[Unilateral Pulmonary Edema during Aortic Valve Replacement through Median Sternotomy].

Unilateral pulmonary edema (UPE) has been reported as a re-expansion pulmonary edema that occurs following rapid re-expansion of a collapsed lung in a patient with pneumothorax or large volume of pleural fluid. Recently, UPE after minimally invasive cardiac surgery through right-sided thoracotomy has received considerable attention because of its increasing morbidity and mortality. However, development of UPE in patients undergoing cardiac surgery through median sternotomy has not generally been recognized. Herein, we present our experience of UPE of the right lung after aortic valve replacement through median sternotomy. UPE may reflect ventilation-induced lung injury in concomitant systemic inflammation by cardiopulmonary bypass. Heterogeneity of lung collapse and wide pleural opening, which induced lung overdistension during recruitement, were considered to be associated with the occurrence of UPE in this case. Preventive measures should be considered for patients with multiple risk factors, and a meticulous recruitment maneuver is required for lung re-expansion during cardiac surgery.

[Adult Cor Triatriatum Found by Chance at the Onset of Myocardial Infarction].

Cor triatriatum sinister is a rare congenital heart disease in which the left atrium is divided into 2 chambers by a membrane, causing resistance to the blood flow to the left ventricle. The onset of symptoms depends upon the effective size of the orifice in the membrane and the associated heart disease. Our case is a 67-year-old woman with cor triatriatum found by chance at the onset of myocardial infarction. Coronary artery bypass surgery and excision of the membrane were successfully performed. Preoperative left ventricular dysfunction was improved after surgery. Imaging examinations such as enhanced computed tomography(CT) and magnetic resonance imaging(MRI) were useful for selecting surgical approach.

Biphasic Force-Frequency Relation Predicts Primary Cardiac Events in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The force-frequency relation (FFR) is a hemodynamic index of the chronotropic relationship between left ventricular (LV) systolic function (percent change in dP/dtmax) and elevation of heart rate. FFR is a marker of myocardial contractile reserve and follows an upward slope in healthy myocardium [monophasic FFR (MoF)], a pattern that becomes biphasic (BiF) under pathological conditions. However, it remains uncertain whether the FFR determines a patient's prognosis. We investigated the promising role of the FFR as a predictor of cardiac events in the setting of hypertrophic cardiomyopathy (HCM).Methods and Results:A total of 113 consecutive patients with HCM (New York Heart Association (NYHA) class I-II) were retrospectively evaluated; 27 (23.9%) had a BiF pattern and they experienced a higher incidence of cardiac events compared with those showing an MoF pattern (median follow-up, 4.7 years; P<0.001). Furthermore, Cox proportional hazard regression analysis revealed that the LV end-diastolic volume index (hazard ratio: 1.051, P=0.014) and BiF pattern (hazard ratio: 15.260, P=0.001) were independent predictors of primary cardiac events. Interestingly, abnormal reductions in myocardial regulatory molecules related to contractility (SERCA2α) were observed exclusively in the patients exhibiting a BiF pattern. CONCLUSIONS: The FFR reflects latent myocardial abnormalities and predicts cardiac events in the setting of HCM, even during the asymptomatic stages of the disease.

Prognostic impact of combined late gadolinium enhancement on cardiovascular magnetic resonance and peak oxygen consumption in ambulatory patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Peak oxygen consumption (peak VO2) and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) are prognostic in heart failure. We investigated whether LGE-CMR and peak VO2combined had additive value in risk stratifying patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Fifty-seven DCM patients underwent CMR and cardiopulmonary exercise testing. Cardiac events were cardiac death, hospitalization for decompensated heart failure, or lethal arrhythmia. Twenty-five (44%) were LGE-positive. The median peak VO2was 18.5 mL·kg(-1)·min(-1). On multivariate analysis, positive LGE (P = .048) and peak VO2(P = .003) were independent cardiac event predictors. Cardiac event risk was significantly higher with positive LGE and peak VO2< 18.5 mL ·kg⁻¹ ·min⁻¹ than with negative LGE and peak VO2≥ 18.5 mL · kg⁻¹ · min⁻¹ (hazard ratio 12.5; 95% CI 1.57-100; P = .017). In 3 patient groups (group A: no LGE, peak VO2≥ 18.5 mL · kg⁻¹ · min⁻¹, n = 18; group B: positive LGE or peak VO2< 18.5 mL · kg⁻¹ · min⁻¹, n = 24; group C: positive LGE and peak VO2< 18.5 mL · kg⁻¹ · min⁻¹, n = 15) during follow-up (71 ± 32 months), group C had higher cardiac event rates than the others. CONCLUSIONS: Combined assessment of LGE-CMR and peak VO2provides additive prognostic information in ambulatory DCM.

