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Background/Objective: To investigate the effect of mycophenolate mofetil (MMF) and rituximab (RTX) on pulmonary function test (PFT) results in a mixed cohort of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), longitudinally followed up for 1 year in a single academic center. Methods: Patients with CTD-ILD were identified in electronic medical records from 1 January 2009 to 30 April 2019. Prescribed MMF and RTX doses, dosage changes, and therapy plans were analyzed individually with improvement in PFT outcomes determined using multivariable linear regression models during 12-month follow-up. Results: Forty-seven patients with CTD-ILD, treated with MMF, RTX, or both, were included. Patients on combined MMF and RTX had worse PFT outcomes at baseline compared with patients on monotherapy. Substantial improvement was observed among all PFT outcomes from baseline to 12 months, regardless of medication dosage or therapy plans. The diffusing capacity of the lungs for carbon monoxide (DLCO) worsened by an average of 7.21 mL/(min*mmHg) (95% CI, 4.08–10.33; p < 0.001) among patients on RTX compared to combined therapy. Patients on higher doses of MMF at baseline experienced an average increase of 0.93 (95% CI, 0.04–1.82) units in DLCO from baseline to 6 months (p = 0.04) and a 2.79% (95% CI, 0.61–4.97%) increase in DLCO from 6 to 12 months (p = 0.02) within patients on concurrent RTX at 6-month follow-up. Conclusions: The treatment of CTD-ILD with MMF and/or RTX was associated with overall improvement in PFT outcomes. Combined therapy resulted in significant improvements in DLCO compared with monotherapy. Higher doses of MMF also provided greater improvements in DLCO.

Background Lipoprotein(a) [Lp(a)] is an independent, causal risk factor for cardiovascular disease. However, it is still unclear whether controlling low-density lipoprotein cholesterol (LDL-C) to optimal levels can attenuate cardiovascular risk mediated by elevated Lp(a), especially in the setting of secondary prevention. Methods Adult patients with a baseline Lp(a) measurement who underwent percutaneous coronary intervention (PCI) and reached their LDL-C target levels (<70 mg/dl) at Mayo Clinic sites between 2006 and 2017 were included. Primary outcomes included major adverse cardiovascular events (MACE) and all-cause mortality. Kaplan–Meier curves were created to compare the survival probabilities among patients with Lp(a) ≥ 50 mg/dl compared with Lp(a) < 50 mg/dl. Multivariable Cox regression analyses were performed to quantify the association of elevated Lp(a) with our relevant outcomes and to control for possible confounders. Results In total, 878 patients (median age: 68 years, and 74% males) who underwent PCI were included for analysis. Of them, 29.7% had elevated Lp(a) ≥ 50 mg/dl. Kaplan–Meier curves did not reveal any significant difference in survival probabilities for elevated Lp(a) for any outcome including MACE (P = 0.91), all-cause mortality (P = 0.26), or the separate MACE components. Similarly, the multivariable analysis showed no significant association for MACE (hazard ratio: 1.07, 95% confidence interval: 0.84–1.37) or all-cause mortality (hazard ratio: 0.98, 95% confidence interval: 0.74–1.30). Conclusion In patients who underwent PCI and have their LDL-C controlled below 70 mg/dl, no significant association was found between elevated Lp(a) ≥ 50 mg/dl and risk for MACE or all-cause mortality.

