Third and Fourth Heart Sounds and Myocardial Fibrosis in Hypertrophic Cardiomyopathy.

BACKGROUND: The 4th heart sound (S4) is commonly heard in patients with hypertrophic cardiomyopathy (HCM). The 3rd heart sound (S3) is also audible in HCM patients regardless of the presence or absence of heart failure. These extra heart sounds may be associated with myocardial fibrosis because myocardial fibrosis has been suggested to affect left ventricular compliance.Methods and Results:The present retrospective study evaluated 53 consecutive HCM patients with sinus rhythm who had no symptoms of heart failure and underwent an initial assessment including phonocardiography, echocardiography, and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI). S3 was detected on phonocardiography in 13% of all patients, and S4 was recorded in 75% of patients. Patients with S3 had a higher incidence of LGE and larger LGE volumes (86% and 11.5±2.4 g/cm, respectively) than patients without S3 (33% and 2.5±0.8 g/cm, respectively; P=0.02 and P=0.002). The presence of S4 was not associated with MRI findings, including the incidence of LGE and LGE volume. The diagnostic value of S3 for the detection of LGE was highly specific (97%), with a low sensitivity (29%). CONCLUSIONS: Myocardial fibrosis, as assessed by LGE, was associated with S3 but not with S4 in patients with HCM. These results may contribute to the risk stratification of patients with HCM.

Unusual clinical course after surgical repair of unruptured aneurysm of sinus of Valsalva.

Aneurysms of the sinus of Valsalva are characterized by dilatation of at least one of the three aortic sinuses. We experienced a case with unruptured aneurysm of the right sinus of Valsalva, in which serial imaging studies were useful in assessing a rare complication after surgical repair. An asymptomatic 75-year-old man underwent patch closure of the aneurysm orifice because of progressive enlargement of the aneurysm. The postoperative course was uneventful, and computed tomography (CT), performed a week after the patch repair, showed no leakage of contrast medium into the isolated aneurysm. Three months later, echocardiography showed decreased size of the aneurysm with heterogeneous echogenicity and possible blood flow in the aneurysm, findings suggestive of thrombus formation and a recurrent fistula. CT with contrast medium showed partial recanalization between the patched aneurysm and the right sinus of Valsalva. Follow-up echocardiography, performed 1 year after surgery, revealed neither definite aneurysm nor shunt flow of Valsalva. The present case highlights that non-invasive follow-up can be an alternative option when carried out with caution in selected patients with incomplete closure of Valsalva aneurysm.

Notched QRS for the assessment of myocardial fibrosis in hypertrophic cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) sometimes develop myocardial fibrosis in association with adverse cardiovascular events. Electrocardiography (ECG) could provide helpful information on myocardial fibrosis in HCM, as in coronary artery disease. METHODS AND RESULTS: A total of 60 patients with HCM without bundle branch block underwent cardiac magnetic resonance imaging (CMR). The extent or location of late gadolinium enhancement (LGE) was examined in relation to 12-lead ECG. A notch on QRS was defined as at least 2 consecutive spikes in the same polarity with a reversal of direction ≥90° and the initial negative deflection ≥0.05 mV. LGE was associated with notched QRS, leftward QRS axis, and prolonged QRS duration, but not with any other findings such as abnormal Q waves, R-wave amplitude, or ST-T changes. Notched QRS was most useful in determining the presence or absence of myocardial fibrosis, with a sensitivity of 70% and a specificity of 81% using a cut-off of the number of leads with notched QRS ≥2. The number of notched QRS leads was positively correlated with LGE volume (P<0.01) and the lead distribution of notched QRS was informative about the location of LGE. CONCLUSIONS: A notch on QRS was useful in estimating myocardial fibrosis as assessed on CMR LGE in HCM patients without bundle branch block.

Right bundle branch block and ventricular septal fibrosis in patients with hypertrophic cardiomyopathy.

