Vulnerability to environmental and climatic health provocations among women and men hospitalized with chronic heart disease: insights from the RESILIENCE TRIAL cohort.

AIMS: We aimed to recruit a representative cohort of women and men with multi-morbid chronic heart disease as part of a trial testing an innovative, nurse-co-ordinated, multi-faceted intervention to lower rehospitalization and death by addressing areas of vulnerability to external challenges to their health. METHODS AND RESULTS: The prospective, randomized open, blinded end-point RESILIENCE Trial recruited 203 hospital inpatients (mean age 75.7 ± 10.2 years) of whom 51% were women and 94% had combined coronary artery disease, heart failure, and/or atrial fibrillation. Levels of concurrent multi-morbidity were high (mean Charlson Index of Comorbidity Score 6.5 ± 2.7), and 8.9% had at least mild frailty according to the Rockwood Clinical Frailty Scale. Including the index admission, 19-20% of women and men had a pre-existing pattern of seasonally linked hospitalization (seasonality). Detailed phenotyping revealed that 48% of women and 40% of men had ≥3 physiological factors, and 15% of women and 16% of men had ≥3 behavioural factors likely to increase their vulnerability to external provocations to their health. Overall, 61-62% of women and men had ≥4 combined factors indicative of such vulnerability. Additional factors such as reliance on the public health system (63 vs. 49%), lower education (30 vs. 14%), and living alone (48 vs. 29%) were more prevalent in women. CONCLUSION: We successfully recruited women and men with multi-morbid chronic heart disease and bio-behavioural indicators of vulnerability to external provocations to their health. Once completed, the RESILIENCE TRIAL will provide important insights on the impact of addressing such vulnerability (promoting resilience) on subsequent health outcomes. REGISTRATION: ClinicalTrials.org: NCT04614428.

Biventricular Function is Impaired in Right Ventricular Septal Pacing-A Prospective Study Using Myocardial Strain Imaging.

BACKGROUND: Left ventricular (LV) dysfunction is known to occur after right ventricular (RV) pacing; the effect on RV function is less well studied. The aim of this study was to assess the impact of RV mid-septal pacing upon RV function using the novel parameters of speckle-tracking derived RV global longitudinal strain (RV GLS) and RV free wall strain (RV FWS), as well as the conventional parameters RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and tricuspid annular systolic velocity (RV S'). METHODS: Thirty-two (32) consecutive patients with normal baseline LV and RV function requiring permanent pacemaker insertion (for high-grade AV block or sinus node dysfunction) were prospectively recruited. Echocardiography was performed prior to implantation, at 1 day, 1 month and 1 year after implantation, with 29 patients completing follow-up. RESULTS: After 1 year, three patients (10%) with otherwise normal RV parameters developed abnormal RV strain patterns. Compared to 1 day after implantation, at 1 year significant reductions were observed in mean RV GLS (-24.8 to -21.8%) RV S' (15.1 to 12.2 cm/s), TAPSE (24.2 to 21.9 mm), RV GLS (-24.8 to -21.8%), left ventricular ejection fraction (LVEF) (66.0 to 57.9%), LV GLS (-19.9 to 17.0), all p<0.01. There was a non-significant reduction for RV FWS (-29.0 to -26.7%, p=0.06) and there was no change in RV FAC (49.1 to 46.9%, p=0.24). CONCLUSION: We report abnormalities of RV strain developing 1 year after pacemaker insertion. Measurement of myocardial strain is emerging as an additional method to detect patients at risk of RV dysfunction in those who have undergone pacemaker implantation.

Role of Cardiac Computed Tomography in Planning Transcatheter Mitral Valve Replacement (TMVR).

PURPOSE OF REVIEW: Transcatheter mitral valve replacement (TMVR) is an evolving and rapidly expanding field within structural interventions, offering renewed treatment options for patients with high-risk mitral valve disease. We aim to highlight and illustrate the importance of cardiac CT in the planning of TMVR. RECENT FINDINGS: As TMVR has evolved, so has the specific nuances of cardiac CT planning, we now understand the importance of accurate annular sizing and valve simulation to predict complications such as neo-LVOT obstruction and paravalvular leak (PVL). More so than any other modality, cardiac CT remains instrumental in accurately planning TVMR from feasibility, device sizing, access, and fluoroscopic angles. Cardiac CT remains the key modality in TMVR evaluation, often the first step in determining patient eligibility through comprehensive procedural planning as well as informing potential outcomes and prognosis. In this review, we discuss the critical role of cardiac computed tomography (CT) and the specific considerations involved in TMVR.

