Diagnosis, Treatment, and Prevention of Cardiovascular Toxicity Related to Anti-Cancer Treatment in Clinical Practice: An Opinion Paper from the Working Group on Cardio-Oncology of the Korean Society of Echocardiography

Cardiovascular (CV) toxicity associated with anti-cancer treatment is commonly encountered and raises critical problems that often result in serious morbidity or mortality. Most cardiac toxicities are related to the cumulative dose of chemotherapy; however, the type of chemotherapy, concomitant agents, and/or conventional CV risk factors have been frequently implicated in CV toxicity. Approximately half of the patients exhibiting CV toxicity receive an anthracycline-based regimen. Therefore, serologic biomarkers or cardiac imagings are important during anti-cancer treatment for early detection and the decision of appropriate management of cardiotoxicity. However, given the difficulty in determining a causal relationship, a multidisciplinary collaborative approach between cardiologists and oncologists is required. In this review, we summarize the CV toxicity and focus on the role of cardiac imaging in management strategies for cardiotoxicity associated with anti-cancer treatment.

The Relationships between Body Mass Index and Left Ventricular Diastolic Function in a Structurally Normal Heart with Normal Ejection Fraction

BACKGROUND: We conducted research to determine the effect of the weight on left ventricular (LV) diastolic function in Asians, who are at greater risk of cardiovascular events compared to individuals from Western countries with similar body mass indices (BMIs). METHODS: We studied 543 participants with structurally normal hearts and normal ejection fractions. Participants were classified as normal-weight (BMI < 23.0 kg/m²), overweight (BMI 23.0–27.4 kg/m²), or obese (BMI ≥ 27.5 kg/m²). Peak E velocity, peak A velocity, and E′ velocity were measured and E/E′ was calculated. RESULTS: Overweight participants had lower E than normal-weight participants (p = 0.001). E′ velocities in overweight and obese participants were less than those in normal weight participants (both p < 0.001). The E/E′ ratio in obese participants was higher compared to the value in normal-weight participants (p < 0.001) and overweight participants (p = 0.025). BMI was associated with E (R = −0.108), A (R = 0.123), E′ (R = −0.229), and E/E′ ratio (R = 0.138) (all p < 0.05). In multivariate analyses, BMI was independently associated with higher A, lower E′, and higher E/E′. The risk of diastolic dysfunction was significantly higher among overweight [adjusted odds ratio: 2.088; 95% confidence interval (CI): 1.348–3.235; p = 0.001] and obese participants (adjusted odds ratio: 5.910; 95% CI: 2.871–12.162; p < 0.001) compared to normal-weight participants. CONCLUSION: Obesity and overweight independently predicted diastolic dysfunction. An optimal body weight lower than the universal cut-off is reasonable for preventing LV heart failure in Asians.

Local Atrial/Ventricular Ratio as an Adjuvant Marker for Catheter Ablation of Atrioventricular Accessory Pathways

BACKGROUND AND OBJECTIVES: The earliest atrial (A)/ventricular (V) activation potential, or accessory pathway (AP) potential are commonly used as ablation targets for atrioventricular (AV) APs. However, these targets are sometimes ambiguous. SUBJECTS AND METHODS: We reviewed 119 catheter ablation cases in 112 patients diagnosed with orthodromic atrioventricular reentrant tachycardia (AVRT) or Wolff-Parkinson-White (WPW) syndrome. Local A/V amplitude potentials with the earliest activation or AP potential were measured shortly before achieving antegrade AP conduction block, ventriculoatrial block during right ventricle (RV) pacing, or AVRT termination with no AP conduction. RESULTS: APs were located in the left lateral (55.5%), left posterior (17.6%), left posteroseptal (10.1%), midseptal (1.7%), right posteroseptal (7.6%), right posterior (1.7%), and right lateral (5.9%) regions. The mean earliest activation time was 16.7±15.5 ms, mean A/V potential was 1.1±0.9/1.0±0.9 mV, and mean A/V ratio was 1.7±2.0. There was no statistically significant difference between the activation methods (antegrade vs. RV pacing vs. orthodromic AVRT) or AP locations (left vs. right atrium). However, when the local A/V ratio was divided into 3 groups (≤0.6, 1.0±0.3, and ≥1.4), the antegrade approach resulted in an A/V ratio greater than 1.0±0.3 (86.7%, p=0.007), and the orthodromic AVRT state resulted in a ratio of less than 1.0±0.3 (87.5%, p<0.001). CONCLUSION: The mean local A/V potential and ratio did not differ by activation method or AP location. However, a different A/V ratio based on activation method (≥1.0±0.3, antegrade approach; and ≤1.0±0.3, orthodromic AVRT state) could be a good adjuvant marker for targeting AV APs.

