Phenotype clustering of hospitalized high-risk patients with COVID-19 - a machine learning approach within the multicentre, multinational PCHF-COVICAV registry.

IMTRODUCTION: The high-risk population of patients with cardiovascular (CV) disease or risk factors (RF) suffering from COVID-19 is heterogeneous. Several predictors for impaired prognosis have been identified. However, with machine learning (ML) approaches, certain phenotypes may be confined to classify the affected population and to predict outcome. This study aimed to phenotype patients using unsupervised ML technique within the International Postgraduate Course Heart Failure Registry for patients hospitalized with COVID-19 and Cardiovascular disease and/or RF (PCHF-COVICAV). MATERIAL AND METHODS: Patients from the eight centres with follow-up data available from the PCHF-COVICAV registry were included in this ML analysis (K-medoids algorithm). RESULTS: Out of 617 patients included into the prospective part of the registry, 458 [median age: 76 (IQR:65-84) years, 55% male] were analyzed and 46 baseline variables, including demographics, clinical status, comorbidities and biochemical characteristics were incorporated into the ML. Three clusters were extracted by this ML method. Cluster 1 (n = 181) represents mainly women with the least number of overall comorbidities and cardiovascular RF. Cluster 2 (n = 227) is characterized mainly by men with non-CV conditions and less severe symptoms of infection. Cluster 3 (n=50) mainly represents men with the highest prevalence of cardiac comorbidities and RF, more extensive inflammation and organ dysfunction with the highest 6-month all-cause mortality risk. CONCLUSIONS: The ML process has identified three important clinical clusters from hospitalized COVID-19 CV and/or RF patients. The cluster of males with severe CV disease, particularly HF, and multiple RF presenting with increased inflammation had a particularly poor outcome.

Myocardial work in chronic kidney disease: insights from the CPH-CKD ECHO Study.

BACKGROUND: Myocardial work is a novel echocardiographic measure that offers detailed insights into cardiac mechanics. We sought to characterize cardiac function by myocardial work in patients with chronic kidney disease (CKD). METHODS: We prospectively enrolled 757 patients with non-dialysis-dependent CKD and 174 age- and sex-matched controls. Echocardiographic pressure-strain loop analysis was performed to acquire the global work index (GWI). Linear regressions were performed to investigate the association between estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) to GWI. RESULTS: Patients with CKD had a mean age of 57 years, 61% were men, and median eGFR was 42 mL/min/1.73 m2. Overall, no difference in GWI was observed between patients and controls (1879 vs. 1943 mmHg%, p = 0.06). However, a stepwise decline in GWI was observed for controls vs. patients with CKD without left ventricular hypertrophy vs. patients with CKD and left ventricular hypertrophy (GWI, 1943 vs. 1887 vs. 1789 mmHg%; p for trend = 0.030). In patients with CKD, eGFR was not associated with GWI by linear regression. However, diabetes modified this association (p for interaction = 0.007), such that per 10 mL/min/1.73 m2 decrease in eGFR, GWI decreased by 22 (9-35) mmHg% (p = 0.001) after multivariable adjustments in patients without diabetes, but with no association between eGFR and GWI in patients with diabetes. No association was observed between UACR and GWI. CONCLUSION: Patients with CKD and left ventricular hypertrophy exhibited lower myocardial work compared to matched controls. Furthermore, decreasing eGFR was associated with decreasing myocardial work only in patients without diabetes. No association to UACR was observed.

The relative vaccine effectiveness of high-dose vs standard-dose influenza vaccines in preventing hospitalization and mortality: A meta-analysis of evidence from randomized trials.

