Role of polyunsaturated fatty acids in Japanese patients with coronary spastic angina.

BACKGROUND: n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of ischemic heart disease. However, there are few reports of a relationship between n-3 PUFAs and coronary spastic angina (CSA). This study aimed to assess the age-dependent role of serum levels of fatty acid in patients with CSA. METHODS AND RESULTS: We enrolled 406 patients who underwent ergonovine tolerance test (ETT) during coronary angiography for evaluation of CSA. All ETT-positive subjects were diagnosed as having CSA. We categorized the patients by age and results of ETT as follows: (1) young (age ≤ 65 years) CSA-positive (n = 32), (2) young CSA-negative (n = 134), (3) elderly (age > 66 years) CSA-positive (n = 36), and (4) elderly CSA-negative (n = 204) groups. We evaluated the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, and dihomo-gamma-linolenic acid. In the young groups, the serum levels of EPA (64.3 ±â€¯37.7 µg/mL vs. 49.4 ±â€¯28.8 µg/mL, p = 0.015) and DHA (135.7 ±â€¯47.6 µg/mL vs. 117.4 ±â€¯37.6 µg/mL, p = 0.020) were significantly higher in the CSA-positive group than in the CSA-negative group, respectively. However, this was not the case with elderly groups. In the multivariate analysis in young groups, the serum levels of EPA (p = 0.028) and DHA (p = 0.049) were independently associated with the presence of CSA, respectively. CONCLUSION: Our results suggested that the higher serum levels of EPA and/or DHA might be involved in the pathophysiology of CSA in the young population but not in the elderly population.

Transient complete atrioventricular block and ST-segment elevation induced by coronary vasospasm due to iatrogenic hyperkalemia: a case report.

BACKGROUND: Hyperkalemia and acute coronary syndrome are not only all responsible for syncope related to complete atrioventricular block, but also share parts of electrocardiogram manifestations. Additionally, they influence each other. CASE PRESENTATION: A 32-year-old Chinese man presented with severe hypokalemia (1.63 mmol/l) at midnight in the emergency room. He developed unexpected rebound hyperkalemia (7.76 mmol/l) after 18 hours of oral and intravenous potassium chloride supplementation at a concentration of about 10 g/day and a rate of 10 mmol/hour. Subsequently, the patient complained of chest discomfort and dyspnea, followed by syncope for several minutes, approximately 2 hours after potassium reduction treatment had been started. The instant electrocardiogram showed complete atrioventricular block and elevated ST segment in the inferolateral leads, which resolved 15 minutes later, before hyperkalemia was corrected. Combined with mild coronary stenosis and negative myocardial injury markers, transient complete atrioventricular block induced by coronary vasospasm due to iatrogenic hyperkalemia was diagnosed. Normal urine potassium excretion, acid-base state, and other examinations made the diagnosis of hypokalemic periodic paralysis possible. CONCLUSIONS: Hyperkalemia may provoke acute coronary syndrome, and early coronary angiography is an effective strategy for identifying the direct cause of acute complete atrioventricular block.

Spasm provocation tests performed under medical therapy: a new approach for treating patients with refractory coronary spastic angina on emergency admission.

Objective There are no objective methods for evaluating the severity of vasospasms in patients with refractory coronary spastic angina (R-CSA) under adequate medical therapy. We examined whether spasm provocation tests performed under adequate medication are useful for evaluating the severity of disease in R-CSA patients on emergency admission. Methods and Results We performed spasm provocation tests before and after the administration of medical therapy in eight R-CSA patients, including one ventricular fibrillation survivor (VF-S) and seven patients with unstable angina (UAP) on emergency readmission. We also performed these tests only after medical therapy on urgent admission in four R-CSA patients, including two patients with UAP, one patient with VF-S and one patient with acute coronary syndrome. All 12 R-CSA patients had been medicated with ≥ 2 vasodilator drugs. Positive coronary spasms were defined as >99% transient narrowing. The coronary artery spasms disappeared in three patients under medication, and mitigation of vasospasticity was observed in three patients. In these six cases we continued the same medications. Meanwhile in two patients, we recommended a consultation for psychosomatic medicine. In contrast, the remaining six R-CSA patients exhibited higher levels of vasospasticity, irrespective of the administration of aggressive medical therapy, in which the doses of vasoactive drugs were increased in order to suppress coronary artery spasms. Conclusion In some R-CSA patients on emergency admission, performing spasm provocation tests under medical therapy is useful for determining the subsequent treatment strategy. Therefore, this test may become a new tool in the treatment of R-CSA.