Erratum: Diagnostic Performance of Intravascular Ultrasound-Derived Minimal Lumen Area to Predict Functionally Significant Non-Left Main Coronary Artery Disease: a Meta-Analysis

In the article, the weighted overall mean MLA cut-off value has been miscalculated. Tha authors deeply apologize for any inconvenience it may have caused.

Combined Use of Neutrophil to Lymphocyte Ratio and C-Reactive Protein Level to Predict Clinical Outcomes in Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: Both neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) are biomarkers associated with poor prognosis of patients with acute myocardial infarction (AMI). However, the combined usefulness of NLR and CRP in predicting adverse outcomes has not been investigated. SUBJECTS AND METHODS: We analyzed 381 consecutive AMI patients who underwent percutaneous coronary intervention (PCI) from January 2012 to January 2014. The endpoints were all-cause mortality, recurrent myocardial infarction (MI), stent thrombosis, repeat revascularization, stroke, and major adverse cardiac and cerebrovascular events (MACCE) at 2-year follow-up. Included patients were divided into 4 groups according to the optimal cut-off values for NLR and CRP on receiver operating characteristic analysis predicting mortality. RESULTS: Patients with both high NLR (>6.30) and high CRP (>0.76) had significantly greater risk of all-cause death and MACCE at 24 months, with no significant increase in the risk of recurrent MI, stent thrombosis, or stroke compared with patients with either low NLR or low CRP, as well as those with low NLR and low CRP. Kaplan-Meier analysis revealed significantly lower survival in patients with high NLR-CRP. On Cox multivariate analysis, high NLR-CRP (hazard ratio 23.172, 95% confidence interval 6.575 to 81.671, p<0.001) was an independent predictor of all-cause death. CONCLUSION: Elevated levels of both NLR and CRP are associated with increased risk of long-term mortality in AMI patients who have undergone PCI.

Impact of Valvuloarterial Impedance on Concentric Remodeling in Aortic Stenosis and Its Regression after Valve Replacement

BACKGROUND: Left ventricle (LV) in patients with aortic stenosis (AS) faces a double hemodynamic load incorporating both valvular stenosis and reduced systemic arterial compliance (SAC). This study aimed to evaluate the impact of global LV afterload on LV hypertrophy (LVH) before and after aortic valve replacement (AVR). METHODS: The study cohort included 453 patients (247 males; mean age, 64 ± 11 years) who underwent AVR. Pre- and post-AVR echocardiographic examinations were retrospectively analyzed including an index of valvuloarterial impedance (Z(VA)) and LV mass index/LV end-diastolic volume index (LVMI/LVEDVI) as a parameter of LVH. RESULTS: Pre-AVR LVMI/LVEDVI was 2.7 ± 0.9 g/mL with an aortic valve area (AVA) of 0.6 ± 0.2 cm². Z(VA) was 5.9 ± 1.9 mm Hg/mL/m² and showed a stronger correlation (β = 0.601, p 1 year after AVR. CONCLUSION: Z(VA) is a major determinant of concentric remodeling in AS before AVR and LVH regression after AVR, which should be incorporated in routine evaluation of AS.

