[Alcohol and the heart : Anecdotes on the history of a checkered relationship]. / Alkohol und Herz : Geschichten zur Geschichte einer wechselvollen Beziehung.

The cultural and natural scientific ambivalence of the heart and alcohol has long been the subject of philosophical, artistic, intellectual and emotional discussions, not uncommonly in a romanticizing manner. The indulgence of alcoholic beverages in moderation is contrasted by the inestimable risks and dangers of alcohol abuse with many cardiovascular implications, such as cardiac arrhythmia, cardiomyopathy and arterial hypertension. The inspirational mental effects of alcohol have been emphasized in many citations from Classical Antiquity through the Middle Ages and even in modern times. In addition to wine and beer many alcoholic drinks, such as Champagne, sparkling wines, whisky (or whiskey), brandy (Cognac) and fruit brandies have a nearly ritual culture of traditions and customs, without which social life would be unthinkable. The interplay between enjoyment and displeasure is emphasized in the year 2016 with the 500-year jubilee of the German purity requirements for beer with countless events, including the Bavarian State Exhibition 2016. Recently, evidence of a neuroprotective effect of alcohol was reported with an improvement of intellectual capacity, which could counteract the widely occurring dementia syndrome. Millions of people could profit from this effect.

Left atrial chamber and appendage function after internal atrial defibrillation: a prospective and serial transesophageal echocardiographic study.

OBJECTIVES: The purpose of this prospective study was to assess left atrial chamber and appendage function after internal atrial defibrillation of atrial fibrillation and to evaluate the time course of recovery. BACKGROUND: External cardioversion of atrial fibrillation may result in left atrial appendage dysfunction ("stunning") and may promote thrombus formation. In contrast to external cardioversion, internal atrial defibrillation utilizes lower energies; however, it is unknown whether the use of lower energies may avoid stunning of the left atrial appendage. METHODS: Transesophageal and transthoracic echocardiography were performed in 20 patients 24 h before and 1 and 7 days after internal atrial defibrillation to assess both left atrial chamber and appendage function. Transthoracic echocardiography was again performed 28 days after internal atrial defibrillation to assess left atrial function. The incidence and degree of spontaneous echo contrast accumulation (range 1+ to 4+) was noted, and peak emptying velocities of the left atrial appendage were measured before and after internal atrial defibrillation. To determine left atrial mechanical function, peak A wave velocities were obtained from transmitral flow velocity profiles. RESULTS: Sinus rhythm was restored in all patients. The mean +/- SD peak A wave velocities increased gradually after cardioversion, from 0.47 +/- 0.16 m/s at 24 h to 0.61 +/- 0.13 m/s after 7 days (p < 0.05) and 0.63 +/- 0.13 m/s after 4 weeks. Peak emptying velocities of the left atrial appendage were 0.37 +/- 0.16 m/s before internal atrial defibrillation, decreased significantly after internal atrial defibrillation to 0.23 +/- 0.1 m/s at 24 h (p < 0.01) and then recovered to 0.49 +/- 0.23 m/s (p < 0.01) after 7 days. The corresponding values for the degree of spontaneous echo contrast were 1.2 +/- 1.2 before internal atrial defibrillation versus 2.0 +/- 1.0 (p < 0.01) and 1.1 +/- 1.3 (p < 0.01) 1 and 7 days after cardioversion, respectively. One patient developed a new thrombus in the left atrial appendage, and another had a thromboembolic event after internal atrial defibrillation. CONCLUSIONS: Internal atrial defibrillation causes depressed left atrial chamber and appendage function and may result in the subacute accumulation of spontaneous echo contrast and development of new thrombi after cardioversion. These findings have important clinical implications for anticoagulation therapy before and after low energy internal atrial defibrillation in patients with atrial fibrillation.

The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy.

OBJECTIVES: We sought to assess the impact of intermittent atrial fibrillation (AF) on health-related quality of life (QoL). BACKGROUND: Intermittent AF is a common condition with little data on health-related QoL questionnaires to guide investigational therapies. METHODS: Outpatients from four centers, with documented AF (n = 152), completed validated QoL questionnaires (Medical Outcomes Study Short Form 36 [SF-36], Specific Activity, Symptom Checklist, Illness Intrusiveness and University of Toronto AF Severity Scales). Comparison groups were made up of healthy individuals (n = 47) and four cardiac control groups: published (n = 78) and created for study (n = 69) percutaneous transluminal coronary angioplasty (PTCA); published heart failure (n = 216) and published postmyocardial infarction (MI) (n = 107). RESULTS: Across all domains of the SF-36, AF patients reported substantially worse QoL than healthy controls (1.3 to 2.0 standard deviation units), with scores of 24%, 23%, 16% and 30% lower than healthy individuals on measures of physical and social functioning, mental and general health, respectively (all p < 0.001). Patients with AF were either significantly worse (p < 0.05, published controls) or as impaired (study controls) as either PTCA or post-MI patients on all domains of the SF-36 and the same as heart failure controls on SF-36 psychological subscales. Patients with AF were as impaired or worse than study PTCA controls on measures of illness intrusiveness, activity limitations and symptoms. Associations between objective disease indexes and subjective QoL measures had poor correlations and accounted for <6% of the total variability in QoL scores. CONCLUSIONS: Quality of life is as impaired in patients with intermittent AF as in patients with significant structural heart disease. Patients' perception of QoL is not dependent on the objective measures of disease severity that are usually employed.

Prevalence of left atrial chamber and appendage thrombi in patients with atrial flutter and its clinical significance.