Effect of Myocardial Tissue Characterization Using Native T1 to Predict the Occurrence of Adverse Events in Patients With Chronic Kidney Disease and Severe Aortic Stenosis.

Among patients with chronic kidney disease (CKD), aortic stenosis (AS) is associated with a significantly higher rate of mortality. We aimed to evaluate whether diffuse myocardial fibrosis, determined using native T1 mapping, has prognostic utility in predicting major adverse cardiovascular events (MACEs), including all-cause mortality or heart failure hospitalization, in patients with CKD and severe AS who are evaluated for transcatheter aortic valve implantation. Cardiac magnetic resonance with T1 mapping using the modified Look-Locker inversion recovery technique was performed in 117 consecutive patients with severe AS and CKD (stage ≥3). Patients were followed up to determine the occurrence of MACE. The mean age of the 117 patients in the cohort was 82 ± 8 years. Native T1 was 1,055 ms (25th- to 75th percentiles 1,031 to 1,078 ms), which is higher than previously reported in healthy controls. Patients with higher T1 times were more likely to have higher N-terminal pro-B-type natriuretic peptide levels (4,122 [IQR 1,578 to 7,980] pg/ml vs 1,678 [IQR 493 to 2,851] pg/ml, p = 0.005) and a history of heart failure (33% vs 9%, p = 0.034). After median follow-up of 3.4 years, MACE occurred in 71 patients (61%). The Society of Thoracic Surgeons predicted risk of mortality score (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.02 to 1.12, p = 0.006), native T1 >1,024 ms (HR 2.10, 95% CI 1.09 to 4.06, p = 0.028), and New York Heart Association class (HR 1.56, 95% 1.09 to 2.34, p = 0.016) were independent predictors of MACE. Longer native T1 was associated with MACE occurrence in patients with CKD and severe AS.

Clinical, functional and prognostic implications of severe atrial dilation in secondary mitral regurgitation.

OBJECTIVE: Atrial dilation is known to be a poor prognostic indicator. However, its clinical, functional and prognostic implications have not been thoroughly explored in secondary mitral regurgitation (SMR). We sought to describe the implications of severe atrial dilation (SAD) in SMR. METHODS: We included all adult patients with severe SMR due to left ventricle dysfunction (with no organic mitral valve disease) who underwent transthoracic echocardiography between January 2012 and March 2021 at our institution. The concomitant presence of severe left atrial (LA) dilation (>48 mL/m2) defined SADMR (SAD in SMR), and these patients were compared with those without SAD. RESULTS: A total of 2011 patients were included (mean age 70% and 41% females), with 71% having SADMR. MR severity and ejection fraction were similar between both groups. Patients with SADMR were older, less females and had more diabetes, but similar rates of atrial fibrillation. Mechanistically, they had lower A wave velocity (0.61 vs 0.72 cm/sec, p<0.001) and more impaired LA reservoir strain (9.7% vs 15.5%, p<0.001). Geometrically, SADMR had shallower leaflets' angulations, lower tenting height, larger annuli and smaller leaflet length/annular diameter ratios (all p<0.001). They underwent fewer MV interventions, although these were associated with better outcomes (log-rank p<0.001). Over the study period, SAD was an independent predictor of mortality (HR 1.26, p=0.04). CONCLUSION: SADMR is associated with specific mechanistic and functional alterations and confers a worse prognosis.

Invasive versus conservative management in patients aged ≥85 years presenting with non-ST-elevation myocardial infarction.