Diagnostic Performance of Intravascular Ultrasound-Derived Minimal Lumen Area to Predict Functionally Significant Non-Left Main Coronary Artery Disease: a Meta-Analysis

BACKGROUND AND OBJECTIVES: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention frequently results in unnecessary stenting due to the low positive predictive value of IVUS-derived minimal lumen area (MLA) for identification of functionally significant coronary stenosis. We appraised the diagnostic accuracy of IVUS-derived MLA compared with the fractional flow reserve (FFR) to assess intermediate coronary stenosis. SUBJECTS AND METHODS: We searched MEDLINE and Cochrane databases for studies using IVUS and FFR methods to establish the best MLA cut-off values to predict significant non-left main coronary artery stenosis. Summary estimates were obtained using a random-effects model. RESULTS: The 17 studies used in our analysis enrolled 3920 patients with 4267 lesions. The weighted overall mean MLA cut-off value was 2.58 mm². The pooled MLA sensitivity that predicted functionally significant coronary stenosis was 0.75 (confidence interval [CI]: 0.72 to 0.77) and the specificity was 0.66 (CI: 0.64 to 0.68). The positive likelihood ratio (LR) was 2.33 (CI: 2.06 to 2.63) and LR (-) was 0.33 (CI: 0.26 to 0.42). The pooled diagnostic odds ratio (DOR) was 7.53 (CI: 5.26 to 10.76) and the area under the summary receiver operating characteristic curve for all the trials was 0.782 with a Q point of 0.720. Meta-regression analysis demonstrated that an FFR cut-off point of 0.75 was associated with a four times higher diagnostic accuracy compared to that of 0.80 (relative DOR: 3.92; 95% CI: 1.25 to 12.34). CONCLUSION: IVUS-derived MLA has limited diagnostic accuracy and needs careful interpretation to correlate with functionally significant non-left main coronary artery stenosis.

Cardiac Hemangioma: A Case Report

Hemangioma of the heart, presenting as a primary cardiac tumor is extremely rare; it accounts for approximately 2% of all primary resected heart tumors. In our patient, the tumor was located in the orifice of the right lower pulmonary vein. Few cases of cardiac hemangiomas have been reported to arise from the left atrial (LA) wall. Left atrial hemangiomas, especially those attached to the LA wall, may be erroneously diagnosed as myxomas. Cardiac hemangioma is a rare disease; furthermore, a tumor arising from the LA wall and misconceived as a myxoma is extremely rare. We removed a mass misdiagnosed as a myxoma; it was pathologically confirmed to be a cardiac capillary hemangioma. Therefore, we report a rare case of a cardiac hemangioma misconceived as a myxoma; the tumor was removed successfully.

Randomized Comparison of the Platelet Inhibitory Efficacy between Low Dose Prasugrel and Standard Dose Clopidogrel in Patients Who Underwent Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: Increased bleeding rates with standard dose prasugrel have led to increased questions about the effectiveness and safety of the lower maintenance dose. We compared platelet inhibitory efficacy between low dose prasugrel and standard dose clopidogrel in patients on maintenance dose dual antiplatelet therapy. SUBJECTS AND METHODS: Forty-three patients who underwent percutaneous coronary intervention were randomized to receive 75 mg clopidogrel (n=23) or 5 mg prasugrel (n=20). Another 20 patients were allocated to 10 mg prasugrel as a reference comparison group. All patients (weight, > or =60 kg; age, 235) was significant lower in the 5 mg prasugrel group than that in the 75 mg clopidogrel group (15.0% vs. 56.5%, p=0.010). CONCLUSION: Prasugrel (5 mg) is more potent antiplatelet therapy than 75 mg clopidogrel in non-low body weight and non-elderly patients on a maintenance dose dual antiplatelet therapy.