Prognostic value of pulmonary hypertension in ambulatory patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: Pulmonary hypertension (PH) because of left-sided heart disease carries a poor prognosis. We investigated whether non-ischemic dilated cardiomyopathy (DCM) with PH is associated with poor prognosis. METHODS AND RESULTS: A total of 256 consecutive DCM patients were enrolled. We measured the ratio of the maximum first derivative of left ventricular pressure (LVdP/dtmax)/systolic blood pressure and pressure half-time (T1/2) as cardiac function. Patients were allocated to 2 groups on the basis of mean pulmonary arterial pressure (mPAP), namely DCM without PH group (mPAP <25 mmHg; n=225) and DCM with PH group (mPAP ≥25 mmHg; n=31). We followed all patients for a mean of 4.3 years for the occurrence of cardiac events, defined as cardiac death or hospitalization for worsening heart failure. Cardiac events were significantly more frequent in the DCM with PH group than in the DCM without PH group (P<0.001). Multivariate Cox regression analysis revealed that mPAP ≥25 mmHg and LV end-systolic volume index were significant independent risk factors for cardiac death. Incidence of cardiac death was significantly higher in patients with DCM with PH than in those without PH [hazard ratio 11.79 (3.18-43.7), P<0.0001]. CONCLUSIONS: The presence of PH was independently associated with an increased incidence of cardiac death in ambulatory patients with DCM.

Relationship of myocardial fibrosis to left ventricular and mitochondrial function in nonischemic dilated cardiomyopathy--a comparison of focal and interstitial fibrosis.

BACKGROUND: Mitochondrial damage is associated with histologic myocardial fibrosis. Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) can be used to identify focal fibrosis. We examined whether myocardial fibrosis on CMR and collagen volume fraction (CVF) from biopsies correlated with left ventricular (LV) and mitochondrial function in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Fifty-nine DCM patients underwent CMR, cardiac catheterization, and endomyocardial biopsy. Minimum first derivative of LV pressure (LVdP/dt(min)) was measured as an index of LV relaxation. Mitochondrial RNA expression was also analyzed. For quantitative analysis of myocardial fibrosis, percentage LGE (%LGE) and CVF were calculated. Patients were divided into 2 groups on the basis of the presence (LGE group; n = 27) or absence (non-LGE group; n = 32) of LGE. Mean CVF and absolute value of LVdP/dt(min) were significantly higher and lower, respectively, in the LGE group than in the non-LGE group. Multivariate analysis revealed that %LGE was an independent determinant of LVdP/dt(min). The abundance of mitochondrial enzyme mRNA was significantly lower in the LGE group. CONCLUSIONS: Noninvasive CMR imaging is more useful in predicting diastolic dysfunction than invasive histologic assessments. In addition, it might indicate mitochondrial dysfunction in DCM.

Association between indoxyl sulfate and cardiac dysfunction and prognosis in patients with dilated cardiomyopathy.

BACKGROUND: Serum indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). The aim of this study was to determine whether serum IS is associated with hemodynamic parameters or cardiac events in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: The 76 patients with DCM had their serum IS and plasma brain natriuretic peptide (BNP) levels measured, and underwent echocardiographic examination. Mean (± standard deviation) left ventricular ejection fraction (LVEF) and BNP levels in the patients were 32.5 ± 10.7% and 204 ± 219 pg/ml, respectively. Patients were divided into 2 groups, low IS (<0.9 µg/ml) and high IS (≥ 0.9 µg/ml), based on the median value of serum IS. Although there were no significant differences in LVEF and BNP between the groups, E/e' was significantly greater in the high IS group than in the low IS group. Furthermore, E/e' was an independent determinant of serum IS level. The risk of a cardiac event was significantly higher in the high IS group than in the low IS group (P=0.014). Moreover, serum IS was a significant predictor of cardiac events even after adjustment for BNP. CONCLUSIONS: Cardiac dysfunction is associated with the serum IS level, which might serve as a new prognostic marker in DCM patients with normal renal function or mild to moderate CKD.

