Worsening Of Congestive Heart Failure Research Articles

Anakinra in the treatment of rheumatic disease

Anakinra is a specific receptor antagonist of interleukin-1 that differs from naturally occurring interleukin-1 receptor antagonist by the presence of a methionine group. It is administered by daily subcutaneous injection. Anakinra improves the clinical signs and symptoms of rheumatoid arthritis, slows radiographic progression and improves patient physical function. The most common adverse event is an injection site reaction. Anakinra has been associated with an increased incidence of serious infections and has an increased standardized incidence ratio for lymphoma. It has not been found to be associated with the development of opportunistic infections, worsening of congestive heart failure or the development of demyelinating disease. It appears to be effective in treating adult Stills disease, systemic-onset juvenile idiopathic arthritis and chronic infantile neurological cutaneous and articular syndrome (also known as neonatal-onset multisystem inflammatory disease syndrome).

Mechanical Dyssynchrony Assessed by Tissue Doppler Imaging Is a Powerful Predictor of Mortality in Congestive Heart Failure With Normal QRS Duration

We sought to test whether the mechanical dyssynchrony assessed by tissue Doppler imaging (TDI) is a predictor of cardiac events in patients with congestive heart failure (CHF) and QRS duration < or =120 ms. The prevalence and prognostic value of mechanical dyssynchrony in patients with CHF and normal QRS duration have not been well clarified. A total of 106 patients (age 63 +/- 11 years) with CHF and ejection fraction (EF) <35% were followed serially; TDI was performed using four basal and four mid-left ventricular segments to assess the time to peak systolic point from R-wave on electrocardiogram (Ts). The standard deviation of Ts (Ts-SD) and the maximal temporal difference of Ts (Ts-diff) of eight segments were used as an indicator of mechanical dyssynchrony. Clinical events included readmission due to worsening of CHF, cardiac transplantation, and death. After 17 +/- 11 months of follow-up, the clinical event rate was 33% including all-cause mortality of 19%. Prolonged Ts-SD (>37 ms) and Ts-diff (>91 ms) were associated with a significant increase in all clinical events. By multivariate analysis, Ts-diff (>91 ms) was an independent risk factor of clinical events and mortality regardless of age, EF, QRS duration, and use of beta-blocking agents. Mean event-free survival was 16.3 months (95% confidence interval [CI] 11.9 to 20.7) in patients with Ts-diff >91 ms and 31.6 months (95% CI 28.0 to 35.1) in those with Ts-diff < or =91 ms, respectively (p < 0.001). Myocardial dyssynchrony assessed by TDI is a powerful predictor of clinical events in CHF with normal QRS.

Anaemia and the heart

Anaemia is common in patients with congestive heart failure (CHF). Its prevalence increases with disease severity as a consequence of renal insufficiency, cytokine production, blood loss, iron deficiency, malnutrition and/or plasma volume overload. Anaemia can contribute to worsening of CHF. There is a nonlinear relationship (U-shaped curve) between haemoglobin and survival. Prevalence of anaemia among elderly people with acute myocardial infarction is high and is associated with more frequent in-hospital events, including death. Anaemia is also associated with higher in-hospital mortality rate after coronary bypass surgery and with all-cause and cardiac mortality after percutaneous coronary interventions. Patients with anaemia and cardiovascular disease have a higher mortality rate after cardiac/noncardiac surgery as compared to those with anaemia but without cardiovascular disease or those with cardiovascular disease but without anaemia. However, not all authors confirmed these findings. Therefore, multicentre trials to clarify this issue are urgently needed. Pleiotropic effects of recombinant human erythropoietin include reduction of myocardial and cerebral infarct size without an increase in haematocrit, neovascularization as well as mobilization of endothelial progenitor cells.

Anakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis

Anakinra (Amgen, Inc.) is a specific receptor antagonist of IL-1 that differs from naturally occurring IL-1 receptor antagonist by the presence of a methionine group. Anakinra has been shown to be of benefit in patients with active rheumatoid arthritis, either when given alone or in combination with methotrexate, as assessed by improvement in clinical signs and symptoms, decreased radiographic progression and improvement in patient function, pain and fatigue, although it appears to be effective in fewer patients than anti-TNF agents. It has a favourable safety profile as demonstrated in clinical trials. The physician and patient must be cognizant of serious infectious episodes. Many of the rare side effects seen with TNF blockers, such as tuberculosis, other opportunistic infections, worsening of congestive heart failure and the development of demyelinating disease, have not been seen in patients treated with anakinra. Anakinra should not be given in combination with anti-TNF agents.