BACKGROUND: Guidelines recommend early coronary angiography (CA) in patients with non-ST-elevation myocardial infarction (NSTEMI) irrespective of age. However, elderly patients are less likely to be treated according to these guidelines due to their perceived high risk and medical comorbidities. Whether an invasive strategy is associated with improved survival in patients aged ≥85 years remains uncertain due to their exclusion from randomised trials. AIMS: Patients were stratified based on whether they underwent invasive management with CA with a view to revascularisation versus conservative management. The primary outcome was long-term mortality. METHODS: Consecutive patients aged ≥85 years presenting to a tertiary centre with NSTEMI between 2008 and 2018 were included in this retrospective cohort study. RESULTS: Of 7591 patients with NSTEMI, 1052 patients aged ≥85 years were included. Ninety-nine (9.4%) patients underwent CA. Those undergoing CA were more likely to be younger, male, live independently, without mobility or cognitive issues (all P < 0.01). Overall, 495 (47%) patients died during a mean follow up of 1.3 ± 1 year. On Cox regression, after adjusting for age, pre-morbid functional status, cognition and cardiovascular risk factors, invasive management was the strongest predictor for survival (hazard ratio 0.47; 95% confidence interval 0.26-0.85; P = 0.01). Invasive management was associated with a trend to increased risk of in-hospital bleeding (6.1% vs 2.6%; P = 0.054) with no significant difference in stroke (2.0% vs 3.8%; P = 0.37). CONCLUSION: In patients aged ≥85 years who presented with NSTEMI, invasive management was associated with improved survival without significant differences in bleeding or stroke. A randomised controlled study assessing the efficacy and safety of invasive management in very elderly patients with NSTEMI is warranted.

Depressed right ventricular systolic function in heart failure due to constrictive pericarditis.

AIMS: Heart failure in constrictive pericarditis (CP) is attributed to impaired biventricular diastolic filling. However, diseases that cause CP due to myocardial infiltration and fibrosis can also impair biventricular systolic function (sf) and contribute to heart failure. This study of patients with CP examined biventricular sf and the effect of myocardial infiltration by pericardial diseases and the resulting fibrosis on ventricular sf. METHODS AND RESULTS: Histopathologic examinations of right ventricular (RV) and left ventricular (LV) myocardia and pericardia were performed on three autopsied hearts of patients with pericardial diseases. Additionally, in 40 adults with clinical heart failure and 40 healthy adults (controls), sf of both ventricles was examined by echocardiography, including strain measurements, and biventricular diastolic filling and pulmonary artery pressures were assessed by cardiac catheterization. Cardiac histopathology indicated thickening of the pericardium with fibrosis, disease infiltrating the myocardium, greater infiltration of the RV than the LV, and an association of pericardial thickness with myocardial infiltrations. Functional analysis indicated that RVsf was impaired on all echo indices, including strain measurement, but LVsf was preserved. CONCLUSIONS: Diseases causing CP are not restricted to the pericardium but also infiltrate the biventricular myocardium and affect the thin-walled RV more than the thick-walled LV, resulting in depressed RVsf. The present results help explain clinical heart failure in the presence of restricted diastolic filling in CP. Depression of RVsf due to progression of fibrosis in the RV myocardium may increase the risk of delayed pericardiectomy.

Periprocedural Echocardiographic Guidance of Transcatheter Mitral Valve Edge-to-Edge Repair Using the MitraClip.

Transcatheter edge-to-edge mitral valve repair is a minimally invasive treatment option for selected patients with moderate to severe or severe mitral regurgitation. Although transcatheter edge-to-edge mitral valve repair offers a significant step forward in the management of mitral regurgitation, the rate of procedural-related complications is not trivial. High-quality periprocedural imaging is important for optimal patient selection and procedural success. In this review, we present a step-by-step approach of the recommended echocardiographic views for transcatheter edge-to-edge mitral valve repair.

Novel Approach to Risk Stratification in Left Ventricular Non-Compaction Using A Combined Cardiac Imaging and Plasma Biomarker Approach.