BACKGROUND: Right bundle branch block (RBBB) is associated with ventricular septal fibrosis in patients with hypertrophic cardiomyopathy (HCM) after alcohol septal ablation, but little data are available in HCM patients without a history of septal ablation. METHODS: Magnetic resonance late gadolinium enhancement (LGE) was performed in 59 HCM patients with no history of alcohol septal ablation. The location and extent of LGE were examined in relation to electrocardiographic features including RBBB. RESULTS: LGE volume was higher in 7 HCM patients with RBBB (7.3±7.4g/cm) than in patients without RBBB (2.9±7.4g/cm, p=0.016). LGE volume was positively correlated to QRS duration of RBBB (correlation coefficient=0.93, p=0.023). The diagnostic value of RBBB was highly specific for the detection of LGE in the ventricular septum, with sensitivity 21% and specificity 94%. CONCLUSIONS: The presence of RBBB may be a simple marker for detecting ventricular septal fibrosis in HCM patients who had no history of alcohol septal ablation. Further studies are necessary to confirm our findings.

Usefulness of high-sensitivity cardiac troponin T and brain natriuretic peptide as biomarkers of myocardial fibrosis in patients with hypertrophic cardiomyopathy.

Myocardial fibrosis assessed by late gadolinium enhancement cardiac magnetic resonance imaging is associated with cardiovascular events in patients with hypertrophic cardiomyopathy (HC), but few data are available regarding the utility of biomarkers for detecting late gadolinium enhancement. The aim of this study was to examine serum levels of myoglobin, cardiac myosin light chain I, high-sensitivity cardiac troponin T (hs-cTnT), and creatine kinase-MB isoenzyme and plasma levels of brain natriuretic peptide (BNP) in relation to late gadolinium enhancement in 53 patients with HC. Levels of hs-cTnT and BNP were higher in 23 patients with late gadolinium enhancement than in 30 patients without it (p <0.01 for both). An hs-cTnT level ≥0.007 ng/ml or a BNP level ≥70 pg/ml had good diagnostic value for detecting late gadolinium enhancement, with sensitivity of 96% or specificity of 90% with the combination of these 2 biomarkers. The extent of late gadolinium enhancement was correlated with BNP level (p <0.01) but not with hs-cTnT level in 23 patients with HC with late gadolinium enhancement. The increase in the extent of late gadolinium enhancement was related to hs-cTnT level in 8 patients during 22 months of follow-up (p = 0.02). In conclusion, the combination of hs-cTnT and BNP is useful in detecting myocardial fibrosis in patients with HC. The findings of this study indicate that hs-cTnT is a direct marker of ongoing myocardial fibrosis and that BNP is a marker of left ventricular overload partially associated with myocardial fibrosis.

Metastatic chordoma to the left ventricle: A case report.

Chordoma is a rare neoplasm of bone that develops from the remnants of the primitive notochord. We present a 78-year-old woman with metastatic chordoma to the left ventricle. She had been diagnosed with sacral chordoma 5 years earlier, and chordoma gradually spread to numerous muscles, the ankle joint of the left leg, bilateral lungs, and the brain, despite repeated surgical excisions and carbon heavy-ion radiotherapy. Positron emission tomography/computed tomography showed an abnormal accumulation in the heart, with features similar to the other metastatic lesions. Transthoracic echocardiography could not provide a clear view of the heart, but multidetector computed tomography revealed that a giant abnormal mass was attached to the apical inferior segment of the left ventricle. The patient stated that she did not want to undergo surgical resection for the cardiac mass. The chordoma has been slowly increasing in size, but she has remained asymptomatic without cardiovascular events for more than a year since the diagnosis of cardiac metastasis. .

Sick sinus syndrome as a late complication after ventricular septal defect surgery.

Ventricular septal defect is a common congenital heart disease for which patch closure technique using cardiopulmonary bypass has been applied for a few decades, resulting in a low incidence of perioperative complications. We report a 26-year-old woman with bradycardia of 25-30 beats per minute, which was considered to be a late-onset complication of surgical closure of an isolated ventricular septal defect performed 21 years earlier. She has been stable for more than 9 months without an implanted pacemaker, although her heart rate was always around 40 beats per minute in scheduled follow-up visits. .

