Haruhiko Higashi

Clinical significance of global two-dimensional strain as a surrogate parameter of myocardial fibrosis and cardiac events in patients with hypertrophic cardiomyopathy

AIMS Late gadolinium enhancement (LGE) on contrast-enhanced magnetic resonance imaging (MRI) in hypertrophic cardiomyopathy (HCM) has been reported to be associated with myocardial fibrosis and cardiac events. In patients with HCM, two-dimensional (2D) strain can identify subclinical global systolic dysfunction despite normal left ventricular (LV) chamber function. Therefore, this study tested the hypothesis that global 2D strain could detect subtle myocardial fibrosis and serve as a novel prognostic parameter in HCM patients. METHODS AND RESULTS Echocardiography and MRI were performed in 48 consecutive patients with HCM and normal chamber function. We measured global longitudinal strain (GLS) in apical two-chamber, four-chamber, and long-axis views using speckle-tracking analysis. The extent of LGE (%LGE = LGE volume/total LV volume) and LV mass index were calculated by MRI using Simpsons rule and custom software. All patients were followed up for major cardiac events. Global longitudinal strain in patients with LGE was significantly lower than that without LGE (-11.8 ± 2.8 vs. -15.0 ± 1.7%, P < 0.001). Multivariate analysis showed that GLS was an independent predictor of %LGE (standard coefficient = 0.627, P < 0.001). During a mean follow-up period of 42 ± 12 months, five patients had cardiac events. When the patients were stratified based on the median level of GLS (-12.9%), all events were observed in the worse GLS group (P = 0.018). CONCLUSION These results suggest that global 2D strain might provide useful information on myocardial fibrosis and cardiac events in HCM patients with normal chamber function.

Impact of type 2 diabetes on serial changes in tissue characteristics of coronary plaques: an integrated backscatter intravascular ultrasound analysis

AIMS Several studies have demonstrated that type 2 diabetes mellitus (T2DM) is associated with accelerated atherosclerosis, which results in an increased risk of coronary vascular events. However, serial changes in plaque characteristics have not been reported in vivo. We evaluated the progression of coronary atherosclerosis in patients with T2DM using an integrated backscatter intravascular ultrasound (IB-IVUS) examination. METHODS AND RESULTS Forty-two T2DM and 48 non-diabetic patients who underwent percutaneous coronary intervention were enrolled in the study. Non-culprit 20-mm length coronary lesions with mild-to-moderate stenosis were measured using a 40-MHz (motorized pullback of 0.5 mm/s) IVUS catheter. IVUS examinations were performed on one target lesion in each patient. Six months later, a follow-up IVUS examination was repeated in the same coronary segment imaged at the baseline examination. T2DM patients demonstrated a greater total plaque volume (TPV; 139 ± 53 vs. 114 ± 45 mm(3), P = 0.02) and total lipid volume (TLV; 67 ± 26 vs. 55 ± 30 mm(3), P = 0.039) at the baseline examination. The progression of TPV (8.6 ± 15.4 vs. -2.2 ± 16.0%, P < 0.01) and TLV (10.8 ± 28.8 vs. -2.5 ± 20.0%, P < 0.05) from the baseline was observed in T2DM patients, but not in non-diabetic patients. The increase in TLV was blunted in T2DM patients who achieved HbA1c levels of <6.5%. CONCLUSION Accelerated plaque progression with an increase in the lipid-rich component of non-culprit plaques was observed in T2DM, despite the use of standard medical treatment. Better glycaemic control ameliorated the worsening of plaque characteristics in T2DM.

Post-resuscitation myocardial microcirculatory dysfunction is ameliorated with eptifibatide.