Introduction: Pulmonary hypertension (PHTN) is common in patients with chronic kidney disease (CKD), however categorization as precapillary or postcapillary is challenging due to the need for invasive right heart catheterization (RHC). Studies have validated transthoracic echocardiography (TTE) to characterize PHTN and ECG-artificial intelligence (AI) to predict diastolic dysfunction risk. The utility of these noninvasive tools in patients with CKD is unknown. Methods: Retrospective analysis of patients with end stage CKD who underwent RHC between 2011 and 2021. Patients with PHTN (pulmonary artery pressure >20mmHg on RHC) were categorized as having precapillary (pulmonary capillary wedge pressure, PCWP, ≤15mmHg and pulmonary vascular resistance, PVR, >2WU) or postcapillary PHTN (PCWP >15mmHg and PVR ≤2WU for isolated postcapillary or PVR >2WU for combined). TTE and ECG within 3 months of RHC were obtained. TTE measurements were used to calculate ePLAR (echocardiographic pulmonary to left atrial ratio); tricuspid regurgitant peak velocity (TRV max ) divided by mitral E/e’. ECGs were analyzed with an AI risk tool for diastolic dysfunction (score 0-3, increasing with increasing risk). Receiver operating curves (ROC) evaluated the performance of these tests. Results: 60 patients were included; 16 (27%) with precapillary and 44 (73%) with postcapillary PHTN. ROC analysis found good accuracy for both ECG-AI diastolic dysfunction risk score to predict precapillary PHTN with AUC 0.724 (sensitivity=60% and specificity=88% for an ECG score value ≤1) and ePLAR with AUC 0.715 (sensitivity=75% and specificity=70% for ePLAR >0.17m/sec). Highest accuracy for detection of precapillary PHTN was reached by combination of ePLAR and ECG-AI tool, with AUC 0.756 (sensitivity=73%, accuracy of 86% for a value ≤1.17). Conclusions: ECG-AI generated diastolic risk score of 0-1 (low risk) and high ePLAR showed good accuracy in characterizing precapillary PHTN in patients with end stage CKD. The combination of these noninvasive tools further increased the diagnostic accuracy, reflecting its potential utility in classification of patients with CKD and PHTN, a crucial determinant of the ideal therapeutic plan in kidney transplant candidates.

Background: ICI-related myocarditis is challenging to diagnose and associated with adverse cardiovascular events and mortality. ICI therapy has also been associated with acute coronary events. There is limited data regarding cardiac troponin T (cTnT) and its association with these cardiovascular outcomes. Methods: All patients treated with ICI at a tertiary institution from 2011 to 2022 were identified, and the charts of those with cTnT measurements were reviewed. In patients with cTnT elevation (cutoff of >14 ng/L), if the Bonaca criteria for myocarditis were met, these patients were labeled as cTnT+/myocarditis+, otherwise as cTnT+/myocarditis-. Patients with non-elevated cTnT values were labeled cTnT-. Medical records were reviewed for baseline characteristics and long-term outcomes, including cardiac death, new heart failure (HF) diagnosis, and MACE (myocardial infarction, TIA/stroke, new HF diagnosis). Kaplan-Meier curves were created to plot the comparison between the three groups. Results: A total of 1669 cancer patients who received ICI therapy had post-ICI cTnT measurements. Mean age was 68.7±11.3, 58.3% were male, with follow-up at 1 year post ICI administration. Of these, 59 patients were cTnT+/myocarditis+, 1077 patients were cTnT+/myocarditis-, and 533 were cTnT-. Survival free of cardiac death, MACE and new HF diagnosis showed a graded response from worst in cTnT+/myocarditis+ patients and best in cTnT- patients; cTnT+/myocarditis- patients had a more favorable but still worse prognosis than cTnT- patients (Figure 1). A cTnT value of 95 ng/L was identified as the best cutoff for the diagnosis of ICI-related myocarditis (AUC 0.82, sensitivity 81.36%, specificity 81.62%). The optimal cTnT cutoff for cardiac death was 576 ng/L (0.70, sensitivity 72%, specificity of 61%) and for MACE 319 ng/L (AUC 0.61, sensitivity 70%, specificity of 52%). Conclusion: In cancer patients receiving ICI therapy cTnT elevations indicate a higher risk of MACE, HF, and cardiac mortality even in patients without myocarditis. Although worst outcomes are seen in those meeting diagnostic criteria for myocarditis.