Diagnostic performance of ultrasonic tissue characterization for subendocardial ischaemia in patients with hypertrophic cardiomyopathy.

AIMS: Hypertrophic cardiomyopathy (HCM) patients often develop left--ventricular subendocardial ischaemia, a cause of chest symptoms, despite normal epicardial coronary arteries. The aim of this study was to examine whether ultrasonic tissue characterization or late gadolinium enhancement on cardiac magnetic resonance imaging can detect subendocardial ischaemia in patients with HCM. METHODS AND RESULTS: Subendocardial ischaemia was quantified on exercise Tc-99m tetrofosmin myocardial scintigraphy in 29 non-obstructive HCM patients with asymmetric septal hypertrophy. Ultrasonic tissue characterization using cyclic variation of integrated backscatter (CV-IB) and late gadolinium enhancement on cardiac magnetic resonance imaging were analysed separately in the right halves and the left halves of the ventricular septum in relation to subendocardial ischaemia. Subendocardial ischaemia was identified in 17 (59%) patients. The ratio of CV-IB in the right-to-left halves of the ventricular septum was significantly higher in patients with subendocardial ischaemia (1.19 ± 0.10) than those without (0.84 ± 0.10, P = 0.04). The optimal cutoff for the detection of subendocardial ischaemia was the ratio of CV-IB >1.0, with a sensitivity of 80%, specificity of 71%, and accuracy of 76%. On the other hand, late gadolinium enhancement was not associated with subendocardial ischaemia in our cohort. CONCLUSION: Ultrasonic tissue characterization using CV-IB separately in the right and left halves of the ventricular septum, but not late gadolinium enhancement on magnetic resonance imaging, provided useful information in detecting subendocardial ischaemia in patients with HCM. Ultrasonic tissue characterization may be useful in selecting patients who will benefit from medications to relieve chest symptoms.

Holter monitoring and long-term prognosis in hypertrophic cardiomyopathy.

OBJECTIVES: Limited data are available regarding Holter monitoring for cardiovascular events except for ventricular tachycardia as a risk marker for sudden death in hypertrophic cardiomyopathy (HCM). We aimed to examine Holter findings in relation to the long-term prognosis in patients with HCM. METHODS: Ambulatory Holter monitoring was performed in 106 HCM patients with sinus rhythm. All were prospectively followed for the composite endpoint of sudden death, cardiovascular death, and hospitalization for heart failure or stroke associated with atrial fibrillation. RESULTS: Cardiovascular events occurred in 19 patients during a mean follow-up of 10.1 years. Neither arrhythmia information nor autonomic information as assessed by heart rate variability and turbulence significantly differed between HCM patients with and without cardiovascular events. Average heart rates were lower in HCM patients with cardiovascular events (64.7 ± 11.2 beats/min) than in those without (73.7 ± 10.2 beats/min, p = 0.001). Multivariate Cox proportional hazards regression analysis after adjustment for baseline characteristics showed that lower average heart rate remained an independent predictor of cardiovascular events (HR: 0.47 per 10 increase; 95% CI: 0.25-0.87; p = 0.016). CONCLUSION: Average heart rate on Holter monitoring predicted long-term prognosis in our cohort. Further multicenter studies are needed to confirm our results.

Intramyocardial calcification in a patient with apical hypertrophic cardiomyopathy.

Intramyocardial calcification is a very rare condition. We report a case of a 72-year-old man with apical hypertrophic cardiomyopathy, who was initially suspected of having a thrombus in the left ventricular apex on echocardiography, but was finally diagnosed as having apical intramyocardial calcification on multidetector computed tomography. The mechanism of developing intramyocardial calcification remains to be elucidated, but the patient has been stable for more than 2 years.

Myocardial perfusion abnormality in the area of ventricular septum-free wall junction and cardiovascular events in nonobstructive hypertrophic cardiomyopathy.

