We aim to review rapidly evolving data regarding clinical benefits of cardiac myosin inhibition in obstructive and non-obstructive hypertrophic cardiomyopathy (HCM). Both EXPLORER-HCM and VALOR-HCM have demonstrated a long-term clinical benefit from mavacamten in decreasing New York Heart Association (NYHA) class and degree of left ventricular outflow tract (LVOT) obstruction with a good safety profile, and potential for favorable long term myocardial remodeling. Similarly SEQUOIA-HCM and MAPLE-HCM demonstrated aficamten significantly decreased LVOT obstruction and symptoms and was more effective than standard medical therapy in improving exercise capacity and decreasing symptoms. Mavacamten (ODYSSEY‑HCM)) did not lead to significant clinical improvement in nonobstructive HCM. For aficamten, randomized evidence in non-obstructive HCM is still accruing. While there is strong evidence in favor of cardiac myosin inhibition in obstructive HCM, our understanding of the potential impact on long-term remodeling, and in heterogenous non-obstructive HCM is still developing. Better understanding of the impact of long-term remodeling and factors that modulate drug efficacy will further guide our use of these medications.

This large contemporary cohort included 3,035 patients (median age 58 years, 57% men); 56% had LGE, including 242 (8%) with LGE > 10%. Most patients have obstructive HCM (71%), 1498 (69%) of which subsequently underwent septal reduction therapy (SRT) at a median of 43 days (interquartile range [IQR] 5-107) from the CMR date (1,485 myectomies and 13 alcohol septal ablations). Over a median of 8.8 years, 331 (11%) primary endpoints occurred (295 cardiovascular deaths [9.7%] and 36 appropriate ICD discharges [1.3%]). On multivariable Cox proportional hazards analysis (adjusted for standard clinical and CMR variables, higher %LGE (1.05 per 1% increase, 95% CI 1.03-1.06; p < 0.001) was associated with primary events. Compared with no LGE, LGE ≥10% was associated with higher risk of the composite endpoint.

BACKGROUND People with type 2 diabetes mellitus (T2DM) are at higher risk of cerebral small vessel disease and left ventricular hypertrophy (LVH), potentially contributing to cognitive decline and dementia. We aimed to describe brain volume and cognitive trajectories over 2 years in a cohort of people with T2DM and to determine whether LVH causes increased brain atrophy and cognitive decline. METHODS Diabetes and Dementia (D2) study is a multicentre observational cohort study in Melbourne, Australia. Participants aged >50 years were recruited via 2 hospital outpatient clinics, 3 private clinics, and study advertisements. Participants with pre-existing cognitive impairment, life-limiting medical illness, and severe chronic renal impairment were excluded. Participants attended study visits for brain MRI, transthoracic echocardiography (TTE), and cognitive testing at baseline and 2 years. The exposure was LVH determined on baseline TTE. Pre-specified outcomes were total brain volume (TBV) change and cognitive decline (z-score change?-1 in any cognitive domain) over 2 years. Regression analyses examined associations between baseline variables and outcomes. A causal inference approach was utilized using inverse probability of treatment weighting to standardize for confounding covariates, excluding participants for non-positivity on age and baseline TBV. RESULTS Participants were recruited 20May2016 to 20March2020: 2378 screened, 702 eligible, 196 consented, 150 baseline and 123 2-year assessments with complete MRI, TTE, and cognitive data (17.4% attrition). At baseline, LVH was associated with female sex, older age, lower educational attainment, lower mood, hypertension, obesity, beta-blocker use, and smaller TBV. Participants with baseline cognitive impairment exhibited greater brain atrophy. Lower educational attainment, hypertension, and lower baseline cognitive scores were associated with cognitive decline. Causal inference analysis included 62 participants with no LVH (20(32%) women; mean [SD]=66.9[5.9] years), and 31 with LVH (17(55%) women, 67.4[5.4] years). LVH caused lower TBV change: standardized mean difference (95% CI) 6.3 (0.1, 12.5) cm3, P=.048. LVH had no effect on cognitive decline. CONCLUSIONS Brain atrophy and cognitive decline were associated with baseline cognitive impairment. LVH caused less brain atrophy and cognitive decline in people with T2DM. We conclude that guideline-directed LVH therapies such as beta-blockers have both cardioprotective (remodelling) and neuroprotective effects. TRIAL REGISTRATION ACTRN12616000546459 UTN: U1111-1181-6659 ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial Australian and New Zealand Clinical Trials website ACTRN12616000546459 ### Clinical Protocols ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval was received from the Human Research Ethics Committee of Austin Health (24 March 2016, HREC/15/Austin/490). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data collected for the study, including individual participant data and a data dictionary defining each field in the set, will be made available upon reasonable request. Proposals should be sent to the corresponding author for approval from the Steering Committee. Deidentified participant data, data dictionary, and imaging analysis pipelines could be shared from Jan 1, 2027. The study protocols, statistical analysis plan, and informed consent form are available from the Australian and New Zealand Clinical Trials website ACTRN12616000546459.

