Vasospastic Attacks Research Articles

Vasodilators for primary Raynaud's phenomenon.

Vasodilators for primary Raynaud's phenomenon.

Epirubicin-induced Kounis syndrome

BackgroundKounis syndrome is an acute coronary syndrome that appears in the setting of anaphylactic reaction or hypersensitivity. Many drugs and environmental exposures have been identified as potential offenders, and diagnosis and treatment can be challenging.Case presentationA 62-year-old man with recurrent bladder cancer underwent an intra-iliac artery epirubicin injection. After the injection, he developed chest pain and a systemic allergic reaction, with electrocardiographic alterations and elevated troponin-I levels. Emergent coronary angiography showed right coronary artery spasm and no stenosis of the other coronary arteries. This reaction was considered compatible with an allergic coronary vasospasm. A diagnosis of Kounis syndrome was made.ConclusionsKounis syndrome is common, but a prompt diagnosis is often not possible. This case is the first to suggest that an intraarterial epirubicin injection could potentially be one of its triggers. All physicians should be aware of the pathophysiology of this condition to better recognize it and start appropriate treatment; this will prevent aggravation of the vasospastic cardiac attacks and yield a better outcome.

Repurposing Cilostazol for Raynaud's Phenomenon

Raynaud 's Phenomenon (RP) results from exaggerated cold-induced vasoconstriction. RP patients suffer from vasospastic attacks and compromised digital blood perfusion leading to a triple color change at the level the fingers. Severe RP may cause ulcers and threaten tissue viability. Many drugs have been used to alleviate the symptoms of RP. These include calcium-channel blockers, cGMP-specific phosphodiesterase type 5 inhibitors, prostacyclin analogs, and angiotensin receptor blockers. Despite their variety, these drugs do not treat RP but rather alleviate its symptoms. To date, no drug for RP has been yet approved by the U.S Food and Drugs Administration. Cilostazol is a selective inhibitor of phosphodiesterase-III, originally prescribed to treat intermittent claudication. Owing to its antiplatelet and vasodilating properties, cilostazol is being repurposed as a potential drug for RP. This review focuses on the different lines of action of cilostazol serving to enhance blood perfusion in RP patients.

Interdigital injection of botulinum toxin for patients with Raynaud phenomenon

Botulinum toxin injection has demonstrated to be a simple and cost-effective option in pain reduction, promoting healing of digital ulcers, and decreasing the frequency of vasospastic attacks in patients with Raynaud phenomenon.1,2 A universal injection technique and optimal dose to achieve adequate symptom control are lacking. Some of the reported procedures, such as proximal and distal palmar injection techniques, are painful and often require sedation or anesthetic blockade.

The Role of Oxidative Stress in the Development of Systemic Sclerosis Related Vasculopathy.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple organs including the skin. SSc often is a lethal disorder, because effective disease-modifying treatment still remains unavailable. Vasculopathy with endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular wall remodeling and rarefaction of capillaries is the hallmark of the disease. Most patients present with vasospastic attacks of the digital arteries referred to as ‘Raynaud’s phenomenon,’ which is often an indication of an underlying widespread vasculopathy. Although autoimmune responses and inflammation are both found to play an important role in the pathogenesis of this vasculopathy, no definite initiating factors have been identified. Recently, several studies have underlined the potential role of oxidative stress in the pathogenesis of SSc vasculopathy thereby proposing a new aspect in the pathogenesis of this disease. For instance, circulating levels of reactive oxygen species (ROS) related markers have been found to correlate with SSc vasculopathy, the formation of fibrosis and the production of autoantibodies. Excess ROS formation is well-known to lead to endothelial cell (EC) injury and vascular complications. Collectively, these findings suggest a potential role of ROS in the initiation and progression of SSc vasculopathy. In this review, we present the background of oxidative stress related processes (e.g., EC injury, autoimmunity, inflammation, and vascular wall remodeling) that may contribute to SSc vasculopathy. Finally, we describe the use of oxidative stress related read-outs as clinical biomarkers of disease activity and evaluate potential anti-oxidative strategies in SSc.

