Noncardiac Side Effects Research Articles

Вопросы безопасности антиаритмической терапии при фибрилляции предсердий

The article discusses the safety of antiarrhythmic therapy for atrial fibrillation in the light of the development of cardiac and non-cardiac side effects, the presence of drug-drug interactions of antiarrhythmic drugs in the near (with anticoagulants) and far circle. The features of the choice of antiarrhythmic therapy for the prevention of relapses of atrial fibrillation, restoration of sinus rhythm, as well as heart rate control are presented, and aspects of the tactics of managing these patients are highlighted.

Evaluation of cardiac and non-cardiac side effects of low dose oxytocin used during caesarean section

Evaluation of cardiac and non-cardiac side effects of low dose oxytocin used during caesarean section

High Grade AV Block Associated with Dipyridamole Infusion

The use of dipyridamole for thallium imaging has proved very successful in demonstrating coronary arterial disease [1]. Dipyridamole causes coronary arteriolar vasodilation by increasing interstitial adenosine levels by inhibition of both adenosine deaminase and facilitated cellular adenosine uptake. Differential flow changes occur in coronary arteries if a significant luminal stenosis exists [2]. Intravenous infusion of dipyridamole is safe although transient noncardiac side effects are common. These side effects are mostly mild and not need to treat although can be treated with aminophylline [5]. High-grade AV block after dipyridamole has been described in few case reports and mostly was associated with transient myocardial ischemia [2-4]. We describe a case of long-lasting high grade AV block following dipyridamole infusion. In context of near normal baseline ECG. In our case the AV block occurred without evidence of ischemia in myocardial perfusion imaging and we think it can be an unexpected adverse effect of dipyridamole and clinicians should be aware of AV block as a possible adverse effect of dipyridamole.

Effectiveness of beta-blockers in the treatment of idiopathic premature ventricular contractions in children

Aim. To evaluate the effectiveness of beta-blockers (BB) in the treatment of idiopathic premature ventricular contractions (PVCs) in children.Material and methods. BBs were prescribed to 27 children with idiopathic PVCs. In 3 (11,1%) patients, side effects (hypotension, bronchial obstruction) was revealed at the beginning of therapy. A total of 24 children were included in the further study (15 boys (62,5%), 9 girls (37,5%). The mean age was 8,3±5,4 years. Data from anamnesis, electrocardiography (ECG), 24-hour ECG monitoring, and echocardiography were analyzed.Results. The 24-hour PVC rate was 33,2±17,7 thousand/day or 26,6±13,2%. In 14 (58,3%) children, we recorded paired PVCs, in 3 (12,5%) — multiform, in 10 (41,7%) — runs of non-sustained VT. There were complaints in 7 (29,2%) children. The follow-up period lasted 369,8±119,1 days. Propranolol was received by 17 (70,8%) patients, metoprolol — by 7 (29,2%). The therapy was effective in 11 (45,8%) patients, while ineffective in 13 (54,2%), among which 5 (20,8%) had an increase in the number of PVCs. The effectiveness of BBs was higher in children under the age of 1 year (p=0,043). Propranolol showed greater efficacy than metoprolol (p=0,047). Less efficiency was observed in female patients and those with pathological heart rate turbulence parameters (p=0,04).Conclusion. The effectiveness of BBs in children with idiopathic PVCs is 45,8%, higher in children aged <1 year and declines with age, decreasing in adolescents to 25%. The use of BBs is limited by non-cardiac side effects in 11,1% of children. Propranolol is more effective than metoprolol.

Atrioventricular (AV) block and sinus arrest associated with dipyridamole infusion.

The use of dipyridamole for thallium-201 imaging has proved very successful in demonstrating coronary arterial disease, and a combination of dipyridamole and dynamic exercise is becoming widely used. Dipyridamole is safe when given intravenously, although transient noncardiac side effects are common; side effects such as chest pain, headache, and dizziness. These side effects are mostly mild, and can be treated with aminophylline. We describe a 45-year-old woman with normal baseline electrocardiography (ECG) and unremarkable physical examination, referred for myocardial thallium scan with dipyridamole. A few seconds after infusion of dipyridamole, her ECG developed first-degree atrioventricular (AV) block, then, 2:1 AV block, complete heart block (CHB), and sinus arrest. After aminophylline infusion, junctional escape rhythm was seen, and a few seconds later, rhythm changed to sinus rhythm. Thallium scan was negative for ischemia. High-grade AV block after dipyridamole has been described in few case reports, and mostly was associated with transient myocardial ischemia; it seems that the presence of conduction abnormalities at baseline is a risk factor. But in our case, the sinus arrest and AV block occurred without evidence of ischemia in myocardial perfusion imaging, and we think it can be an unwanted complication of dipyridamole; clinicians should be aware of bradyarrhythmia as a possible complication of dipyridamole. An alternative explanation is that this arrhythmia can be caused by vagal activity; and another possibility is that the imaging study was false negative.