Background Left ventricular (LV) myocardial extracellular volume (ECV), from cardiac magnetic resonance (CMR) T1 mapping, primarily reflects diffuse fibrosis and is a marker of adverse myocardial remodeling in hypertrophic cardiomyopathy (HCM). Objectives The authors sought to evaluate the prognostic value of ECV beyond established clinical and imaging variables in a large contemporary HCM cohort. Methods We evaluated 1,050 consecutive patients with HCM and preserved LV ejection fraction (≥50%) who underwent CMR, including quantification of ECV (%) and late gadolinium enhancement (LGE) burden (% LV mass, >6 SDs above remote myocardium), between 2012 and 2021. The primary endpoint was a composite of mortality, appropriate implantable cardioverter-defibrillator (ICD) therapy, or heart transplantation. Statistical methods included multivariable Cox proportional hazards regression, restricted cubic spline analysis, assessment of incremental discrimination using changes in the C-statistic, and net reclassification improvement analysis. Results Median age was 60 years (IQR: 49-68 years) with 44% women. Median follow-up was 5.6 years (IQR: 2.5-7.8 years). The primary endpoint occurred in 124 patients (11.8%), including 111 deaths (10.6%), 12 appropriate ICD discharges (1.1%), and 1 heart transplantation (0.1%). In multivariable Cox regression, older age (HR: 1.05, 95% CI: 1.03-1.06; P < 0.001), NYHA functional class ≥II (HR: 1.96, 95% CI: 1.23-3.11; P = 0.004), diabetes mellitus (HR: 1.89, 95% CI: 1.27-2.81; P = 0.002), and higher ECV (HR: 1.05 per 1% increase, 95% CI: 1.02-1.09; P = 0.001) were independently associated with the primary outcome. Patients with ECV ≥32% had lower event-free survival than those with ECV <32% (adjusted HR: 1.81, 95% CI: 1.24-2.64; P < 0.001). Conclusions Myocardial ECV was independently associated with long-term adverse outcomes. Multiparametric CMR assessment may improve risk stratification in HCM.

BACKGROUND:Acute myocardial injury with a nonischemic imaging pattern presents a diagnostic challenge. CASE SUMMARY:A 46-year-old previously healthy man presented with intermittent chest pain and markedly elevated high-sensitivity troponin. Cardiac magnetic resonance imaging showed extensive ring-like subepicardial late gadolinium enhancement involving 10 left ventricular segments but no myocardial edema. Genetic testing subsequently identified a pathogenic variant in the FLNC gene. Follow-up imaging 4 months later showed persistent fibrosis with preserved ventricular function and no arrhythmias. DISCUSSION:Ring-like late gadolinium enhancement is an uncommon but increasingly recognized imaging phenotype associated with genetic cardiomyopathies, particularly involving desmosomal and nondesmosomal genes such as FLNC. Episodes of acute myocardial injury with chest pain and troponin elevation can mimic myocarditis and may represent inflammatory triggers that unmask latent genetic cardiomyopathy. This case highlights the emerging concept of "imagenetics," in which specific imaging phenotypes guide the identification of underlying genetic disease. TAKE-HOME MESSAGES:This case highlights how transient biomarker elevation can unmask an underlying genetic cardiomyopathy. Ring-like late gadolinium enhancement distribution should prompt genetic evaluation, reflecting the emerging concept of "imagenetics."