Usefulness of serum cardiac troponins T and I to predict cardiac molecular changes and cardiac damage in patients with hypertrophic cardiomyopathy.

Cardiac troponins provide diagnostic and prognostic information on ischemic heart disease, but their roles in hypertrophic cardiomyopathy (HCM) are unclear. We sought to investigate the associations between elevated serum cardiac troponins T (cTnT) and I (cTnI) levels and cardiac injury in patients with HCM. We measured serum cTnT and cTnI in a peripheral vein of 73 consecutive HCM patients in stable condition. In addition, to examine the transcardiac release of cTnT and that of cTnI, we measured them in the aortic root and coronary sinus. Mitochondrial- and Ca(2+)-handling-related gene expression assays were analyzed by endomyocardial biopsy specimens. Based on the median value of serum cTnT, we divided the patients into two groups [group A: cTnT < 0.008 ng/mL, (n = 35), group B: cTnT group ≥ 0.008 ng/mL, (n = 38)]. Left ventricular (LV) mass index was significantly higher, while LV ejection fraction was significantly lower, in group B than in group A. Meanwhile, there was a significantly positive correlation between the transcardiac gradient of serum cTnT or cTnI, and the mRNA level of troponin I3 (r = 0.473, r = 0.516, respectively). The mRNA level of troponin T2 significantly correlated with mRNA levels of sarco-endoplasmic reticulum Ca(2+)-ATPase 2, cytochrome c oxidase subunit 5B, and troponin I3 (r = 0.486, r = 0.957, r = 0.633, respectively). These findings indicate that both elevated serum cTnT and cTnI might be associated with cardiac dysfunction in patients with HCM, resulting from the impairment of mitochondrial function and Ca(2+)-handling protein.

[Assessment of cardiac contractile reserve].

Left ventricular (LV) function is usually measured by imaging modalities such as echocardiography under static conditions in patients with dilated cardiomyopathy (DCM). However, some studies have reported that LV contractile function at rest is not reliable for assessment of the reversibility of LV contraction. Therefore, it is important to evaluate LV functional response under dynamic conditions by use of pharmacological as well as exercise stress (contractile reserve). In our studies, LVdP/dtmax was measured at rest and under dobutamine stress using a pigtail catheter with a high-fidelity micromanometer placed into the left ventricle in DCM patients. deltaVdP/dtmax as an index of myocardial contractile reserve was defined as the percentage increase in LVdP/dtmax induced by dobutamine infusion. Firstly, deltaLVdP/dtmax was correlated with peak oxygen consumption by cardiopulmonary exercise testing. In addition, impaired deltaLVdP/dtmax was associated with unfavorable prognosis. Secondly, reduced deltaLVdP/dtmax was associated with an increased washout rate evaluated by myocardial 123I-MIBG and 99mTc-MIBI scintigraphy. Finally, this residual contractile reserve was related to molecular remodeling caused by overactivation of the sympathetic nerve system in DCM patients. This review focused on the current status of contractile reserve with our findings, including procedures for evaluating contractile reserve, clinical implications, and molecular biological significance.

Assessment of respiratory disturbance index determined with a non-restrictive monitor and of autonomic nervous system parameters in heart failure patients: A pilot study.

