- Email: [email protected]
Left Ventricular Noncompaction, Cardiac Magnetic Resonance Imaging, and Neuromuscular Disorders
Correspondence
JACC Vol. 47, No. 6, 2006 March 21, 2006:1228–38 attenuation of inflammation induces atrial remodeling or vice versa. Although this study did not include a control group, the levels of CRP measured compare well to previously published data (1). Levels of CRP decreased after successful ablation to levels comparable with patients suffering from paroxysmal AF or patients in sinus rhythm at increased risk for AF. At that point, additional pharmacologic modification of the inflammatory state with an ACE inhibitor or a statin might be useful to reduce the risk of arrhythmia recurrence (10). Endothelial dysfunction is not influenced by ablation, restoration of sinus rhythm, reverse remodeling, or a decline in inflammatory parameters. This finding confirms previous studies showing sustained endothelial dysfunction despite a restoration of sinus rhythm by cardioversion (11), suggesting that endothelial dysfunction may not be maintained by AF. In conclusion, we found that restoration of sinus rhythm by ablation leads to a decrease of the patient’s inflammatory state and a reverse remodeling of the left atrium. *Martin Rotter, MD *Service de Rythmologie Hôpital Cardiologique du Haut-Léveque Av. de Magellan 33604 Bordeaux-Pessac France E-mail: [email protected] Pierre Jaïs, MD Marie-Christine Vergnes, MD Paquita Nurden, MD Yoshihide Takahashi, MD Prashanthan Sanders, MBBS, PhD Thomas Rostock, MD Mélèze Hocini, MD Fréderic Sacher, MD Michel Haïssaguerre, MD doi:10.1016/j.jacc.2005.12.038
REFERENCES 1. Aviles RJ, Martin DO, Apperson-Hansen C, et al. Inflammation as a risk factor for atrial fibrillation. Circulation 2003;108:3006 –10. 2. Chung MK, Martin DO, Sprecher D, et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001;104: 2886 –91. 3. Conway DS, Pearce LA, Chin BS, et al. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation 2003;107:3141–5. 4. Thambidorai SK, Parakh K, Martin DO, et al. Relation of C-reactive protein correlates with risk of thromboembolism in patients with atrial fibrillation. Am J Cardiol 2004;94:805–7. 5. Haissaguerre M, Sanders P, Hocini M, et al. Changes in atrial fibrillation cycle length and inducibility during catheter ablation and their relation to outcome. Circulation 2004;109:3007–13. 6. Tsao HM, Wu MH, Huan BH, et al. Morphologic remodeling of pulmonary veins and left atrium after catheter ablation of atrial fibrillation: insight from long-term follow-up of three-dimensional magnetic resonance imaging. J Cardiovasc Electrophysiol 2005;16: 7–12. 7. Psychari SN, Apostolou TS, Sinos L, et al. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and
8. 9. 10.
11.
1233
duration of episodes in patients with atrial fibrillation. Am J Cardiol 2005;95:764 –7. Kumagai K, Nakashima H, Urata H, et al. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol 2003;41:2197–204. Nakano Y, Niida S, Dote K, et al. Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation. J Am Coll Cardiol 2004;43:818 –25. L’Allier PL, Ducharme A, Keller PF, et al. Angiotensin-converting enzyme inhibition in hypertensive patients is associated with a reduction in the occurrence of atrial fibrillation. J Am Coll Cardiol 2004;44:159 – 64. Li-Saw-Hee FL, Blann AD, Gurney D, et al. Plasma von Willebrand factor, fibrinogen and soluble P-selectin levels in paroxysmal, persistent and permanent atrial fibrillation. Effects of cardioversion and return of left atrial function. Eur Heart J 2001;22:1741–7.