Neutrophil to Lymphocyte Ratio Predicts Long-Term Clinical Outcomes in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: A higher neutrophil to lymphocyte ratio (NLR) has been associated with poor clinical outcomes in various cardiac diseases. However, the clinical availability of NLR in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has not been known. We evaluated the availability of NLR to predict clinical outcomes in patients with STEMI undergoing primary PCI. SUBJECTS AND METHODS: We analyzed 326 consecutive STEMI patients treated with primary PCI. The patients were divided into tertiles according to NLR: NLR6.53 (n=110). We evaluated the incidence of major adverse cardiac events (MACE), a composite of all causes of death, non-fatal MI, and ischemic stroke at the 12-month follow-up. RESULTS: The high NLR group was associated with a significantly higher rate of 12-month MACE (19.1% vs. 3.7%, p<0.001), 12-month death (18.2% vs. 2.8%, p<0.001), in-hospital MACE (12.7% vs. 2.8%, p=0.010) and in-hospital death (12.7% vs. 1.9%, p=0.003) compared to the low NLR group. In the multivariable model, high NLR was an independent predictor of 12-month MACE {hazard ratio (HR) 3.33 (1.09-10.16), p=0.035} and death {HR 4.10 (1.17-14.46), p=0.028} after adjustment for gender, left ventricular ejection fraction, creatinine clearance, angiographic parameters and factors included in the Thrombolysis in Myocardial Infarction risk score for STEMI. There was a significant gradient of 12-month MACE across the NLR tertiles with a markedly increased MACE hazard in the high NLR group (log rank test p=0.002). CONCLUSION: The NLR is a useful marker to predict 12-month MACE and death in patients with STEMI who have undergone primary PCI.

Incidental Diagnosis of the Unicuspid Aortic Valve with Ascending Aortic Aneurysm in an Asymptomatic Adult

The unicuspid aortic valve is an extremely rare congenital anomaly. It usually presents with aortic stenosis and/or aortic regurgitation. Other cardiovascular complications, such as aortic dilatation and left ventricular hypertrophy can accompany it. Herein, we present a case report of a 50-year-old asymptomatic male patient with unicuspid aortic valve, complicated by ascending aortic aneurysm.

Predictors of Echocardiographic Progression in Patients With Mild Aortic Stenosis

BACKGROUND AND OBJECTIVES: The factors related to the progression of mild aortic stenosis (AS) remain unknown. We wanted to evaluate the long-term outcomes and predictors of echocardiographic progression in patients with mild AS. SUBJECTS AND METHODS: We prospectively included 103 consecutive asymptomatic patients (62.1+/-11.9 years, 31 males) with mild AS. Mild AS was defined as aortic valve (AV) thickening accompanied by a peak aortic jet velocity (AV Vmax) > or =2.0 and or =0.2 m/sec, and cardiac events were defined as cardiac death or AV replacement. RESULTS: During a median echocardiographic follow-up time of 6.0 years, the average change in the AV Vmax was 0.08+/-0.10 m/sec per year. The rate of progression was significantly associated with age, moderate-to-severe AV calcification and the baseline AV Vmax, but not with the serum cholesterol level. The baseline AV Vmax (2.6+/-0.3 m/sec vs. 2.2+/-0.3 m/sec, respectively, p<0.001) and the incidence of moderate-to-severe AV calcification (92.9% vs. 36.5%, respectively, p<0.001) were significantly higher in the rapid progression group than in the slow progression group. The 7-year cardiac event-free survival rate was lower in the rapid progression group than in the slow pro-gression group (87.5+/-8.3% vs. 100%, respectively). CONCLUSION: The progression of AS was slower than expected and it was related to age, the baseline AV Vmax and AV calcification. Because of the marked individual variability in progression, the patients showing rapid progression of AS need closer follow-up.

A Case of Traumatic Tricuspid Regurgitation Caused by Multiple Papillary Muscle Rupture

Traumatic tricuspid regurgitation is a rare complication of blunt chest trauma. With the increase in the number of automobile accidents, traumatic tricuspid regurgitation has become an important problem after blunt chest trauma. It has been reported more frequently because of better diagnostic procedures and a better understanding of the pathology. The early diagnosis of traumatic tricuspid regurgitation is important because traumatic tricuspid injury could be effectively corrected with reparative techniques, early operation is considered to relieve symptoms and to prevent right ventricular dysfunction. Echocardiography can reveal the cause and severity of regurgitation. We experienced a case of tricuspid regurgitation after blunt chest trauma early diagnosis and valve repair were performed. This case reminds the physicians in the emergency department should be aware of this potential complication following non-penetrating chest trauma and echocardiography is useful and should play an early role.