Clinical presentations of left ventricular noncompaction (LVNC) range from asymptomatic cases to ventricular tachyarrhythmia (VT), heart failure (HF), and cerebrovascular accidents (CVA). In this multicenter study, we explored the associations between clinical and imaging characteristics and outcomes of LVNC patients and validated the predictive value of myocardial thinning identified on cardiac magnetic resonance imaging (CMR) as previously described. About 214 adult patients (54% male, mean age 41 ± 16 years) meeting the imaging criteria for LVNC were identified. Myocardial thinning was defined as a 50% or greater diameter reduction of the compacted myocardium compared to a contiguous segment on CMR. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of all-cause mortality, HF hospitalization, left ventricular assist device (LVAD) or heart transplant, cardiac resynchronization therapy (CRT), CVA/transient ischemic attacks (TIA), VT and appropriate implantable cardioverter defibrillator (ICD) therapy. Focal myocardial thinning was observed in 42 patients (20%). Over a median follow-up time of 7 years (IQR, 4 to 10 years), 54 patients (24%) experienced a primary outcome. Patients with myocardial thinning had more cumulative adverse events than those without myocardial thinning (chi-square = 29.516, log-rank < 0.001), even after matching for medical risk score. In a multivariate Cox regression model, myocardial thinning remained associated with outcomes: HR 3.052 (95% CI: 1.569 to 5.937, p = 0.001). Myocardial thinning is associated with adverse cardiovascular events in LVNC patients. Incorporating myocardial thinning into medical risk assessments can improve the prediction and management of adverse outcomes in these patients.

OBJECTIVE:To investigate whether a multifaceted intervention for building resilience to external provocations to health reduced the number of all-cause hospital re-admissions and deaths of people hospitalised with multimorbid heart disease, compared with standard post-discharge management. STUDY DESIGN:Single centre, prospective, open, randomised trial with blinded endpoint acquisition and adjudication (REsilience to Seasonal ILlness and Increased Emergency admissioNs CarE, RESILIENCE). SETTING, PARTICIPANTS:Adults (aged 18 years or older) admitted as emergency medical patients with multimorbid heart disease to Austin Hospital, a tertiary hospital in Melbourne, 19 November 2020 - 28 July 2022, with planned discharge to home. INTERVENTION:Standard post-discharge management, as well as the 12-month active management program: home visits by a nurse, specialist clinical review, and tailored recommendations for optimising clinical management and promoting resilience to external provocations; the nurse coordinated the additional care, provided individualised support, and arranged RESILIENCE physician reviews as required. The comparator group received standard post-discharge management only. MAJOR OUTCOME MEASURE:Proportion of days alive and out of hospital during follow-up (minimum, twelve months) with respect to the maximum number possible. RESULTS:Of 203 participants (mean age, 75.7 years; standard deviation [SD], 10.2 years; 104 women), 103 were randomly allocated to the intervention group, 100 to the standard management group; median follow-up time was 600 days (interquartile range, 416-681 days). A total of 470 hospital admissions and 3874 days of hospital stay during follow-up were recorded for 138 of the 203 trial participants (68%); 38 people (19%) died during follow-up. The days alive and out of hospital proportion was 86.5% (SD, 25.3 percentage points) for the intervention group and 88.3% (SD, 23.5 percentage points) for the standard management group (adjusted difference, 2.04 percentage points; 95% CI, -4.97 to 8.56 percentage points). CONCLUSION:A multifaceted intervention for reducing bio-behavioural vulnerability to external events was ineffective in increasing the proportion of days alive and out of hospital after hospital discharge for people admitted with multimorbid heart disease. However, the program could be modified to improve health outcomes for such people. TRIAL REGISTRATION:ClinicalTrials.gov, NCT04614428 (prospective).