Optimizing anti-TNF treatment in inflammatory bowel disease

Infliximab, the chimeric monoclonal immunoglobulin (Ig)G1 antibody to tumor necrosis factor (TNF) has changed our therapy of Crohn’s disease. Infliximab is indicated in refractory luminal and fistulizing Crohn’s disease. In patients with luminal disease, a single intravenous (IV) dose of 5 mg/kg is efficacious; in fistulizing disease, an IV loading therapy of 5 mg/kg at weeks 0, 2, and 6 is advocated. Because the majority of patients will relapse if not re-treated, a long-term strategy is necessary. The optimal long-term approach is systematic re-treatment with 5 mg/kg every 8 weeks. Episodic therapy on relapse also is possible but is less efficacious and frequently is associated with problems resulting from the formation of antibodies to infliximab (ATI). If treatment is episodic, maintenance therapy with immunosuppression (azathioprine [AZA]/6-mercaptopurine [6-MP] or methotrexate) is mandatory. Trial data suggest that systematic maintenance with 8 weekly doses of infliximab decreases the rate of complications, hospitalizations, and surgeries. These effects probably are achieved thanks to thorough healing of the bowel. Infliximab also is indicated in treating corticosteroid-dependent Crohn’s disease and extraintestinal manifestations of Crohn’s disease. There are no data yet that support its use as first-line therapy. The data in ulcerative colitis (UC) are conflicting and we should await the results of 2 large controlled trials (ACT1 and ACT2) to position infliximab in the treatment of UC. Other anti-TNF strategies have been less effective than infliximab in the treatment of IBD until now. The results with thalidomide are promising but much more research into small molecules inhibiting TNF and other proinflammatory cytokines is necessary. Safety problems with antibody treatment mainly concern immunogenicity leading to infusion reactions, loss of response, and serum sickness—like delayed infusion reactions. The rate of opportunistic infections is increased mainly in patients treated concomitantly with immunosuppression. Other adverse events associated with anti-TNF strategies are demyelinating disease and worsening of congestive heart failure. Malignancy rates in patients treated with anti-TNF strategies do not seem to be increased.

Vasopressin receptor antagonists in heart failure.

There is ample evidence that arginine vasopressin (AVP) is a component of the neurohormonal response to congestive heart failure (CHF). Furthermore, AVP might play a role in the development, progression and worsening of CHF. Because of the need for further improvement in the treatment of CHF, randomized clinical trials were conducted to assess the efficacy and safety of non-peptide AVP receptor antagonists in patients with CHF. In pivotal trials of three non-peptide AVP receptor antagonists, these compounds improved the fluid status, osmotic balance and hemodynamics of patients with CHF. These studies support the approval of this class of agents for the symptomatic treatment of CHF, but long-term studies are required to demonstrate their role in the outcome and quality of life of these patients.

Use of measures of disproportionality in pharmacovigilance: three Dutch examples.

Spontaneous reporting systems for suspected adverse drug reactions (ADRs) remain a cornerstone of pharmacovigilance. In The Netherlands 'the Netherlands Pharmacovigilance Foundation Lareb' maintains such a system. A primary aim in pharmacovigilance is the timely detection of either new ADRs or a change of the frequency of ADRs that are already known to be associated with the drugs involved, i.e. signal detection. Adequate signal detection solely based on the human intellect (case by case analysis or qualitative signal detection) is becoming time consuming given the increasingly large number of data, as well as less effective, especially in more complex associations such as drug-drug interactions, syndromes and when various covariates are involved. In quantitative signal detection measures that express the extent in which combinations of drug(s) and clinical event(s) are disproportionately present in the database of reported suspected ADRs are used to reveal associations of interest. Although the rationale and the methodology of the various quantitative approaches differ, they all share the characteristic that they express to what extent the number of observed cases differs from the number of expected cases. In this paper three Dutch examples are described in which a measure of disproportionality is used in quantitative signal detection in pharmacovigilance: (i) the association between antidepressant drugs and the occurrence of non-puerpural lactation as an example of an association between a single drug and a single event; (ii) the onset or worsening of congestive heart failure associated with the combined use of nonsteroidal anti-inflammatory drugs and diuretics as an example of an association between two drugs and a single event (drug-drug interaction); and the (iii) (co)-occurrence of fever, urticaria and arthralgia and the use of terbinafine as an example of an association between a single drug and multiple events (syndrome). We conclude that the use of quantitative measures in addition to qualitative analysis is a step forward in signal detection in pharmacovigilance. More research is necessary into the performance of these approaches, especially its predictive value, its robustness as well as into further extensions of the methodology.