Letters to the Editor Left Ventricular Noncompaction, Cardiac Magnetic Resonance Imaging, and Neuromuscular Disorders With interest we read the report by Petersen et al. (1) concerning cardiovascular magnetic resonance imaging (CMRI) in patients with left ventricular hypertrabeculation (LVHT), also termed “noncompaction.” Currently, several echocardiographic definitions of LVHT exist, and up to now no CMRI-specific diagnostic criteria for LVHT have been developed (2– 4). We have, however, concerns and doubts as to whether the current study will clarify the confusion regarding the diagnosis of LVHT. According to their definition, the investigators found by CMRI that “areas of non-compaction” were common in healthy volunteers, athletes, patients with hypertrophic or dilated cardiomyopathy, and aortic stenosis. Because these findings were not correlated with echocardiographic or anatomic data, how can Petersen et al. be sure that these areas were indeed “noncompacted” and not just the papillary muscles, false tendons, or aberrant bands, which are common cardiac findings (5)? When assessing the myocardial layers with different degrees of tissue compaction, how did the researchers differentiate myocardium from flow artifacts? Why did they measure the ratio of noncompacted/compacted myocardial layers in diastole and not in systole, as recommended by one of the echocardiographic definitions (3)? How to explain the discrepancy between the relatively smooth endocardial surface as seen on CMRI and the bizarre morphology of trabeculations and deep intertrabecular recesses when examining LVHT patients echocardiographically and at autopsy? Echocardiography often does not visualize with clarity the left ventricular apex. Thus, we do not understand why this cardiac region, which can be much better visualized by CMRI than by echocardiography, was excluded from measurements. According to the investigators, a ratio of noncompacted to compacted myocardial layers ⬎2.3:1 in diastole distinguished “pathological” from “nonpathological” noncompaction. Why did they then diagnose “partial expression” of the disease in Patient #2, with a ratio of only 1.1? What is the distinction between “nonpathological” noncompaction and “partial expression” of noncompaction? According to which echocardiographic criteria was LVHT-diagnosed in the seven patients? Why were other family members of Patient #4,
1234
Correspondence
JACC Vol. 47, No. 6, 2006 March 21, 2006:1226–38
who had a positive family history, not included? Did any of these relatives suffer from a neuromuscular disorder? According to which type was LVHT transmitted in the families? Moreover, which neuromuscular disorder was diagnosed in Patient #7? Did the patient undergo only clinical neurological investigations or were invasive procedures also carried out? Were thrombi detected in any of the investigated patients, particularly in Patient #5, who had systemic embolism? Also, how to explain the pathomechanism of acquired LVHT, where the myocardium was once totally compact? In these cases, pathogenetic explanations other than noncompaction of the embryonic myocardium are required. In conclusion, the distinction between “normal” and “abnormal” trabeculation is a continuing challenge. Commonly accepted diagnostic criteria for LVHT should be developed based on the correlation of pathoanatomical and imaging findings. The diagnosis of LVHT relies on morphological abnormalities and does not require a positive family history, neuromuscular disorders, embolization, or regional wall motion abnormalities as additional diagnostic criteria. *Claudia Stöllberger, MD Josef Finsterer, MD *KA Rudolfstiftung 2nd Medical Department Juchgasse 25 Vienna A-1030 Austria E-mail: [email protected] doi:10.1016/j.jacc.2005.12.035
REFERENCES 1. Petersen SE, Selvanayagam JB, Wiesmann F, et al. Left ventricular non-compaction: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol 2005;46:101–5. 2. Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of left ventricular myocardium. A study of eight cases. Circulation 1990;82:507–13. 3. Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart 2001;86:666 –71. 4. Stöllberger C, Finsterer J, Blazek G. Left ventricular hypertrabeculation/noncompaction and association with additional cardiac abnormalities and neuromuscular disorders. Am J Cardiol 2002;90:899 –901. 5. Tamborini G, Pepi M, Celeste F, et al. Incidence and characteristics of left ventricular false tendons and trabeculations in the normal and pathologic heart by second harmonic echocardiography. J Am Soc Echocardiogr 2004;17:367–74.
