Folkert J. ten Cate

American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines

A 29-year-old Dominican man with a history of intravenous heroin use and hepatitis C presented with a 5-day history of fever, dyspnoea, haemoptysis, pleuritic chest pain, abdominal pain, haematochezia and haematemesis. Initial physical examination was significant for scleral icterus, generalised abdominal tenderness to palpation, melaena and blood-tinged sputum. Blood cultures grew Fusobacterium species. CT scan of the chest revealed multiple bilateral cavitary features in lung fields. At the same time, a neck ultrasound performed demonstrated thrombophlebitis in the right internal jugular vein, confirming the diagnosis of ‘Lemierre’s syndrome’. Treatment was with antibiotics and supportive care for 6 weeks.

EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography.

Roberto M. Lang, MD, FASE*‡, Luigi P. Badano, MD, FESC†‡, Wendy Tsang, MD*, David H. Adams, MD*, Eustachio Agricola, MD†, Thomas Buck, MD, FESC†, Francesco F. Faletra, MD†, Andreas Franke, MD, FESC†, Judy Hung, MD, FASE*, Leopoldo Pérez de Isla, MD, PhD, FESC†, Otto Kamp, MD, PhD, FESC†, Jaroslaw D. Kasprzak, MD, FESC†, Patrizio Lancellotti, MD, PhD, FESC†, Thomas H. Marwick, MBBS, PhD*, Marti L. McCulloch, RDCS, FASE*, Mark J. Monaghan, PhD, FESC†, Petros Nihoyannopoulos, MD, FESC†, Natesa G. Pandian, MD*, Patricia A. Pellikka, MD, FASE*, Mauro Pepi, MD, FESC†, David A. Roberson, MD, FASE*, Stanton K. Shernan, MD, FASE*, Girish S. Shirali, MBBS, FASE*, Lissa Sugeng, MD*, Folkert J. Ten Cate, MD†, Mani A. Vannan, MBBS, FASE*, Jose Luis Zamorano, MD, FESC, FASE†, and William A. Zoghbi, MD, FASE*

Prediction of Improvement of Regional Left Ventricular Function After Surgical Revascularization A Comparison of Low-Dose Dobutamine Echocardiography With 201Tl Single-Photon Emission Computed Tomography

BACKGROUND Although both 201Tl scintigraphy and low-dose dobutamine echocardiography (LDDE) have been proposed as effective methods of assessing myocardial viability, their relative efficacies are unknown. The aim of the present study was to compare the two imaging techniques in the prediction of improvement of regional left ventricular (LV) function after surgical revascularization. METHODS AND RESULTS Thirty-eight patients with severe chronic LV dysfunction (ejection fraction < or = 40%, one or more akinetic [Ak] or severely hypokinetic [SH] segments on resting echocardiogram) who underwent uncomplicated coronary artery bypass graft surgery were studied with simultaneous dobutamine stress echocardiography and poststress reinjection 201Tl single-photon emission computed tomography (SPECT) before surgery. The Ak or SH segments were considered viable by LDDE when wall thickening improved during the infusion of 10 micrograms.kg-1 min 1 dobutamine. Scintigraphic definition of viability was the presence of normal 201Tl uptake, totally reversible defect, partially reversible defect, or moderately severe fixed defect. The postoperative improvement of dyssynergic segments was determined with a rest echocardiogram 3 months after surgery. Of 608 LV segments, 169 were classified as Ak and 51 as SH on resting preoperative echocardiography. Of these, 170 were successfully revascularized. Wall motion during LDDE improved in 33 severely dyssynergic segments and was more frequent in SH than in Ak segments (19 of 44 versus 14 of 126, P < .0001). Viability was detected by 201Tl SPECT criteria in 103 SH or Ak segments. Thirty-two of the 33 segments from LDDE responders were judged viable on 201Tl SPECT, whereas 201Tl viability was also detected in 71 of 137 segments from LDDE nonresponders. The sensitivity and the specificity for the prediction of postoperative improvement of segmental wall motion were 74% (95% confidence interval [CI], 67% to 81%) and 95% (95% CI, 92% to 98%) by LDDE and 89% (95% CI, 84% to 94%) and 48% (95% 40% to 56%) by 201Tl SPECT, respectively. Positive predictive value of LDDE was higher than that of 201Tl SPECT (85%, [95% CI, 80% to 90%] versus 33% [95% CI, 26% to 40%]). Thirty-six patients had angina before and only 1 had angina 3 months after revascularization. High-dose dobutamine echocardiography demonstrated significant reduction in stress-induced ischemia (new or worsening of preexisting wall motion abnormalities) after surgery (from 163 to 23 LV segments). CONCLUSIONS In patients with severe chronic LV dysfunction, LDDE is a good predictor of the improvement of dyssynergic segments after revascularization. Because 201Tl SPECT overestimates the probability of postoperative improvement of dyssynergic segments, LDDE should be the preferred imaging technique for preoperative assessment of these patients.

