Rolf Jenni

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

OBJECTIVES We sought to describe characteristics and outcome in adults with isolated ventricular noncompaction (IVNC). BACKGROUND Isolated ventricular noncompaction is an unclassified cardiomyopathy due to intrauterine arrest of compaction of the loose interwoven meshwork. Knowledge regarding diagnosis, morbidity and prognosis is limited. METHODS Echocardiographic criteria for IVNC include-in the absence of significant heart lesions-segmental thickening of the left ventricular myocardial wall consisting of two layers: a thin, compacted epicardial and an extremely thickened endocardial layer with prominent trabeculations and deep recesses. Thirty-four adults (age >16 years, 25 men) fulfilled the diagnostic criteria and were followed prospectively. RESULTS At diagnosis, mean age was 42 + 17 years, and 12 patients (35%) were in New York Heart Association class III/IV. Left ventricular end-diastolic diameter was 65 + 12 mm and ejection fraction 33 + 13%. Apex and/or midventricular segments of both the inferior and lateral wall were involved in >80% of patients. Follow-up was 44 + 40 months. Major complications were heart failure in 18 patients (53%), thromboembolic events in 8 patients (24%) and ventricular tachycardias in 14 patients (41%). There were 12 deaths: sudden in six, end-stage heart failure in four and other causes in two patients. Four patients underwent heart transplantation. Automated cardioverter/defibrillators were implanted in four patients. CONCLUSIONS Diagnosis of IVNC by echocardiography using strict criteria is feasible. Its mortality and morbidity are high, including heart failure, thrombo-embolic events and ventricular arrhythmias. Risk stratification includes heart failure therapy, oral anticoagulation, heart transplantation and implantation of an automated defibrillator/cardioverter. As IVNC is a distinct entity, its classification as a specific cardiomyopathy seems to be more appropriate.

Isolated Noncompaction of the Myocardium in Adults

OBJECTIVE To describe the entity of isolated ventricular noncompaction (IVNC) and present a series of cases of this rare disorder in an adult population. MATERIAL AND METHODS We review a 10-year experience with the diagnosis of IVNC and discuss the clinical, echocardiographic, and pathologic features of this condition. Echocardiographic diagnostic criteria included the absence of coexisting cardiac abnormalities, the presence of prominent and excessive trabeculations of one or more ventricular wall segments, and intertrabecular spaces perfused from the ventricular cavity. Pathologic examination focused on regions with exaggerated trabeculations and deep intertrabecular spaces. RESULTS IVNC is an unexplained arrest of myocardial morphogenesis previously encountered mainly in pediatric patients. Among 37,555 transthoracic echocardiographic studies performed at our hospital between January 1984 and October 1993, 17 cases of IVNC were identified in adult subjects (14 men and 3 women, 18 to 71 years of age). The mean time from onset of symptoms to correct diagnosis was 3.5 +/- 5.7 years, and the mean duration of follow-up was 30 +/- 28 months. Common clinical symptoms were heart failure, ventricular arrhythmias, and a history of embolic events. Two-dimensional echocardiography revealed 10 patients with left ventricular and 7 (41%) with biventricular IVNC. During a 6-year follow-up period, eight patients died and two underwent heart transplantation. CONCLUSION Although the diagnosis of IVNC in an adult population is often delayed because of similarities with more frequently diagnosed conditions, two-dimensional echocardiography will facilitate the diagnosis of IVNC in this subset of patients. Because of the high incidence of heart failure, ventricular arrhythmias, and embolization in adults with IVNC, early diagnosis is important.

Mutations in Sarcomere Protein Genes in Left Ventricular Noncompaction

Background— Left ventricular noncompaction constitutes a primary cardiomyopathy characterized by a severely thickened, 2-layered myocardium, numerous prominent trabeculations, and deep intertrabecular recesses. The genetic basis of this cardiomyopathy is still largely unresolved. We speculated that mutations in sarcomere protein genes known to cause hypertrophic cardiomyopathy and dilated cardiomyopathy may be associated with left ventricular noncompaction. Methods and Results— Mutational analysis in a cohort of 63 unrelated adult probands with left ventricular noncompaction and no other congenital heart anomalies was performed by denaturing high-performance liquid chromatography analysis and direct DNA sequencing of 6 genes encoding sarcomere proteins. Heterozygous mutations were identified in 11 of 63 samples in genes encoding &bgr;-myosin heavy chain (MYH7), &agr;-cardiac actin (ACTC), and cardiac troponin T (TNNT2). Nine distinct mutations, 7 of them in MYH7, 1 in ACTC, and 1 in TNNT2, were found. Clinical evaluations demonstrated familial disease in 6 of 11 probands with sarcomere gene mutations. MYH7 mutations segregated with the disease in 4 autosomal dominant LVNC kindreds. Six of the MYH7 mutations were novel, and 1 encodes a splice-site mutation, a relatively unique finding for MYH7 mutations. Modified residues in &bgr;-myosin heavy chain were located mainly within the ATP binding site. Conclusions— We conclude that left ventricular noncompaction is within the diverse spectrum of cardiac morphologies triggered by sarcomere protein gene defects. Our findings support the hypothesis that there is a shared molecular etiology of different cardiomyopathic phenotypes.

Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity?

Non-compaction of the left ventricular myocardium (LVNC) has gained increasing recognition during the last 25 years. There is a morphological trait of the myocardial structure with a spectrum from normal variants to the pathological phenotype of LVNC, which reflects the embryogenic structure of the human heart due to an arrest in the compaction process during the first trimester. It must be cautioned not to overdiagnose LVNC: the morphological spectrum of trabeculations, from normal variants to pathological trabeculations with the morphological feature of LVNC must be carefully considered. The classical triad of complications are heart failure, arrhythmias, including sudden cardiac death, and systemic embolic events. Non-compaction of the left ventricular myocardium can occur in isolation or in association with congenital heart defects (CHDs), genetic syndromes, and neuromuscular disorders among others. The clinical spectrum is wide and the outcome is more favourable than in previously described populations with a negative selection bias. Familial occurrence is frequent with autosomal dominant and X-linked transmissions. Different mutations in sarcomere protein genes were identified and there seems to be a shared molecular aetiology of different cardiomyopathic phenotypes, including LVNC, hypertrophic and dilated cardiomyopathies. Thus, genetic heterogeneity, with an overlap of different phenotypes, and the variability of hereditary patterns, raise the questions whether there is a morphological trait from dilated/hypertrophic cardiomyopathy to LVNC and what are the triggers and modifiers to develop either dilated, hypertrophic cardiomyopathy, or LVNC in patients with the same mutation. The variety in clinical presentation, the genetic heterogeneity, and the phenotype of the first transgenetic animal model of an LVNC-associated mutation question the hypothesis that LVNC be a distinct cardiomyopathy: it seems to be rather a distinct phenotype or phenotypic, morphological expression of different underlying diseases than a distinct cardiomyopathy.

Isolated ventricular non-compaction of the myocardium in adults

Isolated ventricular non-compaction (IVNC) in adults is a genetic cardiac disease of emerging importance with a distinct clinical and pathophysiological presentation. The body of evidence for the underlying genetic basis of the disease has also grown. Prognosis remains poor for patients with impaired systolic left ventricular function, as treatment options are very limited. The diagnosis of IVNC, however, is often missed, most often as a consequence of ignorance of the condition. The relevant clinical issues and the emerging concepts of the aetiology of IVNC are summarised.

Cardiac risk after mediastinal irradiation for Hodgkin's disease

PURPOSE To evaluate the risk of cardiac lesions after conventionally fractionated irradiation (Rt) of the mediastine with or without chemotherapy (Ct) in patients with Hodgkins disease (HD) and to relate them to known cardiovascular risk factors. PATIENTS AND METHODS Between 1964 and 1992, 352 (total group) patients with HD were treated with curative intention using Rt with or without Ct including the mediastine and had a follow-up of at least 1 year. More than 96% of the patients had a complete follow-up. One hundred forty-four patients (64% of the living patients, heart study group) have regular follow-up in our department and had a special heart examination including rest and exercise ECG, echocardiography and myocardial perfusion scintigraphy (112 patients). Doses per fraction in the anterior heart region were between 1.3 and 2.1 Gy. Total doses were between 30.0 and 42.0 Gy in 93% of cases. The mean length of follow-up was 11.2 years (range 1.0-31.5 years). Other cardiovascular risk factors evaluated were body mass index, blood pressure, smoking history, diabetes mellitus, hypercholesterolemia and history of coronary artery disease before Rt. RESULTS In the total group, the risk of fatal cardiac ischemic events and/or of sudden unexpected death was significantly higher than expected with a relative risk of 4.2 for myocardial infarction and 6.7 for myocardial infarction or sudden death. In female patients and in patients without other cardiovascular risk factors, the risk of fatal or non-fatal ischemic cardiac events was not significantly different from the expected value. In the subgroup with no cardiovascular risk factors and treatment without Ct, there was no ischemic or other major cardiac event. Echocardiography showed valvular thickenings in a large amount of the patients (the cumulative risk after 30-year follow-up was above 60%) but mostly without hemodynamic disturbance. In patients without hypertension and without coronary artery disease, findings of perfusion scintigraphy and echocardiographic evaluation of systolic and diastolic function were normal. Treatment with Ct was not a significant risk factor for cardiac events but the number of patients whose treatment included adriamycin and with a follow-up exceeding 10 years is to low for a definitive evaluation. CONCLUSIONS In patients without the usual cardiovascular risk factors (smoking, hypertension, obesity, hypercholesterolemia, diabetes mellitus) the risk of serious cardiac lesions after conventionally fractionated irradiation of the mediastinum with an intermediate total dose between 30 and 40 Gy is low. Also the cardiac risk of the combination of this irradiation with Ct including adriamycin with a total dose between 200 and 300 mg/m2 seems low but further long-term observation is necessary.