Background: Atrial fibrillation (AF), the most common clinically managed cardiac arrhythmia, is known to increase the risk of heart failure, stroke, and mortality. Lipoprotein(a) [Lp(a)], a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD), also plays a role in cardiovascular health. However, the influence of Lp(a) on the development of AF, independent of its association with ASCVD, remains unclear. Hypothesis: Elevated Lp(a) may be associated with increased risk of new-onset AF. Methods: A retrospective study was conducted on patients from the three Mayo Clinic sites who had their Lp(a) levels measured and had no prior history of AF. Patients were categorized into two groups based on their serum Lp(a) concentrations: high Lp(a) (≥50 mg/dL) and low Lp(a) (<50 mg/dL). New AF diagnoses were identified during the follow-up period. Survival probabilities between the two Lp(a) groups were compared using the Kaplan–Meier curve and the Log-Rank test. Cox regression analyses, both univariable and multivariable, were performed to evaluate established risk factors and compare the risk of new-onset AF between the high and low Lp(a) groups. Results: A total of 108,930 patients were included (median age: 55 years, 58% males), with a follow-up duration for up to 10 years. Incident AF was detected in 8432 (7.7%) patients. Median serum levels of Lp(a) were significantly higher in patients with AF versus non-AF patients: 15 (IQR 43) vs. 12 (IQR 34) mg/dL, p<0.001. The percentage of patients having elevated Lp(a) was significantly higher in the AF group versus non-AF group: 2119 (25%) vs 21151 (21%), p<0.001. Survival probability for new-onset AF was significantly lower in patients with elevated Lp(a) compared with those with low Lp(a) (log rank p<0.001, Figure 1). In the univariate analysis, high Lp(a) levels were associated with a 17% increase in the risk of AF (HR = 1.17, 95% CIs: 1.12 to 1.23). The multivariate analysis adjusted for well-established risk factors for AF showed a less strong but still significant association, with a 10% increase in AF risk (HR = 1.10, 95% CI: 1.05 to 1.15). Conclusion: Our study suggests that elevated Lp(a) (≥50 mg/dL) seems to be an independent risk factor for new-onset AF. Future prospective studies are still warranted to validate our results.

Background: Secondary prevention after percutaneous coronary interventions (PCIs) is still challenging and lipoprotein(a) [Lp(a)] is believed to be a residual risk factor in this setting. However, the effect of Lp(a) in case of well-controlled low-density lipoprotein cholesterol (LDL-C) is still unclear. The interaction between Lp(a) and LDL-C has been studied in primary prevention but still needs to be investigated in secondary prevention. Hypothesis: Achieving adequate LDL-C control after PCI may reduce the cardiovascular (CV) risk associated with Lp(a). Methods: A retrospective study of consecutive patients who underwent PCI and reached their LDL-C target levels (<70mg/dL) at three academic centers sites between 2006 and 2017. All included patients must have an Lp(a) measurement before the PCI intervention. Clinical outcomes on 10-year follow-up were collected by reviewing the electronic patients' records. The primary outcomes included all-cause mortality (ACM) and major adverse CV events (MACE) including non-fatal MI, ischemic stroke, coronary revascularization, and CV death. Kaplan-Meier curves were created to compare the survival probabilities among patients with high Lp(a) (≥50mg/dL) versus those with low Lp(a) (<50mg/dL). Univariate and multivariate Cox regression analyses were performed to quantify the association of elevated Lp(a) with outcomes and control for potential confounders. Results: In total, 878 patients (median age = 68 years, 74% males) were included in the analysis. Of them, 242 (27.6%) had high Lp(a) ≥50mg/dL. Kaplan Meier analyses did not reveal any significant difference in survival probabilities across the Lp(a) groups for any of the outcomes (Figure 1). The results were consistent in univariate (MACE, HR: 1.08 [95%CIs 0.85-1.35]; ACM, HR: 0.97 [95% CI 0.76-1.23]) and multivariate analyses (MACE, HR: 1.14, [95% CIs 0.90-1.45]; ACM, HR: 1.08 [95% CI 0.84-1.39]). Conclusion: These findings suggest that, in patients who underwent PCI and achieved an LDL-C target of <70 mg/dL, elevated Lp(a) levels were not associated with and increased risk of MACE or mortality. Controlling the LDL-C should still be the cornerstone in secondary prevention after PCI, however, larger prospective studies are still warranted to validate our results.