Safety and efficacy of a new transpulmonary ultrasound contrast agent: Initial multicenter clinical results

Myocardial contrast echocardiography has been found to be a safe and useful technique for evaluating relative changes in myocardial perfusion and delineating areas at risk. Although earlier contrast agents required direct delivery into the coronary arteries or aortic root, a new echocardiographic contrast agent, sonicated albumin microspheres (Albunex), has been found to cross the pulmonary circulation in experimental models. To determine the safety and preliminary efficacy of intravenous injections of Albunex in humans, 71 patients at three independent medical institutions underwent two-dimensional echocardiographic examination before, during and after the administration of three intravenous doses of Albunex, ranging from 0.01 to 0.12 ml/kg body weight. All patients provided a complete history and underwent physical and neurologic examination and laboratory and electrocardiographic evaluation before the injections; all evaluations (except for the history) were repeated at 2 h and 3 days after the injections of Albunex. The efficacy of the injections was qualitatively assessed by two independent blinded observers using a grading system of 0 to +3, with 0 indicating an absence of contrast effect and +3 indicating full opacification of the cavities examined. All injections were well tolerated and no serious side effects were noted in any of the patients. Irrespective of dose group, a cavity opacification greater than or equal to +2 was seen in the right ventricle in 212 (88%) of 240 injections and in the left ventricle in 151 (63%) of 240 injections as judged by the independent observers. The degree of ventricular cavity opacification appeared to be dose and concentration related.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasound contrast imaging: Current and new potential methods

For 10 years, it was thought that ultrasound (US) contrast agents could be sufficiently detected and imaged with the conventional imaging techniques, now referred to as fundamental imaging. However, it turned out that fundamental imaging was not sensitive enough to detect the contrast agents in the presence of tissue. New imaging techniques that are based on specific properties of the contrast agents, such as nonlinear and transient scattering, proved to be more sensitive. US contrast imaging modalities used today are fundamental, second harmonic, harmonic power Doppler, and pulse inversion; new modalities, such as release burst and subharmonic imaging are emerging. Second harmonic imaging is still not optimal for perfusion imaging applications. However, in combination with Doppler techniques such as power Doppler, it is one of the most sensitive techniques currently available. A complete understanding of the US-contrast agent interaction is essential for further improvements of current detection methods, and the development of new imaging techniques.

Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy: Haploinsufficiency, Deranged Phosphorylation, and Cardiomyocyte Dysfunction

