6 respectively after ACP. Thirty-six (71%) patients had fewer HF hospitalisations. When only those who survived more than a year were considered (n = 14), 10 (71%) and 9 (64%) experienced reduced HF (mean: 1.4 episodes per patient) and all-cause hospitalisations (mean: 2.2 episodes per patient) respectively. CONCLUSION: Home-based advance care programme is potentially effective in reducing healthcare utilisation of end-stage HF patients, primarily by reducing HF rehospitalisations, and in probably saving costs as well.