BACKGROUND: There is a link between sympathetic overactivity and sleep-disordered breathing (SDB), and both of which are important indicators of the development of heart failure. To manage the increasing numbers of heart failure patients, any method used to check for them needs to be as non-invasive, simple, and cost-effective as possible. The purpose of this study is to assess screening of SDB with a non-restrictive monitor and the autonomic nervous system in heart failure patients. METHODS: The subjects were 49 patients (mean age: 67 years; male: 78%) hospitalized for worsening heart failure. After stabilization with appropriate medical therapy, each patient simultaneously underwent sleep apnea syndrome (SAS) screening with the SD-101 (Kenzmedico Co. Ltd., Saitama, Japan), which is a novel, non-restrictive, sheet-like monitor for SAS screening, and assessment of heart rate variability (HRV) with a Holter monitor. In addition, we assessed daytime sleepiness by using the Epworth Sleepiness Scale. RESULTS: The mean respiratory disturbance index (RDI) was 21.9 events/h. Males had significantly greater RDI values than females (24.5±11.2 events/h vs. 13.0±6.2 events/h, p<0.001). RDI on SD-101 testing was closely correlated with cyclic variation of heart rate index obtained with a Holter electrocardiogram scanner (r=0.843). Although plasma brain natriuretic peptide level was not correlated with HRV, plasma norepinephrine level was moderately well correlated with the total low- to high-frequency ratio of HRV (r=0.529). CONCLUSIONS: SAS screening is important for heart failure patients, because absence of subjective sleepiness is not reliable in ruling out SDB. The SAS screening with SD-101 might apply for managing heart failure.

Prognostic factors in pulmonary arterial hypertension with Dana Point group 1.

AIMS: To clarify the prognosis and prognostic factors in pulmonary arterial hypertension (PAH) patients in real-world medical practice in the Tokai area in Japan. MAIN METHODS: We conducted a retrospective, multicenter observational study. The data of 81 patients diagnosed with Dana Point group 1 or 1' PAH was collected from January 2005 to January 2013. The primary outcome was all-cause death. KEY FINDINGS: The patients consisted of 34 cases of idiopathic PAH (IPAH), 28 of connective tissue-associated PAH (CTD-PAH), 16 of congenital heart disease-associated PAH (CHD-PAH) and others. Mean age was 51 years and mean observation period was 46 months. The systolic blood pressure (BPs) was 117±23 mm Hg. Pericardial effusion was observed in 27.0% of patients. The mean right atrial pressure (mRAP) was 10.2±7.3 mm Hg. In the univariate Cox regression analysis, WHO-FCS III & IV, a cardiac index (CI)<2.5 L/min/m(2), and the presence of pericardial effusion at baseline were significantly associated with all-cause death. In the multivariate analysis, the pericardial effusion (HR 3.3, 95% CI 1.03-10.63, p=0.04) and mRAP (HR 3.2, 95% CI 1.03-9.83, p=0.04) or CI<2.5 L/min/m(2) (HR 3.89, 95% CI 1.05-14.45, p=0.04) were the independent predictors of mortality. SIGNIFICANCE: The presence of pericardial effusion and mRAP or CI<2.5 L/min/m(2) at diagnosis indicated high mortality.

Cardiopulmonary exercise testing to evaluate the exercise capacity of patients with inoperable chronic thromboembolic pulmonary hypertension: an endothelin receptor antagonist improves the peak PETCO2.

AIMS: The 6-min walking distance is often used for assessing the exercise capacity under the treatment with an endothelin receptor antagonist (ERA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The cardiopulmonary exercise testing (CPX) was reported to be more useful for the patients with pulmonary arterial hypertension (PAH), however, few reports exist in patients with inoperable CTEPH. The aim of this study was to investigate the effects of an oral dual ERA, bosentan, on exercise capacity using CPX in patients with PAH and inoperable CTEPH. MAIN METHODS: This study included all patients diagnosed with 17 PAH and 12 CTEPH in the World Health Organization functional classes II-IV who started treatment with bosentan therapy. They underwent CPX, which was performed before bosentan therapy and at 3 to 6 months of the treatment. KEY FINDINGS: In PAH patients, peak VO2 significantly increased after the bosentan treatment (p=0.009). On the other hand, in CTEPH patients, there were no significant differences in the peak VO2. However, the peak PETCO2 was significantly increased from 23.9±5.2 mm Hg at baseline to 29.3±10.7 mm Hg after the bosentan treatment (p=0.040). In addition, peak heart rate during exercise tended to decrease after the bosentan therapy (p=0.089). SIGNIFICANCE: Bosentan therapy improved peak PETCO2 but not peak VO2 in patients with inoperable CTEPH. These findings demonstrated that CPX is useful for assessing the exercise capacity of patients with PAH and inoperable CTEPH under the treatment with an ERA.