Acil Cerrahi Gerektiren Vagal Sinir Stimulatörlü Hastada Anestezi Yönetimi

Vagal nerve stimulation (VNS) is a method used in patients with drug-resistant epileptic seizures. Apart from epilepsy, it has also been used in migraine, chronic pain and depression. Obstructive sleep apnea, aspiration of gastric contents, vocal cord paralysis, hoarseness, dyspnea and cardiac arrhythmias are common complications in patients with VNS and may cause problems in anesthesia applications. A 25-year-old male patient was scheduled for an emergency operation by orthopedics due to a deep incision and active bleeding in the right knee. The patient was mentally retarded and non-cooperative, and his cardiac and respiratory system examination was normal. The patient, who has had epilepsy since the age of 3, had a VNS device inserted 2 years ago. Blood biochemistry, hemogram and coagulation parameters, ECG, chest radiography and neurology consultation were requested. He was operated on without any intervention to the VNS device. General anesthesia was applied and the patient was intubated. BIS monitoring was applied, there was no problem in the intraoperative period, he was taken to the intensive care unit in the postoperative period. It is recommended that the VNS device be turned off or reprogrammed prior to elective surgery. In emergency situations, the device may not be intervened in any way. Using LMA is not recommended as it may cause airway obstruction. In intubated patients, stimulation of the vagus may cause damage to the vocal cord. Seizures may occur in the perioperative and postoperative period. In the postoperative period, the patient should be followed closely due to respiratory problems and obstructive sleep apnea. Anesthesiologists should be aware of the technical features of non-cardiac implantable electrical devices, side effects and problems that may be encountered during anesthesia applications.

Role of amiodarone in the management of atrial arrhythmias in adult Fontan patients

BackgroundPatients with Fontan circulation are known to be at high risk for developing atrial tachyarrhythmias (AAs). Our objective was to examine the efficacy and safety of amiodarone in the management...

Efficacy and Safety of Low-Dose Amiodarone Therapy for Tachyarrhythmia in Congenital Heart Disease.

Amiodarone (AMD) is a class III anti-arrhythmic drug that is highly effective for tachyarrhythmia treatment. AMD is widely used in adults with congenital heart disease (CHD); however, higher doses of AMD (> 200mg/day) can cause various non-cardiac side effects. The purpose of this study was to assess the efficacy, safety, and adverse events of low-dose AMD (≤ 200mg/day) for tachyarrhythmia in patients with CHD. We retrospectively studied 80 patients with CHD and tachyarrhythmia who received oral low-dose AMD (≤ 200mg/day) from January 2004 to March 2016. Low-dose AMD therapy was used to treat supraventricular tachycardia (SVT) in 51 patients and ventricular tachycardia (VT) in 29 patients. After a mean follow-up of 2.9years for SVT and 3.2years for VT, 36% and 65% of the patients with SVT and VT, respectively, were free from a first tachyarrhythmia recurrence for 3years. The incidence of AMD-induced side effects was 23%, and all these cases consisted of thyroid dysfunction. Low-dose AMD was effective for the treatment of tachyarrhythmia in patients with CHD and had a relatively low incidence of side effects. These findings suggest that low-dose AMD is useful and effective for decreasing the frequency of tachyarrhythmia in patients with CHD and has a low incidence of side effects.

Could Propafenone hydrochloride Cause Visual Hallucination?

Introduction: There may be some cardiac and non-cardiac side effects of propafenone hydrochloride, which is a class IC antiarrhythmic agent used for medical cardioversion in atrial fibrillation and atrial flutter. Case Report: Propafenone hydrochloride (600 mg) was orally administered to a 74-year-old patient with tachycardia due to new-onset atrial fibrillation with rapid ventricular response. After 30 min, sinus bradycardia in response to atropine, swelling and numbness in the tongue, slurred speech, blurred vision, diplopia, spasm and contradiction at the right arm and leg, drowsiness, and visual hallucinations lasting for 24 h developed. The patient recovered without any sequel and was discharged from the coronary intensive care unit. Conclusion: Although propafenone hydrochloride is known to be safe at therapeutic doses, various possible multiple side effects should be considered.