Raynaud-szindrómás betegek életminőségének jellemzői

Raynaud's disease is characterized by episodic vasospastic attacks and digital ischemia usually followed by pain, numbness and cold. Despite the severity of the symptoms, the investigation of the quality of life in this disease received less attention yet. The aim of the study was to examine how the disease affects the patients' quality of life. Semi-structured interviews were made with 28 patients diagnosed with Raynaud's disease. Almost every domain of quality of life is negatively affected. The somatic symptoms cause significant suffering, they are accompanied by loss of functionality; frequent preventive actions are needed; furthermore they affect job performance, commuting and sleep quality. Emotional and cognitive burdens and negative changes in interpersonal relationships were found. The findings of this study show that the disease is present as significant hardship in every aspect of daily life. Because of the decrease in the quality of life and the psychological burdens caused by this chronic disease, not only the basic medical care, but psychological treatment is also indicated. Orv Hetil. 2018; 159(16): 636-641.

Abstract 15383: Clinical Features and Prognosis of Patients Who Survived Ventricular Fibrillation Due to Coronary Artery Spasm

Introduction: Coronary artery spasm can lead to lethal arrhythmia and sudden cardiac death. The aim of this study was to elucidate the clinical features and prognosis of patients who survived cardiac arrest due to coronary artery spasm. Methods: We retrospectively studied consecutive patients who survived ventricular fibrillation out of hospital cardiac arrest due to coronary artery spasm, and discharged neurologically intact. Results: Nineteen patients (18 men and 1 woman, mean age 55 ± 10 years) were enrolled. In all patients, ventricular fibrillation (VF) was documented as the initial rhythm at cardiac arrest. Transient ST-segment elevation during spontaneous attack was observed in 9 patients. Acetylcholine provocation tests were performed and resulted in positive in 15 patients. In 11 patients, cardiac arrest was the first episode of vasospastic attack. All patients were treated with vasodilators including calcium channel blockers. An implantable defibrillator (ICD) was implanted in 12 patients according to the discretion of the attending physician. During a mean follow-up interval of 42 months, 4 episodes of VF were observed in 3 patients and ST-segment elevation myocardial infarction (STEMI) was observed in 1 patient. Two episodes of VF were occurred before the diagnosis of coronary artery spasm was confirmed during the index hospitalization, and the other 2 VF were occurred after ICD implantation. All VF were treated by manual defibrillation or ICD shocks. None of patients developed cardiovascular death. There are no differences in the characteristics of the patients between those with and without recurrence of VF and STEMI. However, medications against coronary artery spasm were discontinued before the cardiac events in all episodes of VF and STEMI. The intervals between cessation of medications and cardiac events were less than 2 days in all cardiac events. Conclusions: The patients who survived cardiac arrest due to coronary artery spasm were at high risk for recurrence of severe ischemia and lethal arrhythmia. Cessation of medication, even within a few days, was closely associated with cardiac events. ICD therapy may be beneficial in patients who survived cardiac arrest due to coronary artery spasm.

Coronary vasospasm-induced periodic ventricular fibrillation and successful ablation through coronary stenting.

Coronary vasospasm-induced ventricular fibrillation (VF) is a well-documented clinical condition, and there are existing reports in medical publications on this subject [1]. Treatment approaches for these patients can be challenging. In most cases, vasodilator therapy relieves anginal and VF episodes, but sometimes, in the case of recurrence, intracardiac defibrillator (ICD) implantation is performed with concomitant medical therapy [2]. When a patient receives multiple ICD shocks for recurrent VF episodes after vasospastic attacks in spite of the use of vasodilator therapy, it is an undesirable situation for both the patient and the doctor. In this paper, we present a case of a patient suffering from this clinical condition that was successfully treated through coronary stent placement.

Differential diagnoses of Raynaud's phenomenon

Raynaud's phenomenon (RP) is characterized by repeated vasospastic attacks of the distal extremities induced by cold, humidity, vibrations or emotional stress. It typically presents a triphasic colour change from white (palor; vasoconstriction) to blue (cyanosis) and red (reactive hyperaemia). The symptoms are based on a primary RP in 90 %. Secondary RP is a symptom of an underlying disease. RP has to be distinguished from other colour changes of the distal extremities like acrocyanosis, erythromelalgia, perniosis and Chilblain-Lupus. Patients history, clinical examination, ANA, ESR/CRP and nailfold capillaroscopy are essential for the early diagnosis of an underlying disease. The initiation of angiologic tests is important in patients with digital ulcers, necrosis or gangrene. Important differential diagnoses in secondary RP are autoimmune rheumatic diseases like systemic sclerosis and systemic lupus erythematodes as well as vascular diseases like arterial occlusions and compression syndromes or concomitant medication (i. e. beta-blocker).