Background— Mutations in the MYBPC3 gene, encoding cardiac myosin-binding protein C (cMyBP-C), are a frequent cause of familial hypertrophic cardiomyopathy. In the present study, we investigated whether protein composition and function of the sarcomere are altered in a homogeneous familial hypertrophic cardiomyopathy patient group with frameshift mutations in MYBPC3 (MYBPC3mut). Methods and Results— Comparisons were made between cardiac samples from MYBPC3 mutant carriers (c.2373dupG, n=7; c.2864_2865delCT, n=4) and nonfailing donors (n=13). Western blots with the use of antibodies directed against cMyBP-C did not reveal truncated cMyBP-C in MYBPC3mut. Protein expression of cMyBP-C was significantly reduced in MYBPC3mut by 33±5%. Cardiac MyBP-C phosphorylation in MYBPC3mut samples was similar to the values in donor samples, whereas the phosphorylation status of cardiac troponin I was reduced by 84±5%, indicating divergent phosphorylation of the 2 main contractile target proteins of the &bgr;-adrenergic pathway. Force measurements in mechanically isolated Triton-permeabilized cardiomyocytes demonstrated a decrease in maximal force per cross-sectional area of the myocytes in MYBPC3mut (20.2±2.7 kN/m2) compared with donor (34.5±1.1 kN/m2). Moreover, Ca2+ sensitivity was higher in MYBPC3mut (pCa50=5.62±0.04) than in donor (pCa50=5.54±0.02), consistent with reduced cardiac troponin I phosphorylation. Treatment with exogenous protein kinase A, to mimic &bgr;-adrenergic stimulation, did not correct reduced maximal force but abolished the initial difference in Ca2+ sensitivity between MYBPC3mut (pCa50=5.46±0.03) and donor (pCa50=5.48±0.02). Conclusions— Frameshift MYBPC3 mutations cause haploinsufficiency, deranged phosphorylation of contractile proteins, and reduced maximal force-generating capacity of cardiomyocytes. The enhanced Ca2+ sensitivity in MYBPC3mut is due to hypophosphorylation of troponin I secondary to mutation-induced dysfunction.

Hypertrophic cardiomyopathy in a large community-based population: Clinical outcome and identification of risk factors for sudden cardiac death and clinical deterioration

OBJECTIVES This study evaluates the clinical course and identifies risk factors for sudden cardiac death (SCD) and clinical deterioration in hypertrophic cardiomyopathy (HCM) in a large community-based population. Comparison was made with data from six tertiary referral and six nonreferral institutions. BACKGROUND Hypertrophic cardiomyopathy is a disease with marked heterogeneity in clinical presentation and prognosis. Risk factors for SCD are not well defined in patients free of referral bias. METHODS Between 1970 and 1999, 225 consecutive patients (mean age [+/-SD] 41+/-16 years) were examined and followed at yearly intervals. RESULTS Forty-four deaths were recorded of which 27 cases were cardiovascular. Fourteen patients died suddenly, six were successfully resuscitated, and seven patients died of congestive heart failure. The annual mortality, annual cardiac mortality, and annual mortality due to sudden death were 1.3%, 0.8%, and 0.6%, respectively. At least one New York Heart Association (NYHA) functional class deterioration was reported in 33% of the patients with a significant (> or =50 mm Hg) left ventricular outflow tract (LVOT) gradient in contrast to 7% without obstruction. The presence of syncope was related to SCD (p < 0.05). Younger age and more severe functional limitation distinguishes patients from in hospital-based centers from the ones in community-based centers. CONCLUSIONS Hypertrophic cardiomyopathy is a benign disease in an unselected population with a low incidence of cardiac death. Syncope was associated with a higher incidence of SCD and patients with a significant LVOT obstruction were more susceptible to clinical deterioration.

Accurate Measurement of Left Ventricular Ejection Fraction by Three-dimensional Echocardiography A Comparison With Radionuclide Angiography

BACKGROUND Three-dimensional echocardiography is a promising technique for calculation of left ventricular ejection fraction, because it allows its measurement without geometric assumptions. However, few data exist that study its reproducibility and accuracy in patients. METHODS AND RESULTS Twenty-five patients underwent radionuclide angiography and three-dimensional echocardiography that used the rotational technique (2 degrees interval and ECG and respiratory gating). Left ventricular volume and ejection fraction were calculated by use of Simpsons rule at a slice thickness of 3 mm. Analyses were performed to define the largest slice thickness required for accurate calculation of left ventricular volume and ejection fraction. Three-dimensional echocardiography showed excellent correlation with radionuclide angiography for calculation of left ventricular ejection fraction (mean +/- SD, 38.9 +/- 19.8 and 38.5 +/- 18.0, respectively; r = .99); their mean difference was not significant (0.03 +/- 0.17; P = .3), and they had a close limit of agreement (-0.385, 0.315). Intraobserver variability for radionuclide angiography and three-dimensional echocardiography was 4.2% and 2.6%, respectively, whereas interobserver variability was 6.2% and 5.3%, respectively. There was no significant difference between left ventricular volume and ejection fraction calculated at a slice thickness of 3 mm and that calculated at different slice thicknesses up to 24 mm. However, the standard deviation of the mean difference showed a stepwise increase, particularly at thicknesses > 15 mm. At a slice thickness of 15 mm, the probability of three-dimensional echocardiography to detect > or = 6% difference in ejection fraction was 80%. CONCLUSIONS Three-dimensional echocardiography has excellent correlation with radionuclide angiography for calculation of left ventricular ejection fraction in patients and has an observer variability similar to that of radionuclide angiography. We recommend the use of a 15-mm-thick slice for accurate and rapid measurement of left ventricular volume and ejection fraction.

