Liang-Han Ling

Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance, and is associated with left ventricular diastolic dysfunction

BackgroundThe presence of myocardial fibrosis is associated with worse clinical outcomes in hypertrophic cardiomyopathy (HCM). Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) sequences can detect regional, but not diffuse myocardial fibrosis. Post-contrast T1 mapping is an emerging CMR technique that may enable the non-invasive evaluation of diffuse myocardial fibrosis in HCM. The purpose of this study was to non-invasively detect and quantify diffuse myocardial fibrosis in HCM with CMR and examine its relationship to diastolic performance.MethodsWe performed CMR on 76 patients - 51 with asymmetric septal hypertrophy due to HCM and 25 healthy controls. Left ventricular (LV) morphology, function and distribution of regional myocardial fibrosis were evaluated with cine imaging and LGE. A CMR T1 mapping sequence determined the post-contrast myocardial T1 time as an index of diffuse myocardial fibrosis. Diastolic function was assessed by transthoracic echocardiography.ResultsRegional myocardial fibrosis was observed in 84% of the HCM group. Post-contrast myocardial T1 time was significantly shorter in patients with HCM compared to controls, consistent with diffuse myocardial fibrosis (498 ± 80 ms vs. 561 ± 47 ms, p < 0.001). In HCM patients, post-contrast myocardial T1 time correlated with mean E/e’ (r = −0.48, p < 0.001).ConclusionsPatients with HCM have shorter post-contrast myocardial T1 times, consistent with diffuse myocardial fibrosis, which correlate with estimated LV filling pressure, suggesting a mechanistic link between diffuse myocardial fibrosis and abnormal diastolic function in HCM.

Predictive value of impedance changes for real-time contact force measurements during catheter ablation of atrial arrhythmias in humans

BACKGROUND Catheter-tissue contact force (CF) determines radiofrequency (RF) ablation lesion size. Impedance changes during RF delivery are used as surrogate markers for CF. The relationship between impedance and real-time CF in humans remains unknown. OBJECTIVES To determine whether impedance changes have predictive value for real-time CF during catheter ablation of atrial arrhythmias. METHODS Real-time CF, force-time integral, and impedance were measured in 2265 RF lesions for atrial fibrillation or flutter in 34 patients. Operators were blinded to CF measurements. Impedance preablation, at 5-second intervals for 30 seconds after the RF onset, maximal impedance fall and time to impedance plateau during RF were correlated with CF. Average CF was divided into low (≤20 g), intermediate (21-60 g), and high (>60 g) categories. RESULTS Preablation impedance poorly correlated with preablation CF (R = .07). Maximal impedance fall modestly correlated with average CF and force-time integral (R = .32 and .37, respectively). There was a large degree of overlap in impedance fall between different CF categories. A maximal impedance fall of 10 Ω could predict average CF of >20 g, with a sensitivity and specificity of 71% and 53% and a positive and negative predictive value of 51% and 49%, respectively. Impedance fall was only able to differentiate between different CF categories ≥15 seconds after the RF onset. Higher CFs moderately correlated with delayed plateau in impedance (R = .41). CONCLUSIONS Impedance measurements (both baseline and impedance fall) are, at best, moderately efficacious as surrogate markers for predicting real-time catheter-tissue CF. These findings highlight the importance of real-time CF measurements, rather than impedance changes to optimize ablation efficacy.

Pulmonary vein isolation: The impact of pulmonary venous anatomy on long-term outcome of catheter ablation for paroxysmal atrial fibrillation

BACKGROUND Circumferential pulmonary vein (PV) isolation is the cornerstone of catheter ablation for atrial fibrillation (AF); however, PV reconnection remains problematic. OBJECTIVE To assess the impact of PV anatomy on outcome after AF ablation. METHODS One hundred two patients with paroxysmal AF underwent cardiac magnetic resonance (60%) or computed tomography (40%) before AF ablation. PV anatomy was classified according to the presence of common PVs, accessory PVs, PV branching pattern, and the dimensions of the PV ostia, intervenous ridges (IVRs), and the left PV-left atrial appendage ridge. RESULTS Four discrete PVs were present in 48(47%) of the patients: a left common PV in 38(37%), a right common PV in 2(2%), an accessory right PV in 20(20%), and left PV in 4(4%). At a mean follow-up of 12 ± 4 months, 75 of 102 (74%) patients were free of recurrent AF. A LCPV was associated with an increase in freedom from AF (87% vs 66% for 4 PV anatomy; P = .03). Greater left IVR length (16.9 ± 3.5 mm vs 14.0 ± 3.0 mm; P ≤ .001) and width (1.4 ± 0.6 mm vs 1.1 ± 0.6 mm; P = .02) were associated with increased AF recurrence. After multivariate analysis, abnormal anatomy (LCPV or accessory PV) and left IVR length were found to be the only independent predictors of freedom from AF. CONCLUSIONS Four discrete PVs are present in the minority of patients with paroxysmal AF undergoing PV isolation. The presence of a LCPV is associated with an increased freedom from AF after catheter ablation. PV anatomy may in part explain the variable outcome to electrical isolation in patients with paroxysmal AF.

