Surgical coronary revascularization and percutaneous coronary intervention were demonstrated to be effective treatments for coronary artery disease. However, the optimal revascularization strategy remains unclear in certain patient subsets. The recently published Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial is a randomized study evaluating the use of CABG versus PCI in diabetic patients with multivessel coronary disease. The purpose of this study was to review the available literature based on randomized trials and observational studies in order to allow clinicians to make evidence-based decisions when treating diabetic patients with multivessel coronary disease. The current evidence suggests that CABG should remain the standard of care for this patient population.

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Appropriate use of biomarkers is clinically important for identifying heart failure in its early stage, optimizing risk stratification, and managing patients. This article describes established and traditional biomarkers as well as novel biomarkers reflective of myocardial stress, myocardial damage, extracellular matrix, oxidative stress, inflammation, renal function, micro RNAs, and heart failure with preserved left ventricular ejection fraction. This review focuses on the recent advances in cardiac and non-cardiac biomarkers of heart failure and their appropriate use in clinical practice.

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This study aimed to evaluate on-pump versus off-pump coronary artery bypass grafting (CABG) in patients with a high-risk operative profile.
The pre-, intra- and post-operative data of high-risk patients with additive European system for cardiac operative risk evaluation (additive Euro-SCORE) over 6 undergoing isolated CABG from January 2008 to December 2011 in this center were investigated and retrospectively analyzed. Using the propensity score-matching method, those patients with similar pre- and intra-operative characteristics were selected and their early clinical outcomes were compared.
From January 2008 to December 2011, 485 consecutive patients (398 males, with a mean age of 70.9 ± 9.0 years) whose additive Euro-SCORE was over 6 were entered into this study. Off-pump coronary bypass grafting (OPCAB) was performed in 58.1% (n = 282), and the remaining patients underwent conventional coronary artery bypass grafting (CCABG). After propensity score matching, the two groups of patients (90 OPCAB patients versus 90 CCABG patients) were similar with regard to pre- and intra-operative characteristics but not duration of surgical procedure. No significant differences in hospital mortality were found. Compared to CCABG, high-risk patients undergoing OPCAB had significantly lower prevalence of postoperative respiratory failure and postoperative renal failure (6.7% versus 17.8%, P = 0.0386, 5.6% versus 16.7%, P = 0.0307, respectively). Through multivariate logistic regression analysis, type of procedure (CCABG versus OPCAB), as an independent risk factor, had an impact on the postoperative respiratory failure (OR = 2.36, 95%CI 1.44-4.97, P = 0.0312) and postoperative renal failure (OR = 2.86, 95%CI 1.61-5.81, P = 0.0037).
Compared with CCABG, OPCAB reduced postoperative respiratory and renal morbidity in high-risk patients.

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Catheter ablation has been established to be an effective therapy for drug-refractory paroxysmal AF and is recommended as the treatment of choice for many patients, including those with a permanent pacemaker (PM). However, the clinical efficacy of catheter ablation of paroxysmal AF in patients with a permanent PM for atrioventricular block (AVB) is not clear. Twenty-nine patients with a permanent PM for AVB (AVB + PM group), and 145 age- and gender-matched control patients (on a 1:5 basis) without AVB and without a permanent PM (no-AVB + no-PM group), were included in this study. Atrial fibrillation (AF) recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30 seconds beyond 3 months after catheter ablation in the absence of any antiarrhythmic treatment. During a mean follow-up period of 14.2 ± 8.6 months (range, 3–30 months), 54 patients (31.0%) developed recurrence of AF. The recurrence rate was higher in the AVB + PM group than in the no-AVB + no-PM group (48.3% versus 27.6%, P = 0.005). Cox regression analysis with adjustment for age, valvular heart disease, AVB and a PM together, left atrial (LA) diameter and PV isolation identified LA diameter (hazard ratio 1.054, 95% confidence interval 1.001–1.110, P = 0.047) and AVB and a PM together (hazard ratio 2.095, 95% confidence interval 1.109–3.960, P = 0.023) as two independent predictors of recurrence of AF. Patients with a permanent PM for AVB were at an increased risk of recurrence of AF after catheter ablation.