OBJECTIVES: To summarize current evidence of high-dose influenza vaccine (HD-IV) vs standard-dose (SD-IV) regarding severe clinical outcomes. METHODS: A prespecified meta-analysis was conducted to assess relative vaccine effectiveness (rVE) of HD-IV vs SD-IV in reducing the rates of (1) pneumonia and influenza (P&I) hospitalization, (2) all hospitalizations, and (3) all-cause death in adults ≥ 65 years in randomized controlled trials. Pooled effect sizes were estimated using fixed-effects models with the inverse variance method. RESULTS: Five randomized trials were included encompassing 105,685 individuals. HD-IV vs SD-IV reduced P&I hospitalizations (rVE: 23.5 %, [95 %CI: 12.3 to 33.2]). HD-IV vs SD-IV also reduced rate of all-cause hospitalizations (rVE: 7.3 %, [95 %CI: 4.5 to 10.0]). No significant differences were observed in death rates (rVE = 1.6 % ([95 %CI: -2.0 to 5.0]) in HD-IV vs SD-IV. Sensitivity analyses omitting trials with participants sharing the same comorbidity, trials with ≥ 100 events, and random-effects models provided comparable estimates for all outcomes. CONCLUSIONS: HD-IV reduced the incidence of P&I and all-cause hospitalization vs SD-IV in adults ≥ 65 years in randomized trials, through no significant difference was observed in all-cause death rates. These findings, supported by evidence from several randomized studies, can benefit from replication in a fully powered, individually randomized trial.

Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin, and Amoxicillin.

Background: Prior research has raised concerns regarding the use of macrolides and their association with an increased risk of cardiovascular events. Methods: We conducted a cohort study, where we explored the cardiovascular risks associated with the treatment of COPD patients using macrolide antibiotics-namely azithromycin, clarithromycin, and roxithromycin-with amoxicillin serving as a reference. The study focused on COPD patients in an outpatient setting and included a thorough 3-year follow-up. Patients were categorized into four groups based on their treatment. The primary analysis utilized an adjusted Cox model, supplemented by sensitivity analysis through inverse probability of treatment weighting. Results: No significant differences were found in major adverse cardiovascular events (MACE-stroke, acute myocardial infarction, cardiovascular death) between the macrolide groups, and the amoxicillin/hazard ratios (HR) were azithromycin HR = 1.01, clarithromycin HR = 0.99, and roxithromycin HR = 1.02. Similarly, sensitivity analysis showed no disparities in all-cause mortality and cardiovascular death among the groups. Conclusions: Overall, the study revealed no evidence of increased risk of MACE, all-cause mortality, or cardiovascular death in COPD patients treated with these macrolides compared to amoxicillin over a 3-year period.

European Association of Cardiovascular Imaging (EACVI) survey on Cardiovascular Multimodality Imaging in Acute Myocarditis.

AIMS: To assess the current role of cardiac imaging in the diagnosis, management, and follow-up of patients with acute myocarditis (AM) through an European Association of Cardiovascular Imaging survey. METHODS AND RESULTS: A total of 412 volunteers from 74 countries responded to the survey. Most participants worked in tertiary centres(56%). All participants had access to echocardiography, while 79% and 75% had access to cardiac computed tomography (CCTA) and cardiac magnetic resonance (CMR), respectively. Less than half(47%) had access to myocardial biopsy and only 5% used this test routinely. CMR was performed within 7 days of presentation in 73% of cases. Non-ischemic late gadolinium enhancement (LGE,88%) and high-signal intensity in T2-weighted images(74%) were the most used diagnostic criteria for AM. CCTA was preferred to coronary angiography by 47% of participants to exclude coronary artery disease. Systematic prescription of beta-blockers and ACEi was reported by 38% and 32% of participants. Around a quarter of participants declared considering LGE burden as a reason to treat. Most participants (90%) reported performing a follow-up echocardiogram, while 63% scheduled a follow-up CMR. The main reason for treatment discontinuation was improvement of left ventricular ejection fraction(89%), followed by LGE regression(60%). In two-thirds of participants the decision to resume high-intensity sport was influenced by residual LGE. CONCLUSION: This survey confirms the high utilization of cardiac imaging in AM, but reveals major differences in how cardiac imaging is used and how the condition is managed between centres, underlining the need for recommendation statements in this topic.

The role of aetiology in cardiac manifestations of chronic kidney disease: the CPH-CKD ECHO study.