Amiodarone neurotoxicity: the other side of the medal

Abstract The efficacy of amiodarone is tempered by its toxicity, with 50% of long-term users discontinuing the drug. The non-cardiac side effects of amiodarone may involve central and peripheral nervous system. We studied two patients treated with amiodarone for 46 and 15 months respectively. Both patients exhibited progressive distal extremity weakness, impaired perception, loss of deep reflexes. Electrophysiology identified a widespread, sensorimotor polyneuropathy with features of axonal loss and demyelination. Visual evoked potentials (VEPs) showed prolonged P100 latency bilaterally in absence of visual symptoms or brain magnetic resonance imaging (MRI) abnormalities. Extensive laboratory examinations excluded known causes of peripheral neuropathies. At 21 months after amiodarone withdrawal, P100 latency of case 1 VEPs returned to normal, whereas polyneuropathy continued to progress. In the second patient neuropathy has worsened similarly over 2 years whereas P100 latency of VEPs recovered to normal within 7 months after withdrawal of amiodarone. These findings may suggest different mechanisms of toxicity, which could be due to amiodarone pharmacokinetic and its metabolite effects on the peripheral nerves, as opposed to the optic nerve. We emphasize that use of amiodarone needs monitoring of patients at risk of development side effects.

Kardiovaskuläre Pharmakotherapie

Adverse side effects of drugs are a significantly underestimated problem in modern medicine. In this review article, we summarize common adverse side effects of cardiovascular drugs. In particular, we highlight the factors promoting these adverse side effects in patients, including reduced hepatic or renal clearance in elderly patients that often requires dosage adjustment. Pharmacodynamic and pharmacokinetic interactions between drugs (e.g. through the cytochrome P450 system or P-glycoproteins) can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. The most prominent cardiac side effects include arrhythmias, e.g. atrioventricular (AV) block, drug-induced long-QT syndrome and torsade de pointes and altered inotropy. Non-cardiac side effects are subsequently discussed grouped by drug class. A better understanding of the risks and side effects of cardiovascular drugs is expected to reduce the mortality and morbidity associated with adverse side effects.

Management of Atrial Fibrillation in Critically Ill Patients

Atrial fibrillation (AF) is common in ICU patients and is associated with a two- to fivefold increase in mortality. This paper provides a reappraisal of the management of AF with a special focus on critically ill patients with haemodynamic instability. AF can cause hypotension and heart failure with subsequent organ dysfunction. The underlying mechanisms are the loss of atrial contraction and the high ventricular rate. In unstable patients, sinus rhythm must be rapidly restored by synchronised electrical cardioversion (ECV). If pharmacological treatment is indicated, clinicians can choose between the rate control and the rhythm control strategy. The optimal substance should be selected depending on its potential adverse effects. A beta-1 antagonist with a very short half-life (e.g., esmolol) is an advantage for ICU patients because the effect of beta-blockade on cardiovascular stability is unpredictable in those patients. Amiodarone is commonly used in the ICU setting but has potentially severe cardiac and noncardiac side effects. Digoxin controls the ventricular response at rest, but its benefit decreases in the presence of adrenergic stress. Vernakalant converts new-onset AF to sinus rhythm in approximately 50% of patients, but data on its efficacy and safety in critically ill patients are lacking.

Medical, Surgical and Interventional Management of Hypertrophic Cardiomyopathy With Obstruction

Patients with hypertrophic cardiomyopathy (HCM) are classified as having hypertrophic obstructive cardiomyopathy (HOCM) if a left ventricular outflow tract (LVOT) gradient is present at rest or during provocation, as with Valsalva maneuver or exercise. Management of HCM in general and HOCM in particular encompasses (1) activity restriction with avoidance of volume depletion, (2) prevention of sudden cardiac death, (3) control of symptoms, and (4) screening of relatives. Those patients at high risk of sudden cardiac death (SCD) should be offered an implantable cardioverter-defibrillator (ICD). Pharmacologic treatment of symptoms in patients with HOCM consists of negative inotropic drugs, namely beta blockers, and disopyramide; a nondihydropyridine calcium channel blocker (CCB), usually verapamil, may be used in patients with noncardiac side-effects of beta blockers. Patients who have a dual-chamber pacemaker (PM) or ICD should undergo a trial of pacing with short atrioventricular (AV) delay. For patients with intolerable symptoms despite optimal conservative therapy, septal reduction therapy (SRT) should be considered and should be performed by experienced operators in institutions with multidisciplinary HCM programs. Younger patients with extreme hypertrophy are usually offered septal myectomy, while older patients, and those with important comorbidities are usually directed to alcohol septal ablation (ASA). For patients for whom either therapy is appropriate, there should be a balanced discussion with the patients of the benefits and risks of the 2 procedures.