Prevalence of Echocardiographic Features Suggesting Cardiac Sarcoidosis in Patients With Pacemaker or Implantable Cardiac Defibrillator

BACKGROUND AND OBJECTIVES: Basal septal thinning or localized aneurysmal dilatation without coronary artery disease has been described as a characteristic finding suggestive of cardiac sarcoidosis. We sought to assess the prevalence of this characteristic echocardiographic finding in patients with pacemaker (PM) or implantable cardiac defibrillator (ICD). SUBJECTS AND METHODS: Echocardiography of patients who received PM or ICD were retrospectively analyzed. Patients with marked thinning and akinesia confined to the basal septum (type 1), or posterolateral wall resulting in localized aneurysmal outward bulging (type 2) without history of myocardial infarction or significant coronary stenosis were included for analysis. RESULTS: Among 1,357 consecutive patients, 21 exhibited suggestive echocardiographic findings (type 1/2=15/6) with a mean ejection fraction of 37+/-11%. The prevalence was 1.2% in the PM group and 4.0% in the ICD group. Only 3 patients showed histologically confirmable sarcoidosis in lymph nodes, lung and heart, respectively. Endomyocardial biopsy was attempted in 6 patients, but failed to demonstrate sarcoidosis. The 1-, 2-, 4- and 6-year clinical events (death, cardiac transplantation and hospital admission)-free survival rates were 100%, 85.7+/-7.6%, 75.0+/-9.7% and 48.6+/-12.4%, respectively. During follow-up, two patients with PM underwent ICD implantation, and another underwent heart transplantation. CONCLUSION: Prevalence of echocardiographic features suggesting prevalence of cardiac sarcoidosis is low in patients who underwent device implantation. However, considering the very low yield of endomyocardial biopsy and the rare extracardiac manifestations in cardiac sarcoidosis, characteristic echocardiographic findings could be an adjunctive diagnostic criterion in these patients.

Comparison of Plaque Composition in Diabetic and Non-Diabetic Patients With Coronary Artery Disease Using Multislice CT Angiography

BACKGROUND AND OBJECTIVES: Plaque composition rather than degree of luminal narrowing may be predictive of future coronary events in high risk patients. The purpose of this study was to compare degree of plaque burden and composition with multislice computed tomography (MSCT) angiography between diabetic and non-diabetic patients. SUBJECTS AND METHODS: A total of 452 consecutive MSCT angiography examinations were performed between July 2007 and June 2009. Of these, the patients who underwent invasive coronary angiography were evaluated for the presence and type of atherosclerotic plaque and severity of luminal narrowing. RESULTS: Ninety two (46 in the diabetic group and 46 in the non-diabetic group) patients underwent both MSCT angiography and invasive coronary angiography. Among them, 30 patients (65.2%) in the diabetic group and 26 patients (56.5%) in the non-diabetic group had significant coronary narrowing on MSCT angiography. Sixteen patients (34.8%) in the diabetic group and 15 patients (32.6%) in non-diabetic group underwent coronary angioplasty and stenting. Forty-two patients (93.3%) in the diabetic group and 39 patients (88.6%) in the non-diabetic group had multiple types of coronary plaque (p=0.485). MSCT angiography was similar to conventional coronary angiography in its ability to predict significant coronary artery disease in that the area under the curve was 0.88 (95% confidence interval, 0.81 to 0.95). Diabetic patients had more mixed plaque compared with non-diabetic patients. CONCLUSION: Differences in coronary plaque composition between diabetic and non-diabetic patients can be determined noninvasively by MSCT angiography. In patients with diabetes, mixed plaque types contribute to the total plaque burden to a higher degree than in non-diabetic patients.

A Case of Loeffler's Endocarditis Associated with Churg-Strauss Syndrome

Loeffler's endocarditis is generally caused by hypereosinophilic syndrome. It is a restrictive cardiomyopathy characterized with eosinophilia and eosionophilic penetration leading to the fibrous thickening of endocardium of both ventricles, apical obliteration and heart failure. We report a case of a 23-year-old male with Loeffler's endocarditis caused by Churg-Strauss syndrome. The echocardiogram showed that biventricular failure with large thrombus in left ventricle. His symptoms and typical echocardiographic findings markedly improved within 2 months after treatment for Churg-Strauss syndrome.