Myocardial perfusion abnormality in the left ventricle is known to be prognostic in patients with hypertrophic cardiomyopathy (HCM). Magnetic resonance imaging and necropsy studies on HCM hearts revealed myocardial lesions predominating in the area of ventricular septum-free wall junction. We assessed perfusion abnormality in this area and correlated it with the prognosis of HCM patients. We performed exercise Tc-99m tetrofosmin myocardial scintigraphy in 55 patients with nonobstructive HCM. Perfusion abnormalities were semiquantified using a 5-point scoring system in small areas of anterior junctions of basal, mid, and apical short axis views in addition to a conventional 17-segment model. All patients were prospectively followed for sudden death, cardiovascular death and hospitalization for heart failure or stroke associated with atrial fibrillation. Cardiovascular events occurred in 10 patients during an average follow-up period of 5.7 years. Stress and rest scores from anterior junction, and conventional summed stress score were significantly higher in patients with cardiovascular events than without (all P < 0.05). Anterior junction stress score of >2 produced a sensitivity of 50% and a specificity of 98% for cardiovascular events and was an independent predictor (hazard ratio 8.33; 95% confidence interval, 1.61-43.5; P = 0.01), with rest scores producing similar values, which were higher than summed stress score of >8 (5.68; 1.23-26.3; P = 0.03). The absence of myocardial perfusion abnormality in the narrow area of anterior junction differentiated HCM patients with low-risk.

Silent pulmonary artery dissection in a centenarian.

Pulmonary artery dissection is an extremely rare and fatal disease that is difficult to diagnose. We report a case of a 97-year-old woman with heart failure, who was diagnosed as having silent pulmonary artery dissection by chance during transthoracic echocardiography. Surgical treatment for pulmonary artery dissection was not performed, but the patient has been doing well in a sanatorium for more than 2 years, being a centenarian.

Sclerosing mesenteritis presenting as protein-losing enteropathy: a fatal case.

Sclerosing mesenteritis is a rare, benign disorder characterized by non-specific and chronic inflammation of the mesenteric adipose tissue. The disease usually presents with gastrointestinal symptoms and abdominal masses. The long-term prognosis is favorable, but it often becomes severe. In the present report we describe a 77-year-old man who presented with diarrhea, massive ascites and an abdominal mass. The rapid deterioration of the general condition of the patient limited invasive examinations and left the primary disease unclear. Despite symptomatic therapy, malnutrition and hypovolemia were prolonged, and he died. The definitive diagnosis of sclerosing mesenteritis and the cause of the fatal outcome were disclosed at autopsy. This case indicates that sclerosing mesenteritis is a potentially-fatal disease and the need for aggressive treatment should be discussed.

Three-layer ultrasonic tissue characterization of the ventricular septum is predictive of prognosis in patients with non-obstructive hypertrophic cardiomyopathy.

AIMS: A necropsy study of patients with hypertrophic cardiomyopathy (HCM) who died at a young age exhibited marked disarray and fibrosis in the mid-wall layer of the left ventricular (LV) myocardium. We assessed ultrasonic tissue characteristics in the three layers of the ventricular septum (VS), and correlated the result with long-term prognosis in HCM. METHODS AND RESULTS: The magnitude of cyclic variation of integrated backscatter (CV-IB) was calculated in the three layers of the VS and the whole aspect of the LV posterior wall in 58 non-obstructive HCM patients and 20 healthy controls. All HCM patients were prospectively followed for an average period of 7.1 years for the occurrence of cardiac death or hospitalization due to heart failure. Each CV-IB of four regions was lower in HCM patients than in controls (all P < 0.01). CV-IB of the VS mid-wall layer was lower in 14 HCM patients with cardiac events than in patients without (5.4 ± 0.6 vs. 7.4 ± 0.5 dB, P = 0.033) although CV-IB of three other regions did not differ between the two groups. The optical cut-off point of %CV-IB <90%, i.e. the ratio of CV-IB in the VS mid-wall layer to the mean value in the layers on both sides, was an independent predictor of cardiac events (hazard ratio, 6.12; 95% confidence interval, 1.62-66.6; P = 0.013), with a positive predictive value of 44% and particularly with a high negative predictive value of 91%. CONCLUSION: Patients with non-obstructive HCM are not likely to undergo cardiac events in the near future, when the CV-IB value is not significantly lower in the VS mid-wall layer than in the layers on both sides.

