No-Implant Interatrial Shunt for HFpEF: 6-Month Outcomes From Multicenter Pilot Feasibility Studies.

BACKGROUND: Most approaches to the creation of an interatrial shunt require placement of a permanent implant to maintain patency. OBJECTIVES: The goal of this study was to investigate the safety and efficacy of a no-implant interatrial shunt for patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF). METHODS: This was a multicenter, uncontrolled study of patients with HFpEF/HFmrEF and NYHA functional class ≥II, ejection fraction >40%, and pulmonary capillary wedge pressure (PCWP) during supine exercise ≥25 mm Hg with PCWP-to-right atrial gradient ≥5 mm Hg. Follow-up was through 6 months with imaging to assess shunt durability. RESULTS: A total of 28 patients were enrolled: mean age was 68 ± 9 years, and 68% were female. Baseline resting and peak exercise PCWP were 19 ± 7 mm Hg and 40 ± 11 mm Hg, respectively. All procedures displayed technical success with confirmation of left-to-right flow (shunt diameter 7.1 ± 0.9 mm). At 1 month, peak exercise PCWP decreased 5.4 ± 9.6 mm Hg (P = 0.011) with no change in right atrial pressure. There were no serious device or procedure-related adverse events through 6 months. Mean 6-minute walk distance increased 101 ± 71 meters (P < 0.001); Kansas City Cardiomyopathy Questionnaire Overall Summary Score increased 26 ± 19 points (P < 0.001); N-terminal pro-B-type natriuretic peptide decreased 372 ± 857 pg/mL (P = 0.018); and shunt patency was confirmed with unchanged diameter. CONCLUSIONS: In these feasibility studies of a no-implant interatrial shunt, HFpEF/HFmrEF shunts exhibited stability with favorable safety and early efficacy signals. The results show promise toward this new approach for treating patients with HFpEF/HFmrEF and an appropriate hemodynamic profile. (Evaluation of the Safety and Feasibility of a Percutaneously Created Interatrial Shunt to Alleviate Heart Failure Symptoms in Patients With Chronic Heart Failure and Preserved or Mid-Range Left Ventricular Ejection Fraction [ALLEVIATE-HF-1]; NCT04583527; Evaluation of the Safety and Effectiveness of a Percutaneously Created Interatrial Shunt to Alleviate Heart Failure Symptoms in Patients With Chronic Heart Failure and Preserved or Mid-Range Left Ventricular Ejection Fraction [ALLEVIATE-HF-2]; NCT04838353).

Mineralocorticoid receptor antagonists, heart failure and predictive biomarkers.

The mineralocorticoid receptor is a steroid hormone receptor that is well known for its involvement in fluid and electrolyte homeostasis in epithelial cells present in the distal nephron. The inappropriate activation of this receptor is now known to be implicated in various pathophysiological mechanisms in heart failure. Mineralocorticoid receptor antagonists offer substantial clinical benefit in patients with heart failure with reduced ejection fraction; however, for patients with heart failure with preserved ejection fraction, the treatment benefit is less clear. Biomarkers that can predict response to mineralocorticoid receptor antagonist treatment do not currently exist. Potential biomarkers may be modulated either directly by the mineralocorticoid receptor or indirectly via downstream effects and be able to reflect treatment outcomes, particularly changes in key parameters of cardiac health and function. A biomarker or set of biomarkers that can reliably predict responsiveness to mineralocorticoid receptor antagonist treatment at an early stage may allow for the selection of patients who are most likely to benefit from treatment thereby avoiding any unnecessary side effects associated with the use of these medications.

Management of Acute Decompensated Heart Failure in Rural Versus Metropolitan Settings: An Australian Experience.