Comorbidity of atrial fibrillation and heart failure

Atrial fibrillation (AF) and heart failure (HF) are evolving epidemics, together responsible for substantial human suffering and health-care expenditure. Ageing, improved cardiovascular survival, and epidemiological transition form the basis for their increasing global prevalence. Although we now have a clear picture of how HF promotes AF, gaps remain in our knowledge of how AF exacerbates or even causes HF, and how the development of HF affects the outcome of patients with AF. New data regarding HF with preserved ejection fraction and its unique relationship with AF suggest a possible role for AF in its aetiology, possibly as a trigger for ventricular fibrosis. Deciding on optimal treatment strategies for patients with both AF and HF is increasingly difficult, given that results from trials of pharmacological rhythm control are arguably obsolete in the age of catheter ablation. Restoring sinus rhythm by catheter ablation seems successful in the medium term and improves HF symptoms, functional capacity, and left ventricular function. Long-term studies to examine the effect on rates of stroke and death are ongoing. Guidelines continue to evolve to keep pace with this rapidly changing field.

Atrial Electrical and Structural Remodeling Associated with Longstanding Pulmonary Hypertension and Right Ventricular Hypertrophy in Humans

Atrial Remodeling in Pulmonary Hypertension. Introduction: Pulmonary hypertension (PH) is common to a range of cardiopulmonary conditions and is associated with atrial arrhythmias. However, little is known of the isolated atrial effects of PH and right atrial dilatation (RA) in humans. To avoid the confounding effects of PH‐associated disease states, we performed detailed electrophysiological (EP) and electroanatomic (EA) mapping of the RA in patients with idiopathic PH.

Evaluating the Utility of Circulating Biomarkers of Collagen Synthesis in Hypertrophic Cardiomyopathy

Background— In hypertrophic cardiomyopathy (HCM), accumulation of myocardial collagen may play a central role in the pathogenesis of diastolic dysfunction and arrhythmia. Previous studies have suggested that peripheral levels of byproducts of collagen synthesis are reflective of myocardial extracellular matrix metabolism, although this has not been validated in detail. Given the potential clinical utility of such biomarkers, we sought to validate the assumed relationship between peripheral markers and myocardial fibrosis in HCM. Methods and Results— Fifty patients with HCM and 25 healthy controls underwent peripheral venous sampling to determine plasma concentrations of key collagen precursors (procollagen I and III N-terminal propeptides [PINP, PIIINP]). Contrast-enhanced cardiac magnetic resonance imaging was performed to quantify regional (by late-gadolinium enhancement) and diffuse (by T1 mapping) myocardial fibrosis. Nineteen subjects also underwent simultaneous arterial and coronary sinus blood sampling (to derive transcardiac concentration gradients of PINP, PIIINP, and C-terminal telopeptide of type I collagen) and right heart catheterization. Despite cardiac magnetic resonance evidence of regional (late-gadolinium enhancement quantity, 6.4±8.0%) and diffuse (T1 time, 478±79 ms) myocardial fibrosis in patients with HCM, peripheral levels of collagen precursors were similar compared with control subjects (PINP, 45.9±22.9 versus 53.4±25.9 &mgr;g/L; P=0.21; PIIINP, 4.8±1.7 versus 4.4±1.1 &mgr;g/L; P=0.26). No significant net positive transcardiac concentration gradient was detected for either biomarker of collagen synthesis. Conclusions— The cardiac contribution to peripheral levels of byproducts of collagen synthesis in patients with HCM is insignificant. Furthermore, peripheral levels of these biomarkers do not accurately reflect myocardial collagen content in these patients.