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Some patients with persistent atrial fibrillation (AF) acquire long-term freedom from AF by pulmonary vein (PV) isolation alone. The aim of the present study was to evaluate the characteristics of their atrial substrate.
We studied 20 patients with persistent AF to examine the distribution of fractionated atrial potentials (FAP) and that of the anatomic sites of ganglionated plexi (GPs) with vagal reflexes elicited by high frequency stimulation (HFS) with the use of the CARTO system before and after the PV isolation.
Both the %FAP area defined as a proportion of the FAP area to the total left atrial area (34.3 ± 10.3 to 21.5 ± 10.2%; P < 0.0001) and number of GP sites with vagal reflexes (4.0 [3.0, 5.0] to 2.0 [1.0, 2.8]; P < 0.0001) were markedly decreased after the PV isolation. Seven (35%) patients had AF recurrences, and they had a greater %FAP area after the PV isolation than those without (32.8 [22.1, 37.3] versus 13.8 [10.9, 19.9]%; P = 0.0049). A %FAP area after the PV isolation of > 20% was significantly associated with an AF recurrence (odds ratio 20.0, 95% confidence interval 2.26470.34; P = 0.018). No significant difference was found between the patients with and without AF recurrence in the reduction rate of anatomic sites of GPs with a vagal reflex induced by the HFS.
A more marked reduction in the FAP area by the PV isolation was significantly associated with a better outcome in patients with persistent AF.

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This study aimed to explore the effects of pioglitazone treatment on progression from persistent atrial fibrillation (AF) to permanent atrial fibrillation in diabetes mellitus (DM) patients and to investigate the possible mechanisms involved in those effects.
A total of 146 diabetes mellitus (DM) patients with firstly identified persistent AF were selected. Seventy patients were randomized into the pioglitazone (30 mg/day) group and 76 into the placebo group. Pro-collagen type I carboxyterminal peptide (PICP), advanced glycation end products (AGEs), and angiotensin II were assayed and left atrial diameter (LA diameter) was measured at the first presence of persistent AF, and at 6 and 14 months of follow-up. The time point of identification of permanent AF and the incidence of permanent AF in the patients were all recorded.
Thirty-seven (49%) of the 76 patients in the placebo group and 21 (30%) of the 70 patients in the pioglitazone group progressed to permanent AF (P = 0.028). No significant differences existed in the follow-up time (20.5 ± 3.97 months for pioglitazone group versus 20.9 ± 4.14 months for placebo group) between the two groups (P = 0.535). In the pioglitazone group, no significant change was found in angiotensin II level. The PICP level did not change significantly at 6-months of follow-up, but decreased significantly at 14-months of follow-up (P = 0.032). The AGE (P = 0.037 at 6-month follow-up, P < 0.035 at 14-month follow-up) level was significantly lower at both 6 and 14-months of followup.
By lowering the PICP level, pioglitazone treatment may decrease the incidence of permanent AF in DM patients with persistent AF, which may be associated with the suppressing effect of pioglitazone on AGEs.

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Anticoagulants such as warfarin are recommended for patients with atrial fibrillation (AF) to decrease stroke risk associated with thrombus formation in the left atrium (LA). In a subgroup of patients, however, warfarin is unable to prevent LA thrombus formation at therapeutic doses. This study characterized the clinical and echocardiographic features of patients having warfarin-resistant LA thrombus.
Of the 1364 nonvalvular AF patients examined by transesophageal echocardiography, 431 received warfarin. A total of 10 patients (2.3% of warfarin-treated patients) exhibited LA thrombus formation even during warfarin treatment at a dose and duration sufficient for increasing the prothrombin time–international normalized ratio (PT–INR) to the therapeutic range for ≥ 30 days. Categorical regression analysis revealed that decreased LA appendage (LAA) flow velocity, greater LA spontaneous echocardiographic contrast (LASEC), and lower left ventricular ejection fraction (LVEF) significantly contributed to residual LA thrombus (P < 0.05 for all). Receiver operating characteristic (ROC) curve analysis indicated that higher right ventricular systolic pressure, which suggests LA pressure (area under curve, 0.85), LV mass index (0.81), and LA dimension (0.68), as well as lower LAA flow velocity (0.92) and LVEF (0.91) predicted warfarinresistant LA thrombus formation (all P < 0.05).
These results suggest that blood stasis secondary to heart failure contributes to the formation of warfarin-resistant LA thrombus. We propose that therapies to increase LVEF should be administered together with warfarin for AF patients with heart failure to decrease stroke risk.