Blunted peripheral vasodilatory response is a hallmark of progressive deterioration in mild to moderate congestive heart failure

Background: Several reports have shown that dilatory response to acetylcholine (ACh) and nitroprusside (SNP) is blunted in the limb vasculature in patients with congestive heart failure (CHF). However, it is not yet known whether this vascular dysfunction is related to clinical outcome. We have examined the relationship between peripheral vasodilatory response and prognosis of CHF. Methods and Results: A total of 46 patients with mild to moderate CHF were enrolled (mean age 56 years). Changes in forearm blood flow (FBF) during intra-arterial infusion of ACh and SNP were determined by plethysmography. FBF changes above baseline for each dose were cumulated and used as an index of endothelium-dependent (ACh) response and endothelium-independent (SNP) response, respectively. During the follow-up period (mean 32 months), 9 patients were admitted to the hospital for treatment of worsening refractory CHF, and 6 patients died suddenly or developed life-threatening arrhythmia. By Kaplan-Meier analysis, when all cardiac events were included, no significant differences were observed between any levels of vascular response in terms of prognosis. However, when deterioration events were analyzed separately, patients with SNP responses below the median (7.4 mL/min/dL) had significantly higher rates of hospital admission caused by worsening CHF than those with above the median responses (P <.05). This relationship was not found between ACh response and clinical outcome. By Cox multivariate analysis, blunted vasodilatory response to SNP was a significant predictor of worsening CHF (χ2 = 3.95; P <.05). Conclusion: This study has shown that patients with mild to moderate CHF showing a blunted vascular response to SNP rather than ACh were admitted to the hospital more frequently because of deterioration of CHF. This finding suggests that changes in vascular smooth muscle and/or vascular structure in the peripheral vasculature may be a critical element in the worsening of CHF.

Meta-analysis of the Risk of Torsades de Pointes in patients treated with intravenous racemic sotalol.

Intravenous (IV) racemic sotalol is useful for the treatment of multiple tachydysrhythmias. The authors hypothesized that the risk of torsades de pointes (TdP) in patients treated with a single IV infusion of sotalol is lower than the 2-4% risk associated with chronic oral sotalol therapy. A MEDLINE search under the subject heading "sotalol" was made of all publications involving humans written in English or German from 1966 to October 1, 2000. A meta-analysis of all original reports including patients who were given a single infusion of at least 1.5 mg/kg or 100 mg of IV sotalol over 30 minutes or less was performed. Potential variables predictive of TdP were assessed. The primary outcome was the observation of TdP associated with IV sotalol infusion. Secondary measurements included hypotension, bradycardia, and worsening of congestive heart failure. All excluded studies and case reports were also examined for evidence of TdP associated with IV sotalol treatment. The search included 1,005 publications. There were 37 reports in which 962 patients received IV sotalol and met the inclusion criteria. There was one report of self-terminating TdP lasting 10 seconds among the 962 patients included in the study. There was no report of TdP associated with only IV racemic sotalol administration in any of the excluded studies. If it is assumed that the risk of TdP is homogeneous in the population of patients treated with IV sotalol, then based on the 962 included patients, the rate of TdP is 0.1% (95% CI = 0.003% to 0.6%). The overall risk of TdP in patients treated with a single infusion of IV sotalol is low compared with that in patients given chronic oral sotalol therapy.