[Kounis syndrome secondary to an allergic reaction to metamizole]. / Síndrome de Kounis secundario a reacción alérgica a metamizol.

Severe cardiovascular events, such as coronary vasospasm or acute myocardial infarction can occur during anaphylactic reactions. Although rare, this cause of ischaemic heart disease is known. We present the case of a patient who suffered an angina episode after an anaphylactic reaction due tot administering metamizole, with no significant lesions observed in the coronary catheterisation.

Nitrate tolerance as a possible cause of multidrug-resistant coronary artery spasm.

Coronary spasm can usually be controlled by administration of Ca antagonists. However, there are some cases of coronary spasm whose attacks cannot be controlled even with large doses of Ca antagonist and/or its combination with nitrates. Here we describe the case of a 41-year-old man whose attacks of coronary spasm were resistant to the combined administration of nitrates, Ca antagonists, and a statin. The attacks were alleviated and disappeared after withdrawal of nitrates and recurred after readministration of a nitroglycerin patch. The involvement of nitrate tolerance in the pathogenesis of multidrug resistant coronary spasm was revealed and its implication discussed.

Effects of treatment with once-daily nifedipine CR and twice-daily benidipine on prevention of symptomatic attacks in patients with coronary spastic angina pectoris-Adalat Trial vs Coniel in Tokyo against Coronary Spastic Angina (ATTACK CSA).

BACKGROUND: We compared the efficacy of once-daily treatment with nifedipine CR 40 mg (NR) and twice-daily treatment with benidipine 4 mg (BD) in patients with coronary spastic angina (CSA) registered in 3 cardiovascular institutes in Tokyo. METHODS AND RESULTS: CSA was diagnosed by an ischemic ST change during Holter ECG monitoring or drug-induced test. Thirty patients were randomly allocated to either NR or BD group. The number of symptomatic attacks and the total frequency of short-acting nitrates were examined based on the data in diaries written by patients. There were no significant differences in the baseline characteristics between the two groups. The median number (25-75% quartile) of attacks per week was significantly decreased in NR group, i.e., 1.0 (0.8-2.0) at baseline, 0.0 (0.0-1.0) after 4 weeks of treatment, and 0.0 (0.0-0.0) after 8 weeks of treatment (P=0.0093, P=0.0002, Wilcoxon's rank-sum test). No significant decrease was observed in BD, i.e. 1.0 (0.5-2.0) at baseline, 1.3 (0.0-3.0) after 4 weeks, and 0.0 (0.0-1.0) after 8 weeks. The number of attacks was fewer in NR than in BD group (P=0.074, P=0.015, U-test for difference). CONCLUSION: Once-daily treatment with NR 40 mg was more effective than twice-daily treatment with BD in the prevention of CSA attacks.

Capecitabine-induced cardiotoxicity: when to suspect? How to manage? A case report.

We present a case of capecitabine-induced cardiac toxicity manifested by chest pain, ST-segment elevation and ventricular tachycardia. Symptoms and ECG alterations were completely reversible after withdrawal of the drug. Coronary angiography demonstrated the absence of epicardial coronary spasm. We suggest cardiac monitoring with ECG Holter and effort ECG during the first days of drug administration. Prompt evaluation of chest pain in this setting is of paramount importance.