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The aims of this study were to quantify the geometrical differences in left ventricular (LV) dyssynchrony in patients with heart failure (HF) using cine-tagged MRI, and to investigate the relationship between dyssynchrony and major adverse cardiac events (MACE) in HF.
In 67 patients with HF [mean LV ejection fraction (LVEF), 34%], cardiac MRI using a 3-Tesla scanner was performed. The dyssynchrony time between septal and lateral segments (SL-DT) and between basal and apical segments (BA-DT) was computed by cross-correlation analysis of the strain time-curves from the cine-tagged MRI. After receiving optimal medical treatment, all patients were followed-up for a mean period of 27 months. The primary endpoint was MACE that consisted of cardiac death or HF hospitalization or a left ventricular assist device due to refractory pump failure. Multivariate logistic regression analysis was performed to determine the ability of SL-DT, BA-DT, and HF biomarkers to predict MACE.
Multivariate logistic regression analysis showed that the odds ratio to predict MACE was 0.935 for LVEF (P = 0.021), 1.016 for BA-DT (P = 0.026), and 0.971 for systolic blood pressure (P = 0.126).
The results show that basal-apical dyssynchrony is an independent predictor of MACE in HF patients.

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Albuminuria and a high plasma aldosterone concentration (PAC) are prognosis factors predicting a poor outcome for cardiovascular disease. We examined here the effects of benidipine, a T/L-type calcium channel blocker (CCB), on albuminuria and PAC.
Thirty-one patients with essential hypertension who received an L-type CCB and achieved the target blood pressure (BP) indicated by the Treatment Guidelines of the Japan Society of Hypertension (JSH2009) were investigated. The Ltype CCB under treatment was switched to benidipine at a dose in which equivalent BP reduction was expected. BP and estimated glomerular filtration rate at 6 months after switching to benidipine were not significantly different from those at baseline. The urinary-albumin-creatinine ratio (UACR) decreased significantly by 36.9% (P = 0.001). No significant change was observed in plasma renin activity (P = 0.063). The PAC of all patients decreased significantly by 11.8% (P = 0.002). When analyzed by daily doses of benidipine, the PAC appeared to have decreased in patients who received 4 mg per day of benidipine (n = 14), although statistical significance was not reached (P = 0.096). The PAC in patients who received 8 mg per day of benidipine (n =17) was significantly reduced by 13.2% (P = 0.017).
In hypertensive patients whose BP is controlled by L-type CCB, switching to the T/L-type CCB benidipine maintained BP control and reduced UACR. In addition, the high dose of benidipine reduced the PAC independent of BP control. These results suggest the T/L-type CCB benidipine may contribute to cardio-renal protection in addition to lowering BP.

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Central aortic pressure waveform (AoPW) is the summation of a forward–traveling wave generated by the left ventricle and a backward-traveling wave caused by the reflection of the forward wave. The aim of this study was to evaluate the effect of ventricular-vascular coupling on the morphology of AoPW in chronic heart failure patients with different degrees of left ventricular systolic dysfunction (LVSD) using pulse wave analysis (PWA). PWA of AoPW and left ventricular (LV) function were evaluated by applanation tonometry in 26 control subjects, in 12 patients with left ventricular ejection fraction (LVEF) ≤ 30%, and in 14 patients with LVEF > 30%. Augmentation pressure, augmentation index, wasted energy, and ejection duration were lower in patients with LVEF ≤ 30% than in those with LVEF > 30% and in control subjects. Furthermore, augmentation index showed an inverse correlation with Doppler mitral E-wave amplitude (r = -0.40; P = 0.04) and E/A ratio (r = -0.42; P = 0.03) and a direct correlation with deceleration time of mitral E-waves (r = 0.39; P = 0.04). In patients with severe LVSD (LVEF ≤ 30%), aortic wave reflections negatively interfere with LV function and induce a shortening of ejection duration. In contrast, AoPW is similar in patients with moderate LVSD (LVEF > 30%) and in control subjects.