PURPOSE: We investigated the associations between cardiac parameters and aetiologies of CKD in an exploratory study. METHODS: The study population consisted of 883 participants, 174 controls and 709 patients with aetiologies of CKD including diabetic nephropathy/renovascular KD in diabetes mellitus, hypertensive/renovascular nephropathy, tubulointerstitial nephritis, glomerulonephritis/vasculitis, polycystic KD (PKD), and CKD of unknown origin. Echocardiographic measures included left ventricular (LV) ejection fraction, global longitudinal, area, and radial strain, E/e' ratio, and LV mass index. These were compared between each aetiological group and controls in unadjusted and adjusted analysis. RESULTS: In unadjusted analysis, patients with diabetic nephropathy/renovascular KD in diabetes mellitus, had impaired LV ejection fraction (Median [IQR]: 56% [49.9,60.69] vs. 60.8% [57.7,64.1]), global longitudinal (mean ± SD: 13.1 ± 3.5% vs. 15.5 ± 2.6%), area (24.1 ± 5.8% vs. 28.5 ± 4.2%), and radial strain (36.2 ± 11.2% vs. 44.1 ± 9.7%), and increased LV mass index (89.1 g/m2 [71.8,104.9] vs. 69,0 g/m2 [57.9,80.8]) and E/e' ratio (10.6 [8.5,12.6] vs. 7 [5.8,8.3], p < 0.001 for all) compared with controls. Associations were similar for CKD of unknown origin. Patients with hypertensive/renovascular nephropathy had impaired global longitudinal and area strain, and higher E/e' ratio. Patients with glomerulonephritis/vasculitis had higher LV mass index, while patients with PKD had better global longitudinal strain than controls. All findings remained significant in adjusted analysis, except for the impaired global longitudinal strain in hypertensive/renovascular nephropathy. CONCLUSION: Glomerulonephritis/vasculitis, hypertensive/renovascular nephropathy, CKD of unknown origin, and diabetic nephropathy/renovascular KD in diabetes mellitus were increasingly associated with adverse cardiac findings, while PKD and tubulointerstitial nephritis were not. Aetiology might play a role regarding the cardiac manifestations of CKD.

Predictors of heart failure readmission and all-cause mortality in patients with acute heart failure.

BACKGROUND: Predischarge risk stratification of patients with acute heart failure (AHF) could facilitate tailored treatment and follow-up, however, simple scores to predict short-term risk for HF readmission or death are lacking. METHODS: We sought to develop a congestion-focused risk score using data from a prospective, two-center observational study in adults hospitalized for AHF. Laboratory data were collected on admission. Patients underwent physical examination, 4-zone, and in a subset 8-zone, lung ultrasound (LUS), and echocardiography at baseline. A second LUS was performed before discharge in a subset of patients. The primary endpoint was the composite of HF hospitalization or all-cause death. RESULTS: Among 350 patients (median age 75 years, 43% women), 88 participants (25%) were hospitalized or died within 90 days after discharge. A stepwise Cox regression model selected four significant independent predictors of the composite outcome, and each was assigned points proportional to its regression coefficient: NT-proBNP ≥2000 pg/mL (admission) (3 points), systolic blood pressure < 120 mmHg (baseline) (2 points), left atrial volume index ≥60 mL/m2 (baseline) (1 point) and ≥ 9 B-lines on predischarge 4-zone LUS (3 points). This risk score provided adequate risk discrimination for the composite outcome (HR 1.48 per 1 point increase, 95% confidence interval: 1.32-1.67, p < 0.001, C-statistic: 0.70). In a subset of patients with 8-zone LUS data (n = 176), results were similar (C-statistic: 0.72). CONCLUSIONS: A four-variable risk score integrating clinical, laboratory and ultrasound data may provide a simple approach for risk discrimination for 90-day adverse outcomes in patients with AHF if validated in future investigations.

Effects of high-dose versus standard-dose quadrivalent influenza vaccine among patients with diabetes: A post-hoc analysis of the DANFLU-1 trial.