The Importance of Genetic Counseling, DNA Diagnostics, and Cardiologic Family Screening in Left Ventricular Noncompaction Cardiomyopathy

Background—Left ventricular (LV) noncompaction (LVNC) is a distinct cardiomyopathy featuring a thickened bilayered LV wall consisting of a thick endocardial layer with prominent intertrabecular recesses with a thin, compact epicardial layer. Similar to hypertrophic and dilated cardiomyopathy, LVNC is genetically heterogeneous and was recently associated with mutations in sarcomere genes. To contribute to the genetic classification for LVNC, a systematic cardiological family study was performed in a cohort of 58 consecutively diagnosed and molecularly screened patients with isolated LVNC (49 adults and 9 children). Methods and Results—Combined molecular testing and cardiological family screening revealed that 67% of LVNC is genetic. Cardiological screening with electrocardiography and echocardiography of 194 relatives from 50 unrelated LVNC probands revealed familial cardiomyopathy in 32 families (64%), including LVNC, hypertrophic cardiomyopathy, and dilated cardiomyopathy. Sixty-three percent of the relatives newly diagnosed with cardiomyopathy were asymptomatic. Of 17 asymptomatic relatives with a mutation, 9 had noncompaction cardiomyopathy. In 8 carriers, nonpenetrance was observed. This may explain that 44% (14 of 32) of familial disease remained undetected by ascertainment of family history before cardiological family screening. The molecular screening of 17 genes identified mutations in 11 genes in 41% (23 of 56) tested probands, 35% (17 of 48) adults and 6 of 8 children. In 18 families, single mutations were transmitted in an autosomal dominant mode. Two adults and 2 children were compound or double heterozygous for 2 different mutations. One adult proband had 3 mutations. In 50% (16 of 32) of familial LVNC, the genetic defect remained inconclusive. Conclusion—LVNC is predominantly a genetic cardiomyopathy with variable presentation ranging from asymptomatic to severe. Accordingly, the diagnosis of LVNC requires genetic counseling, DNA diagnostics, and cardiological family screening.

Importance of transducer position in the assessment of apical rotation by speckle tracking echocardiography.

BACKGROUND Speckle tracking echocardiography is increasingly used to quantify left ventricular (LV) twist. However, one of the limitations of the assessment of LV twist by speckle tracking echocardiography is the crucial dependence on correct acquisition of a LV apical short-axis. This study sought to assess the influence of transducer position on LV apical rotation measurements. METHODS The study population consisted of 58 consecutive healthy volunteers (mean age 38 +/- 13 years, 25 men). To obtain parasternal short-axis images at the LV apical level, the following protocol was used. From the standard parasternal position (LV and aorta most inline, with the mitral valve tips in the middle of the sector) an as-circular-as-possible short-axis image of the LV apex, just proximal to the level with end-systolic LV luminal obliteration, was obtained by angulation of the transducer (position 1). From this position, the position of the transducer was changed to one (position 2) and two (position 3) intercostal spaces more caudal with subsequent similar transducer adaptations. RESULTS In 8 volunteers (14%) parasternal image quality was insufficient for speckle tracking echocardiography. In 13 volunteers (22%) the LV apical short-axis could only be obtained from one transducer position. In the remaining volunteers with two (n = 27) or three (n = 10) available transducer positions, a more caudal transducer position was associated with increased measured LV apical rotation. Mean measured LV apical rotation was 5.2 +/- 1.8 degrees at position 1, 7.3 +/- 2.6 degrees at position 2 (P < .001), and 8.7 +/- 2.2 degrees at position 3 (P < .001 vs position 1 and P < .05 vs position 2). CONCLUSION A more caudal transducer position is associated with increased measured LV apical rotation.