Nifedipine for high altitude pulmonary oedema

In a laboratory at 4559 m six subjects with high altitude pulmonary oedema (HAPO) characterised by clinical signs, severe hypoxaemia, widened alveolar-arterial oxygen gradient, pulmonary hypertension, and alveolar oedema on chest radiography were treated with nifedipine. Despite continued exercise at the same altitude this treatment, without supplementary oxygen, resulted in clinical improvement, better oxygenation, reduction of alveolar arterial oxygen gradient and pulmonary artery pressure, and progressive clearing of alveolar oedema. Nifedipine offers a potential emergency treatment for HAPO when descent or evacuation is impossible and oxygen is not available. The findings also suggest that hypoxic pulmonary hypertension is essential in the pathogenesis of HAPO.

Paravalvular leakage after mitral valve replacement: improved long-term survival with aggressive surgery?

BACKGROUND Following mitral valve replacement, surgical closure of paravalvular leaks is usually advised in severely symptomatic patients and in those requiring blood transfusions for persisting haemolysis. However, the long-term prognosis of less symptomatic patients or those not needing blood transfusions is unknown. METHODS Between 1987 and 1997, we observed 96 patients with mitral paravalvular leakage. A paraprosthetic leak was diagnosed after a median time of 119 days (range: 1 day-23 years) after primary mitral valve replacement. During an average follow-up of 5 years (range: 1-23 years), 50/96 patients were referred for surgical closure. RESULTS Compared with patients who received conservative treatment, those referred for surgery had a significantly lower mean preoperative haematocrit (P = 0.002) with a higher proportion of patients being in the NYHA class III/IV (P = 0.03). Age, gender, left ventricular function and number and size of leaks did not differ between the groups. The 30-day postoperative mortality for valve reoperation was 6% (3/50); during follow-up three further patients died, resulting in an overall mortality rate of 12%. In the group treated conservatively there was a mortality rate of 26% (12/46). Thus, the actuarial survival for patients referred for surgery was 98, 90 and 88% after 1, 5 and 10 years, compared with 90, 75 and 68% for patients treated conservatively (long-rank P = 0.03). In addition, there was a significant increase in mean haematocrit levels (P = 0.0001) and an improvement in NYHA class III/IV symptoms (P = 0.002), vertigo (P = 0.001) and fatigue (P = 0.001) after surgery. CONCLUSIONS Following mitral valve replacement, a more aggressive surgical treatment is recommended for patients with paraprosthetic leaks. Surgery should be offered to less symptomatic patients, as well as those not requiring blood transfusion.

Pulmonary Arterial Hypertension Related to HIV Infection: Improved Hemodynamics and Survival Associated with Antiretroviral Therapy

This study aimed to assess the long-term course of pulmonary arterial hypertension related to infection with human immunodeficiency virus (PAHRH) and the influence of antiretroviral therapy (ART) on its characteristics. We retrospectively analyzed all 47 patients in the Swiss HIV Cohort Study in whom PAHRH was diagnosed. Among 35 patients who underwent follow-up Doppler echocardiography, the right ventricular systolic pressure over right atrial pressure gradient increased by a median of 25 mm Hg in 9 patients who had not received ART, decreased by a median of 3 mm Hg in 12 patients who had received nucleoside analogs, and decreased by a median of 21 mm Hg in 14 patients who had received highly active ART (HAART) (P<.005). Among all 47 patients, median duration of survival after PAHRH diagnosis was 2.7 years. HAART significantly decreased mortality due to PAHRH as well as other causes. This study suggests a beneficial effect of combination ART in patients with PAHRH.

Persisting myocardial sinusoids of both ventricles as an isolated anomaly : Echocardiographic, angiographic, and pathologic anatomical findings

The persistence of myocardial sinusoids in both ventricles as an isolated anomaly is described. A 21-year-old patient had progressive heart failure considered as cardiomyopathy of obscure etiology. Two-dimensional echocardiography demonstrated channel-like structures in the thickened myocardium of both hypokinetic ventricles. Angiography showed a honeycomblike inner contour in both ventricles. Autopsy proved the diagnosis of persistent sinusoids in a thickened myocardium.