Factors Influencing Non-cardiac Side Effects of Dipyridamole When Used for Myocardial Perfusion Stress Testing

PurposeThis study evaluates whether patient demographic information can be used to predict the non-cardiac side effects experienced during myocardial perfusion imaging (MPI) procedures using dipyridamole. BackgroundHeart disease is a major cause of death in the industrialized world. MPI of coronary blood flow using radiopharmaceuticals is frequently used to assess coronary artery disease. Pharmacological methods can be used to increase coronary blood flow with vasodilators such as dipyridamole or adenosine, or inotropic and chronotropic agents such as dobutamine or arbutamine. The side effects of these agents are recognized, but little is known about the factors that influence their frequency and severity. MethodsOne hundred and nineteen patients scheduled for myocardial perfusion pharmacological stress testing using dipyridamole participated in the study. Patient demographic data, which included age, sex, body mass index (BMI), diabetic status, smoker status, and daily aspirin usage, were collected before the start of the procedure. Patients underwent a 1-day rest and stress MPI procedure. The radiopharmaceuticals used were 99mTc-Myoview or 201Tl. The pharmacological stress procedure used dipyridamole injections based on body weight. Aminophylline was injected at the end of the stress session. Gated single photon emission computed tomography was performed for both rest and stress images. Once the patients completed the procedure, they were given a questionnaire that asked them to report the severity of any side effects experienced from the dipyridamole. Specific data types determined the statistical test best suited for analysis. The Chi-square test was used to evaluate the nominal scale data (sex, diabetic status, aspirin usage, and smoker status), Mann-Whitney test was used to compare nominal scale data and ordinal scale data (side effect severity), Student’s t-test r was used for ratio scale data (age, BMI, and percent of population), and multiple linear regression and multiple logistic regression tests were used to evaluate multiple variables. ResultsA total of 119 patients were surveyed (58 male, 61 female). The average age was 67.7 years (10.7 year standard deviation). There were no statistically significant differences in the male and female demographics except for daily aspirin usage (more common with males). Headaches were the most common side effect (50% of all patients), followed by dizziness (26%), flushing (24%), chest pain (19%), and nausea (18%). Correlations were found between patients experiencing no side effects with age (r = −0.607) and sex (P = .034); headaches with age (r = −0.706) and BMI (r = 0.464); chest pain with diabetic status (P = .017); dizziness with diabetic status (P = .039); and nausea with age (r = −0.612). ConclusionSide effects of dipyridamole are generally known, but the factors influencing incidence and severity are not. This study has shown that patient demographic information normally gathered before MPI procedures can help determine the frequency and severity of some side effects. Providing more accurate information to a patient on the possible side effects could help reduce patient anxiety and improve patient cooperation.

Skin biopsy–proven flecainide‐induced neuropathy

Flecainide acetate is a classic Ic antiarrhythmic agent used to treat a variety of cardiac arrhythmias. Non-cardiac side effects usually affect the central nervous system. Few case reports of possible flecainide-induced peripheral neuropathy have been reported. We report this unique case in that flecainide-induced sensory neuropathy was confirmed with skin biopsy, and subsequent improvement of neuropathy was documented with assessment of intraepidermal nerve fiber density in a repeat nerve biopsy.