A case of Gitelman's Syndrome with Chronic Hypotension and Normomagnesemia / 대한신장학회지

Gitelman's syndrome is a heritable renal disorder characterized by hypomagnesemia, hypokalemia and hypocalciuria. Interestingly, we have experienced one patient who had chronic hypotension, normal serum magnesium level, normal plasma ionized magnesium level, hypokalemia and hypocalciuria. Immunohistochemistry showed the absence of NCCT staining in renal tissues of the patient. We report the case of atypical Gitelman's syndrome with a brief review of related literature.

A Case of Acute Respiratory Distress Syndrome Caused By Zinc Fume Inhalation / 결핵및호흡기질환

The Inhalation of certain freshly formed metal oxides can cause metal fume fever, which is an acute, self-limiting, flu-like illness. The most common cause of this syndrome is the inhalation of zinc oxide. The inhalation of zinc oxide can lead to tracheobronchiolitis, chemical pulmonary edema or to respiratory failure and acute respiratory distress syndrome(ARDS). We encountered a 43-years-old man who developed severe dyspnea after inhaling of zinc oxide while working for 5 hours in a closed space. He was diagnosed with ARDS and was treated successfully with glucocorticoid. We report a case of ARDS caused by the inhalation of zinc fumes.

Comparison of oral N-acetylcysteine(NAC) and prehydration for preventing contrast-induced nephropathy in patients with renal dysfunction / 대한내과학회지

BACKGROUND: Contrast induced nephropathy (CIN) is an important cause of acute renal failure in patients with renal dysfunction. We investigated whether oral NAC alone was sufficient to prevent CIN to the same extent as hydration in patients with renal dysfunction, and whether these treatments resulted in diffierences in the urinary excretion of nitric oxide, a vasodilator. METHODS: A total of 27 patients with renal dysfunction, who underwent radiographic examination with nonionic and low osmolar contrast, were randomly assigned to receive either NAC (600 mg orally twice daily; N=11) or 0.45% saline hydration (1 mL/kg/Hr; N=16) 12 hours prior to and 12 hours after the contrast procedure. We measured serum creatinine (sCr), fractional excretion of sodium (FENa), creatinine clearance (CCr), and urinary nitrite before and after contrast administration. RESULTS: The mean volume of contrast used was similar in the two groups (100.9+/-54.8 mL vs 114.7+/-38 mL; p=0.43), as was baseline sCr in the two groups (2.31+/-1.59 mg/dL vs 2.18+/-1.41 mg/dL; p=0.98). Treatment did not significantly affect the incidence of CIN, with 18.2% and 12.5% in the NAC group and hydration group, respectively (p=1.0). The urinary nitrite/creatinine ratio (micro mol/mg) was 1.26+/-0.57 and 1.43+/-0.64 at baseline and 48 hours after contrast exposure in the NAC group, respectively, and 0.80+/-0.40 and 1.18+/-0.60 in the hydration group, respectively, which were not significantly different. FENa increased significantly after contrast exposure in the NAC group compared with hydration group (p=0.04) CONCLUSIONS: NAC alone may prevent CIN. When bolus hydration is contraindicated in patients with renal dysfunction, administration of NAC alone may be sufficient.

A Case of Choledocho-Duodeno-Colonic Fistula / 대한소화기내시경학회지

Biliary-enteric fistula is a rare disease, and the common causes of biliary-enteric fistula are gallstone, peptic ulcer, malignancy and trauma. It is known that the most common type of biliary-enteric fistula is the cholecysto-duodenal fistula, yet the combination of choledocho-duodeno-colonic fistula is a rare finding. A 78-year-old woman was admitted because she had suffered with right upper quadrant pain, a febrile sense and chills for 2 days. We confirmed the choledocho-duodeno-colonic fistula by performing gastroduodenoscopy, abdominal CT and an upper GI series. So, we report here on an usual case of choledocho-duodeno-colonic fistula, along with a review of the relevant literatures.