REPLY We thank Drs. Stöllberger and Finsterer for their interest in our report (1). Many of the questions they raise reflect concern with how we selected our study population. Their suggestion of enrolling only symptomatic patients, however, with subsequent access to pathoanatomical specimens in order to establish diagnostic criteria would heavily bias findings to the severe end of the spectrum. Concerns raised by Drs. Stöllberger and Finsterer do not recognize that the likelihood of any individual with a ratio of thicknesses between the trabecular and compact myocardium ⬎2.3:1 suffering from pathological noncompaction, when ex-
pressed as the posterior probability, depends on the pretest probability or prevalence. A patient with a known family history of noncompaction and a 1 in 2 chance of having inherited the condition in autosomal dominant fashion would have a 97% chance of suffering from pathological noncompaction. In contrast, given the estimated prevalence of significant noncompaction of 1 in every 2,000 members of the normal population (2), the posterior probability would only be 26%. This Bayesian calculation (3) exemplifies the importance of taking into account the pretest probability, especially in diseases with relatively low prevalence. We included one patient with left ventricular noncompaction on the basis of marked electrocardiographic changes, a family history of left ventricular noncompaction, and a distinct bilaminar appearance of the trabeculated and compacted layers of the myocardium. Based on imaging findings alone, this patient would not have been diagnosed with left ventricular noncompaction. Interestingly, this patient very recently developed symptomatic cardiac failure. This patient, now with clinical evidence of disease, but in the face of an initially nondiagnostic ratio between the trabecular and compacted layers, must now be assumed partially to express the disease, whereas a healthy volunteer with a low pretest probability would be interpreted as having nonpathological noncompaction. We agree that the pathophysiological mechanisms leading to left ventricular noncompaction are not fully understood. Our data on the segmental distribution of trabeculated myocardium, nonetheless, support the hypothesis of an early arrest during the embryological process of compaction. Our experience is that trabeculations can be more readily visualized in the relaxed heart. Magnetic resonance imaging (MRI) allows easy delineation of the epicardial border in both systole and diastole, in contrast to echocardiography, with poor epicardial delineation in diastole. State-of-the-art sequences, such as steadystate free precession, are not prone to flow artifacts, as once seen with the older sequences employing gradient echo techniques. The new sequences permit clear distinction between the trabeculations and the compacted myocardium. This makes this imaging technique ideal to distinguish noncompaction from papillary muscles, false tendons, and aberrant bands, because it has the accuracy to permit analysis of the entirety of the ventricular mass. We are surprised that Drs. Stöllberger and Finsterer raise this point as it is widely acknowledged that MRI, unlike echocardiography, does not suffer from this caveat. Because of the constraints of space, we can only answer some of the further enquiries concerning the patients studied. An apical thrombus was detected by contrast-enhanced MRI in the patient with a history of systemic embolism. We enrolled all first-degree members of our families with left ventricular noncompaction who agreed to participate in the study and to undergo screening. None of our patients, including the seventh patient, had a family history of neuromuscular disorders. Our patients with left ventricular noncompaction and a positive family history showed an autosomal dominant pattern of transmission. In conclusion, our study demonstrated the high diagnostic accuracy of cardiovascular MRI for left ventricular noncompaction. Owing to the importance of pretest probabilities, we disagree with the view that the diagnosis of left ventricular noncompaction should rely exclusively on morphological abnormalities. Thus, assessments using either echocardiography or cardiovascular MRI can at best contribute to the clinical diagnosis.
JACC Vol. 47, No. 6, 2006 March 21, 2006:1228–38 attenuation of inflammation induces atrial remodeling or vice versa. Although this study did not include a control group, the levels of CRP measured compare well to previously published data (1). Levels of CRP decreased after successful ablation to levels comparable with patients suffering from paroxysmal AF or patients in sinus rhythm at increased risk for AF. At that point, additional pharmacologic modification of the inflammatory state with an ACE inhibitor or a statin might be useful to reduce the risk of arrhythmia recurrence (10). Endothelial dysfunction is not influenced by ablation, restoration of sinus rhythm, reverse remodeling, or a decline in inflammatory parameters. This finding confirms previous studies showing sustained endothelial dysfunction despite a restoration of sinus rhythm by cardioversion (11), suggesting that endothelial dysfunction may not be maintained by AF. In conclusion, we found that restoration of sinus rhythm by ablation leads to a decrease of the patient’s inflammatory state and a reverse remodeling of the left atrium. *Martin Rotter, MD *Service de Rythmologie Hôpital Cardiologique du Haut-Léveque Av. de Magellan 33604 Bordeaux-Pessac France E-mail: [email protected] Pierre Jaïs, MD Marie-Christine Vergnes, MD Paquita Nurden, MD Yoshihide Takahashi, MD Prashanthan Sanders, MBBS, PhD Thomas Rostock, MD Mélèze Hocini, MD Fréderic Sacher, MD Michel Haïssaguerre, MD doi:10.1016/j.jacc.2005.12.038
REFERENCES 1. Aviles RJ, Martin DO, Apperson-Hansen C, et al. Inflammation as a risk factor for atrial fibrillation. Circulation 2003;108:3006 –10. 2. Chung MK, Martin DO, Sprecher D, et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001;104: 2886 –91. 3. Conway DS, Pearce LA, Chin BS, et al. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation 2003;107:3141–5. 4. Thambidorai SK, Parakh K, Martin DO, et al. Relation of C-reactive protein correlates with risk of thromboembolism in patients with atrial fibrillation. Am J Cardiol 2004;94:805–7. 5. Haissaguerre M, Sanders P, Hocini M, et al. Changes in atrial fibrillation cycle length and inducibility during catheter ablation and their relation to outcome. Circulation 2004;109:3007–13. 6. Tsao HM, Wu MH, Huan BH, et al. Morphologic remodeling of pulmonary veins and left atrium after catheter ablation of atrial fibrillation: insight from long-term follow-up of three-dimensional magnetic resonance imaging. J Cardiovasc Electrophysiol 2005;16: 7–12. 7. Psychari SN, Apostolou TS, Sinos L, et al. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and
8. 9. 10.