Esophageal hematoma after atrial fibrillation ablation: incidence, clinical features, and sequelae of esophageal injury of a different sort

Background— Esophageal hematoma recently has been reported as a form of esophageal injury after atrial fibrillation (AF) ablation, attributed to the use of transesophageal echocardiography (TEE). We sought to determine the incidence, clinical features, and sequelae of this form of esophageal injury. Methods and Results— This was a prospective series of 1110 AF ablation procedures performed under general anesthesia (GA) over 9 years. TEE was inserted after induction of GA to exclude left atrial appendage thrombus, define cardiac function, and guide transseptal puncture. The procedural incidence of esophageal hematoma was 0.27% (3/1110 procedures, mortality 0%). Odonyphagia, regurgitation, and hoarseness were the predominant symptoms, with an onset within 12 hours. There was absence of fever and neurological symptoms. Chest computed tomography excluded atrio-esophageal fistula and was diagnostic of esophageal hematoma localized to either the upper esophagus or extending the length of the mid and lower esophagus; endoscopy confirmed the diagnosis. Management was conservative in all cases comprising of ceasing oral intake and anticoagulation. Long term sequelae included esophageal stricture formation requiring dilatation, persistent esophageal dysmotility (mid esophageal hematoma), and vocal cord paralysis, resulting in hoarse voice (upper esophageal hematoma). Conclusions— Esophageal hematoma is a rare but important differential diagnosis for esophageal injury after TEE-guided AF ablation under GA, and can result in significant patient morbidity. Key clinical features differentiate presentation of esophageal hematoma from that of an atrio-esophageal fistula.Background— Esophageal hematoma recently has been reported as a form of esophageal injury after atrial fibrillation (AF) ablation, attributed to the use of transesophageal echocardiography (TEE). We sought to determine the incidence, clinical features, and sequelae of this form of esophageal injury. Methods and Results— This was a prospective series of 1110 AF ablation procedures performed under general anesthesia (GA) over 9 years. TEE was inserted after induction of GA to exclude left atrial appendage thrombus, define cardiac function, and guide transseptal puncture. The procedural incidence of esophageal hematoma was 0.27% (3/1110 procedures, mortality 0%). Odonyphagia, regurgitation, and hoarseness were the predominant symptoms, with an onset within 12 hours. There was absence of fever and neurological symptoms. Chest computed tomography excluded atrio-esophageal fistula and was diagnostic of esophageal hematoma localized to either the upper esophagus or extending the length of the mid and lower esophagus; endoscopy confirmed the diagnosis. Management was conservative in all cases comprising of ceasing oral intake and anticoagulation. Long term sequelae included esophageal stricture formation requiring dilatation, persistent esophageal dysmotility (mid esophageal hematoma), and vocal cord paralysis, resulting in hoarse voice (upper esophageal hematoma). Conclusions— Esophageal hematoma is a rare but important differential diagnosis for esophageal injury after TEE-guided AF ablation under GA, and can result in significant patient morbidity. Key clinical features differentiate presentation of esophageal hematoma from that of an atrio-esophageal fistula.

Irregular Rhythm Adversely Influences Calcium Handling in Ventricular Myocardium: Implications for the Interaction Between Heart Failure and Atrial Fibrillation