No Significant Effect of Ginkgo Biloba Special Extract EGb 761 in the Treatment of Primary Raynaud Phenomenon

Medicinal treatment of vasospastic Raynaud phenomenon is limited to primarily vasodilator medicines. To explore the possible beneficial effects and tolerability of 120 mg two times a day of Ginkgo Biloba special extract EGb 761 in patients suffering from Raynaud disease (RD) (primary Raynaud phenomenon). In a placebo-controlled, double-blind, pilot study, 41 patients with RD were randomized to either the active treatment group (EGb 761, n = 21) or placebo group for 10 weeks, after an initial 2-week run-in phase. The primary efficacy variables were self-reported changes of the frequency, duration, and severity of vasospastic attacks between the placebo-controlled run-in phase and the end of the study. Most of the patients were female, and both groups were perfectly matched with respect to demographic characteristics. The frequency of daily attacks reduced from 3.6 ± 2.3 to 2.4 ± 2.6 (-33%) in the EGb 761 group and from 2.9 ± 2.0 to 2.0 ± 1.8 (-31%) in the placebo group with no significant difference according to the ordinary least squares test (P = 0.3564). Furthermore, no significant differences were found with respect to the duration and severity of vasospastic attacks between the EGb 761 and placebo groups (P = 0.4392 and P = 0.7187, respectively). In all, 17 adverse events (AEs) were reported, 6 AEs from 5 patients in the EGb 761 group and 11 AEs from 8 patients in the placebo group. Serious AEs did not occur. EGb 761 treatment showed an excellent safety profile in patients with RD but could not demonstrate a statistically significant reduction in clinically relevant symptoms compared with placebo.

Coronary Artery Spasm

Case presentation: A 37-year-old man was admitted in the early morning hours to the emergency department after experiencing excruciating chest pain. The patient was a heavy smoker who gave a history of several previous similar but less intense episodes of pain during the past 2 years; most of them also during the early morning hours. One of his earlier attacks was associated with sensing his heart “bouncing.” In addition, he had experienced several episodes of “palpitations” without pain. On admission, ECG showed a 2 to 3 mm ST elevation which returned to baseline quickly, concomitant with his pain subsiding. Cardiac biomarkers were normal but C-reactive protein was elevated. Twenty-four hours later, a treadmill test showed good exercise capacity and no ST changes even at target heart rate. The clinical and ECG pictures pointed to the diagnosis of a vasospastic-type Printzmetal angina, and the patient responded well to calcium blockers and long-term nitroglycerin therapy and remained symptom-free throughout a 2-year follow-up. Severe chest pain, usually without physical effort and with a concurrent ECG showing transient ST elevation, is the key for the diagnosis of coronary artery spasm (CAS) (Figure 1). Diagnosis of the silent variety of CAS is possible if the vasospastic attack occurs under medical observation or during ambulatory ECG monitoring,1 but long-term surveillance may be needed to establish the diagnosis. Exercise testing may also be helpful, although approximately equal numbers of patients show ST depression, ST elevation, or no change whatsoever during the exercise.2 Further pharmacological testing, such as provocation with intravenous ergonovine, should be used only under special conditions and with extreme care2 (Table 1). Figure. Surface …

The transient appearance of collateral circulation during coronary spasm

This article reports a case of transient augmentation of collateral circulation due to spontaneous coronary arterial spasm during angiography. The patient's electrocardiogram revealed ST-segment depression during vasospastic attack; this depression differs from the typical change of the ST-segment elevation in coronary spasm without collateral circulation.

Raynaud's Phenomenon.

Raynaud's phenomenon may be primary (idiopathic) or secondary. Primary Raynaud's phenomenon is very common in young women, especially in cool climates. Treatment of patients with primary disease is usually much more successful than treatment of patients with secondary disease. Most patients respond to conservative measures. Reassurance that they will not lose digits or limbs is helpful. They should avoid instigating vasospastic attacks, which are usually caused by cold plus pressure on the digits. Reflex sympathetic vasoconstriction can be avoided by wearing warm clothing, including hats. Mittens are more protective than gloves, which separate the fingers. Many patients find chemical hand and foot warmers very useful. Pavlovian conditioning and biofeedback may be helpful if the patient is willing to spend the time. Underlying disease should be treated or instigating causes avoided in secondary Raynaud's phenomenon. In the more severe cases of primary Raynaud's phenomenon as well as in secondary cases, drug therapy is often beneficial. Calcium entry blockers have yielded the best results. Forms of nifedipine with extended action should be prescribed; felodipine or isradipine can be tried if nifedipine cannot be tolerated owing to frequent side effects. When these drugs fail or are not tolerated, sympatholytic drugs (eg, prazosin, reserpine, guanethidine) have benefited some patients. We have not found nitroglycerin preparations to be of benefit. In severe digital ischemia that does not respond to drug therapy, digital artery sympathectomy may help heal digital ulcers. Cervicodorsal sympathectomy is not recommended for upper extremity symptoms, but lumbosacral sympathectomy will often cure vasospastic attacks of the toes.