OBJECTIVES:Coronary artery calcium (CAC) scoring measures calcific plaque burden to assess cardiovascular risk. The relationship between CAC and primary hyperparathyroidism (PHPT), a disease linked to increased cardiovascular risk, is yet to be defined. We thus evaluated the relationship between PHPT and CAC scores. METHODS:Patients who underwent CAC scoring from January 1, 2015, to December 31, 2024, were retrospectively identified via electronic records. Patients with concurrent serum calcium and parathyroid hormone levels within 1 year of CAC testing were included. Cardiovascular risk was stratified by CAC scores (low-intermediate: 0-99, high: ≥100) and compared between PHPT and non-PHPT groups. CAC scores were then sub-analyzed in the PHPT cohort stratified by cardiovascular risk and PHPT subtype. RESULTS:Four hundred fifteen patients (75 PHPT and 340 non-PHPT) were included. The PHPT group was more likely to have greater coronary calcific burden (67 vs 50% with CAC scores ≥100, P = .04). PHPT also independently predicted CAC scores ≥100 [odds ratio 1.5 (95% CI: 1.1-2.7), P = .03]. Subgroup analysis revealed higher CAC scores in male versus female patients with PHPT [495 (IQR: 51-634) vs 6 (IQR: 0-190), P < .01]. Longer periods of untreated PHPT disease were associated with moderate-to-severe coronary calcific burden [odds ratio 1.2 (95% CI: 1.1-1.3), P < .01]. CONCLUSIONS:Patients with PHPT had higher proportions of CAC scores ≥100, suggesting greater cardiovascular event risk. Men with PHPT had significantly higher CAC scores compared to women, and untreated parathyroid disease was associated with moderate-to-severe coronary calcific burden. Therefore, routine screening may be considered in PHPT populations to evaluate for cardiovascular risk.

Clinical Presentation: A 62-year-old male with a complex medical history, including pulmonary sarcoidosis, diabetes, constrictive pericarditis post partial pericardial stripping, cirrhosis, and congestive heart failure, presented with signs and symptoms of volume overload. Despite increasing diuretics and previous paracentesis, his condition continued to deteriorate. There were raising concerns for constrictive pericarditis due to cardiac sarcoidos. Echocardiography (TEE) showed pericardial thickening and calcification adjacent to the left ventricle and dilated IVC 2.4 cm (TTE). Cardiac magnetic resonance imaging (CMR) demonstrated conical deformity of the ventricles, thickened pericardium with signal void suggestive of calcification. Computed Tomography (CT) showed significant near circumferential pericardial calcifications. Subsequent catheterization confirmed constriction and identified a right coronary artery lesion. Following this, the patient underwent a redo pericardiectomy and coronary artery bypass grafting, at the Cleveland Clinic. However, his post-operative course was marked by complex challenges, including multi-organ dysfunction, the need for tracheostomy, feeding tube, renal replacement therapy, and recurrent ascites. Despite intensive care, his condition did not improve, leading to a transition to comfort care and eventually the patient passed away in December 2023. Discussion: This case highlights the intricate management of a patient with a myriad of underlying health issues. While multimodality imaging is pivotal in ensuring accurate preoperative diagnosis and guiding surgical interventions, it is important to acknowledge that challenges may persist in the postoperative phase. This case study underscores the vital role of multimodality imaging, irrespective of post-surgical outcomes, in facilitating precise diagnosis and delivering optimal patient care. The subsequent referral to the Cleveland Clinic for redo surgery, followed by a challenging and ultimately palliative care journey, shows the complexity of her clinical course and the importance of multimodality imaging and comprehensive care strategies.

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.