Background: Myocarditis is a dreaded complication of immune-checkpoint inhibitor (ICI) therapy but challenging to diagnose. There are no published data comparing the two leading diagnostic criteria for ICI myocarditis and their association with cardiovascular events. Methods: Patients treated with ICI and cardiac Troponin (cTnT) measurements thereafter at a tertiary institution from 2011 to 2022 were identified. Charts were reviewed for ICI-related myocarditis according to the Bonaca et. al criteria and the ESC-ICOS guideline criteria. A propensity matched control group was identified of patients treated with ICI but without developing myocarditis. Medical records were reviewed for baseline characteristics and long-term outcomes, including cardiac death, MACE (myocardial infarction, TIA/stroke, new heart failure diagnosis), and arrhythmias (V-tach, A-fib, complete heart block). Results: A total of 59 patients were identified as having a diagnosis of ICI-related myocarditis per Bonaca criteria (16 having definite, 13 probable and 30 possible myocarditis), and 47 met the ESC-ICOS guideline criteria. Mean age was 73.1±10.2 years, 60.1% were male, median follow-up was 2.5 years. ICI-related myocarditis as diagnosed by both diagnostic criteria had prognostic value for cardiac death (HR 13.94, 95%CI 1.84-105.64, p=0.011 per Bonaca, HR 6.22, 95%CI 1.77-21.88, p=0.004 per ESC-ICOS), MACE, (HR 3.17, 95%CI 1.34-7.47, p=0.008 per Bonaca, HR 2.97, 95%CI 1.37-6.45, p=0.006 per ESC-ICOS), and arrhythmias (HR 1.93, 95%CI 1.10-3.38, p=0.022 per Bonaca, HR 2.09, 95%CI 1.21-3.60, p<0.001 per ESC-ICOS), (Figures 1 and 2). There was no significant difference for cardiac death (AUC 0.75 for Bonaca, AUC 0.74 for ESC, p=0.765) or MACE (AUC 0.66 for Bonaca, AUC 0.66 for ESC, p=0.916) when both criteria were compared with each other. Conclusion: The ESC-ICOS criteria were more restrictive than the Bonaca criteria for the diagnosis of ICI-related myocarditis but similar in terms of prognostic value.

Background: New-onset atrial fibrillation (AF) is common among kidney transplant (KTx) recipients and is associated with reduced patient survival. Predictors of AF after KTx are not well understood, although AF can be associated with traditional and non-traditional risk factors. While artificial intelligence-enabled electrocardiography (AI-ECG) has shown promise in predicting incident AF, its predictive and prognostic implications in the KTx population have not yet been evaluated. Hypothesis: AI-ECG can predict new-onset AF and carries prognostic implications in patients undergoing KTx. Aims: To evaluate the clinical implications of applying AI-ECG to the preoperative ECGs of recipients of a KTx. Methods: Patients without a history of AF who underwent KTx at three referral centers between 2011 and 2021, with at least one preoperative ECG, were included in this retrospective study. Preoperative ECGs were analyzed using a previously developed AI-ECG algorithm to estimate the probabilities of new-onset AF. Based on these probabilities, patients were categorized into two groups: high and low probability of incident AF. The optimal cut-off value for the AI-ECG tool was determined using ROC analysis. The incidence of new-onset AF and mortality at 5 years post KTx were compared between these two groups using univariate and multivariate Cox regression analyses. Results: In total, 6246 patients were included (mean age 52.9 ±14.3 years, 58.7% males). A pre-transplant AI-ECG probability of AF >10% was identified as the most accurate cutoff point to distinguish between patients at low risk and high risk of incident AF (ROC = 0.72). The study found that a preoperative AI-ECG high risk of AF demonstrated not only a strong association with new-onset AF (HR 2.54, 95%CI 2.02-3.19, p<0.001 on multivariable analysis, Figure 1A ) but was also associated with an increased risk of mortality both on univariate (HR 2.73, 95%CI 2.34-3.18, p<0.001) and multivariate (HR 1.57, 95%CI 1.29-1.91, p<0.001 ) analysis at 5-year follow-up ( Figure 1B ). Conclusion: The application of AI-ECG to a single widely available test may help assess the risk of new-onset AF and mortality in patients undergoing KTx. Accurate risk stratification may identify a high-risk subgroup of transplant recipients who can benefit from closer AF monitoring, risk factor modification, and early management.

The assessment of left atrial strain (LAS) has emerged as an essential component in the evaluation of cardiac function, especially in pathologies such as heart failure and atrial fibrillation. This narrative review aims to outline the available methods for assessing LAS with a major emphasis on speckle-tracking echocardiography techniques. Other imaging modalities, including cardiac magnetic resonance and cardiac computed tomography, also provide important information on LA dynamics but have disadvantages with respect to cost and availability. The current narrative review underlines basic concepts such as the accurate assessment of LAS and discusses the clinical relevance of LAS by pointing out its significant diagnostic and prognostic role in several cardiovascular conditions. The aim of this article is to discuss the current integration of LAS into clinical practice with a view to further improving patient management and treatment strategies.