AIM: High-dose quadrivalent influenza vaccine (QIV-HD) has been shown to be more effective than standard-dose (QIV-SD) in reducing influenza infection, but whether diabetes status affects relative vaccine effectiveness (rVE) is unknown. We aimed to assess rVE on change in glycated haemoglobin [HbA1c (∆HbA1c)], incident diabetes, total all-cause hospitalizations (first + recurrent), and a composite of all-cause mortality and hospitalization for pneumonia or influenza. METHODS: DANFLU-1 was a pragmatic, open-label trial randomizing adults (65-79 years) 1:1 to QIV-HD or QIV-SD during the 2021/22 influenza season. Cox proportional hazards regression was used to estimate rVE against incident diabetes and the composite endpoint, negative binomial regression to estimate rVE against all-cause hospitalizations, and ANCOVA when assessing rVE against ∆HbA1c. RESULTS: Of the 12 477 participants, 1162 (9.3%) had diabetes at baseline. QIV-HD, compared with QIV-SD, was associated with a reduction in the rate of all-cause hospitalizations irrespective of diabetes [overall: 647 vs. 742 events, incidence rate ratio (IRR): 0.87, 95% CI (0.76-0.99); diabetes: 93 vs. 118 events, IRR: 0.80, 95% CI (0.55-1.15); without diabetes: 554 vs. 624 events, IRR: 0.88, 95% CI (0.76-1.01), pinteraction = 0.62]. Among those with diabetes, QIV-HD was associated with a lower risk of the composite outcome [2 vs. 11 events, HR: 0.18, 95% CI (0.04-0.83)] but had no effect on ∆HbA1c; QIV-HD adjusted mean difference: ∆ + 0.2 mmol/mol, 95% CI (-0.9 to 1.2). QIV-HD did not affect the risk of incident diabetes [HR 1.18, 95% CI (0.94-1.47)]. CONCLUSIONS: In this post-hoc analysis, QIV-HD versus QIV-SD was associated with an increased rVE against the composite of all-cause death and hospitalization for pneumonia/influenza, and the all-cause hospitalization rate irrespective of diabetes status.

Left Atrial Strain Predicts Subclinical Atrial Fibrillation Detected by Long-term Continuous Monitoring in Elderly High-Risk Individuals.

BACKGROUND: Left atrial (LA) speckle tracking provides detailed information on atrial function. Its utility for predicting subclinical atrial fibrillation (SCAF) is unclear. Therefore, we sought to investigate whether LA strain measures could predict SCAF detected by long-term continuous rhythm monitoring. METHODS: This was an echocardiographic substudy of the LOOP study, where elderly at risk of stroke were randomized to receive a loop recorder (Reveal LINQ) or control. Participants who received a loop recorder were included in this analysis. Echocardiography included LA reservoir, conduit, and contraction strain. Participants were followed with continuous rhythm monitoring for SCAF (≥6 minutes). Cox proportional hazards regression was applied to adjust for atrial fibrillation risk factors. RESULTS: In total, 956 participants were eligible for analysis. Median continuous rhythm monitoring was 35 months (IQR, 20-40 months), during which 278 (29%) were diagnosed with SCAF. The mean age was 74 years, 56% were male, median CHA2DS2-VASc-score was 4. LA reservoir strain was an independent predictor of SCAF after multivariable adjustments (HR, 1.04 [1.02-1.05], per 1% decrease) and so was contraction strain. The findings were unchanged in competing risk analyses and in participants with normal LA size and diastolic function. Participants with low reservoir strain (<33%) had a significantly higher risk of SCAF compared with those with high reservoir strain (incidence rate, 14.5 [12.4-16.9] versus 9.8 [8.2-11.8] events/100 person-years). The same was noted for low versus high contraction strain. CONCLUSIONS: LA reservoir and contraction strain are independent predictors of SCAF in elderly at risk of stroke. This also applies to individuals with normal LA size and diastolic function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Aortic Root Dimension Using Transthoracic Echocardiography: Results from the Copenhagen City Heart Study.

