Using a commercially available assay that measures cytomegalovirus (CMV)-specific T-cell immunity to predict protection against CMV: A prospective, blinded clinical study.

The Viracor CMV-T-cell immunity Panel (TCIP) measures %CMV-specific CD4+ and CD8+ T-cells. In this blinded clinical study, we evaluated the performance of the TCIP in predicting CMV events. Prospectively enrolled donor or recipient CMV-seropositive kidney transplant recipients (KTR) were evaluated with monthly TCIP testing until either discontinuation of valganciclovir prophylaxis or CMV DNAemia prompting treatment initiation. Also, prospectively enrolled KTR with low-level untreated DNAemia or after completion of treatment were evaluated for progression or relapse of CMV infection. Among 46 KTR, those with CMV events had significantly lower %CMV-specific CD8+ T-cells (p = 0.024), and the CMV protection ROC AUC was significant (AUC 0.78, p = 0.026). The positive predictive values of CD4+ and CD8+ T-cell positivity >0.2 % for CMV protection were: 96.3 % for CMV DNAemia prompting treatment initiation, 92.6 % for any DNAemia, 100 % for DNAemia >1000 IU/mL. The TCIP could be a useful adjunct tool in individualized management of CMV infection.

Identifying risk of adverse outcomes in COVID-19 patients via artificial intelligence-powered analysis of 12-lead intake electrocardiogram.

BACKGROUND: Adverse events in COVID-19 are difficult to predict. Risk stratification is encumbered by the need to protect healthcare workers. We hypothesize that artificial intelligence (AI) can help identify subtle signs of myocardial involvement in the 12-lead electrocardiogram (ECG), which could help predict complications. OBJECTIVE: Use intake ECGs from COVID-19 patients to train AI models to predict risk of mortality or major adverse cardiovascular events (MACE). METHODS: We studied intake ECGs from 1448 COVID-19 patients (60.5% male, aged 63.4 ± 16.9 years). Records were labeled by mortality (death vs discharge) or MACE (no events vs arrhythmic, heart failure [HF], or thromboembolic [TE] events), then used to train AI models; these were compared to conventional regression models developed using demographic and comorbidity data. RESULTS: A total of 245 (17.7%) patients died (67.3% male, aged 74.5 ± 14.4 years); 352 (24.4%) experienced at least 1 MACE (119 arrhythmic, 107 HF, 130 TE). AI models predicted mortality and MACE with area under the curve (AUC) values of 0.60 ± 0.05 and 0.55 ± 0.07, respectively; these were comparable to AUC values for conventional models (0.73 ± 0.07 and 0.65 ± 0.10). There were no prominent temporal trends in mortality rate or MACE incidence in our cohort; holdout testing with data from after a cutoff date (June 9, 2020) did not degrade model performance. CONCLUSION: Using intake ECGs alone, our AI models had limited ability to predict hospitalized COVID-19 patients' risk of mortality or MACE. Our models' accuracy was comparable to that of conventional models built using more in-depth information, but translation to clinical use would require higher sensitivity and positive predictive value. In the future, we hope that mixed-input AI models utilizing both ECG and clinical data may be developed to enhance predictive accuracy.

Recent-onset atrial fibrillation: a study exploring the elements of Virchow's triad after cardioversion.

PURPOSE: Atrial fibrillation (AF) imposes an inherent risk for stroke and silent cerebral emboli, partly related to left atrial (LA) remodeling and activation of inflammatory and coagulation systems. The aim was to explore the effects of cardioversion (CV) and short-lasting AF on left atrial hemodynamics, inflammatory, coagulative and cardiac biomarkers, and the association between LA functional recovery and the presence of a prior history of AF. METHODS: Patients referred for CV within 48 h after AF onset were prospectively included. Echocardiography and blood sampling were performed immediately prior, 1-3 h after, and at 7-10 days after CV. The presence of chronic white matter hyperintensities (WMH) on magnetic resonance imaging was related to biomarker levels. RESULTS: Forty-three patients (84% males), aged 55±9.6 years, with median CHA2DS2-VASc score 1 (IQR 0-1) were included. The LA emptying fraction (LAEF), LA peak longitudinal strain during reservoir, conduit, and contractile phases improved significantly after CV. Only LAEF normalized within 10 days. Interleukin-6, high-sensitivity cardiac-troponin-T (hs-cTNT), N-terminal-pro-brain-natriuretic peptide, prothrombin-fragment 1+2 (PTf1+2), and fibrinogen decreased significantly after CV. There was a trend towards higher C-reactive protein, hs-cTNT, and PTf1+2 levels in patients with WMH (n=21) compared to those without (n=22). At 7-10 days, the LAEF was significantly lower in patients with a prior history of AF versus those without. CONCLUSION: Although LA stunning resolved within 10 days, LAEF remained significantly lower in patients with a prior history of AF versus those without. Inflammatory and coagulative biomarkers were higher before CV, but subsided after 7-10 days, which altogether might suggest an enhanced thrombogenicity, even in these low-risk patients.