Coronary vasospasm with myocardial stunning in a patient with colon cancer receiving adjuvant chemotherapy with FOLFOX regimen.

Colorectal cancer (CRC) represents a major public health problem accounting for > 1 million cases of new cancers and about half a million deaths worldwide. The risk of recurrence remains high despite curative surgery in early disease stages. The incremental benefit in absolute recurrence-free survival from 5-fluorouracil (5-FU)-based regimens in young patients with high-risk colon cancer is not insignificant. We present a case of a 57-year-old otherwise healthy white man who was treated with adjuvant chemotherapy consisting of modified 5-FU/leucovorin/oxaliplatin (FOLFOX6) regimen for stage III colon cancer. He experienced significant cardiotoxicity related to infusional 5-FU. Because of his young age and high-risk cancer, the patient opted to continue with adjuvant bolus 5-FU-containing chemotherapy after a lengthy discussion. With close cardiac monitoring and treatment with calcium channel blocker to prevent coronary vasospasm, he was able to successfully complete adjuvant chemotherapy. Currently, there are no guidelines for predicting a patient's risk for 5-FU-induced cardiotoxicity. Similarly, there is no uniform management of this 5-FU-related induced cardiotoxicity. We believe that our case report, with a brief review of related literature, might help fill some of this vacuum.

Coronary spasm induced by capecitabine mimicks ST elevation myocardial infarction.

Capecitabine is a chemotherapeutic prodrug that is metabolised to 5-fluorouracil. Supported by the National Institute for Health and Clinical Excellence guidance it is now first-line adjuvant treatment for metastatic colorectal cancer in the UK. Although cardiac chest pain and myocardial ischaemia are well recognised side effects of 5-fluorouracil, their association with capecitabine is not widely appreciated. Two cases are described of coronary spasm secondary to capecitabine in patients referred for emergency invasive treatment of presumed ST elevation myocardial infarction (STEMI). The contemporary treatment of acute coronary syndromes involves aggressive antiplatelet therapy, anticoagulation and cardiac catheterisation. This treatment, although beneficial in most patients, is associated with a small but significant risk of bleeding complications. A wider appreciation of the potential for capecitabine to induce spasm mimicking STEMI is important in order to reduce the risk of the administration of thrombolytics and other potentially dangerous drugs and have a higher threshold for referral for emergency angiography.

[Inhibitory effect and acting mechanism of Tongxinluo on IL-1beta-mediated coronary intimal hyperplasia and 5-hydroxytryptamine-induced coronary vasospasm in small swine].

OBJECTIVE: To observe the inhibitory effect of Tongxinluo (TXL) on coronary vaso spasm in small swine in vivo, and to investigate its possible acting mechanism. METHODS: The model of coronary atherosclerosis in 16 male small swines was established by left thoracotomy after anesthesia, isolated the sections of left anterio-descending branch and proximal end of rotator branch with similar outer diameter, and encapsulated them with paper-towel holding 2.5 microg interleukin-1beta. Two weeks later, the condition of coronary vasospasm induced by catheter intra-coronary injection of 5-hydroxytryptamine (5-HT, 10 microg/kg) was observed through coronary artery contrast examination. The 12 swines with successfully formed coronary vaso spasm were randomly divided into 2 groups, the TXL group and the control group. They were fed with special diet, but TXL 1 g/(kg d) was administered additionally to the TXL group for 4 weeks. The observation on coronary vasospasm was repeated 1 week after discontinuation of TXL treatment, then the animals were sacrificed, their vascular sections enclosed with IL-1beta was taken to conduct the pathologic examination and to detect the expressions of Rho kinase mRNA and its substrate myosin- binding subunit phosphorylation (MBS-P) by RT-PCR and Western blot method. RESULTS: Coronary artery contrast showed that local coronary stenosis occurred in the 12 model swines to different extents (20% - 30%, and vascular spasm on them could be induced by 5-HT. At the time of repeating examination, 11 vascular sections in the control group still maintain their positive spasm reaction to 5-HT, but only 2 in the TXL group did so, the reaction turned to negative in 1 and 10 in the two groups respectively. Pathological examination showed that different degrees of macrophage aggregation could be found in both groups. The degree of lumen stricture and endometrial hyperplasia in the TXL group was obviously attenuated than those in the control group. The expressions of Rho kinase mRNA and MBS-P in the control group were up-regulated obviously. As compared with those in the control group, they were inhibited significantly in the TXL group, as (71.5 +/- 2.4) vs (98.2 +/- 7.7)% and 16,633 +/- 1,390 vs 25,818 +/- 4,745, respectively (all P < 0.05). CONCLUSION: TXL could obviously inhibit the coronary intimal hyperplasia mediated by IL-1beta and coronary vasospasm induced by 5-HT, one of its mechanisms is possibly the inhibition on the intracellular Rho kinase mRNA expression in the IL-1beta enclosed vascular section to decrease the level of MBS-P.