BACKGROUND The post-cardiac arrest syndrome includes a decline in myocardial microcirculation function. Inhibition of the platelet IIb/IIIa glycoprotein receptor has improved myocardial microvascular function post-percutaneous coronary intervention. Therefore, we evaluated such inhibition with eptifibatide for its effect on myocardial microcirculation function post-cardiac arrest and resuscitation. METHODS Four groups of swine were studied in a prospective, randomized, blinded, placebo-controlled protocol including; eptifibatide administered during CPR (Group 1, n=5), after resuscitation (Group 2, n=4), during and after resuscitation (Group 3, n=5), or placebo (Group 4, n=10). CPR was initiated following 12min of untreated VF. Those successfully resuscitated were studied during a 4-h post-resuscitation period. Coronary flow reserve, a measure of microcirculation function (in the absence of coronary obstruction), as well as parameters of left ventricular systolic and diastolic function, were measured pre-arrest and serially post-resuscitation. RESULTS Coronary flow reserve was preserved during the post-resuscitation period, indicating normal microcirculatory function in the eptifibatide-treated animals, but not in the placebo-treated group. However, LV function declined equally in both groups during the first 4h after cardiac arrest. CONCLUSION Inhibition of platelet IIb/IIIa glycoprotein receptors with eptifibatide post-resuscitation prevented myocardial microcirculation dysfunction. Left ventricular dysfunction post-resuscitation was not improved with eptifibatide, and perhaps transiently worse at 30min post-resuscitation. Post-cardiac arrest ventricular dysfunction may require a multi-modality treatment strategy for successful prevention or amelioration.

A case of caseous calcification of the mitral annulus: A potential source of embolic stroke

Mitral annular calcification (MAC) is a common finding especially among the elderly. Caseous calcification of the mitral annulus (CCMA) is a rare variant of MAC, which may be mistaken for an intracardiac tumor or abscess. The clinical significance of CCMA and its potential as a source for cerebral embolism is not known. A 76-year-old woman with an acute ischemic stroke was found to have CCMA on echocardiography apparent as a round mass with a central echolucent area and an echo-dense smooth border, in the periannular position of the mitral valve. She subsequently suffered a second embolic stroke. The central cavity of the CCMA seemed to communicate with the left atrium on echocardiography, suggesting the causal relationship between the second brain attack and the CCMA. She was anticoagulated and has not suffered any further strokes. Previous case reports have suggested that CCMA is a benign condition. This detailed report suggests that CCMA may be a potential source of embolic stroke.

Usefulness of transthoracic Doppler echocardiography for noninvasive assessment of coronary blood flow in a patient with symptomatic myocardial bridging

Myocardial bridging (MB) is a congenital anomaly characterized by systolic compression of the tunnelled arterial segment. MB may cause myocardial ischaemia due to abnormal coronary blood flow. We report a case of MB in which transthoracic Doppler echocardiography was used to evaluate the long-term effect of beta-blocker therapy on abnormal coronary blood flow. In this case, beta-blocker therapy with bisoprolol (5.0 mg/day) for 1 month eliminated the patients symptoms and normalized coronary blood flow through the tunnelled arterial segment.

Usefulness of Adjunctive Pulse Infusion Thrombolysis After Failed Aspiration for Massive Intracoronary Thrombus

Slow/no-reflow phenomenon during emergent percutaneous coronary intervention in patients with ST-elevation myocardial infarction (STEMI) results in a poor prognosis. A high thrombus burden was an independent predictor of angiographic slow/no-reflow phenomenon. We experienced a case of a STEMI patient with massive intracoronary thrombus. In our case, a massive red thrombus was aspirated easily by adjunctive pulse infusion thrombolysis (PIT) after failed aspiration. Adjunctive pulse infusion thrombolysis after failed aspiration might be a useful strategy to prevent the slow/no-reflow phenomenon in STEMI patients with massive intracoronary thrombus.