Increased renin immunostaining in preglomerular arterioles after myocardial infarction in the rat

In previous studies we demonstrated that the intrarenal circulation is vasoconstricted in congestive heart failure (CHF) and that pharmacologic inhibition of the renin-angiotensin system reversed the renal hemodynamic abnormalities. In the current investigation we tested the hypothesis that renin expression is increased in renal arterioles in CHF. Male Sprague-Dawley rats were studied 4 to 6 weeks after left coronary artery ligation and compared with sham-operated and normal age-matched controls. Renal vascular trees were microdissected and immunostained with a polyclonal renin antiserum. Renin immunostaining was localized to the afferent arterioles, with a greater percentage of arterioles staining in rats with CHF (55.3% ± 2.1%) than in sham-operated (43.9% ± 1.9%) or normal age controls (37.6% ± 2.2%). Rats with CHF more frequently exhibited multiple bands of renin staining within a single arteriole (24.9% ± 1.8%) as compared with sham-operated (13.3% ± 1.9%) and normal age controls (11.3% ± 1.4%). Juxtaglomerular apparatus staining was similar in all groups. These data indicate that renin-containing cells are increased in the afferent arteriole in CHF. Increased renin in the preglomerular arterioles may activate local angiotensin production, leading to intrarenal vasoconstriction, reduced nephron blood flow, sodium and water retention, and worsening of congestive heart failure. (J Lab Clin Med 2001;137:21-7)

Intermittent 6-month low-dose dobutamine infusion in severe heart failure: DICE Multicenter Trial

Background Patients with end-stage heart failure are often refractory to maximal oral therapy, and they have high mortality rates, poor quality of life, and frequent hospitalizations with elevated health care costs. Intermittent dobutamine therapy has been suggested as an additional option in this clinical setting. Methods and Results Thirty-eight patients clinically stable for at least 48 hours with standard treatment, New York Heart Association (NYHA) functional class III or IV, cardiac index ≤2.2 L/min/m 2, and left ventricular ejection fraction ≤30% were randomly assigned to ambulatory intermittent dobutamine or optimal standard treatment. Dobutamine was infused at 2.5 μg/kg/min with a portable pump 48 hours/week for 6 months. The primary study end point was the reduction of hospitalizations for worsening of congestive heart failure (CHF); changes in NYHA functional class, 6-minute walking test, and mortality rates were secondary end points. During the 6-month follow-up, all patients in dobutamine and control groups underwent weekly clinical visits with serum sodium and potassium measurement. Baseline characteristics were age 65 ± 2 years, NYHA class III/IV 17/21, ejection fraction 22% ± 1%, and cardiac index 1.89 ± 0.1 L/min/m 2, without differences between treatment groups. Hospitalizations for all causes over a 6-month period were 17 and 11 in control and dobutamine groups; 11 of 17 and 7 of 11 were for worsening CHF. Four control patients but none in the dobutamine group had 2 or more hospitalizations for worsening of CHF. There were no significant differences in NYHA functional class and in 6-minute walking test. Three patients in the control group died and 5 in the dobutamine group died. Two patients in the dobutamine group underwent heart transplantation. Protocol was discontinued in the dobutamine group for severe ventricular arrhythmias (1 patient), infusion system failure (1 patient), and consent withdrawal (1 patient). In 3 patients in the dobutamine group, drug dose was increased to 5 μg/kg/min because of CHF. Conclusions Six-month intermittent low-dose dobutamine administration was well tolerated by patients with severe CHF; it did not improve the functional status and did not significantly increase the mortality rate as found with higher dobutamine doses in other studies. Hospitalizations for all causes and for worsening of CHF tended to be fewer in the dobutamine group. (Am Heart J 1999;138:247-53.)

Long-term clinical and echocardiographic outcome in patients with mitral stenosis treated with percutaneous transvenous mitral commissurotomy.