Background Left ventricular non-compaction remains a poorly described entity, which has led to challenges of overdiagnosis. We aimed to evaluate if the presence of a thin compacted myocardial layer portends poorer outcomes in individuals meeting cardiac magnetic resonance criteria for left ventricular non-compaction . Methods and Results This was an observational, retrospective cohort study involving individuals selected from the Cleveland Clinic Foundation cardiac magnetic resonance database (N=26 531). Between 2000 and 2018, 328 individuals ≥12 years, with left ventricular non-compaction or excessive trabeculations based on the cardiac magnetic resonance Petersen criteria were included. The cohort comprised 42% women, mean age 43 years. We assessed the predictive ability of myocardial thinning for the primary composite end point of major adverse cardiac events (composite of all-cause mortality, heart failure hospitalization, left ventricular assist device implantation/heart transplant, ventricular tachycardia, or ischemic stroke). At mean follow-up of 3.1 years, major adverse cardiac events occurred in 102 (31%) patients. After adjusting for comorbidities, the risk of major adverse cardiac events was nearly doubled in the presence of significant compacted myocardial thinning (hazard ratio [HR], 1.88 [95% CI, 1.18‒3.00]; P=0.016), tripled in the presence of elevated plasma B-type natriuretic peptide (HR, 3.29 [95% CI, 1.52‒7.11]; P=0.006), and increased by 5% for every 10-unit increase in left ventricular end-systolic volume (HR, 1.01 [95% CI, 1.00‒1.01]; P=0.041). Conclusions The risk of adverse clinical events is increased in the presence of significant compacted myocardial thinning, an elevated B-type natriuretic peptide or increased left ventricular dimensions. The combination of these markers may enhance risk assessment to minimize left ventricular non-compaction overdiagnosis whilst facilitating appropriate diagnoses in those with true disease.

Severe Atrial Functional Mitral Regurgitation: Clinical and Echocardiographic Characteristics, Management and Outcomes.

OBJECTIVES: This study was designed to compare the clinical and echocardiographic characteristics, management, and outcomes of severe atrial functional mitral regurgitation (AFMR) to primary mitral regurgitation (PMR). BACKGROUND: AFMR remains poorly defined clinically. METHODS: Consecutive patients who underwent transesophageal echocardiography at our institution between 2011 and 2018 for severe mitral regurgitation with preserved left ventricular function were screened. We excluded patients with endocarditis, any form of cardiomyopathy, or prior mitral intervention. The absence of leaflet pathology defined AFMR. Outcomes included death and heart failure hospitalizations. RESULTS: A total of 283 patients were included (AFMR = 14%, PMR = 86%). Compared to PMR, patients with AFMR had more comorbidities, including hypertension (94.9% vs. 76.2%; p = 0.015), diabetes mellitus (46.2% vs. 18.4%; p < 0.001), long-standing atrial fibrillation (28.2% vs. 13.1%; p = 0.015), prior nonmitral cardiac surgery (25.6% vs. 9.8%; p = 0.004), and pacemaker placement (33.3% vs. 13.5%; p = 0.002). They also had higher average E/e' (median [interquartile range]:16.04 [13.1 to 22.46] vs. 14.1 [10.89 to 19]; p = 0.036) and worse longitudinal left atrial strain peak positive value (16.86 ± 12.15% vs. 23.67 ± 14.09%; p = 0.002) compared to PMR. During follow-up (median: 22 months), patients with AFMR had worse survival (log-rank p = 0.009) and more heart failure hospitalizations (log-rank p = 0.002). They were also less likely to undergo mitral valve intervention (59.0% vs. 83.6%; p = 0.001), although surgery was associated with improved survival (log-rank p = 0.021). On multivariable regression analysis, AFMR was independently associated with mortality [adjusted odds ratio: 2.61, 95% confidence interval: 1.17 to 5.83; p = 0.02]. CONCLUSIONS: AFMR constitutes an under-recognized high-risk group, with significant comorbidities, limited therapeutic options, and poor outcomes.

Improvement in left ventricular mechanics following medical treatment of constrictive pericarditis.