Background Apical hypertrophic cardiomyopathy (aHCM) is a distinct variant characterized by predominant hypertrophy of the left ventricle apex. Objectives This study sought to describe aHCM patients' characteristics and develop a risk score for aHCM patients. Methods A total of 462 patients (age 58 ± 15 years, 68% male) diagnosed with aHCM were included. The primary end point was death, appropriate defibrillator discharge, or need for cardiac transplantation. Variables showing potential association with the composite end point were considered to develop an aHCM-specific risk score. Results At baseline, 67% patients were asymptomatic and 69% had no risk factors for sudden death. On echocardiography, the mean left ventricle ejection fraction, left atrial volume index, and right ventricular systolic pressure were 64% ± 8%, 36 ± 15 ml/m2, and 32 ± 10 mm Hg, respectively, with 51(11%) demonstrating an apical aneurysm. Baseline cardiac magnetic resonance, performed in 246 (53%) patients, demonstrated delayed gadolinium enhancement in 170 (71%) patients (mean percentage of 4.9% ± 6.6%). At age 6.3 ± 4.8 years, the composite events occurred in 80 (17%, death in 62 [13%]) patients. The aHCM-specific risk score, incorporating age, apical aneurysm, left atrial volume index, serum creatinine, and right ventricular systolic pressure, demonstrated good discrimination (C-statistic = 0.75) with an expected to observed ratio of 1.02 and a calibration slope of 0.91. The risk score ranged between 0 and 8 points, with a higher score associated with higher composite events. Conclusions aHCM constituted 6.8% of our overall HCM cohort with a composite event rate of 2.8%/year. The aHCM risk score provided good discrimination in predicting the composite primary end point, with a higher score associated with a higher rate of events.

AIMS We aimed to recruit a representative cohort of women and men with multimorbid chronic heart disease as part of a trial testing an innovative, nurse-coordinated, multi-faceted intervention to lower rehospitalisation and death by addressing areas of vulnerability to external challenges to their health. METHODS AND RESULTS The prospective, randomised 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 multimorbidity were high (mean Charlson Index of Comorbidity Score 6.3 ± 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 hospitalisation (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% versus 49%), lower education (30% versus 14%) and living alone (48% versus 29%) were more prevalent in women. CONCLUSIONS We successfully recruited women and men with multimorbid 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.

Introduction: As the prominence of online chat-based artificial intelligence (AI) platforms increases, medical students and residents in training may be inclined to utilize these tools as supplementary resources while preparing for their United States Medical Licensing Board (USMLE) examinations. Hypothesis: The aim of this study was to assess the performance of ChatGPT 4.0 in responding to cardiovascular (CV) clinical vignettes from USMLE sample questions provided by the National Board of Medical Examiners (NBME). Methods: We extracted the 31 CV clinical vignettes from the official NBME USMLE Step 2 Clinical Knowledge and Step 3 self-assessments, and submitted them to ChatGPT 4.0. The clinical cases encompassed a range of topics such as preventive medicine, congenital heart disease, valvular heart disease, electrophysiology, heart failure, and pericardial disease. Each of the 31 cases had a MCQ: 29/31 had at least 5 answer choices, while the remaining 2 had 4 answer choices each. The performance of the AI model was assessed using the NBME-provided answers. Subsequently, two experienced cardiologists independently reviewed the explanations provided by the model for each case and classified them as “accurate” - if they aligned with appropriate guidelines, and as “inaccurate” if they conveyed incorrect or inappropriate information. Results: The AI model attained a grade of 90.3% (28/31). The initial agreement between the 2 reviewers was near perfect with a Cohen’s Kappa of 0.85. Any identified discrepancies were subsequently addressed and resolved. Of the correctly answered questions, accurate explanations were provided by the AI model in 89.2% of cases (25/28). Conclusions: The high performance of ChatGPT 4.0, suggests it could be an effective additional CV study resource for residents and medical students preparing for the USMLE Step 2 CK and Step 3 exams.