Long-term follow-up after percutaneous transvenous mitral commissurotomy (PTMC) is limited. Ninety-four middle-aged (51+/-9 years) mitral stenosis patients who underwent successful PTMC were followed up with annual echocardiography for 6.1+/-1.4 years. PTMC success was defined as either mitral valve area (MVA) >1.5 cm2 or a MVA of more than twice the pre-procedural value, together with no worsening of mitral regurgitation >grade 2+. Mitral valve replacement (MVR), worsening of congestive heart failure (CHF), and thromboembolism were sought for survival analysis. Restenosis was defined as loss of more than 50% of the initial procedural MVA gain. Functional limit of daily activities was assessed through a questionnaire. The study population was divided into group 1 (post-procedural MVA >2.0 cm2), group 2 (MVA > 1.5 cm2 and < or = 2.0 cm2) and group 3 (MVA < or = 1.5 cm2). The 6-year survival with freedom from MVR, CHF, thromboembolism, and combined events (MVR+CHF) was 92%, 95%, 91%, and 88%, respectively. No group 1 patient experienced MVR or CHF. Restenosis was predominant in group 3. Deterioration of daily activities during follow-up was not observed in group 1; however, it was significant in group 2 (p<0.05) and group 3 (p<0.001). These results demonstrated that patients who attained a large MVA (>2.0cm2) immediately after PTMC maintained their procedural benefit with less clinical complication and with less limitation of daily activity.

Hemodynamic predictors of early intoleranceand long-term effects of propranolol in dilated cardiomyopathy

Background: Fifty-six patients with dilated cardiomyopathy (DCM) (aged 14–68 years) andbackground therapy of angiotensin-converting enzyme inhibitors, diuretics, and digoxin were given an initial challenge of propranolol in gradually increasing doses. These patients were studied noninvasively and hemodynamically and subjected to right ventricle biopsy. Methods and Results: Forty-four patients tolerated propranolol and received the drug for 6 months; 12 patients deteriorated after starting the drug with worsening of congestive heart failure and/or hypotension. The patients who did not tolerate propranolol had higher left ventricular end-diastolic dimension (73 ± 8 vs 66 ± 8 mm, P < .05), and severe mitral regurgitation was more common. Hemodynamically these patients had higher heart rate, right ventricular end-diastolic pressure, mean pulmonary artery pressure, mean pulmonary artery wedge pressure, and left ventricular end-diastolic pressure (102 ± 16 vs 89 ± 12 beats/min, 15 ± 7 vs 9 ± 4, 39 ± 16 vs 31 ± 12, 28 ± 8 vs 21 ± 8, 28 ± 8 vs 22 ± 8 mmHg, respectively, P < .01). These patients had a significantly lower cardiac index (1.9 ± 0.6 vs 2.5 ± 0.6 L/min/m 2, P < .01). Forty patients completed 6 months follow-up evaluation and were further subjected to repeat noninvasive and hemodynamic study. There was a significant improvement in New York Heart Association class, cardiothoracic ratio, and left ventricular end-diastolic dimension (68% vs 62%, 66 ± 8 vs 62 ± 7 mm, respectively, P < .01), while the ejection fraction (EF) rose from 23 to 35% ( P < .001). Hemodynamically, there was a significant decrease in heart rate, right ventricular end-diastolic pressure, mean pulmonary artery pressure, mean pulmonary artery wedge pressure, and left ventricular end-diastolic pressure (91 ± 14 vs 71 ± 5 beats/min, 9 ± 4 vs 5 ± 3, 32 ± 11 vs 22 ± 7, 25 ± 9 vs 17 ± 8, 21 ± 7 vs 14 ± 4 mmHg, P < .05). The cardiac index rose from 2.3 ± 0.6 to 3.2 ± 0.7 L/min/m 2 ( P < .01). Conclusions: Propranolol in dilated cardiomyopathy is associated with significant intolerance. Those who tolerate propranolol seem to have long-term beneficial effects. This study is limited as it is uncontrolled and nonrandomized.