11.
1233
duration of episodes in patients with atrial fibrillation. Am J Cardiol 2005;95:764 –7. Kumagai K, Nakashima H, Urata H, et al. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol 2003;41:2197–204. Nakano Y, Niida S, Dote K, et al. Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation. J Am Coll Cardiol 2004;43:818 –25. L’Allier PL, Ducharme A, Keller PF, et al. Angiotensin-converting enzyme inhibition in hypertensive patients is associated with a reduction in the occurrence of atrial fibrillation. J Am Coll Cardiol 2004;44:159 – 64. Li-Saw-Hee FL, Blann AD, Gurney D, et al. Plasma von Willebrand factor, fibrinogen and soluble P-selectin levels in paroxysmal, persistent and permanent atrial fibrillation. Effects of cardioversion and return of left atrial function. Eur Heart J 2001;22:1741–7.
Letters to the Editor Left Ventricular Noncompaction, Cardiac Magnetic Resonance Imaging, and Neuromuscular Disorders With interest we read the report by Petersen et al. (1) concerning cardiovascular magnetic resonance imaging (CMRI) in patients with left ventricular hypertrabeculation (LVHT), also termed “noncompaction.” Currently, several echocardiographic definitions of LVHT exist, and up to now no CMRI-specific diagnostic criteria for LVHT have been developed (2– 4). We have, however, concerns and doubts as to whether the current study will clarify the confusion regarding the diagnosis of LVHT. According to their definition, the investigators found by CMRI that “areas of non-compaction” were common in healthy volunteers, athletes, patients with hypertrophic or dilated cardiomyopathy, and aortic stenosis. Because these findings were not correlated with echocardiographic or anatomic data, how can Petersen et al. be sure that these areas were indeed “noncompacted” and not just the papillary muscles, false tendons, or aberrant bands, which are common cardiac findings (5)? When assessing the myocardial layers with different degrees of tissue compaction, how did the researchers differentiate myocardium from flow artifacts? Why did they measure the ratio of noncompacted/compacted myocardial layers in diastole and not in systole, as recommended by one of the echocardiographic definitions (3)? How to explain the discrepancy between the relatively smooth endocardial surface as seen on CMRI and the bizarre morphology of trabeculations and deep intertrabecular recesses when examining LVHT patients echocardiographically and at autopsy? Echocardiography often does not visualize with clarity the left ventricular apex. Thus, we do not understand why this cardiac region, which can be much better visualized by CMRI than by echocardiography, was excluded from measurements. According to the investigators, a ratio of noncompacted to compacted myocardial layers ⬎2.3:1 in diastole distinguished “pathological” from “nonpathological” noncompaction. Why did they then diagnose “partial expression” of the disease in Patient #2, with a ratio of only 1.1? What is the distinction between “nonpathological” noncompaction and “partial expression” of noncompaction? According to which echocardiographic criteria was LVHT-diagnosed in the seven patients? Why were other family members of Patient #4,
1234
Correspondence
JACC Vol. 47, No. 6, 2006 March 21, 2006:1226–38
who had a positive family history, not included? Did any of these relatives suffer from a neuromuscular disorder? According to which type was LVHT transmitted in the families? Moreover, which neuromuscular disorder was diagnosed in Patient #7? Did the patient undergo only clinical neurological investigations or were invasive procedures also carried out? Were thrombi detected in any of the investigated patients, particularly in Patient #5, who had systemic embolism? Also, how to explain the pathomechanism of acquired LVHT, where the myocardium was once totally compact? In these cases, pathogenetic explanations other than noncompaction of the embryonic myocardium are required. In conclusion, the distinction between “normal” and “abnormal” trabeculation is a continuing challenge. Commonly accepted diagnostic criteria for LVHT should be developed based on the correlation of pathoanatomical and imaging findings. The diagnosis of LVHT relies on morphological abnormalities and does not require a positive family history, neuromuscular disorders, embolization, or regional wall motion abnormalities as additional diagnostic criteria. *Claudia Stöllberger, MD Josef Finsterer, MD *KA Rudolfstiftung 2nd Medical Department Juchgasse 25 Vienna A-1030 Austria E-mail: [email protected] doi:10.1016/j.jacc.2005.12.035
REFERENCES 1. Petersen SE, Selvanayagam JB, Wiesmann F, et al. Left ventricular non-compaction: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol 2005;46:101–5. 2. Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of left ventricular myocardium. A study of eight cases. Circulation 1990;82:507–13. 3. Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart 2001;86:666 –71. 4. Stöllberger C, Finsterer J, Blazek G. Left ventricular hypertrabeculation/noncompaction and association with additional cardiac abnormalities and neuromuscular disorders. Am J Cardiol 2002;90:899 –901. 5. Tamborini G, Pepi M, Celeste F, et al. Incidence and characteristics of left ventricular false tendons and trabeculations in the normal and pathologic heart by second harmonic echocardiography. J Am Soc Echocardiogr 2004;17:367–74.