BACKGROUND: Acute decompensated heart failure (ADHF) is the most common cause of hospital admission in patients over 65, with poorer outcomes demonstrated in rural versus metropolitan areas. The aim of this study was to compare the in-hospital and post-discharge management of ADHF patients admitted to rural versus metropolitan hospitals in Victoria. METHODS: Data from the Victorian Cardiac Outcomes Registry, Heart Failure (VCOR-HF) project was used. This was a prospective, observational, non-randomised study of consecutive patients admitted to participating hospitals in Victoria, Australia, with ADHF as their primary diagnosis over four 30-day periods during consecutive years. All patients were followed up for 30 days post discharge. RESULTS: 1,357 patients (1,260 metropolitan, 97 rural) were admitted to study hospitals with ADHF during the study periods. Cohorts were similar in age (average 76.87±13.12 yrs) and percentage of male gender (56.4% overall). Metropolitan patients were more likely to have diabetes (44.4% vs 34.0%, p=0.046), kidney disease (65.8% vs 37.1%, p<0.01) and anaemia (31.9% vs 19.6%, p=0.01). There was no significant difference in length of stay between metropolitan and rural patients (7.49 vs 6.37 days, p=0.12). There was no significant difference between metropolitan and rural patients in 30-day rehospitalisations (19.1% vs 11.6%, p=0.07, respectively) and all-cause 30-day mortality (8.2% vs 4.1%, p=0.15, respectively). Metropolitan patients were significantly more likely to have seen their general practitioner (GP) (68.1% vs 53.2%, p<0.01) or attend an outpatient clinic (35.9% vs 10.6%, p<0.01) by 30 days. There was no significant difference in number of days to follow-up of any kind between groups. Referrals to a heart failure home visiting program remained low overall (19.9%). CONCLUSION: There was no significant difference in 30-day rehospitalisations or mortality between patients admitted to rural versus metropolitan hospitals. Geographical discrepancies were noted in follow-up by 30 days, with significantly more metropolitan patients having seen a doctor by 30 days post-discharge. Overall follow-up rates remain suboptimal.

Characteristics and Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction Compared to Heart Failure With Reduced Ejection Fraction: Insights From the VCOR Heart Failure Snapshot.

BACKGROUND: Heart failure is increasing in prevalence, creating a greater public health and economic burden on our health care system. With a rising proportion of hospitalisations for heart failure with preserved ejection fraction (HFpEF) compared to heart failure with reduced ejection fraction (HFrEF) and lack of proven therapies for HFpEF, patient characterisation and defining clinical outcomes are important in determining optimal management of heart failure patients. There is scarce Australian-specific data with regards to the burden of disease of patients with HFpEF which further limits our ability to appropriately manage this syndrome. AIM: To determine the characteristics, management practices and outcomes of patients with HFpEF compared to patients diagnosed with HFrEF. METHOD: Data was sourced from the Victorian Cardiac Outcomes Registry-Heart Failure (VCOR-HF) snapshot of patients admitted with acute heart failure to one of 16 Victorian health services between 2014-2017 over one consecutive month annually. Outcomes measured were in-hospital mortality, and 30-day readmission and mortality. RESULTS: Of the 1,132 HF patients, 436 patients were diagnosed with HFpEF and were more likely to be female (59%) and older (81.5±9.8 vs 73.2±14.5 years). They were also more likely to have hypertension (80%), atrial fibrillation (59.9%), chronic obstructive airways disease (36.2%) and chronic kidney disease (68.8%). Patients with HFrEF were more likely to have ischaemic heart disease with a history of previous myocardial infarction (36.6%), percutaneous coronary intervention and cardiac bypass surgery (35.2%). There were no significant differences in 30-day mortality between HFpEF and HFrEF (10.2% vs 7.8%; p=0.19, respectively) and 30-day readmission rates (22.1% vs 25.9%; p=0.15, respectively). CONCLUSION: VCOR-HF Snapshot data provides important insight into the burden of acute heart failure. Whilst patients with HFpEF and HFrEF have differing clinical profiles, morbidity, mortality and re-admission rates are similar.

The Effect of Transitional Care on 30-Day Outcomes in Patients Hospitalised With Acute Heart Failure.

BACKGROUND: Patients admitted to hospital with acute heart failure (AHF) are at increased risk of readmission and mortality post-discharge. The aim of the study was to examine health service utilisation within 30 days post-discharge from an AHF hospitalisation. METHODS: This was a prospective, observational, non-randomised study of consecutive patients hospitalised with acute HF to one of 16 Victorian hospitals over a 30-day period each year and followed up for 30 days post-discharge. The project was conducted annually over three consecutive years from 2015 to 2017. RESULTS: Of the 1,197 patients, 56.3% were male with an average age of 77±13.23 years. Over half of the patients (711, 62.5%) were referred to an outpatient clinic and a third (391, 34.4%) to a HF disease management program. In-hospital mortality was 5.1% with 30 day-mortality of 9% and readmission rate of 24.4%. Patients who experienced a subsequent readmission less than 10 days post-discharge and between 11 and 20 days post-discharge had a five- to six-fold increase in risk of mortality (adjusted OR 5.02, 95% CI 2.11-11.97; OR 6.45, 95% CI 2.69-15.42; respectively) compared to patients who were not readmitted to hospital. An outpatient appointment within 30 days post-discharge significantly reduced the risk of 30-day mortality by 81% (95% CI 0.09-0.43). CONCLUSION: Patients admitted to hospital with AHF who experience a subsequent readmission within 20 days post-discharge are at increased risk of dying. However, early follow-up post-discharge may reduce this risk. Early post-discharge follow-up is vital to address this vulnerable period after a HF admission.

