Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis

Experimental work during the past 15 years has demonstrated that endothelial cells in the heart play an obligatory role in regulating and maintaining cardiac function, in particular, at the endocardium and in the myocardial capillaries where endothelial cells directly interact with adjacent cardiomyocytes. The emerging field of targeted gene manipulation has led to the contention that cardiac endothelial-cardiomyocytal interaction is a prerequisite for normal cardiac development and growth. Some of the molecular mechanisms and cellular signals governing this interaction, such as neuregulin, vascular endothelial growth factor, and angiopoietin, continue to maintain phenotype and survival of cardiomyocytes in the adult heart. Cardiac endothelial cells, like vascular endothelial cells, also express and release a variety of auto- and paracrine agents, such as nitric oxide, endothelin, prostaglandin I(2), and angiotensin II, which directly influence cardiac metabolism, growth, contractile performance, and rhythmicity of the adult heart. The synthesis, secretion, and, most importantly, the activities of these endothelium-derived substances in the heart are closely linked, interrelated, and interactive. It may therefore be simplistic to try and define their properties independently from one another. Moreover, in relation specifically to the endocardial endothelium, an active transendothelial physicochemical gradient for various ions, or blood-heart barrier, has been demonstrated. Linkage of this blood-heart barrier to the various other endothelium-mediated signaling pathways or to the putative vascular endothelium-derived hyperpolarizing factors remains to be determined. At the early stages of cardiac failure, all major cardiovascular risk factors may cause cardiac endothelial activation as an adaptive response often followed by cardiac endothelial dysfunction. Because of the interdependency of all endothelial signaling pathways, activation or disturbance of any will necessarily affect the others leading to a disturbance of their normal balance, leading to further progression of cardiac failure.

/pdf/cardiac-endothelial-myocardial-signaling-its-role-in-cardiac-2fjkofy30k.pdf

Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity

The heart in higher vertebrates develops from a simple tube into a complex organ with four chambers specialized for efficient pumping at pressure. During this period, there is a concomitant change in the level of myocardial organization. One important event is the emergence of trabeculations in the luminal layers of the ventricles, a feature which enables the myocardium to increase its mass in the absence of any discrete coronary circulation. In subsequent development, this trabecular layer becomes solidified in its deeper part, thus increasing the compact component of the ventricular myocardium. The remaining layer adjacent to the ventricular lumen retains its trabeculations, with patterns which are both ventricle- and species-specific. During ontogenesis, the compact layer is initially only a few cells thick, but gradually develops a multilayered spiral architecture. A similar process can be charted in the atrial myocardium, where the luminal trabeculations become the pectinate muscles. Their extent then provides the best guide for distinguishing intrinsically the morphologically right from the left atrium. We review the variations of these processes during the development of the human heart and hearts from commonly used laboratory species (chick, mouse, and rat). Comparison with hearts from lower vertebrates is also provided. Despite some variations, such as the final pattern of papillary or pectinate muscles, the hearts observe the same biomechanical rules, and thus share many common points. The functional importance of myocardial organization is demonstrated by lethality of mouse mutants with perturbed myocardial architecture. We conclude that experimental studies uncovering the rules of myocardial assembly are relevant for the full understanding of development of the human heart.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/%28SICI%291097-0185%2820000401%29258%3A4%3C319%3A%3AAID-AR1%3E3.0.CO%3B2-O

Developmental patterning of the myocardium.

tion of pulse pressure does not necessarily parallel that of systolic and diastolic blood pressure. J Hypertens 2000;18:1159–1163. 2. Sesso HD, Stampfer MJ, Rosner B, Gaziano JM, Hennekens CH. Two-year changes in blood pressure and subsequent risk of cardiovascular disease in men. Circulation 2000;102:307–312. 3. Benetos A, Zureik M, Morcet J, Thomas F, Bean K, Safar M, Ducimetiere P, Guize L. A decrease in diastolic blood pressure combined with an increase in systolic blood pressure is associated with a higher cardiovascular mortality in men. J Am Coll Cardiol 2000;35:673–680. 4. Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A, Santucci C, Reboldi G. Ambulatory blood pressure: an independent predictor of prognosis in essential hypertension (erratum). Hypertension 1995;25:462. 5. Schillaci G, Reboldi G, Verdecchia P. High-normal serum creatinine is a predictor of cardiovascular risk in essential hypertension. Arch Intern Med 2001;161:886–891. 6. Mancia G, Zanchetti A, Agabiti-Rosei E, Benemio G, De Cesaris R, Fogari R, Pessina A, Porcellati C, Rappelli A, Salvetti A, et al. Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy. Circulation 1997;95:1464–1470. 7. Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Pede S, Porcellati C. Ambulatory pulse pressure: a potent predictor of total cardiovascular risk in hypertension. Hypertension 1998;32:983–988. 8. Mancia G, Parati G. Ambulatory blood pressure monitoring and organ damage. Hypertension 2000;36:894–900. 9. Mancia G, Bertinieri G, Grassi G, Parati G, Pomidossi G, Ferrari A, Gregorini L, Zanchetti A. Effects of blood pressure measured by the doctor on patient’s blood pressure and heart rate. Lancet 1983;2:695–698. 10. Khattar RS, Senior R, Lahiri A. Cardiovascular outcome in white-coat versus sustained mild hypertension: a 10 year follow-up study. Circulation 1998;98: 1982–1987. 11. Staessen JA, Thijs L, Fagard R, O’Brien ET, Clement D, de Leeuw PW, Mancia G, Nachev C, Palatini P, Parati G, Tuomilehto J, Webster J. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. JAMA 1999;282:539–546. 12. Redon J, Campos C, Narciso ML, Rodicio JL, Pascual JM, Ruilope LM. Prognostic value of ambulatory blood pressure monitoring in refractory hypertension. A prospective study. Hypertension 1998;31:712–718. 13. Ohkubo T, Imai Y, Tsuji I, Nagai K, Watanabe N, Minami N, Itoh O, Bando T, Sakuma M, Fukao A, Satoh H, Hisamichi S, Abe K. Prediction of mortality by ambulatory blood pressure monitoring versus screening blood pressure measurements: a pilot study in Ohasama. J Hypertens 1997;15:357–364.