Serial Magnetic Resonance Imaging after Electrical Cardioversion of Recent Onset Atrial Fibrillation in Anticoagulant-Naïve Patients - A Prospective Study Exploring Clinically Silent Cerebral Lesions.

BACKGROUND: Patients with atrial fibrillation (AF) have a high incidence of cognitive impairment, which may be related to clinically silent microembolism causing cerebral infarctions. OBJECTIVE: To explore the occurrence and timing of silent brain lesions following electrical cardioversion (CV) of recent onset AF in anticoagulant-naïve patients and to study related effects on cognitive function and biomarkers of cerebral damage, S100b. METHODS: Patients with AF duration > 48 hours were prospectively included. Brain magnetic resonance imaging (MRI) and S100b, were obtained prior, after and 7-10 days following CV. Trail making tests (TMT-A and TMT-B) and their difference, ΔΤΜΤ, were assessed prior to CV, 7-10 days and 30 days after CV. RESULTS: Forty-three patients (84% males) with median CHA2DS2-VASc score 1 (interquartile range 0-1) were included. Sequential MRI, including diffusion weighted scans, showed no new brain lesions after CV. Chronic white matter hyperintensities were present at baseline in 21/43 (49%) patients. The S100b (µg/l) levels increased significantly from baseline, (mean ±SD) 0.0472±0.0182 to 0.0551±0.0185 after CV, p=0.001 and then decreased 7-10 days after CV to 0.0450±0.0186, p <.;0.001. Consecutive TMT scores improved successively after CV, being statistically and clinically significant for TMT-B (p<0.01) and ΔΤΜΤ (p=0.005) between 7-10 days and 30 days after CV (Reliable Change Index >1.96). CONCLUSIONS: New brain lesions could not be detected on MRI after CV, but the high incidence of white matter hyperintensities and the transient increase in S100b may indicate transient or minor brain damage undetectable by MRI thus heightening the need to reevaluate thromboembolic risk prior to CV even in low risk patients.

Preferred QT correction formula for the assessment of drug-induced QT interval prolongation.

INTRODUCTION: There is debate on the optimal QT correction method to determine the degree of the drug-induced QT interval prolongation in relation to heart rate (DeltaQTc). METHODS: Forty-one patients (71 +/- 10 years) without significant heart disease who had baseline normal QT interval with narrow QRS complexes and had been implanted with dual-chamber pacemakers were subsequently started on antiarrhythmic drug therapy. The QTc formulas of Bazett, Fridericia, Framingham, Hodges, and Nomogram were applied to assess the effect of heart rate (baseline, atrial pacing at 60 beats/min, 80 beats/min, and 100 beats/min) on the derived DeltaQTc (QTc before and during antiarrhythmic therapy). RESULTS: Drug treatment reduced the heart rate (P < 0.001) and increased the QT interval (P < 0.001). The heart rate increase shortened the QT interval (P < 0.001) and prolonged the QTc interval (P < 0.001) by the use of all correction formulas before and during antiarrhythmic therapy. All formulas gave at 60 beats/min similar DeltaQTc of 43 +/- 28 ms. At heart rates slower than 60 beats/min, the Bazett and Framingham methods provided the most underestimated DeltaQTc values (14 +/- 32 ms and 18 +/- 34 ms, respectively). At heart rates faster than 60 beats/min, the Bazett and Fridericia methods yielded the most overestimated DeltaQTc values, whereas the other 3 formulas gave similar DeltaQTc increases of 32 +/- 28 ms. CONCLUSIONS: Bazett's formula should be avoided to assess DeltaQTc at heart rates distant from 60 beats/min. The Hodges formula followed by the Nomogram method seem most appropriate in assessing DeltaQTc.

Heart rate-dependence of QTc intervals assessed by different correction methods in patients with normal or prolonged repolarization.

BACKGROUND: There is a continuing debate about the optimal method for QT interval adjustment to heart rate changes. We evaluated the heart rate dependence of QTc intervals derived from five different QT correction methods. METHODS: Study patients (n = 123, age 68 +/- 11 years) were dual-chamber device recipients with baseline normal or prolonged QT interval who had preserved intrinsic ventricular activation with narrow QRS complexes. Patients were classified to either Normal-QT (n = 69) or Prolonged-QT (n = 54) groups. Serial QT intervals were recorded at baseline (52 +/- 3 beats per minute) and following atrial pacing stages at 60, 80, and 100 beats per minute. The QTc formulae of Bazett, Fridericia, Sagie-Framingham, Hodges, and Karjalainen-Nomogram were applied to assess the effect of heart rate on the derived QTc values by using linear mixed-effects models. RESULTS: Heart rate had a significant effect on QTc regardless of the formula used (P < 0.05 for all formulae). The Bazett's formula demonstrated the highest QTc variability across heart rate stages (highest F values) in both patient groups (in the total cohort, F = 175.9). In the following rank order, the formulae Hodges, Karjalainen-Nomogram, Sagie-Framingham, and Fridericia showed similar QTc heart rate dependence at both slower and faster heart rates in both patient groups (F = 21.8, 25.6, 28.8, 36.9, in the total cohort, respectively). CONCLUSIONS: Of the studied QTc formulae, the Bazett appeared the most heart rate dependent. Our results suggest the use of Hodges and the Karjalainen-Nomogram secondly to ensure least heart rate dependence of QTc intervals in patients with either normal or prolonged repolarization.

Effect of pregnancy on clinical status and ventricular function in women with heart disease.

BACKGROUND: Pregnant women with heart disease (HD) are at an increased risk for maternal and neonatal adverse events. However, the effect of pregnancy on clinical status and ventricular function in women with HD has not been examined in a controlled study. METHODS AND RESULTS: Ninety-three women with HD were studied longitudinally. Of these, fifty-three underwent clinical and echocardiographic evaluation before and 1.5+/-1.1 years after pregnancy (pregnancy group), whereas forty served as controls matched for age (28.6+/-4.6 versus 28.5+/-6.6, p=0.88), diagnosis, and length of follow-up (2.9+/-1.4 versus 2.6+/-1.1, p=0.23). NYHA functional class remained unchanged in both groups during follow-up. End diastolic and end systolic dimensions and shortening fraction of the morphologic left ventricle also remained unchanged. Furthermore, systemic and subpulmonary ventricular function remained unchanged in the pregnancy and control groups on semiquantitative analysis. Pregnancy, however, was associated with a persisting increase in subpulmonary ventricular size in patients with tetralogy of Fallot (ToF) which was not present in tetralogy controls. Furthermore, diagnosis of ToF was the only predictor of an increase in subpulmonary ventricular size after pregnancy on univariate logistic regression analysis (OR 8.8[95% CI 1.9-41.1], p=0.006). CONCLUSIONS: In this longitudinal controlled study amongst women with HD no deleterious midterm effects of pregnancy on clinical status and right and left ventricular function were found. However, pregnancy was associated with a persisting increase in subpulmonary ventricular size, attributable to patients with repaired ToF. This may have prognostic implications and merits further investigation.

Usefulness of rate regulation through continuous ventricular pacing in patients with drug-controlled slower atrial fibrillation and normal or depressed left ventricular systolic function.

We studied 33 clinically stable patients with permanent atrial fibrillation (AF), implanted with a ventricular demand rate-responsive (VVIR) pacemaker or an automatic defibrillator, in order to evaluate whether continuous right ventricular apex pacing (VP) conferring rate regulation may be advantageous when compared with slower drug-controlled AF. Devices were chronically programmed at ventricular backup pacing. Patients were divided in two groups according to their normal (n = 17) or depressed (n = 16) left ventricular systolic function (LVSF). Ventricular function was studied by using tissue Doppler and color M-mode and echocardiography, as well as B-type natriuretic peptide (BNP) measurements. Baseline data during AF were compared to corresponding measurements following a 1-month pacing period after the devices were programmed at a base rate of 70 beats/min. In both groups, VP worsened some indexes of left and right ventricular function (P < 0.05) without significantly affecting cardiac output, left ventricular filling pressures and BNP (P = not significant). We conclude that VP should not be considered advantageous compared to slower AF.

Adverse effects of continuous ventricular pacing in patients with slower atrial fibrillation and normal left ventricular systolic function.

BACKGROUND: Both heart rate irregularity during chronic atrial fibrillation (AF) and ventricular desynchronization imposed by ventricular pacing may compromise ventricular function. We investigated whether heart rhythm regularization achieved through ventricular overdrive pacing (VP) gives additional benefit over rate control alone in patients with AF. METHODS: We studied 27 patients (mean age 72 +/- 7 years) with AF and normal left ventricular (LV) systolic function who were implanted with a common VVIR pacemaker. Cardiac function was assessed by using serial echocardiographic conventional, tissue Doppler imaging (TDI) and color M-Mode (CMM) examinations, together with B-type natriuretic peptide (BNP) measurements. Baseline data were obtained during AF (mean heart rate 58 +/- 5 beats/minute) with the pacemakers programmed to ventricular mere back-up pacing. These data were compared to the corresponding measurements following a 2-week VP period after the devises had been programmed to a lower rate of 70 beats/min, ensuring most of the time continuing VP. RESULTS: Continuous VP compared to AF, reduced the LV cardiac index (2.28 +/- 0.44 l/min/m(2) vs 2.33 +/- 0.39 l/min/m(2), P < 0.05), increased the LV end-systolic volume (38 +/- 14 mL vs 35 +/- 11 mL, P < 0.05), and decreased the TDI-derived systolic and diastolic mitral velocity (8.1 +/- 1.8 cm/s vs 8.3 +/- 1.6 cm/s, and 8.1 +/- 1.8 cm/s vs 8.3 +/- 1.6 cm/s, respectively, both P < 0.05) and the CMM-derived transmitral early diastolic flow propagation velocity (37.6 +/- 9.2 vs 41.5 +/- 9.7, P < 0.05). Following VP, both ratios E/Ea and E/Vp showed a trend toward increase (P = NS), whereas BNP rose up to 25.5% (median value, from 111 pg/mL to 165 pg/mL, P < 0.01). CONCLUSION: VP may be considered disadvantageous compared to slower AF.

Unfavourable effects of continuous, atrial-synchronised ventricular pacing on ventricular systolic and diastolic function in patients with normal left ventricular ejection fraction: usefulness of tissue and colour Doppler echocardiography.

INTRODUCTION: Conventional, atrial-synchronised, right ventricular apical pacing (VP) may compromise ventricular function by causing ventricular desynchronisation. The aim of this study was to evaluate the long-term effects of VP on left and right ventricular systolic and diastolic function. METHODS: We studied 21 clinically stable dual-chamber pacemaker recipients (mean age 68 +/- 9 years) with normal left ventricular (LV) systolic function. Patients were in long-term sinus rhythm and had intrinsic ventricular activation with narrow QRS complexes. In an intrapatient model, baseline echocardiographic and tissue Doppler imaging (TDI), colour M-Mode (CMM) examinations, as well as plasma B-type natriuretic peptide (BNP) data, were compared to corresponding measurements following a 3-month period of continuous VP. RESULTS: Following VP we noted significant increases in LV end-systolic volume (p < 0.001) and isovolumic relaxation time (p < 0.05), as well as a significant decline in LV systolic function based on ejection fraction (p < 0.001) and TDI-Sa (p < 0.05). VP was associated with worse LV diastolic function, based on CMM-Vp (p < 0.05) and increased E/Vp ratio (p < 0.05), but with similar E/Ea ratio and BNP levels (p: NS). CONCLUSIONS: VP appears to impair LV systolic and diastolic function and may predispose to higher LV filling pressures.