Chronotropic incompetence and autonomic dysfunction in patients without structural heart disease.

AIMS: An attenuated heart rate response to exercise, termed chronotropic incompetence (CI), has been reported to be an independent predictor of cardiovascular mortality. We examined the change in autonomic function during exercise testing and correlated the results with CI. METHODS AND RESULTS: Exercise testing using a bicycle ergometer was performed in 172 patients who had no evidence of cardiac disease. Chronotropic incompetence was defined as the failure to achieve 85% of the age-predicted maximum heart rate, heart rate reserve <80%, or chronotropic response index <0.80. We analysed the relationship between CI and the change in two components of heart rate variability during exercise testing: high-frequency (HF) component (0.15-0.40 Hz) as an index of vagal modulation and the ratio of low-frequency (LF) component (0.04-0.15 Hz) to HF component as an index of sympathovagal balance. Heart rate variability indexes before exercise were similar in patients with and without CI. Percentage changes after exercise in the ratio of LF to HF component were higher in patients with CI than in those without CI (84 +/- 15 vs. 41 +/- 16%, P < 0.05), whereas percentage changes in an HF component were similar in the two groups. CONCLUSION: Our data suggested that CI in patients without structural heart disease was mainly caused by a pathophysiological condition in which sympathetic activation was not well translated into heart rate increase. Further study is needed to determine the post-synaptic sensitivity of the beta-adrenergic receptor pathway in relation to CI.

Vagal enhancement as evidence of residual ischemia after inferior myocardial infarction.

BACKGROUND: Acute inferior myocardial infarction (MI) often induces transient sinus bradycardia through vagal enhancement, known as Bezold-Jarisch reflex, which is explained by preferential distribution of vagal nerve in the inferior wall. We examined vagal activity in relation to the occurrence of residual ischemia in patients with old inferior MI and assessed its diagnostic usefulness. METHODS: Exercise myocardial scintigraphy was performed in 15 patients with old inferior MI, 19 angina pectoris (AP) patients with inferior ischemia but no MI, and 32 control subjects who had no evidence of cardiac disease. We analyzed the connection of residual ischemia in old MI with ST-segment response to exercise and with vagal activity as determined by coefficient of component variance of high frequency (CCV(HF)). RESULTS: Exercise-induced percentage change in CCV(HF) was higher in patients with old MI and residual ischemia (18.8 +/- 13.5%) and AP (5.5 +/- 9.7%) than old MI but no residual ischemia (-24.1 +/- 4.9%) or control (-22.8 +/- 4.5%, P = 0.006). Percentage change in CCV(HF) > -5% had a good diagnostic value for the detection of residual ischemia in patients with old inferior MI with sensitivity of 83%, specificity of 89%, accuracy of 87%, and positive likelihood ratio of 7.50, which was higher than that of ST-segment depression (67%, 50%, 56%, and 1.33). CONCLUSIONS: Vagal enhancement was associated with residual ischemia in old inferior MI as well as inferior AP. Measurement of CCV(HF) is useful in improving the diagnostic reliability of exercise electrocardiography in patients with old inferior MI.

Septal Q wave as a marker of septal ischemia in hypertrophic cardiomyopathy.

BACKGROUND: Small Q waves in the left lateral leads are termed septal q waves, and their response to exercise has been reported to be a marker of septal ischemia in coronary artery disease. Patients with hypertrophic cardiomyopathy (HCM) sometimes develop septal ischemia in the absence of coronary stenosis, but little data are available concerning the association of the septal q wave response with septal ischemia. METHODS AND RESULTS: Exercise electrocardiography and Tc-99m-tetrofosmin myocardial scintigraphy were recorded to detect myocardial ischemia in 29 HCM patients with asymmetric septal hypertrophy. The septal q wave amplitude was summed up in V(5) and V(6) during exercise testing, and the results were correlated with septal ischemia defined as a regional septal ischemia or a part of diffuse subendocardial ischemia. A decrease in the sum of the septal q wave amplitude during exercise testing yielded a sensitivity of 100% and specificity 33% for regional septal ischemia, and a sensitivity of 100% and specificity of 43% for diffuse subendocardial ischemia, although an absent septal q wave at rest provided a low sensitivity for the detection of regional septal ischemia (43%) and diffuse subendocardial ischemia (33%). CONCLUSIONS: The septal q wave response to exercise is a useful marker of septal ischemia in HCM with asymmetric septal hypertrophy.