Effects of transvenous regional guanethidine block in the treatment of critical finger ischemia.

The objective of this study was to determine the effects of transvenous regional guanethidine block in the treatment of patients with critical finger ischemia. Twenty-seven patients (17 collagen vascular disease, four thromboangiitis obliterans, three embolism, three atherothrombosis) presenting with ischemic rest pain and/or ulcerations of the fingers received a single block with 5 mg guanethidine injected in 60 mL into the clinically more affected hand under 30 minutes of arterial arrest. Marked hyperemia was induced in the treated upper limb, increases (p < 0.01) in finger blood flow, finger skin temperature, and laser Doppler flux were higher and longer lasting than in forearm blood flow, persisting for a whole month. Effects in patients with ischemic finger ulcers were less pronounced than in those without, yet statistically significant increases of all evaluated parameters were observed in these patients too. No effects were seen in the contralateral untreated upper limb or in systemic blood pressure. Subjective symptoms (reduction of rest pain, numbness, vasospastic attacks) were improved in 25/27 (92.6%) patients, ischemic rest pain disappeared in 20/27 (74.1%), and complete healing of finger tip ulcerations within 1 month was achieved in 10/12 (83.3%) affected patients. No side effects were observed. This described method combines good clinical efficacy with lack of undesirable side effects and can be repeated easily. Therefore, this technique is recommended for broader clinical use.

Rational use of calcium-channel antagonists in Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a peripheral circulatory disorder characterized by sudden episodes of digital artery spasm, often precipitated by cold temperature or emotional stress. Although the cause of RP is not fully known, it appears to involve inappropriate adrenergic response to cold stimuli. Treatment of RP is conservative in most patients, but in patients with severe disease includes the use of agents that promote digital vasodilation. The calcium-channel antagonists, particularly the dihydropyridine derivative nifedipine, are the most thoroughly studied drug class for the treatment of RP. Approximately two thirds of patients respond favorably, with significant reductions in the frequency and severity of vasospastic attacks. Nifedipine use is often limited by the appearance of adverse vasodilatory effects such as headache or peripheral edema. The newer second-generation dihydropyridines such as amlodipine, isradipine, nicardipine, and felodipine also appear to be effective in patients with RP and may be associated with fewer adverse effects.

The effects of thromboxane A2 inhibition (Picotamide) and angiotensin II receptor blockade (Losartan) in primary Raynaud's phenomenon

To assess the role of thromboxane A2 and of angiotensin II in patients with primary Raynaud's phenomenon. After an eight-day run-in period, the patients were enrolled in a single-blind, cross-over, study. Patients were examined at the Ambulatory for Microcirculatory Diseases of the Clinic of Internal Medicine, University Hospital, Verona. Fifteen subjects affected by primary Raynaud's phenomenon were included. A piezoelectric plethysmography to evaluate the distensibility of the digital arteries as the ratio between peak time (PT) and total time (TT), and an oscillometric blood pressure recorder were used after the run-in period, and after a two-week course of picotamide (300 mg b.i.d., i.e. two times daily) or losartan (12.5 mg once daily) with an interval of a week of placebo between the active treatments. The tests were performed after every treatment in basal condition and during mental stress. The patients reported in a diary the number and the severity (from 0 to 4 +) of the vasospastic crises. The change in TP/TT ratio appeared statistically significant only after losartan treatment, both in basal condition and during mathematical stress. Both pharmacological treatments, with respect to placebo, showed an improvement of the scores, derived from the number and severity of vasospastic attacks, but only the therapy with losartan determined a statistically significant improvement. The inhibition of the type 1 receptor for angiotensin II seems highly effective in the reduction of the vasospastic crises in the subjects with primary Raynaud's phenomenon. According to our experience, losartan could be used more extensively in the treatment of these patients besides arterial hypertension.