Findings regarding the relation between aortic size and risk factors are heterogeneous. This study aimed to generate new insights from a population-based adult cohort on aortic root dimensions and their association with age, anthropometric measures, and cardiac risk factors and evaluate the incidence of acute aortic events. Participants from the fifth examination round of the Copenhagen City Heart study (aged 20 to 98 years) with applicable echocardiograms and no history of aortic disease or valve surgery were included. Aorta diameter was assessed at the annulus, sinus of Valsalva, sinotubular junction, and the tubular part of the ascending aorta. The study population comprised 1,796 men and 2,316 women; mean age: 56.4 ± 17.0 and 56.9 ± 18.1 years, respectively. Men had larger aortic root diameters than women regardless of height indexing (p <0.01). Age, height, weight, systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, hypertension, diabetes, ischemic heart disease, and smoking were positively correlated with aortic sinus diameter in the crude and gender-adjusted analyses. However, after full adjustment, only height, weight, and diastolic blood pressure remained significantly positively correlated with aortic sinus diameter (p <0.001). For systolic blood pressure and pulse pressure, the correlation was inverse (p <0.001). During follow-up (median 5.4 [quartile 1 to quartile 3 4.5 to 6.3] years), the incidence rate of first-time acute aortic events was 13.6 (confidence interval 4.4 to 42.2) per 100,000 person-years. In conclusion, beyond anthropometric measures, age, and gender, diastolic blood pressure was the only cardiac risk factor that was independently correlated with aortic root dimensions. The number of aortic events during follow-up was low.

Podcast: Need for Quality Evidence for Decision-Making on Seasonal Influenza Vaccines.

Seasonal influenza is usually considered an acute respiratory infection with a full recovery within a week. In addition to the traditional outcomes, there is now evidence of indirect effects in terms of neurological and functional complications. Major organ systems can be affected, underlining the need for preventative measures against infection. The aim of this podcast, featuring Dr. Ann Falsey, Dr. Stefania Maggi, and Dr. Tor Biering-Sørensen, is to outline influenza complications beyond acute respiratory disease, as well as discussing the need for quality of evidence when evaluating influenza vaccines. Assessing the benefits of vaccination can be challenging. To ensure a high quality of evidence, the innovative randomization of patients within the study design to avoid bias and the assessment of additional outcomes beyond immunogenicity as well as the inclusion of a broad population-including frail or vulnerable individuals-are essential. Studies leveraging nationwide registries such as the DANFLU-2 trial in Denmark highlight the advantages of a digitalized healthcare system for conducting large-scale randomized trials. Furthermore, large-scale trials such as the Gravenstein study have supplied a sizable body of evidence supporting the use of high-dose influenza vaccine in older adults. In conclusion, achieving a high quality of evidence is key for decision-making on seasonal influenza vaccines.

Rationale and design of NUDGE-FLU-CHRONIC and NUDGE-FLU-2: Two nationwide randomized trials of electronic nudges to increase influenza vaccination among patients with chronic diseases and older adults during the 2023/2024 influenza season.

BACKGROUND: Yearly influenza vaccination is strongly recommended for older adults and patients with chronic diseases including cardiovascular disease (CVD); however, vaccination rates remain suboptimal, particularly among younger patients. Electronic letters incorporating behavioral nudges are highly scalable public health interventions which can potentially increase vaccination, but further research is needed to determine the most effective strategies and to assess effectiveness across different populations. The purpose of NUDGE-FLU-CHRONIC and NUDGE-FLU-2 are to evaluate the effectiveness of electronic nudges delivered via the Danish governmental electronic letter system in increasing influenza vaccination among patients with chronic diseases and older adults, respectively. METHODS: Both trials are designed as pragmatic randomized implementation trials enrolling all Danish citizens in their respective target groups and conducted during the 2023/2024 influenza season. NUDGE-FLU-CHRONIC enrolls patients aged 18-64 years with chronic diseases. NUDGE-FLU-2 builds upon the NUDGE-FLU trial conducted in 2022/2023 and aims to expand the evidence by testing both previously successful and new nudges among adults ≥65 years during a subsequent influenza season. Persons with exemptions from the electronic letter system are excluded from both trials. In both trials, participants are randomized in a 2.45:1:1:1:1:1:1 ratio to either receive no electronic letter (usual care) or to receive one of 6 different behaviorally informed electronic letters. NUDGE-FLU-CHRONIC has randomized 299,881 participants with intervention letters delivered on September 24, 2023, while NUDGE-FLU-2 has randomized 881,373 participants and delivered intervention letters on September 13, 2023. Follow-up is currently ongoing. In both trials, the primary endpoint is receipt of influenza vaccination on or before January 1, 2024, and the secondary endpoint is time to vaccination. Clinical outcomes including respiratory and cardiovascular hospitalizations, all-cause hospitalization, and mortality are included as prespecified exploratory endpoints. Prespecified individual-level pooled analyses will be conducted across NUDGE-FLU, NUDGE-FLU-CHRONIC, and NUDGE-FLU-2. DISCUSSION: NUDGE-FLU-CHRONIC is the first nationwide randomized trial of electronic nudges to increase influenza vaccination conducted among 18-64-year-old high-risk patients with chronic diseases. NUDGE-FLU-2 will provide further evidence on the effectiveness of electronic nudges among older adults ≥65 years. Collectively, the NUDGE-FLU trials will provide an extensive evidence base for future public health communications. TRIAL REGISTRATION: NUDGE-FLU-CHRONIC: Clinicaltrials.gov: NCT06030739, registered September 11, 2023, https://clinicaltrials.gov/study/NCT06030739. NUDGE-FLU-2: Clinicaltrials.gov: NCT06030726, registered September 11, 2023, https://clinicaltrials.gov/study/NCT06030726.