OBJECTIVE: Patients with constrictive pericarditis (CP) with active inflammation may show resolution with anti-inflammatory therapy. We aimed to investigate the impact of anti-inflammatory medications on constrictive pathophysiology using echocardiography in patients with CP. METHODS: We identified 35 patients with CP who were treated with anti-inflammatory medications (colchicine, prednisone, non-steroidal anti-inflammatory drugs) after diagnosis of CP (mean age 58±13; 80% male). Clinical resolution of CP (transient CP) was defined as improvement in New York Heart Association class during follow-up. We assessed constrictive pathophysiology using regional myocardial mechanics by the ratio of peak early diastolic tissue velocity (e') at the lateral and septal mitral annulus by tissue Doppler imaging (lateral/septal e') or the ratio of the left ventricular lateral and septal wall longitudinal strain (LSlateral/LSseptal) by two-dimensional speckle-tracking echocardiography. Longitudinal data were analysed using a mixed effects model. RESULTS: During a median follow-up of 323 days, 20 patients had transient CP, whereas 15 patients had persistent CP. Transient CP had higher baseline erythrocyte sedimentation rates (ESR) (p=0.003) compared with persistent CP. There were no significant differences in LSlateral/LSseptal and lateral/septal e'. During follow-up, only transient CP showed improvement in lateral/septal e' (p<0.001) and LSlateral/LSseptal (p=0.003), and recovery of inflammatory markers was similar between the two groups. In the logistic model, higher baseline ESR and greater improvement in lateral/septal e' and LSlateral/LSseptal were associated with clinical resolution of CP using anti-inflammatory therapy. CONCLUSIONS: Improvement of constrictive physiology detected by lateral/septal e' and LSlateral/LSseptal was associated with resolution of clinical symptoms after anti-inflammatory treatment. Serial monitoring of these markers could be used to identify transient CP.

Role of Computed Tomography Angiography in Setting of Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is an infrequent cause of acute coronary syndrome, predominantly affecting young women. Catheter-based coronary angiography is the gold standard diagnostic test, especially when coupled with intracoronary imaging. Conservative management in stable patients is the preferred approach given the increased risk of complications associated with percutaneous interventions. Noninvasive coronary computed tomography angiography (CTA) has a potential role in the diagnosis and follow-up of SCAD. CTA also plays a role in screening for extracoronary vascular abnormalities frequently associated with SCAD. The goal of this article is to review the potential role of CTA in evaluating SCAD.

SMARTphone-based, early cardiac REHABilitation in patients with acute coronary syndromes: a randomized controlled trial.

BACKGROUND: There are well-documented treatment gaps in secondary prevention of coronary heart disease with a lack of clearly defined strategies to assist early physical activity after acute coronary syndromes (ACS). Smartphone technology may provide an innovative platform to close these gaps. OBJECTIVES: The primary goal of this study was to assess whether a smartphone-based, early cardiac rehabilitation program improved exercise capacity in patients with ACS. METHODS: A total of 206 patients with ACS across six tertiary Australian hospitals were included in this randomized controlled trial. Participants were randomized to usual care (UC; including referral to traditional cardiac rehabilitation), with or without an adjunctive smartphone-based cardiac rehabilitation program (S-CRP) upon hospital discharge. The primary endpoint was change in exercise capacity, measured by the change in 6-minute walk test distance at 8 weeks when compared to baseline, between groups. Secondary endpoints included uptake and adherence to cardiac rehabilitation, changes in cardiac risk factors, psychological well-being and quality of life status. RESULTS: Of the 168 patients with complete follow-up (age 56 ± 10 years; 16% females), 83 were in the S-CRP. At 8-week follow-up, the S-CRP group had a clinically significant improvement in 6-minute walk test distance (Δ117 ± 76 vs. Δ91 ± 110 m; P = 0.02). Patients in the S-CRP were more likely to participate (87% vs. 51%, P < 0.001) and adhere (72% vs. 22%, P < 0.001) to a cardiac rehabilitation program. Compared to UC, patients receiving S-CRP had similar smoking cessation rates, LDL-cholesterol levels, blood pressure reduction, depression, anxiety and quality of life measures (all P = NS). CONCLUSION: In patients with ACS, a S-CRP, as an adjunct to UC improved exercise capacity at 8 weeks in addition to participation and adherence to cardiac rehabilitation (Australian New Zealand Clinical Trials Registry; ACTRN12616000426482).

Incidental Thoracic Aortic Dilation on Chest Computed Tomography in Patients With Atrial Fibrillation.