REPLY We thank Drs. Stöllberger and Finsterer for their interest in our report (1). Many of the questions they raise reflect concern with how we selected our study population. Their suggestion of enrolling only symptomatic patients, however, with subsequent access to pathoanatomical specimens in order to establish diagnostic criteria would heavily bias findings to the severe end of the spectrum. Concerns raised by Drs. Stöllberger and Finsterer do not recognize that the likelihood of any individual with a ratio of thicknesses between the trabecular and compact myocardium ⬎2.3:1 suffering from pathological noncompaction, when ex-
pressed as the posterior probability, depends on the pretest probability or prevalence. A patient with a known family history of noncompaction and a 1 in 2 chance of having inherited the condition in autosomal dominant fashion would have a 97% chance of suffering from pathological noncompaction. In contrast, given the estimated prevalence of significant noncompaction of 1 in every 2,000 members of the normal population (2), the posterior probability would only be 26%. This Bayesian calculation (3) exemplifies the importance of taking into account the pretest probability, especially in diseases with relatively low prevalence. We included one patient with left ventricular noncompaction on the basis of marked electrocardiographic changes, a family history of left ventricular noncompaction, and a distinct bilaminar appearance of the trabeculated and compacted layers of the myocardium. Based on imaging findings alone, this patient would not have been diagnosed with left ventricular noncompaction. Interestingly, this patient very recently developed symptomatic cardiac failure. This patient, now with clinical evidence of disease, but in the face of an initially nondiagnostic ratio between the trabecular and compacted layers, must now be assumed partially to express the disease, whereas a healthy volunteer with a low pretest probability would be interpreted as having nonpathological noncompaction. We agree that the pathophysiological mechanisms leading to left ventricular noncompaction are not fully understood. Our data on the segmental distribution of trabeculated myocardium, nonetheless, support the hypothesis of an early arrest during the embryological process of compaction. Our experience is that trabeculations can be more readily visualized in the relaxed heart. Magnetic resonance imaging (MRI) allows easy delineation of the epicardial border in both systole and diastole, in contrast to echocardiography, with poor epicardial delineation in diastole. State-of-the-art sequences, such as steadystate free precession, are not prone to flow artifacts, as once seen with the older sequences employing gradient echo techniques. The new sequences permit clear distinction between the trabeculations and the compacted myocardium. This makes this imaging technique ideal to distinguish noncompaction from papillary muscles, false tendons, and aberrant bands, because it has the accuracy to permit analysis of the entirety of the ventricular mass. We are surprised that Drs. Stöllberger and Finsterer raise this point as it is widely acknowledged that MRI, unlike echocardiography, does not suffer from this caveat. Because of the constraints of space, we can only answer some of the further enquiries concerning the patients studied. An apical thrombus was detected by contrast-enhanced MRI in the patient with a history of systemic embolism. We enrolled all first-degree members of our families with left ventricular noncompaction who agreed to participate in the study and to undergo screening. None of our patients, including the seventh patient, had a family history of neuromuscular disorders. Our patients with left ventricular noncompaction and a positive family history showed an autosomal dominant pattern of transmission. In conclusion, our study demonstrated the high diagnostic accuracy of cardiovascular MRI for left ventricular noncompaction. Owing to the importance of pretest probabilities, we disagree with the view that the diagnosis of left ventricular noncompaction should rely exclusively on morphological abnormalities. Thus, assessments using either echocardiography or cardiovascular MRI can at best contribute to the clinical diagnosis.