Clinical Outcomes With Electronic Nudges to Increase Influenza Vaccination : A Prespecified Analysis of a Nationwide, Pragmatic, Registry-Based, Randomized Implementation Trial.

BACKGROUND: In the NUDGE-FLU (Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake) trial, electronic letters incorporating cardiovascular (CV) gain-framing and repeated messaging increased influenza vaccination by approximately 1 percentage point. OBJECTIVE: To evaluate the effects of the successful nudging interventions on downstream clinical outcomes. DESIGN: Prespecified exploratory analysis of a nationwide randomized implementation trial. (ClinicalTrials.gov: NCT05542004). SETTING: The 2022 to 2023 influenza season. PARTICIPANTS: 964 870 Danish citizens aged 65 years or older. INTERVENTION: Usual care or 9 different electronically delivered behavioral nudging letters. MEASUREMENTS: Cardiovascular, respiratory, and other clinical end points during follow-up from intervention delivery (16 September 2022) through 31 May 2023. RESULTS: The analysis set included 691 820 participants. Hospitalization for pneumonia or influenza occurred in 3354 of 346 327 (1.0%) participants in the usual care group, 396 of 38 586 (1.0%) in the CV gain-framing group (hazard ratio [HR], 1.06 [95% CI, 0.95 to 1.18]; versus usual care), and 403 of 38 231 (1.1%) in the repeated letter group (HR, 1.09 [CI, 0.98 to 1.21]; versus usual care). In the usual care group, 44 682 (12.9%) participants were hospitalized for any cause, compared with 5002 (13.0%) in the CV gain-framing group (HR, 1.00 [CI, 0.97 to 1.03]; versus usual care) and 4965 (13.0%) in the repeated letter group (HR, 1.01 [CI, 0.98 to 1.04]; versus usual care). A total of 6341 (1.8%) participants died in the usual care group, compared with 721 (1.9%) in the CV gain-framing group (HR, 1.02 [CI, 0.94 to 1.10]; versus usual care) and 646 (1.7%) in the repeated letter group (HR, 0.92 [CI, 0.85 to 1.00]; versus usual care). LIMITATION: Prespecified but exploratory analysis, potential misclassification of events in routinely collected registry data, and results may not be generalizable to other health systems or countries with other racial compositions and/or cultural or societal norms. CONCLUSION: In a prespecified exploratory analysis, modest increases in influenza vaccination rates seen with electronic nudges did not translate into observable improvements in clinical outcomes. Seasonal influenza vaccination should remain strongly recommended. PRIMARY FUNDING SOURCE: Sanofi.

Left atrial strain is associated with long-term mortality in acute coronary syndrome patients.