Patients with atrial fibrillation (AF) have risk factors that predispose to thoracic aneurysmal disease (TAD) and atherosclerosis. In this study in patients with AF, we assessed the occurrence of incidental TAD and assessed if a validated predictive score used to predict AF, the CHARGE-AF score, was associated with greater aortic dimensions. We also assessed the prevalence of coronary calcification. We conducted a cross-sectional study of 1,000 consecutive patients with AF undergoing chest multidetector CT during evaluation for pulmonary vein isolation. A dilated aortic root or ascending aorta (AA, dimension/ body surface area >2.05 cm/m2) were found in 195 (20%). A total of 12 (1%) had significant aortic aneurysmal enlargement of > 5.0 cm. Advancing age, a bicuspid aortic valve, hypertension, and male gender were associated with increased aortic dimensions. Aortic root dimensions increased linearly (p < 0.001) and ascending aortic dimensions increased nonlinearly across CHARGE-AF deciles (p < 0.001). Nearly two-thirds (63%) had coronary calcification, 38% of whom were not on lipid-lowering therapy. In conclusion, in patients with AF undergoing gated chest CT, 1 in 5 had previously undetected TAD, with a small proportion having significantly aneurysmal dimensions approaching surgical thresholds. Risk factors previously established to increase the propensity to develop AF are also associated with increased TAD. These findings raise the need to consider a surveillance strategy for TAD in patients with AF, particularly in those with other risk factors for aortic disease. A high prevalence of coronary calcium was also detected, representing an opportunity to optimize statin therapy in patients with AF.

Renin-angiotensin system inhibition and risk of infection and mortality in COVID-19: a systematic review and meta-analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, enters human cells by binding of its viral protein to the aminopeptidase angiotensin-converting enzyme 2 (ACE2). This has led to speculation whether treatment with renin-angiotensin system (RAS) inhibitors was associated with an increased likelihood of a positive test for COVID-19 and risk of mortality. AIMS: We performed a systematic review and meta-analysis to investigate whether RAS inhibitors increased the likelihood of a positive test or death/severe illness in patients with COVID-19. METHODS: A systematic search of MEDLINE, PubMed and EMBASE was conducted for studies stratified by the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Pooled analysis was performed using a random-effects model. RESULTS: Seven trials of 73 122 patients were included. Overall, 16 624 (22.7%) patients had a positive COVID-19 test and 7892 (10.8%) were on a RAS inhibitor. RAS inhibitors were not associated with higher likelihood of a positive COVID-19 test result (odds ratio (OR) 0.97 (95% CI 0.97-1.05, P = 0.48) with low heterogeneity. This was comparable when stratifying by use of each medication class. The use of RAS inhibitors was also not associated with mortality or severe illness (OR 0.89, 95% CI 0.73-1.07, P = 0.21) with moderate heterogeneity. CONCLUSION: Use of ACEI or ARB was not associated with a heightened susceptibility for a positive diagnosis of COVID-19. Furthermore, they were not associated with increased illness severity or mortality due to COVID-19. Randomised controlled trials are needed to address definitively the potential benefits or harms of RAS inhibitors in patients with COVID-19.

Mavacamten: a novel small molecule modulator of ß-cardiac myosin for treatment of hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a common known monogenetic cardiovascular disorder which frequently leads to symptoms such as dyspnea and exercise intolerance. Current guideline-recommended pharmacotherapies have variable therapeutic responses. Mavacamten, a small molecule modulator of ß-cardiac myosin, reduces hypercontractility, a central mechanism in the pathogenesis of HCM. Mavacamten has recently been evaluated in Phase 2 and 3 clinic trials for obstructive and nonobstructive symptomatic HCM. AREAS COVERED: This article reviews available preclinical and clinical trials assessing the efficacy and safety of Mavacamten for the treatment of symptomatic obstructive and nonobstructive HCM. EXPERT OPINION: Findings from Phase 2 and 3 trials suggest that Mavacamten represents a very promising new therapy for the treatment of symptomatic patients with HCM. Treatment leads to an improvement in symptomatic and physiologic metrics for symptomatic patients with HCM with minimal adverse events. Patients with obstructive HCM demonstrated a significant improvement in LVOT gradient, NYHA functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ), Overall Summary Score (OSS), and numerical rating scale (NRS) dyspnea scores; and patients with both obstructive and nonobstructive HCM had significant improvement in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations.