Recognition of fibrotic infarct density by the pattern of local systolic-diastolic myocardial electrical impedance

Myocardial electrical impedance is a biophysical property of the heart that is influenced by the intrinsic structural characteristics of the tissue. Therefore, the structural derangements elicited in a chronic myocardial infarction should cause specific changes in the local systolic-diastolic myocardial impedance, but this is not known. This study aimed to characterize the local changes of systolic-diastolic myocardial impedance in a healed myocardial infarction model. Six pigs were successfully submitted to 150 min of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 4 weeks later, myocardial impedance spectroscopy (1–1000 kHz) was measured at different infarction sites. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow (ABF) were also recorded. A total of 59 LV tissue samples were obtained and histopathological studies were performed to quantify the percentage of fibrosis. Samples were categorized as normal myocardium (50%). Resistivity of normal myocardium depicted phasic changes during the cardiac cycle and its amplitude markedly decreased in dense scar (18 ± 2 ·cm vs. 10 ± 1 ·cm, at 41 kHz; P < 0.001, respectively). The mean phasic resistivity decreased progressively from normal to heterogeneous and dense scar regions (285 ± 10 ·cm, 225 ± 25 ·cm, and 162 ± 6 ·cm, at 41 kHz; P < 0.001 respectively). Moreover, myocardial resistivity and phase angle correlated significantly with the degree of local fibrosis (resistivity: r = 0.86 at 1 kHz, P < 0.001; phase angle: r = 0.84 at 41 kHz, P < 0.001). Myocardial infarcted regions with greater fibrotic content show lower mean impedance values and more depressed systolic-diastolic dynamic impedance changes. In conclusion, this study reveals that differences in the degree of yocardial fibrosis can be detected in vivo by local measurement of phasic systolic-diastolic bioimpedance spectrum. Once this new bioimpedance method could be used via a catheter-based device, it would be of potential clinical applicability for the recognition of fibrotic tissue to guide the ablation of atrial or ventricular arrhythmias.Award-winningPostprint (published version

Electrophysiological and histological characterization of atrial scarring in a model of isolated atrial myocardial infarction

Background: Characterization of atrial myocardial infarction is hampered by the frequent concurrence of ventricular infarction. Theoretically, atrial infarct scarring could be recognized by multifrequency tissue impedance, like in ventricular infarction, but this remains to be proven. Objective: This study aimed at developing a model of atrial infarction to assess the potential of multifrequency impedance to recognize areas of atrial infarct scar. Methods: Seven anesthetized pigs were submitted to transcatheter occlusion of atrial coronary branches arising from the left coronary circumflex artery. Six weeks later the animals were anesthetized and underwent atrial voltage mapping and multifrequency impedance recordings. The hearts were thereafter extracted for anatomopathological study. Two additional pigs not submitted to atrial branch occlusion were used as controls. Results: Selective occlusion of the atrial branches induced areas of healed infarction in the left atrium in 6 of the 7 cases. Endocardial mapping of the left atrium showed reduced multi-frequency impedance (Phase angle at 307 kHz: from -17.1° ± 5.0° to -8.9° ± 2.6°, p < .01) and low-voltage of bipolar electrograms (.2 ± 0.1 mV vs. 1.9 ± 1.5 mV vs., p < .01) in areas affected by the infarction. Data variability of the impedance phase angle was lower than that of bipolar voltage (coefficient of variability of phase angle at307 kHz vs. bipolar voltage: .30 vs. .77). Histological analysis excluded the presence of ventricular infarction. Conclusion: Selective occlusion of atrial coronary branches permits to set up a model of selective atrial infarction. Atrial multifrequency impedance mapping allowed recognition of atrial infarct scarring with lesser data variability than local bipolar voltage mapping. Our model may have potential applicability on the study of atrial arrhythmia mechanisms.Peer ReviewedPostprint (published version

Electrophysiological effects of selective atrial coronary artery occlusion in humans

Background-The arrhythmogenesis of ventricular myocardial ischemia has been extensively studied, but models of atrial ischemia in humans are lacking. This study aimed at describing the electrophysiological alterations induced by acute atrial ischemia secondary to atrial coronary branch occlusion during elective coronary angioplasty.; Methods and Results-Clinical data, 12-lead ECG, 12-hour Holter recordings, coronary angiography, and serial plasma levels of high-sensitivity troponin T and midregional proatrial natriuretic peptide were prospectively analyzed in 109 patients undergoing elective angioplasty of right or circumflex coronary arteries. Atrial coronary branches were identified and after the procedure patients were allocated into two groups: atrial branch occlusion (ABO, n= 17) and atrial branch patency (non-ABO, n= 92). In comparison with the non-ABO, patients with ABO showed: (1) higher incidence of periprocedural myocardial infarction (20% versus 53%, P= 0.01); (2) more frequent intra-atrial conduction delay (19% versus 46%, P= 0.03); (3) more marked PR segment deviation in the Holter recordings; and (4) higher incidence of atrial tachycardia (15% versus 41%, P= 0.02) and atrial fibrillation (0% versus 12%, P= 0.03). After adjustment by a propensity score, ABO was an independent predictor of periprocedural infarction (odds ratio, 3.4; 95% confidence interval, 1.01-11.6, P< 0.05) and atrial arrhythmias (odds ratio, 5.1; 95% confidence interval, 1.2-20.5, P= 0.02).; Conclusions-Selective atrial coronary artery occlusion during elective percutaneous transluminal coronary angioplasty is associated with myocardial ischemic damage, atrial arrhythmias, and intra-atrial conduction delay. Our data suggest that atrial ischemic episodes might be considered as a potential cause of atrial fibrillation in patients with chronic coronary artery disease.Peer ReviewedPostprint (author's final draft

Prognostic value of discharge heart rate in acute heart failure patients: more relevant in atrial fibrillation?

[Abstract] Aims. The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known especially in atrial fibrillation (AF) patients. The aim of the study was to evaluate the impact of admission HR, discharge HR, HR difference (admission-discharge) in AHF patients with sinus rhythm (SR) or AF on long- term outcomes. Methods. We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry. Logistic regression models were used to estimate the association between admission HR, discharge HR and HR difference and one- year all-cause mortality and HF readmission. Results. The mean age of the study population was 72 ± 12 years. Of these, 594 (42.4%) were female, 655 (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one year all-cause mortality (Relative risk (RR) = 1.182, confidence interval (CI) 95% 1.024–1.366, p = 0.022) in SR. In AF patients discharge HR was associated with one year all cause mortality (RR = 1.276, CI 95% 1.115–1.459, p ≤ 0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction. Conclusions. In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients

Renal Function Impact in the Prognostic Value of Galectin-3 in Acute Heart Failure

[Abstract] Introduction: Galectin-3 (Gal-3) is an inflammatory marker associated with the development and progression of heart failure (HF). A close relationship between Gal-3 levels and renal function has been observed, but data on their interaction in patients with acute HF (AHF) are scarce. We aim to assess the prognostic relationship between renal function and Gal-3 during an AHF episode. Materials and methods: This is an observational, prospective, multicenter registry of patients hospitalized for AHF. Patients were divided into two groups according to estimated glomerular filtration rate (eGFR): preserved renal function (eGFR ≥ 60 mL/min/1.73 m2) and renal dysfunction (eGFR <60 mL/min/1.73 m2). Cox regression analysis was performed to evaluate the association between Gal-3 and 12-month mortality. Results: We included 1,201 patients in whom Gal-3 values were assessed at admission. The median value of Gal-3 in our population was 23.2 ng/mL (17.3-32.1). Gal-3 showed a negative correlation with eGFR (rho = -0.51; p < 0.001). Gal-3 concentrations were associated with higher mortality risk in the multivariate analysis after adjusting for eGFR and other prognostic variables [HR = 1.010 (95%-CI: 1.001-1.018); p = 0.038]. However, the prognostic value of Gal-3 was restricted to patients with renal dysfunction [HR = 1.010 (95%-CI: 1.001-1.019), p = 0.033] with optimal cutoff point of 31.5 ng/mL, with no prognostic value in the group with preserved renal function [HR = 0.990 (95%-CI: 0.964-1.017); p = 0.472]. Conclusions: Gal-3 is a marker of high mortality in patients with acute HF and renal dysfunction. Renal function influences the prognostic value of Gal-3 levels, which should be adjusted by eGFR for a correct interpretation.Grant No. RD06-0003-0000 Grant No. RD12/0042/000

Serum Potassium Dynamics During Acute Heart Failure Hospitalization

[Abstract] Background. Available information about prognostic implications of potassium levels alteration in the setting of acute heart failure (AHF) is scarce. Objectives. We aim to describe the prevalence of dyskalemia (hypo or hyperkalemia), its dynamic changes during AHF-hospitalization, and its long-term clinical impact after hospitalization. Methods. We analyzed 1779 patients hospitalized with AHF who were included in the REDINSCOR II registry. Patients were classified in three groups, according to potassium levels both on admission and discharge: hypokalemia (potassium  5 mEq/L). Results. The prevalence of hypokalemia and hyperkalemia on admission was 8.2 and 4.6%, respectively, and 6.4 and 2.7% at discharge. Hyperkalemia on admission was associated with higher in-hospital mortality (OR = 2.32 [95% CI: 1.04–5.21] p = 0.045). Among patients with hypokalemia on admission, 79% had normalized potassium levels at discharge. In the case of patients with hyperkalemia on admission, 89% normalized kalemia before discharge. In multivariate Cox regression, dyskalemia was associated with higher 12-month mortality, (HR = 1.48 [95% CI, 1.12–1.96], p = 0.005). Among all patterns of dyskalemia persistent hypokalemia (HR = 3.17 [95% CI: 1.71–5.88]; p < 0.001), and transient hyperkalemia (HR = 1.75 [95% CI: 1.07–2.86]; p = 0.023) were related to reduced 12-month survival. Conclusions. Potassium levels alterations are frequent and show a dynamic behavior during AHF admission. Hyperkalemia on admission is an independent predictor of higher in-hospital mortality. Furthermore, persistent hypokalemia and transient hyperkalemia on admission are independent predictors of 12-month mortality.This work is funded by the Instituto de Salud Carlos III (Ministry of Economy, Industry, and Competitiveness) and co-funded by the European Regional Development Fund, through the CIBER in cardiovascular diseases (CB16/11/00502)

Early detection of acute transmural myocardial ischemia by the phasic systolic-diastolic changes of local tissue electrical impedance

Myocardial electrical impedance is influenced by the mechanical activity of the heart. Therefore, the ischemia-induced mechanical dysfunction may cause specific changes in the systolic-diastolic pattern of myocardial impedance, but this is not known. This study aimed to analyze the phasic changes of myocardial resistivity in normal and ischemic conditions. Myocardial resistivity was measured continuously during the cardiac cycle using 26 different simultaneous excitation frequencies (1 kHz–1 MHz) in 7 anesthetized open-chest pigs. Animals were submitted to 30 min regional ischemia by acute left anterior descending coronary artery occlusion. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow were recorded simultaneously. Baseline myocardial resistivity depicted a phasic pattern during the cardiac cycle with higher values at the preejection period (4.19 ± 1.09% increase above the mean, P < 0.001) and lower values during relaxation phase (5.01 ± 0.85% below the mean, P < 0.001). Acute coronary occlusion induced two effects on the phasic resistivity curve: 1) a prompt (5 min ischemia) holosystolic resistivity rise leading to a bell-shaped waveform and to a reduction of the area under the LV pressure-impedance curve (1,427 ± 335 vs. 757 ± 266 O·cm·mmHg, P < 0.01, 41 kHz) and 2) a subsequent (5–10 min ischemia) progressive mean resistivity rise (325 ± 23 vs. 438 ± 37 O·cm at 30 min, P < 0.01, 1 kHz). The structural and mechanical myocardial dysfunction induced by acute coronary occlusion can be recognized by specific changes in the systolic-diastolic myocardial resistivity curve. Therefore these changes may become a new indicator (surrogate) of evolving acute myocardial ischemiaPeer Reviewe

Early detection of acute transmural myocardial ischemia by the phasic systolic-diastolic changes of local tissue electrical impedance

Myocardial electrical impedance is influenced by the mechanical activity of the heart. Therefore, the ischemia-induced mechanical dysfunction may cause specific changes in the systolic-diastolic pattern of myocardial impedance, but this is not known. This study aimed to analyze the phasic changes of myocardial resistivity in normal and ischemic conditions. Myocardial resistivity was measured continuously during the cardiac cycle using 26 different simultaneous excitation frequencies (1 kHz–1 MHz) in 7 anesthetized open-chest pigs. Animals were submitted to 30 min regional ischemia by acute left anterior descending coronary artery occlusion. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow were recorded simultaneously. Baseline myocardial resistivity depicted a phasic pattern during the cardiac cycle with higher values at the preejection period (4.19 ± 1.09% increase above the mean, P < 0.001) and lower values during relaxation phase (5.01 ± 0.85% below the mean, P < 0.001). Acute coronary occlusion induced two effects on the phasic resistivity curve: 1) a prompt (5 min ischemia) holosystolic resistivity rise leading to a bell-shaped waveform and to a reduction of the area under the LV pressure-impedance curve (1,427 ± 335 vs. 757 ± 266 O·cm·mmHg, P < 0.01, 41 kHz) and 2) a subsequent (5–10 min ischemia) progressive mean resistivity rise (325 ± 23 vs. 438 ± 37 O·cm at 30 min, P < 0.01, 1 kHz). The structural and mechanical myocardial dysfunction induced by acute coronary occlusion can be recognized by specific changes in the systolic-diastolic myocardial resistivity curve. Therefore these changes may become a new indicator (surrogate) of evolving acute myocardial ischemiaPeer Reviewe

Recognition of fibrotic infarct density by the pattern of local systolic-diastolic myocardial electrical impedance

Myocardial electrical impedance is a biophysical property of the heart that is influenced by the intrinsic structural characteristics of the tissue. Therefore, the structural derangements elicited in a chronic myocardial infarction should cause specific changes in the local systolic-diastolic myocardial impedance, but this is not known. This study aimed to characterize the local changes of systolic-diastolic myocardial impedance in a healed myocardial infarction model. Six pigs were successfully submitted to 150 min of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 4 weeks later, myocardial impedance spectroscopy (1–1000 kHz) was measured at different infarction sites. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow (ABF) were also recorded. A total of 59 LV tissue samples were obtained and histopathological studies were performed to quantify the percentage of fibrosis. Samples were categorized as normal myocardium (50%). Resistivity of normal myocardium depicted phasic changes during the cardiac cycle and its amplitude markedly decreased in dense scar (18 ± 2 ·cm vs. 10 ± 1 ·cm, at 41 kHz; P < 0.001, respectively). The mean phasic resistivity decreased progressively from normal to heterogeneous and dense scar regions (285 ± 10 ·cm, 225 ± 25 ·cm, and 162 ± 6 ·cm, at 41 kHz; P < 0.001 respectively). Moreover, myocardial resistivity and phase angle correlated significantly with the degree of local fibrosis (resistivity: r = 0.86 at 1 kHz, P < 0.001; phase angle: r = 0.84 at 41 kHz, P < 0.001). Myocardial infarcted regions with greater fibrotic content show lower mean impedance values and more depressed systolic-diastolic dynamic impedance changes. In conclusion, this study reveals that differences in the degree of yocardial fibrosis can be detected in vivo by local measurement of phasic systolic-diastolic bioimpedance spectrum. Once this new bioimpedance method could be used via a catheter-based device, it would be of potential clinical applicability for the recognition of fibrotic tissue to guide the ablation of atrial or ventricular arrhythmias.Award-winnin

Response by Álvarez-García et al. to Letters Regarding article, “Electrophysiological effects of selective atrial coronary artery occlusion in humans”

Peer ReviewedPostprint (published version