To investigate the long-term prognostic value of the left atrial (LA) strain indices - peak atrial longitudinal strain (PALS), peak conduit strain (PCS), and peak atrial contractile strain (PACS) in acute coronary syndrome (ACS) patients in relation to all-cause mortality. This retrospective study included ACS patients treated with percutaneous coronary intervention (PCI) and examined with echocardiography. Exclusion criteria were non-sinus rhythm during echocardiography, missing images, and inadequate image quality for 2D speckle tracking analysis of the LA. The endpoint was all-cause death. Multivariable Cox regression which included relevant clinical and echocardiographic measures was utilized to assess the relationship between LA strain parameters and all-cause mortality. A total of 371 were included. Mean age was 64 years and 76% were male. Median time to echocardiography was 2 days following PCI. During a median follow-up of 5.7 years, 83 (22.4%) patients died. Following multivariable analysis, PALS (HR 1.04, 1.01-1.06, p = 0.002, per 1% decrease) and PCS (HR 1.05, 1.01-1.09, p = 0.006, per 1% decrease) remained significantly associated with all-cause mortality. PALS and PCS showed a linear relationship with the outcome whereas PACS was associated with the outcome in a non-linear fashion such that the risk of death increased when PACS < 18.22%. All LA strain parameters remained associated with worse survival rate when restricting analysis to patients with left atrial volume index < 34 ml/m2. Reduced LA function as assessed by PALS, PCS, and PACS were associated with an increased risk of long-term mortality in patients with ACS.

Clinical implications of subclinical left ventricular dysfunction in heart failure with preserved ejection fraction: The PARAGON-HF study.

AIMS: Left ventricular (LV) subclinical impairment has been described in heart failure with preserved ejection fraction (HFpEF). We assessed the relationship between LV myocardial deformation by strain imaging and recurrent hospitalization for heart failure (HF) or cardiovascular death in a large international HFpEF population. METHODS AND RESULTS: We assessed two-dimensional speckle-tracking based global longitudinal strain (GLS) in 790 patients (mean age 74 ± 8 years, 54% female) with adequate image quality enrolled in the PARAGON-HF echocardiography study. We examined the relationship of GLS with total HF hospitalizations and cardiovascular death (the primary composite outcome) after accounting for clinical confounders. Approximately 47% of the population had evidence of LV subclinical dysfunction, defined as absolute GLS <16%. Impaired GLS was significantly associated with higher values of circulating baseline N-terminal pro-B-type-natriuretic peptide. After a median follow-up of 3.0 years, there were 407 total HF hospitalizations and cardiovascular deaths. After multivariable adjustment, worse GLS was associated with a greater risk for the primary composite outcome (adjusted hazard ratio per 1% decrease: 1.06; 95% confidence interval 1.02-1.11; p = 0.008). GLS did not modify the treatment effect of sacubitril/valsartan compared with valsartan for the composite outcome (p for interaction >0.1). CONCLUSIONS: In a large HFpEF population, impaired LV function was observed even among patients with preserved ejection fraction, and was associated with an increased risk of total HF hospitalizations or cardiovascular death, accounting for clinical confounders. These findings highlight the key role of subtle LV systolic impairment in the pathophysiology of HFpEF.

Right Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: Potential Value of Strain Echocardiography.

Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy, characterized by abnormal cell adhesions, disrupted intercellular signaling, and fibrofatty replacement of the myocardium. These changes serve as a substrate for ventricular arrhythmias, placing patients at risk of sudden cardiac death, even in the early stages of the disease. Current echocardiographic criteria for diagnosing arrhythmogenic right ventricular cardiomyopathy lack sensitivity, but novel markers of cardiac deformation are not subject to the same technical limitations as current guideline-recommended measures. Measuring cardiac deformation using speckle tracking allows for meticulous quantification of global systolic function, regional function, and dyssynchronous contraction. Consequently, speckle tracking to quantify myocardial strain could potentially be useful in the diagnostic process for the determination of disease progression and to assist risk stratification for ventricular arrhythmias and sudden cardiac death. This narrative review provides an overview of the potential use of different myocardial right ventricular strain measures for characterizing right ventricular dysfunction in arrhythmogenic right ventricular cardiomyopathy and its utility in assessing the risk of ventricular arrhythmias.