New advances in the pharmacologic approach to circulatory shock

Anesthesiologists continue to play important roles in all aspects of critical care medicine. Although a unique pharmacology has evolved for use in the intensive care unit (ICU),’ much of the pharmacologic approach to the critically ill patient remains similar to the pharmacologic approach used for other perioperative conditions. Perhaps no area of critical care pharmacotherapy has evolved with more rapidity or more frustration than the pharmacologic approach to the treatment of circulatory shock. The purpose of this review is to detail our present approach to the treatment of this life-threatening condition, and to provide insight into the new avenues for therapy. Circulatory shock is an important cause of morbidity and mortality in acutely ill, hospitalized patients. Although commonly divided into four major types of circulatory shock (cardiogenic, hypovolemic, obstructive, and distributive), all forms of circulatory shock involve inadequate tissue perfusion and inadequate cellular oxygen (0,) delivery.* Cardiogenic shock is most often a consequence of acute myocardial infarction (MI), but it can also be a secondary consequence of valvular heart disease, worsening of congestive heart failure, myocardial trauma, and. so forth. Hypovolemic shock is usually due to hemorrhage, but it may also be a consequence of adrenal insufftciency or diabetes insipidus. Obstructive shock is usually due to pulmonary embolism or pericardial tamponade. Finally, distributive shock includes circulatory shock due to anaphylaxis, spinal cord shock, or, most commonly, septic shock. It is in the area of the treatment of septic shock that most new information has been realized. F!ecent evidence supports the concept that we may be missing the potential for cardiogenic or obstructive shock by failing to recognize myocardial injury in critically ill patients,3 and failing to recognize the extremely high prevalence of deep venous thrombosis in medical ICU patients despite the administration of prophylactic therapy.4 Thus, it may be that patients are predisposed to myocardial injury, which may develop into cardiogenic shock, and that patients may be at risk for the development of obstructive shock due to pulmonary emboli. Theise two recent realizations prompt me to suggest that screening critically injured patients for the possibility of myocardial injury if they have been traumatically injured is reasonable, and that patients should probably be screened with Doppler ultrasound for deep venous thrombosis. Before getting into some of the new treatment strategies used in septic shock

Left Ventricular Systolic Dysfunction Precipitated by Verapamil in Cardiac Amyloidosis

Cardiac amyloidosis produces a restrictive cardiomyopathy with impaired diastolic function. We report a case in which low-dose verapamil resulted in marked worsening of congestive heart failure, as a result of a profound negative inotropic effect. Withdrawal of verapamil therapy demonstrated a return of systolic function to normal with improvement in heart failure. We postulate that patients with cardiac amyloidosis may be exceptionally sensitive to the negative inotropic effects of calcium-channel blockers either because of abnormal binding to amyloid fibrils or because their usual vasodilator effects are blunted.

Comparative hemodynamics of antiarrhythmic drugs

It is important to consider the hemodynamic effects of antiarrhythmic drugs, because the majority of patients who require these drugs already have compromised cardiac function. The presently available antiarrhythmic agents vary in their potential for producing negative inotropic effects on the myocardium; they vary, as well, as to the mechanisms by which these effects are produced. The drugs in each of the Vaughan-Williams' classes are discussed in terms of the extent to which they affect cardiac output and the mechanisms by which they may depress cardiac function. Practically all antiarrhythmic agents can decrease cardiac output when administered intravenously. However, when given orally to patients with congestive heart failure, amongst Class I agents, encainide and mexilitine appear to have a reasonably good safety record with respect to the worsening of congestive heart failure. Class III antiarrhythmics also appear to be well tolerated in patients with severe LV dysfunction.

Safety of Long‐Term Propafenone Therapy for Cardiac Arrhythmia ‐ Experience with 774 Patients

Long term propafenone therapy was initiated in 774 patients who were evaluated at 27 centers in the United States. The average duration of therapy was 183 days. During the treatment period, at least one toxic side effect occurred in 448 patients (58%). The most common reported adverse reactions were cardiovascular in 209 patients (27%), central nervous system in 160 patients (21%), and gastrointestinal in 159 patients (21%). Of those with cardiovascular side effects, 41 (5.3%) had aggravation of arrhythmia, 26 (3.4%) had the induction or worsening of congestive heart failure, and 65 (8.4%) had new conduction abnormalities. Although side effects were frequent, drug discontinuation due to the adverse reaction was necessary in only 114 patients (14.7%). The majority of side effects were dose related especially when 900 mg/day was administered. Additionally, the incidence of toxicity was directly related to age.We conclude that side effects are frequent during long‐term propafenone therapy, but most are mild, dose related, and do not limit the use of the drug. Drug discontinuation because of an adverse reaction is only infrequently required. It is recommended that drug therapy begin with low doses (150 mg t.i.d) with careful and slow titration up to a maximum of 900 mg/day.