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The efficacy of tolvaptan for treating heart failure has already been shown. Adequate data relating to the effect of tolvaptan on the correlation of water balance in renal disease are not available. A retrospective study was conducted on the efficacy and adverse reactions of tolvaptan for treating nephrotic syndrome.
The subjects were 26 patients with chronic kidney failure due to diabetic nephropathy with heart failure who were administered tolvaptan and seen between December 2011 and October 2013. The endpoints were urinary output, physical findings, and blood analyses. The expression of aquaporin-2 in the collecting duct, which is related to the action of tolvaptan, was investigated by immunohistochemistry using the kidney tissue obtained for the diagnosis.
Responses were seen in 19 of the patients. In the histopathological investigation there was severe glomerulosclerosis in patients with diabetic nephropathy, but the responders were noticeable in that they only had mild tubulointerstitial damage. Non-responders exhibited profound tubulointerstitial damage. The expression of aquaporin-2 was determined in 8 patients, of which 7 were responders who tested positive for aquaporin-2. The remaining case was a non-responder who showed no expression of aquaporin-2.
Tolvaptan is considered effective for some cases of nephrotic syndrome. There are no clear parameters for predicting an effect, but the present study showed that aquaporin-2 was expressed in the epithelial cells of the collecting ducts of tolvaptan responders.

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CD40 plays an important role in the pathogenesis of myocarditis, and inhibition of CD40 expression could be a promising treatment for myocarditis. In this study, we used an animal model, experimental autoimmune myocarditis (EAM), to investigate whether CD40 siRNA could be exploited for myocarditis therapy.
Lewis rats were immunized with purified porcine cardiac myosin to induce EAM or were injected with phosphatebuffered saline (PBS) alone (PBS group), scrambled small interfering RNA (siRNA) (negative control group), or CD40siRNA (CD40 siRNA group).
CD40 siRNA treatment suppressed the increase in heart weight/body weight ratio, and attenuated the severity of myocardial lesions. Cytokine production, including Th1-type cytokines, was significantly suppressed in rats with myocarditis after CD40 siRNA treatment; however, production of Th2-type cytokines was higher. Specific knockdown of CD40 in EAM rats resulted in increased FOXP3 gene expression and the CD25+ CD4+ subpopulation of T cells but also a decrease in CD80 and CD86 expression. Lymphocyte (T and B cell) proliferation in response to myosin stimulation was significantly inhibited by CD40 silencing.
CD40-siRNA is a useful tool for inhibiting in vivo CD40 expression, and it could have therapeutic potential in the prevention and treatment of myocarditis in humans.

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Excimer laser coronary atherectomy (ELCA) is based on ultraviolet energy and is capable of disintegrating atheroma, without burning or grossly fragmenting it. ELCA has proven effective in the percutaneous treatment of a variety of complex lesions, including chronic total occlusions (CTO) and severely calcified lesions, in case of balloon failure-tocross or failure-to-expand. Here we present a case of a successful CTO recanalization with ELCA after balloon failure, review the literature on this topic, and present an algorithm outlining the management of this challenging clinical scenario.

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Fenestration-related massive aortic regurgitation is rare. The underlying mechanism is reported to be rupture of the fenestrated fibrous strand, and most ruptured cords have been reported in the bicuspid valve or in the right coronary cusp of the tricuspid aortic valve. We encountered a rare case of acute aortic regurgitation due to fibrous strand rupture in the fenestrated left coronary cusp. Preoperative echocardiography detected left coronary cusp prolapse, and operative findings revealed rupture of a fibrous strand in the left coronary cusp. For cases such as this, preoperative echocardiography would be useful for appropriate diagnosis.