Capecitabine induced vasospastic angina.

Cardiotoxicity is a recognised side effect of intravenous 5-fluorouracils. In the two case reports described we demonstrate similar cardiotoxic side effects seen with the use of capecitabine. With the increasing use of oral adjuvant chemotherapeutic agents, capecitabine should be used with caution in those patients with existing coronary artery disease.

A case of suspected vasospastic angina related to S-1 administration.

A 58-year-old male with advanced gastric cancer underwent a total gastrectomy after neoadjuvant chemotherapy with paclitaxel and cisplatin. The combination chemotherapy was resumed postoperatively as adjuvant chemotherapy. Although no recurrence was observed after 6 months of adjuvant chemotherapy,the patient elected to receive further adjuvant chemotherapy with an oral drug. On the night of November 9,2006, he began taking S-1 at a dose of 50 mg twice daily. Fifty minutes after taking the first 50 mg of S-1,he experienced a squeezing chest pain at rest that was later accompanied by diaphoresis and nausea. The pain continued for approximately one hour,but had subsided by the time he reached an emergency room. Coronary angiography revealed a 50% eccentric stenosis in the proximal site of the right coronary artery,but there was no coronary lesion which could caused myocardial ischemia. Cardiac scintigraphy using 123I-BMIPP (123I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid) showed a decreased uptake of BMIPP within the posterior wall,which improved one month later,so transient myocardial ischemia was confirmed. Since vasospastic angina related to S-1 administration was highly suspected,re-administration of S-1 was not performed. The patient is not currently receiving chemotherapy and remains under surveillance for relapse.

Biological and analytical characterization of two extracts from Valeriana officinalis.

The anticoronaryspastic and antibronchospastic activities of ethanolic and aqueous extracts of Valeriana officinalis L. roots were investigated in anaesthetized guinea-pigs and the results were correlated with the qualitative/quantitative chemical composition of the extracts in order to account for some of the common uses of this plant. The protective effects of orally administered ethanolic and aqueous extracts (50, 100 and 200 mg/kg) were evaluated against pitressin-induced coronary spasm and pressor response in guinea-pigs and were compared with those of nifedipine. Furthermore, the protective effects against histamine-induced and Oleaceae antigen challenge-induced bronchospasm were evaluated. Finally, the two valerian extracts were analytically characterized by qualitative and quantitative chromatographic analysis. The results showed that the two valeriana extracts possessed significant anticoronaryspastic, antihypertensive and antibronchospastic properties. These were similar to those exhibited by nifedipine and are due to the structural features of the active principles they contain. This study justifies the traditional use of this plant in the treatment of some respiratory and cardiovascular disorders.

[Angina pectoris and ST-elevation after chemotherapy with 5-fluorouracil]. / Angina Pectoris und ST-Hebungen nach Chemotherapie mit 5-FU.