Raynaud's phenomenon

Raynaud's phenomenon (RP) may affect as many 20–30% of young women [1] and have an overall prevalence in the population of approximately 10% [2]. In the UK RP is the blanket term used to describe any form of cold related vasospasm and can be further subdivided into Raynaud's syndrome (RS) where there is an associated disorder and primary Raynaud's disease (RD) where there is not. In the USA the terminology most used is primary RP and secondary RP. Australasia uses RP and RS interchangeably and thus care must be taken with literature comparisons to ensure the different terminologies are used in a standard fashion. Most workers define their population in terms of CTD association, otherwise at the start of each paper and until a standard nomenclature is accepted, this practice should continue. By far the largest group of patients presenting to their primary care physician are those with the primary disorder. However, recent studies have shown that the phenomenon may pre-date systemic illness by up to two decades. Since the development of sensitive laboratory procedures, we now know that more than half of the patients referred to hospital because of RP will have an associated systemic disease [1, 3, 4]. There is a wide spectrum of disease associated with RS including those reported in the mystery cases (i.e., drug-induced RS), that associated with thromboangiitis obliterans and with occupational vibration exposure. The best recognised of the associated disorders are the connective tissue disorders (CTDs) and RS of occupational origin (Table 1). View this table: Table 1 Conditions associated with Raynaud's phenomenon RS accompanies systemic sclerosis (SSC) in 95% of cases and also in the majority of patients with mixed connective tissue disease (MCTD) (85%). Between 10–45% of patients with systemic lupus erythematosus also suffer vasospastic attacks as do 33% of Sjogren's syndrome patients …

Induction of polymorphic ventricular tachycardia by programmed ventricular stimulation in vasospastic angina pectoris

This study was designed to examine the ventricular vulnerability of patients with vasospastic angina. Fourteen patients (mean age 57 ± 9 years) with vasospastic angina underwent electrophysiologic testing during the asymptomatic phase (baseline) and after the relief of acetylcholine-induced spasm with isosorbide dinitrates. Twenty patients without structural heart disease served as a control group. By programmed ventricular stimulation, polymorphic ventricular tachycardia (VT) was induced at baseline in 6 of 14 patients, with 1 patient developing ventricular fibrillation and 7 of 14 patients developing repetitive ventricular responses. After isosorbide dinitrate, polymorphic VT was induced in only 1 patient who had ventricular fibrillation at baseline. Repetitive ventricular responses were induced in 3 of 5 patients who had VT at baseline and in 4 of the 7 patients with repetitive ventricular responses at baseline. There was a significant difference in the incidences and severity of induced ventricular arrhythmias between the 2 phases (p <0.01). Among 20 control subjects, repetitive ventricular responses were induced only in 6 patients, but no VT was induced. There was a significant difference in the incidence of induced ventricular arrhythmias and VT at baseline between the vasospastic angina and control groups (p <0.001 and <0.01, respectively). Thus, patients with vasospastic angina had increased ventricular vulnerability, even during the symptom-free period without ischemic events, which could predispose to the development of life-threatening arrhythmias aggravated by vasospastic attacks.

Blockade of vasospastic attacks by alpha-2 adrenergic but not alpha-1 adrenergic antagonists in idiopathic Raynaud's disease: Freedman RR, Baer RP, Mayes MD. Circulation 92:1448, 1995

Blockade of vasospastic attacks by alpha-2 adrenergic but not alpha-1 adrenergic antagonists in idiopathic Raynaud's disease: Freedman RR, Baer RP, Mayes MD. Circulation 92:1448, 1995

Blockade of Vasospastic Attacks by α 2 -Adrenergic but Not α 1 -Adrenergic Antagonists in Idiopathic Raynaud’s Disease

Idiopathic Raynaud's disease is characterized by cold-induced digital vasospasms, but its origin has not been established. Previous research has shown that peripheral vascular alpha 2-adrenergic receptors are hypersensitive to local cooling in these patients, but the role of alpha 1-adrenergic receptors is not clear. Moreover, the role of adrenergic receptors in the production of actual vasospastic symptoms has not been investigated. We studied 23 patients with idiopathic Raynaud's disease who were screened using conservative criteria. They were randomly assigned to receive brachial artery infusions of an alpha 1-antagonist, an alpha 2-antagonist, or both while vasospastic attacks were induced by cooling in the laboratory. Each patient's hands were photographed, and the number of attacks in the infused hand was compared with the number in the contralateral hand. The number of fingers (mean +/- SEM) with attacks in infused hands was yohimbine 0.3 +/- 0.3, prazosin 2.3 +/- 0.3, and both drugs 0.6 +/- 0.2. The difference between prazosin and the other two drug groups was significant (P < .001). These findings demonstrate that activation of alpha 2-adrenergic receptors but not alpha 1-adrenergic receptors is necessary for the production of vasospastic attacks in idiopathic Raynaud's disease.