Prospective Evaluation of the Utility of Whole Exome Sequencing in Dilated Cardiomyopathy.

Background Dilated cardiomyopathy may be heritable but shows extensive genetic heterogeneity. The utility of whole exome sequencing as a first-line genetic test for patients with dilated cardiomyopathy in a contemporary "real-world" setting has not been specifically established. Using whole exome sequencing with rigorous, evidence-based variant interpretation, we aimed to identify the prevalence of a molecular diagnosis in patients with dilated cardiomyopathy in a clinical setting. Methods and Results Whole exome sequencing was performed in eligible patients (n=83) with idiopathic or familial dilated cardiomyopathy. Variants were prioritized for curation in up to 247 genes and classified using American College of Medical Genetics and Genomics-based criteria. Ten (12%) had a pathogenic or likely pathogenic variant. Eight (10%) participants had truncating TTN variants classified as variants of uncertain significance. Five (6%) participants had variants of unknown significance according to strict American College of Medical Genetics and Genomics criteria but classified as either pathogenic or likely pathogenic by other clinical laboratories. Pathogenic or likely pathogenic variants were found in 8 genes (all within tier 1 genes), 2 (20%) of which are not included in a standard commercially available dilated cardiomyopathy panel. Using our bioinformatics pipeline, there was an average of 0.74 variants of uncertain significance per case with ≈0.75 person-hours needed to interpret each of these variants. Conclusions Whole exome sequencing is an effective diagnostic tool for patients with dilated cardiomyopathy. With stringent classification using American College of Medical Genetics and Genomics criteria, the rate of detection of pathogenic variants is lower than previous reports. Efforts to improve adherence to these guidelines will be important to prevent erroneous misclassification of nonpathogenic variants in dilated cardiomyopathy genetic testing and inappropriate cascade screening.

Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study.

BACKGROUND: Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy. OBJECTIVES: The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF. METHODS: This multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months. RESULTS: A total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p < 0.0001) and normalized (LVEF ≥50%) in 58% versus 9% (p = 0.0002). In those undergoing CA, the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF (10.7%; p = 0.0069) and normalization at 6 months (73% vs. 29%; p = 0.0093). CONCLUSIONS: AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741).

Successful percutaneous closure of an extremely large secundum atrial septal defect during pregnancy.

Atrial septal defects (ASDs) are one of the most of the most common acyanotic congenital heart lesions. Awareness of potential clinical presentations and complications during pregnancy is essential for those managing these patients. We report successful percutaneous closure of an extremely large secundum ASD, using the largest available percutaneous ASD closure device in a 27-year-old pregnant female. Large ASDs may have their initial clinical presentation and diagnosis during pregnancy. If indicated, percutaneous closure can be performed safely. Only a very small number of cases have previously reported this being performed safely during pregnancy.

Imaging Guidance for Transcatheter Aortic Valve Replacement: Is Transoesophageal Echocardiography the Gold Standard?

Transcatheter aortic valve replacement (TAVR) is traditionally performed under cardiac imaging guidance. In the early TAVR experience, intra-procedural transoesophageal echocardiography (TOE) is recommended to guide device deployment, in the context of general anaesthesia (GA). Intra-procedural TOE imaging is particularly useful during TAVR deployment as a contrast-saving strategy for patients with renal impairment. Evidence has emerged recently demonstrating that in selected patients, transthoracic echocardiography (TTE) can be used to provide intra-procedural guidance for TAVR. Additionally, there is a growing body of evidence supporting the performance of TAVR using fluoroscopy alone, without additional cardiac imaging. This article aims to provide a contemporary review of the various procedural imaging approaches for TAVR guidance, comparing the relative strengths and weaknesses of each approach (Table 1).

South Asians and Anglo Australians with heart disease in Australia.

OBJECTIVES: The aim of the present study was to determine cardiovascular disease (CVD) risk tactors and compare presentation and severity of ischaemic heart disease (IHD) among South Asians (SAs) and Anglo Australians (AAs). METHODS: A retrospective clinical case audit was conducted at a public tertiary hospital. The study population included SA and AA patients hospitalised for IHD. Baseline characteristics, evidence of diabetes and other CVD risk factors were recorded. Angiography data were also included to determine severity, and these were assessed using a modified Gensini score. RESULTS: SAs had lower mean (± s.d.) age of IHD presentation that AAs (52 ± 9 vs 55 ± 9 years, respectively; P = 0.02), as well as a lower average body mass index (BMI; 26 ± 4 vs 29 ± 6 kg/m2, respectively; P = 0.005), but a higher prevalence of type 2 diabetes (57% vs 31%, respectively; P = 0.00 1). No significant differences were found in coronary angiography parameters. There were no significant differences in the median (interquartile range) Gensini score between SAs and AAs (43.5 (27-75) vs 44 (26.5-68.5), respectively), median vessel score (1 (1-2) vs 2 (1-3), respectively) or multivessel score (37% (33/89) vs 54% (22/41), respectively). CONCLUSIONS: The findings show that in those with established IHD, cardiovascular risk factors, such as age at onset and BMI, differ between SAs and AAs and these differences should be considered in the prevention and management of IHD.