We report on the case of a 64 year old male who received chemotherapy for a metastatic squamous cell carcinoma of the oropharynx. The chemotherapeutic regimen consisted of 5-fluorouracil (5-FU) and cisplatin. Six hours after completion of the first 24 h continuous infusion of 5-FU, the patient developed severe chest pain accompanied by vegetative symptoms and a pronounced ST-elevation of the precordial leads. Under the suspicion of an acute anterior myocardial infarction an immediate coronary angiogram was performed, demonstrating a total occlusion of the left anterior descending (LAD) coronary artery close to the left main stem. The other coronary arteries appeared smooth. After the intracoronary administration of nitroglycerine, the LAD reopened spontaneously without any residual stenosis, paralleled by complete relief of all symptoms. Therefore, 5-FU induced coronary spasm was diagnosed. After initial therapy with intravenous nitrate followed by oral calcium channel blocker, the patient remained free of symptoms and no rise in cardiac enzymes were noted. The chemotherapeutic regimen was changed to cisplatin plus docetaxel. No new attacks of chest pain occurred and the antivasospastic therapy could be stopped without further events.

Influence of high-dose leucovorin and 5-fluorouracil chemotherapy regimen on P wave duration and dispersion.

BACKGROUND: Although 5-fluorouracil (5-FU)-related cardiotoxicity is well known, atrial arrhythmia, as a potentially serious complication has not been studied in detail. The aim of this study was to determine the P max and Pd in the electrocardiograms (ECG) of patients receiving 5-FU treatment. METHODS: Twenty-five patients (mean age: 62 years) receiving a 5-FU bolus plus continuous infusion with calcium leucovorin over 48 h and with normal pre-treatment cardiac physical examinations, ECG and echocardiography were enrolled. P maximum (P max), P minimum (P min) and P dispersion (Pd) (maximum minus minimum P wave duration) were measured from the 12-lead ECG at the 0th and 48th hour of the first chemotherapy cycle. Echocardiography was also obtained in all patients at the same times. RESULTS: Clinical cardiotoxicity was observed in two patients. P max and Pd were both significantly longer after 5-FU treatment at the 48th hour (P < 0.001). P min did not change (P > 0.05). CONCLUSION: Treatment with 5-FU based regimens may increase Pd and prolong the P max in cancer patients. These alterations may be predictive of patients at risk of atrial arrhythmias during 5-FU treatment.

Acute severe coronary spasm associated with initial first dose of 5-fluorouracil chemotherapy.

Among the various pathophysiologic mechanisms proposed to explain the 5-fluorouracil cardiotoxicity, coronary vasospasm, occurring most frequently after the completion of the second or third dose of the cycle, has gained wide acceptance. We describe what to our knowledge is the first observation of typical Prinzmetal variant angina occurring very early after having started a 5-fluorouracil infusion administered as a chemotherapy regimen to a 66-year-old man with an adenocarcinoma of the right colon.

[Cardiotoxicity of 5-fluorouracil. Clinical relevance of palliative radiochemotherapy of malignant head-neck tumors]. / Kardiotoxizität des 5-Fluorouracil. Klinische Relevanz bei palliativer Radiochemotherapie von malignen Kopf-Hals-Tumoren.

BACKGROUND: In the past cardiotoxicity has been increasingly reported as 5-fluorouracil is widely used as well in curative adjuvant as in palliative chemotherapy of malignant neoplasms. METHODS: We report on two cases of 5-fluorouracil-associated cardiotoxicity on palliative treatment of head and neck cancer and evaluate the importance of intensive drug monitoring. RESULTS: 5-fluorouracil-associated cardiotoxicity occurs with an incidence of 1.1-4.5%. Ischaemic cardiopathy due to vasospasms is believed to be the most common manifestation. CONCLUSIONS: Since most patients with head and neck cancer have risk factors for cardiovascular disease, 5-fluorouracil-associated cardiotoxicity should not be underestimated and patients should be monitored carefully.