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We have performed bilateral pulmonary artery banding operations combined with planned percutaneous balloon dilatation at banding sites for patients with hypoplastic left heart syndrome and related anomalies. Here, we report a case of Fontan completion in a patient who underwent aortic arch repair and a bidirectional Glenn procedure following flowadjustable bilateral pulmonary artery banding. The patient had a double-inlet left ventricle, a hypoplastic right ventricle, a hypoplastic aortic arch, and coarctation of the aorta. She underwent banding at 9 days of age and balloon dilatation at 2 months. The Damus–Kaye–Stansel anastomosis, aortic arch repair, and bidirectional Glenn procedure were performed at 5 months of age, and the extracardiac Fontan procedure was performed at 1.5 years.

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Giant cell arteritis (GCA) is an autoimmune disease characterized by granulomatous inflammation in the wall of medium-sized and large-sized arteries, and it usually occurs in patients over 50 years of age.¹⁾ Symptoms are nonspecific, and include fatigue, fever, and headache.²⁾ It is occasionally combined with aortic complications, and ruptures resulting in death. These complications occur as late events, usually several years after diagnosis and often after other symptoms have subsided.³⁾ Physicians should therefore be alert for complications of the large arteries in GCA. Here we present a case of GCA combined with ascending aortic dissection and rupture 3 weeks after diagnosis.

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We report three pediatric heart transplant (HTx) patients whose respiratory symptoms were successfully controlled with long-term, low-dose macrolide administration (clarithromycin: CAM; approximately 2.5 mg/kg bid). The first case was an 18-year-old boy who underwent HTx at the age of three for dilated cardiomyopathy (DCM). Beginning at age 5, he had repeated fevers and respiratory symptoms. He was diagnosed with chronic sinusitis at age 11 and sinobronchial syndrome with mild bronchiectasis at age 14. Administration of long-term, low-dose CAM and otolaryngeal topical therapy led to significant improvement of his symptoms. The second case was a 7-year-old boy who underwent HTx for DCM at age one. Starting at age 4, he had repeated fevers and cough due to atelectasis and pneumonia. As antibiotics and respiratory physical therapy proved ineffective, he received long-term, low-dose CAM, resulting in successful control of his atelectasis and recurrent pneumonia. The third case was a 13-year-old boy who underwent HTx at age 6 for DCM. He had chronic sinusitis starting at age 7, and was diagnosed with obstructive sleep apnea syndrome at age 10. Adenotonsillectomy and continuous positive airway pressure support therapy were indicated. At age 13, long-term, lowdose CAM administration was started following mycoplasma infection. In all three cases, the levels of calcineurin inhibitors (cyclosporine and tacrolimus) and everolimus were kept in the optimal range with careful drug monitoring. Longterm, low-dose macrolide administration effectively prevents and treats respiratory complications in pediatric HTx patients as long as attention is paid to potential drug interactions.

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An error appeared in the article titled “Interictal Electrocardiographic and Echocardiographic Changes in Patients With Generalized Tonic-Clonic Seizures” by Mahmoud M. Ramadan, Nader El-Shahat, Ashraf A. Omar, Mohamed Gomaa, Tamer Belal, Sherif A. Sakr, Mohammad Abu-Hegazy, Hazem Hakim, Heba A. Selim, Sabry Omar (Vol. 54, No. 3, 171-175, 2013).
The name of the last author on page 171 and the back cover should be “Sabry Omar” and not “Sabry A. Omar”.

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Eiji Nozaki, MD has been named winner of the 2014 UEDA Heart Award. He received a diploma and ¥500,000 in award money.

The title of his article is as follow :

Occurrence of Cardiovascular Events After the 2011 Great East Japan Earthquake and Tsunami Disaster.

Int Heart J 2012 ; 54(5) : 247-253

November 2014

International Heart Journal Association

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