Comparison of Self-Expanding and Mechanically Expanded Transcatheter Aortic Valve Prostheses.

OBJECTIVES: The aim of this study was to determine whether transcatheter aortic valve replacement (TAVR) with the mechanically expanded Lotus valve (Boston Scientific, Natick Massachusetts) offers potential benefits over treatment with the self-expanding CoreValve (Medtronic, Minneapolis, Minnesota). BACKGROUND: New-generation transcatheter aortic valve systems are emerging in clinical trials and practice with design features aimed at improving safety and efficacy. To date, these devices have not been compared systematically with current-generation devices. METHODS: A total of 100 patients (83.4 ± 4.8 years of age, 44% male, Society of Thoracic Surgeons Predicted Risk of Mortality score of 5.5 ± 2.4) were assessed. Fifty consecutive patients undergoing a Lotus transcatheter aortic valve replacement were enrolled and compared with 50 matched patients treated with a CoreValve. An independent core laboratory reviewed all echocardiographic data, and an independent clinical events committee adjudicated all events. RESULTS: Valve Academic Research Consortium 2-defined device success was 84% and 64% in the Lotus and CoreValve cohorts, respectively (p = 0.02). This difference was driven by lower rates of moderate or greater aortic regurgitation (4% vs. 16.7%, respectively; p = 0.04) and higher rates of successfully implanting a single device in the correct anatomic position (100% vs. 86%, respectively; p = 0.06). Cardiovascular mortality rate (0% vs. 4%, respectively; p = 0.32), major stroke rate (4% vs. 2%, respectively; p = 0.56), and permanent pacemaker insertion rate (28% vs. 18%, respectively; p = 0.23) were not different at 30 days in the Lotus and CoreValve cohorts. CONCLUSIONS: In this matched comparison of high surgical risk patients undergoing transcatheter aortic valve replacement, the use of the Lotus device was associated with higher rates of Valve Academic Research Consortium 2-defined device success compared with the CoreValve. This was driven by higher rates of correct anatomic positioning and lower incidences of moderate paraprosthetic regurgitation. The clinical significance of these differences needs to be tested in a large randomized, controlled trial.

Relationship of aortic annular eccentricity and paravalvular regurgitation post transcatheter aortic valve implantation with CoreValve.

BACKGROUND: Significant paravalvular aortic regurgitation (PAR) after transcatheter aortic valve implantation (TAVI) is associated with negative clinical consequences. We hypothesize that increased eccentricity of the aortic annulus is associated with greater PAR. METHODS: Patients with severe aortic stenosis underwent multidetector computed tomography (MDCT) before successful TAVI with the Medtronic CoreValve bioprosthesis. The smallest (D(min)) and largest (D(max)) orthogonal diameters in the basal ring of the aortic annulus were determined. We defined circularity of aortic annulus using the eccentricity index (1 - D(min)/D(max)). The primary endpoint was early occurrence of significant PAR, defined as > grade II PAR by postprocedural aortography. RESULTS: Eighty-four patients, mean age 83 ± 4 years with a mean aortic valve area of 0.7 ± 0.2 cm² were included. Twenty patients had postprocedural PAR > grade II. Using a receiver operating characteristic (ROC) analysis, eccentricity index correlated with significant PAR (AUC = 0.834; P=.034). A retrospectively determined eccentricity index cut-off of >0.25 was related to significant PAR with a sensitivity of 80%, specificity of 86%, and negative predictive value of 95% (P<.001). On univariate logistic regression, eccentricity index of >0.25 (P<.001) and device implantation depth (P=.015) correlated with significant PAR, while other parameters such as annular calcification and cover index did not. On multivariate analysis including only parameters with P<.1 on univariate analysis, eccentricity index >0.25 was the sole independent predictor of significant PAR. CONCLUSION: Eccentricity index is related to significant PAR after TAVI with Medtronic CoreValve. Further larger studies are required to determine the utility of this novel index in screening suitable patients for this procedure.