Endocardial Catheter Ablation for Refractory Ventricular Tachycardia Associated with Coronary Artery Disease

Percutaneous endocardial electrode catheter ablation using stored direct current (DC) electrical energy was performed in five patients with recurrent ventricular tachycardia (VT) refractory to many antiarrhythmic drugs, including amiodarone. All had prior myocardial infarction and poor left ventricular function with ejection fractions ranging from 20% to 40%. Endocardial catheter and pace mappings were used to localize the earliest site of activation during VT. Under general anesthesia, two to six shocks with 200 to 300 joules DC energy per shock were delivered to the localized sites. Immediate complications included ventricular fibrillation in one patient, transient QRS complex widening in two patients, transient complete AV block with persistent first-degree AV block in one patient, and transient asystole in two patients. None had inducible VT immediately following ablation, or 4 to 6 days later; none had evidence of intracardiac clot by two-dimensional (2D) echocardiography on the third to fifth day. Peak creatine kinase ranged from 189 to 1610 IU/L with 9% to 18% MB fraction. During a follow-up of 6 to 30 months, three patients had no recurrence of VT. Two patients had recurrent VT with a slower rate, which was controlled with antiarrhythmic drugs. None had worsening of congestive heart failure. Two patients died of nonarrhythmic causes. We conclude that nonsurgical endocardial ablation of VT with an electrode catheter is effective for the treatment of refractory VT in selected patients with coronary artery disease.

Decline in inducibility of sustained ventricular tachycardia from two to twenty weeks after acute myocardial infarction

To determine temporal evolution of sustained ventricular arrhythmias inducible after acute myocardial infarction (AMI), serial programmed ventricular stimulation (PVS) was performed in 27 patients 15 ± 4 and 150 ± 28 days after AMI. These patients did not have worsening of congestive heart failure or angina, coronary artery bypass surgery or spontaneous sustained ventricular tachycardia (VT) in the period between 2 PVS studies. During initial PVS, sustained VT or ventricular fibrillation (VF) was inducible in 17 patients (group I) and was not inducible in 10 (group II). Late PVS in group I induced sustained VT or VF in 8 patients (47%) and nonsustained VT or no VT in 9 (53%). A decrease in late inducibility of sustained VT VF was greater for arrhythmias induced during initial PVS by triple extrastimuli and burst pacing than for those induced by double extrastimuli (88% vs 25%, p < 0.04), but appeared to be unrelated to the morphologic characteristics or cycle length of the initially induced sustained VT or VF and to other clinical, hemodynamic or angiographic variables. During late PVS in 10 group II patients, sustained VT or VF remained noninducible in 9 (90% concordance); in 1 patient sustained VT was induced. During a mean follow-up of 14 ± 5 months since late PVS, none of 27 patients had spontaneous sustained VT and 2 patients in group I died suddenly. Thus, in survivors of AMI, inducibility of sustained VT or VF decreased by half during late PVS performed 5 months after the index AMI, but noninducibility 2 weeks after AMI had a high long-term reproducibility. These findings indicate the presence of an unstable electrophysiologic substrate in the first 3 to 6 months after AMI and should be taken into consideration when interpreting the results of PVS in patients with relatively recent myocardial infarction.

Acute intravenous and long-term oral hemodynamic effects of encainide

The short- and long-term hemodynamic effects of encainide, a new class IC antiarrhythmic agent, were studied in 25 patients (mean age 61 ± 11) with complex symptomatic ventricular arrhythmia and left ventricular dysfunction. Ninety-two percent had previous myocardial infarction and 8% had dilated cardiomyopathy. Seventy-five percent had congestive heart failure, class III or IV, according to the New York Heart Association. All patients underwent a nuclear ventriculogram performed at least 3 days after discontinuing previous antiarrhythmic drugs. Nuclear ventriculograms were repeated 1 to 6 weeks later while the patients were receiving therapeutic doses of encainide ranging from 75 to 1,200 mg/day. Nuclear ventriculograms were also repeated after 6 months or 1 year of encainide therapy in 16 of these patients. Encainide did not have significant effects on heart rate, blood pressure, left ventricular ejection fraction, systolic or end-diastolic volumes. None of the patients showed a worsening of congestive heart failure during encainide therapy. These results compare favorably with those of other class I antiarrhythmic agents. A review of published reports on the hemodynamic effects of intravenous encainide shows it to have a mild but statistically significant dose-related depressant effect on cardiac function. This effect, however, appears to be no different from that of other newer class I agents.