Left ventricular hypertrabeculation/noncompaction and association with additional cardiac abnormalities and neuromuscular disorders

Case Presentation: A 42-year-old woman was referred to the Hypertrophic Cardiomyopathy Clinic. A diagnosis of apical hypertrophic cardiomyopathy had been given 16 years earlier on the basis of echocardiographic findings. Left ventricular systolic function was reportedly at the lower limit of normal 5 years earlier.

The patient gave a 6-month history of mild dyspnea occurring during exertion. Although still active, her exercise tolerance had decreased. She also complained of more frequent and sustained episodes of rapid palpitations associated with shortness of breath. She had occasional episodes of heavy, burning discomfort in the chest during activity and while at rest.

There was no family history of cardiomyopathy, although first degree relatives had not been screened. Her heart rate was 74. Blood pressure was 110/70. Jugular venous pressure was normal. Carotid pulse volume and contour were normal. The first and second heart sounds were normal. There was a presystolic apical impulse and a prominent S4 gallop. There was no S3 gallop. A grade III/VI, harsh, midsystolic murmur was heard best at the upper left sternal border. There was no diastolic murmur.

The ECG showed sinus rhythm, normal QRS duration, and left ventricular hypertrophy with repolarization changes. An echocardiogram demonstrated marked thickening and heavy trabeculation of the apical half of the left ventricle. Color Doppler displayed flow within the deep intertrabecular recesses. The left ventricle was not dilated. There was diffuse left ventricular hypokinesis with an ejection fraction of 20% to 25%. The right ventricle appeared to be more heavily trabeculated than usual. No additional abnormalities were present. The findings were consistent with isolated noncompaction of the ventricular myocardium.

Noncompaction of the ventricular myocardium is a cardiomyopathy thought to be caused by arrest of normal embryogenesis of the endocardium and myocardium. This abnormality is often associated with other congenital cardiac defects, but it …

Noncompaction of the Ventricular Myocardium

Aims Isolated ventricular non-compaction is a rare congenital cardiomyopathy with a high morbidity and mortality due to malignant arrhythmias and pump failure. Areas affected by non-compaction are characterized by increased trabecularization and deep inter-trabecular spaces. We hypothesized perfusion defects in these areas and performed positron emission tomography to evaluate the myocardial perfusion in non-compacted areas.

Methods and Results Five children (age 10–14 years) with isolated ventricular non-compaction underwent positron emission tomography using N-13-ammonia as flow marker and intravenous dipyridamole for stress testing. Myocardial blood flow was quantified using the positron emission tomography time–activity curves in non-compacted areas and normal myocardium, which were diagnosed by echocardiography, magnetic resonance imaging, and angiography. Coronary angiography, performed in two children with extensive forms of left ventricular non-compaction, demonstrated normal coronary arteries. Myocardial blood flow measurements at rest and after dipyridamole application demonstrated 16–33% and 32–57% perfusion impairment, respectively, in non-compacted areas compared to normal myocardium. Areas of restricted myocardial perfusion corresponded well to the non-compacted areas, defined echographically and by magnetic resonance imaging.

Conclusion Positron emission tomography demonstrates restricted myocardial perfusion and decreased flow reserve in areas of ventricular non-compaction in children. The myocardial perfusion defects in non-compacted areas may be the cause of myocardial damage and possibly form the basis of arrhythmias and pump failure.

/pdf/myocardial-ischaemia-in-children-with-isolated-ventricular-22bse3rk5u.pdf

G Junga

Papers

Myocardial ischaemia in children with isolated ventricular non-compaction