Experience of appendicular thermal therapy applied to a patient with a left ventricular assist device awaiting heart transplantation

Thermal therapy for heart failure is recognized to improve clinical symptoms. We describe our experience with appendicular thermal therapy applied to a patient fitted with an extracorporeal left ventricular assist device (LVAD) who was wait-listed for a heart transplant. A 21-year-old male with end-stage heart failure due to dilated cardiomyopathy was fitted with a LVAD. His general condition stabilized after LVAD placement and the status of his heart failure has remained at NYHA class II for the past 13 months. However, his cardiac function did not sufficiently recover to discontinue LVAD support. We conducted appendicular thermal therapy using a steam foot bath and heated gloves for 2 weeks. Immediately after thermal therapy, his average sublingual temperature increased from 36.3 to 37.0 degrees C and the grade of mitral regurgitation, as well as LV ejection fraction and endothelial function improved. Furthermore, levels of oxidative and anti-oxidative stress markers decreased and increased, respectively, after 2 weeks of therapy. No complications developed. We conclude that appendicular thermal therapy was safe in this patient waiting for a heart transplant and who had an extracorporeal LVAD, and that the procedure might be beneficial for others with end-stage heart failure.

Intracoronary Optical Coherence Tomography-Derived Virtual Fractional Flow Reserve for the Assessment of Coronary Artery Disease

Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Optical coherence tomography (OCT) provides accurate visualization of coronary artery morphology. The aim of this study was to investigate the relation between FFR and OCT-derived FFR. We retrospectively analyzed 31 lesions (25 left anterior descending arteries, 2 left circumflex arteries, and 4 right coronary arteries) in 31 patients with moderate-to-severe coronary stenosis, who underwent OCT and FFR measurements simultaneously. OCT-derived FFR was calculated by the original algorithm, which was calculated using the following equation based on fluid dynamics: ΔP = FV + SV2, where V is the flow velocity, F is the coefficient of pressure loss because of viscous friction (Poiseuille resistance), and S is the coefficient of local pressure loss because of abrupt enhancement (flow separation). Mean values of % diameter stenosis by quantitative coronary angiography and FFR were 55.2 ± 14.0% and 0.70 ± 0.14, respectively. OCT-derived FFR showed a stronger linear correlation with FFR measurements (r = 0.89, p <0.001; root mean square error = 0.062 FFR units) than quantitative coronary angiography % diameter stenosis (r = -0.65, p <0.001), OCT measurements of minimum lumen area (r = 0.68, p <0.001), and % area stenosis (r = -0.70, p <0.001). OCT-derived FFR has the potential to become an alternative method for the assessment of functional myocardial ischemia, and may elucidate the relation between coronary morphology and FFR.

A Novel Truncating LMNA Mutation in Patients with Cardiac Conduction Disorders and Dilated Cardiomyopathy

The cardiac phenotype of laminopathies is characterized by cardiac conduction disorders (CCDs) and dilated cardiomyopathy (DCM). Although laminopathies have been considered monogenic, they exhibit a remarkable degree of clinical variability. This case series aimed to detect the causal mutation and to investigate the causes of clinical variability in a Japanese family with inherited CCD and DCM.Of the five family members investigated, four had either CCD/DCM or CCD alone, while one subject had no cardiovascular disease and acted as a normal control. We performed targeted resequencing of 174 inherited cardiovascular disease-associated genes in this family and pathological mutations were confirmed using Sanger sequencing. The degree of clinical severity and variability were also evaluated using long-term medical records. We discovered a novel heterozygous truncating lamin A/C (LMNA) mutation (c.774delG) in all four subjects with CCD. Because this mutation was predicted to cause a frameshift mutation and premature termination (p.Gln258HisfsTer222) in LMNA, we believe that this LMNA mutation was the causal mutation in this family with CCD and laminopathies. In addition, gender-specific intra-familiar clinical variability was observed in this Japanese family where affected males exhibited an earlier onset of CCD and more severe DCM compared to affected females. Using targeted resequencing, we discovered a novel truncating LMNA mutation associated with CCD and DCM in this family characterized by gender differences in clinical severity in LMNA carriers. Our results suggest that in patients with laminopathy, clinical severity may be the result of multiple factors.

Incremental value of left atrial active function measured by speckle tracking echocardiography in patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) impairs left ventricular (LV) diastolic function leading to left atrial (LA) dilatation. Because Doppler echocardiography cannot accurately assess LV diastolic function in hearts with heterogeneous hypertrophy, assessment of LA function might be useful for risk stratification of patients with HCM. This study aimed to elucidate the impact of LA function on outcome in patients with patients.