Background—Despite adequate rate control, the combination of atrial fibrillation with heart failure (HF) has been shown, in a number of studies, to hasten HF progression. In this context, we aimed to test the hypothesis that an irregular ventricular rhythm causes an alteration in ventricular cardiomyocyte excitation–contraction coupling which contributes to the progression of HF. Methods and Results—We investigated the effects of electrical field stimulation (average frequency 2 Hz) in an irregular versus regular drive train pattern on the expression of calcium-handling genes and proteins in rat ventricular myocytes. The effect of rhythm on intracellular calcium transients was examined using Fura-2AM fluorescence spectroscopy. In conjunction, calcium-handling protein expression was examined in left ventricular samples obtained from end-stage HF patients, in patients with either persistent atrial fibrillation or sinus rhythm. Compared with regularly paced ventricular cardiomyocytes, in cells paced irregularly for 24 hours, there was a significant reduction in the expression of sarcoplasmic reticulum calcium (Ca2+) ATPase together with reduced serine-16 phosphorylation of phospholamban. These findings were accompanied by a 59% reduction (P<0.01) in the peak Ca2+ transient in irregulary paced myocytes compared with those with regular pacing. Consistent with these observations, we observed a 54% (P<0.05) decrease in sarcoplasmic reticulum Ca2+ATPase protein expression and an 85% (P<0.01) reduction in the extent of phosphorylation of phospholamban in the left ventricular myocardium of HF patients in atrial fibrillation compared with those in sinus rhythm. Conclusions—Together, these data demonstrate that ventricular rhythmicity contributes significantly to excitation–contraction coupling by altering the expression and activity of key calcium-handling proteins. These data suggest that control of rhythm may be of benefit in patients with HF.Background— Despite adequate rate control, the combination of atrial fibrillation with heart failure (HF) has been shown, in a number of studies, to hasten HF progression. In this context, we aimed to test the hypothesis that an irregular ventricular rhythm causes an alteration in ventricular cardiomyocyte excitation–contraction coupling which contributes to the progression of HF. Methods and Results— We investigated the effects of electrical field stimulation (average frequency 2 Hz) in an irregular versus regular drive train pattern on the expression of calcium-handling genes and proteins in rat ventricular myocytes. The effect of rhythm on intracellular calcium transients was examined using Fura-2AM fluorescence spectroscopy. In conjunction, calcium-handling protein expression was examined in left ventricular samples obtained from end-stage HF patients, in patients with either persistent atrial fibrillation or sinus rhythm. Compared with regularly paced ventricular cardiomyocytes, in cells paced irregularly for 24 hours, there was a significant reduction in the expression of sarcoplasmic reticulum calcium (Ca2+) ATPase together with reduced serine-16 phosphorylation of phospholamban. These findings were accompanied by a 59% reduction ( P <0.01) in the peak Ca2+ transient in irregulary paced myocytes compared with those with regular pacing. Consistent with these observations, we observed a 54% ( P <0.05) decrease in sarcoplasmic reticulum Ca2+ATPase protein expression and an 85% ( P <0.01) reduction in the extent of phosphorylation of phospholamban in the left ventricular myocardium of HF patients in atrial fibrillation compared with those in sinus rhythm. Conclusions— Together, these data demonstrate that ventricular rhythmicity contributes significantly to excitation–contraction coupling by altering the expression and activity of key calcium-handling proteins. These data suggest that control of rhythm may be of benefit in patients with HF.

Catheter ablation of atrial fibrillation in patients with heart failure: impact of maintaining sinus rhythm on heart failure status and long-term rates of stroke and death

AIMS Catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) can improve left ventricular (LV) function and HF symptoms. We aimed to investigate whether long-term maintenance of sinus rhythm impacts on hard outcomes such as stroke and death. METHODS AND RESULTS An international multicentre registry was compiled from seven centres for consecutive patients undergoing catheter ablation of AF. Long-term freedom from AF was examined in patients with and without HF. The impact of maintaining sinus rhythm on rates of stroke and death was also examined. A total of 1273 patients were included: 171 with HF and 1102 without. Median follow-up was 3.1 years (IQR 2.0-4.3). The final procedure success rate was no different for paroxysmal AF (PAF) (78.7 vs. 85.7%, P = 0.186), but significantly different for persistent AF (57.3 vs. 75.8%, P < 0.001). Multivariate analysis showed that HF independently predicted recurrent arrhythmia [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.2-2.4, P = 0.002]. New York Heart Association class decreased from 2.3 ± 0.7 at baseline to 1.5 ± 0.8 at follow-up (P < 0.001). Left ventricular ejection fraction (LVEF) increased from 34.3 ± 9.0 to 45.8 ± 12.8% (P < 0.001). Recurrent AF was strongly predictive of stroke or death in HF patients (HR 8.33, 95% CI 1.86-37.7, P = 0.001). CONCLUSION Long-term success rates for persistent (but not paroxysmal) AF ablation are significantly lower in HF patients. Left ventricular function and HF symptoms were improved following ablation. In HF patients, recurrent arrhythmia strongly predicted stroke and death during follow-up.

The transesophageal echo probe may contribute to esophageal injury after catheter ablation for paroxysmal atrial fibrillation under general anesthesia: a preliminary observation

The transesophageal echo probe (TEE) is commonly used before and during atrial fibrillation (AF) ablation under general anesthesia (GA). We sought to determine the potential contribution of the TEE probe to esophageal injury after pulmonary vein isolation (PVI) alone for paroxysmal AF.