ANTIARRHYTHMIC EFFICACY OF PROPAFENONE IN PATIENTS WITH PERSISTENT ATRIAL FIBRILLATION

Aim. To assess propafenone antiarrhythmic efficacy and optimal timing of the drug administration for relief of persistent atrial fibrillation (PAF). Material and methods. 24 patients (19 men, 5 women, aged 53,8±13,3) with PAF (duration is more than 7 days) were included in the study. PAF was confirmed clinically as well as by ECG and daily ECG monitoring. Indications for sinus rhythm recovery by propafenone were defined in according to the ACC/AHA/ESC recommendations (2006). 12-lead ECG was performed before the fist administration and 2, 4, 8, 12, 24 hours and some next days after propafenone therapy start. Echocardiography and thyroid hormone tests were also performed. Propafenone was administered additionally to standard treatment of the underlying disease and oral anticoagulants. The first dose of propafenone was 300 mg, after 4 hours patients received next dose of 300 mg if atrial fibrillation persisted and no side effects were observed, then doses of 300 mg were administered every 6-8 hours (but not more than 900-1200 mg per day) during 5 days. Maintenance propafenone dose of 450-600 mg daily was used in case of sinus rhythm recovery. Results. Sinus rhythm was restored in 41,6% of patients taking propafenone, and time of sinus rhythm recovery was 53,1±28,9 hours after therapy start. Propafenone antiarrhythmic efficacy in the loading dose (300 mg) was 4,2%. Propafenone efficacy during the first 24 hours (dose of 700±282,8 mg) was 12,5%. The maximum rate of sinus rhythm recovery was observed during the first 2-3 days of propafenone receiving (60% of all patients with rhythm recovery). Patients with unrecovered sinus rhythm had longer duration of PAF in comparison with this in effectively treated patients, 105,8±89,0 vs 39,7±38,9 days (p<0,05), respectively, as well as the more prominent basal pulse deficit, 24,6±15,0 vs 13,56±5,7 beats per minute (p<0,05), respectively. Cardiac and transient noncardiac side effects were registered in 8,6 and 4,3% of patients taking propafenone in dose of 900-1200 mg/day, respectively. Side effects did not require propafenone therapy cessation. Conclusion. Propafenone (900-1200 mg/day) antiarrhythmic efficacy in PAF was 41,6%. The probability of sinus rhythm recovery was maximal during the first 2-3 days. Ineffectively treated patients had longer duration of PAF last episode and more prominent basal pulse deficit in comparison with these in effectively treated patients. Transient side effects not requiring propafenone (900-1200 mg/day) withdrawal were observed in 12,6% of patients.

Atrial-selective drugs for treatment of atrial fibrillation

Atrial fibrillation (AF) is accompanied by a high risk of thromboembolic complications necessitating anticoagulation therapy. Arrhythmias have a high tendency to become persistent. Catheter ablation techniques are highly effective in the treatment of AF; however, these procedures are far too costly and time-consuming for the routine treatment of large numbers of AF patients. Moreover, many patients prefer drug treatment although conventional antiarrhythmic drugs are moderately effective and are burdened with severe cardiac and noncardiac side effects. New antifibrillatory drugs developed for the treatment of AF include multichannel blockers with a high degree of atrial selectivity. The rationale of this approach is to induce antiarrhythmic actions only in the atria without conferring proarrhythmic effects in the ventricles.Atrial selective drug action is expected with ion channel blockers targeting ion channels that are expressed predominantly in the atria, i.e., Kv1.5 (I(Kur)), or Kir 3.1 and Kir 3.4 (I(K,ACh)). Na(+) channel blockers that dissociate rapidly may exert atrial selectivity because of subtle differences in atrial and ventricular action potentials. Finally, atrial-selective targets may evolve due to disease-specific processes (e.g., rate-dependent Na(+) channel blockers, selective drugs against constitutively active I(K,ACh) channels).

Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

The combination therapy of doxorubicin and trastuzumab has been proven to be highly effective for metastatic breast cancer (MBC) patients with Her2/neu over-expressing tumors. However, this regimen is characterized by frequent cardiac toxicity, occurring in 27% of all treated patients and aggravating when the two substances are given concurrently. Pegylated liposomal doxorubicin (PLD) as a single agent reduces significantly cardiac toxicity and maintains efficacy compared to conventional doxorubicin. This prospective open labeled, multicenter phase II study assessed the potential cardiotoxicity and efficacy of PLD and trastuzumab as first and second line combination therapy in Her2/neu over-expressing MBC patients. Patients with Her2 over-expressing, measurable MBC with a baseline left ventricular ejection fraction (LVEF) > or =50% were treated with PLD 40 mg/m(2) every 4 weeks for 6 up to 9 cycles and weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg). Cardiotoxicity was defined as the appearance of clinical signs or symptoms of congestive heart failure in combination with a decrease in LVEF < or =44% or > or =10 units below the normal value of 50% in the obligatory, subsequently performed transthoracic echocardiography. Due to conflicting interests, the planned accrual goal of 30 patients was not reached. Finally 16 patients were enrolled. Ten patients presented with more than one metastatic site and six of them were in second-line therapy. The median LVEF in the study cohort was 66.1 +/- 8.68% at baseline, 62.7 +/- 5.11% after 6 cycles of therapy, 64.4 +/- 7.61% at the first follow up and did not change significantly (61.0 +/- 5.56% even at the 5th follow-up). Six out of 12 assessable patients (50.0%) demonstrated a clinical benefit and after a median follow-up of 15.4 months a median progression free survival of 9.67 and a median overall survival of 16.23 months. Non-cardiac side effects were mild with only 3 CTC grade 3 events of 247 treatment cycles (1.2%) and no grade 4 toxicities. The combination of PLD and trastuzumab in patients with Her2/neu over-expressing metastatic breast cancer is a safe, feasible and effective therapy. However, cardiac function should be monitored at close intervals. Due to the promising clinical response rates and mild toxicity profile in this prognostically unfavorable group, this combination therapy should be evaluated in larger studies.

Symptom-limited exercise combined with dipyridamole stress: Prognostic value in assessment of known or suspected coronary artery disease by use of gated SPECT imaging

Combining vasodilator and exercise stress reduces noncardiac side effects, improves image quality, and enhances the detection of ischemia, compared with suboptimal exercise or vasodilator stress alone. However, prognostic data with combined protocols are limited. Consecutive patients (n = 2064) who underwent symptom-limited exercise and dipyridamole stress with gated single-photon emission computed tomography (SPECT) imaging, without early revascularization, were studied. Subsequent cardiac death or nonfatal myocardial infarction was related to exercise and gated SPECT variables. Cox proportional hazards regression modeling was performed to identify predictors of adverse outcome. Annualized event rates in patients with normal and abnormal images were 0.96% and 2.71%, respectively (P < .001). With abnormal imaging, annualized event rates were 0.86% and 3.13% in patients with average to high and fair or poor functional capacity, respectively (P = .019). Abnormal imaging, a severely reduced post-stress ejection fraction, transient ischemic dilation, and fair or poor functional capacity emerged as predictors of adverse outcome. Accordingly, patients were stratified into low-risk, intermediate-risk, and high-risk cohorts with annualized event rates of 0.94%, 2.24%, and 8.19%, respectively (P < .001 in any two-way comparison). A protocol that combines symptom-limited exercise and dipyridamole stress with gated SPECT imaging provides highly effective risk stratification for adverse outcomes.

Comparison between dobutamine stress and combination of handgrip exercise with dobutamine stress in myocardial perfusion SPECT

We compared the efficacy, side effects of combined handgrip exercise and dobutamine stress with dobutamine stress alone during myocardial perfusion imaging in patients unable to exercise, and in whom vasodilator stress was contraindicated. We studied 126 consecutive patients (89 male, 37 female; mean age 63+/-8 years) referred for dobutamine stress myocardial perfusion SPECT. Patients were divided into Group A (n=63), who underwent only dobutamine stress and group B (n=63) who were subjected to combined handgrip exercise and dobutamine infusion. In group A patients, dobutamine was administered at a starting dose of 5 microg x kg(-1) x min(-1) increased to 10, 20 and 30 microg x kg(-1) x min(-1) to a maximum dose of 40 microg x kg(-1) x min(-1) at 3 min intervals until the target heart rate (THR, 85% of age predicted maximum heart rate) or other standard end point criteria were achieved. Group B patients were made to perform handgrip exercise 3 min prior to dobutamine infusion and continued throughout the administration of dobutamine. In group A, 11 (17.6%) patients failed to achieve target heart rate even with infusion of maximum dose of dobutamine compared to two (3.2%) in group B (P<0.01). The mean dose of dobutamine infused in group A was significantly higher than in group B (36.2 vs. 23.5 microg x kg(-1) x min(-1), P<0.01). Minor non-cardiac side effects like anxiety; flushing and nausea were observed in 25% of group A and in 11% of group B (P<0.05). Cardiac side effects and arrhythmias in group A and B were observed in 22% vs. 14.3% and 9.5% vs. 1.6% respectively (statistically insignificant). Combination of handgrip exercise with dobutamine reduces the total dose of dobutamine required to achieve target heart rate and likely to minimize the side effects associated with dobutamine.