Vagal enhancement due to subendocardial ischemia as a cause of abnormal blood pressure response in hypertrophic cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) often develop myocardial ischemia in association with abnormal blood pressure response to exercise. Vagal nerves mediate cardioinhibitory stimuli, with little knowledge regarding vagal response to myocardial ischemia in patients with HCM. METHODS: Exercise Tc-99m-tetrofosmin myocardial scintigraphy was performed in 59 HCM patients and 39 controls who had no evidence of cardiac disease. We examined how reversible regional perfusion abnormality and transient left ventricular cavity dilation, a parameter of subendocardial ischemia, are related to vagal modulation as assessed by coefficient of high frequency component variance (CCV(HF)) on heart rate variability. We then correlated the results with abnormal blood pressure response to exercise, defined as failed increase >or=25 mm Hg during exercise. RESULTS: Regional perfusion abnormality and left ventricular cavity dilation were observed in 26 and 21 HCM patients, respectively. The percentage change of CCV(HF) from before to after exercise was higher in HCM patients with left ventricular cavity dilation than without or controls (5.2+/-9.8%, -23.5+/-5.7%, -14.5+/-5.5%, P=0.004). By contrast, the change of CCV(HF) was similar in HCM patients with regional perfusion abnormality, those without, and controls. The change of CCV(HF) was correlated with exercise-induced increase in systolic blood pressure (rho=-0.64, P<0.001); HCM patients with abnormal blood pressure response were characterized by a higher percentage change in CCV(HF) (50.0+/-18.3%). CONCLUSIONS: Subendocardial ischemia provoked vagal enhancement in patients with HCM, which may be related to the development of abnormal blood pressure response to exercise.

R-wave amplitude response to myocardial ischemia in hypertrophic cardiomyopathy.

BACKGROUND AND PURPOSE: R-wave amplitude change during exercise has been reported to enhance diagnostic value for myocardial ischemia in coronary heart disease. METHODS: We summed up R-wave amplitude in all the 12 leads during exercise testing and correlated the results with regional myocardial ischemia or diffuse subendocardial ischemia as detected by scintigraphy in 49 patients with hypertrophic cardiomyopathy (HCM) and 16 controls. RESULTS: The sum of R-wave amplitude decreased during exercise in patients with HCM (mean, 12.4 mV to 11.7 mV, P < .01) as well as in controls (8.0 mV to 7.7 mV, P < .05). Percent changes in the sum of R-wave amplitude did not differ between 4 subgroups of patients with HCM: one having both regional and subendocardial ischemia, one only the former, one only the latter, and one neither of them (mean, 6.5%, 7.7%, 4.6%, and 5.1%; P = .79). CONCLUSIONS: R-wave amplitude response to exercise failed to demonstrate myocardial ischemia in our patients with HCM.

[Biventricular noncompaction detected by magnetic resonance imaging: a case report].

We report a case of biventricular noncompaction in whom magnetic resonance imaging revealed prominent trabeculations in the right ventricle as in the left ventricle. A 58-year-old man was referred to our hospital complaining of appetite loss and leg edema. Chest radiography showed cardiomegaly without pulmonary congestion. The diagnosis was right ventricular heart failure with congestive liver causing elevated liver enzyme. Transthoracic echocardiography showed prominent trabeculations and deep recesses in the inferolateral wall and apex of the left ventricle with the end-diastolic dimension of 64mm and ejection fraction of 29%. Magnetic resonance imaging demonstrated right ventricular noncompaction which remained unclear on echocardiography. Prominent trabeculations in the dilated right ventricle were confirmed by right ventriculography. The ejection fraction was 23%.