OBJECTIVES: The study was done to assess the prevalence of left atrial (LA) chamber and appendage thrombi in patients with atrial flutter (AFl) scheduled for electrophysiologic study (EPS), to evaluate the prevalence of thromboembolic complications after transesophageal echocardiographic (TEE)-guided restoration of sinus rhythm and to evaluate clinical risk factors for a thrombogenic milieu. BACKGROUND: Recent studies showed controversial results on the prevalence of atrial thrombi and the risk of thromboembolism after restoring sinus rhythm in patients with AFl. METHODS: Between 1995 and 1999, patients with AFl who were scheduled for EPS were included in the study. After transesophageal assessment of the left atrial appendage and exclusion of thrombi, an effective anticoagulation was initiated and patients underwent EPS within 24 h. RESULTS: We performed 202 EPSs (radiofrequency catheter ablation, n = 122; overdrive stimulation, n = 64; electrical cardioversion, n = 16) in 139 consecutive patients with AFl. Fifteen patients with a thrombogenic milieu were identified. All of them had paroxysmal atrial fibrillation (AF). Transesophageal echocardiography revealed LA thrombi in two cases (1%). After EPS no thromboembolic complications were observed. Diabetes mellitus, arterial hypertension and a decreased left ventricular ejection fraction were found to be independent risk factors associated with a thrombogenic milieu. CONCLUSIONS: The findings of a low prevalence of LA appendage thrombi (1%) in patients with AFl and a close correlation between a history of previous embolism and paroxysmal AF support the current guidelines that patients with pure AFl do not require anticoagulation therapy, whereas patients with AFl and paroxysmal AF should receive anticoagulation therapy. In addition, the presence of clinical risk factors should alert the physician to an increased likelihood for a thrombogenic milieu.

Transverse conduction capabilities of the crista terminalis in patients with atrial flutter and atrial fibrillation.

OBJECTIVES: In this study, the transverse conduction capabilities of the crista terminalis (CT) were determined during pacing in sinus rhythm in patients with atrial flutter and atrial fibrillation. BACKGROUND: It has been demonstrated that the CT is a barrier to transverse conduction during typical atrial flutter. Mapping studies in animal models provide evidence that this is functional. The influence of transverse conduction capabilities of the CT on the development of atrial flutter remains unclear. METHODS: The CT was identified by intracardiac echocardiography. The atrial activation at the CT was determined during programmed stimulation with one extrastimulus at five pacing sites anteriorly to the CT in 10 patients with atrial flutter and 10 patients with atrial fibrillation before and after intravenous administration of 2 mg/kg disopyramide. Subsequently, atrial arrhythmias were reinduced. RESULTS: At baseline, pacing with longer coupling intervals resulted in a transverse pulse propagation across the CT. During shorter coupling intervals, split electrograms and a marked alteration of the activation sequence of its second component were found, indicating a functional conduction block. In patients with atrial flutter, the longest coupling interval that resulted in a complete transverse conduction block at the CT was significantly longer than that in patients with atrial fibrillation (285 +/- 49 ms vs. 221 +/- 28 ms; p < 0.05). After disopyramide administration, a transverse conduction block occurred at longer coupling intervals as compared with baseline (287 +/- 68 ms vs. 250 +/- 52 ms; p < 0.05). Subsequently, a sustained atrial arrhythmia was inducible in 15 of 20 patients. This was atrial flutter in three patients with previously documented atrial fibrillation and in eight patients with history of atrial flutter. Mapping revealed a conduction block at the CT in all of these patients. CONCLUSIONS: It was found that the CT provides transverse conduction capabilities and that the conduction block during atrial flutter is functional. Limited transverse conduction capabilities of the CT seem to contribute to the development of atrial flutter.

Quality of life in patients with atrial fibrillation.

Atrial fibrillation (AF) is a frequent and costly health care problem. In patients with AF, the restoration and maintenance of sinus rhythm is the primary therapeutic goal. The most frequent strategy for maintaining sinus rhythm after restoration is the use of antiarrhythmic drugs. The efficacy of therapy in AF has been predominantly measured using objective criteria such as mortality and morbidity. In recent years, the importance of quality of life (QoL) as an outcome measure has been recognized. However, few studies in the literature have examined QoL in patients with AF using properly validated tools. In addition, the specific impact of antiarrhythmic drug treatment on QoL in patients with AF has not been assessed. These issues are now being addressed in several ongoing studies. This article attempts to define QoL, makes recommendations on how QoL might be assessed, reviews our current knowledge regarding QoL in patients with AF, and discusses new clinical trials currently assessing QoL in patients with AF.

Role of smooth muscle cell death in advanced coronary primary lesions: implications for plaque instability.

OBJECTIVE: Instability of coronary atheroma leads to the onset of acute coronary syndromes including myocardial infarction and death, as well as to the progression of the arteriosclerotic disease. As yet, the underlying factors and mechanisms causing plaque rupture are not completely understood. Since a low content of smooth muscle cells (SMCs) apparently plays a key role, the question points to the events leading to the loss of intimal SMCs. METHODS: We compared coronary atherectomy specimens from 25 patients with unstable angina to those from 25 patients with stable angina. Transmission electron microscopy was used to identify intimal cell population, to detect stage and cell type of apoptosis, and to differentiate between apoptosis and necrosis. RESULTS: Plaques associated with unstable angina contained more macrophages/lymphocytes and significantly less SMCs (P = 0.01), compared with stable angina plaques. Specific cell death forms, apoptosis and necrosis, were present in all coronary atheroma. As key findings, both the proportion of SMCs undergoing apoptosis and the frequency of cytoplasmic remnants of apoptotic SMCs (matrix vesicles) were significantly increased in unstable versus stable angina lesions (P = 0.002 and P = 0.002). In addition, cellular necrosis was more frequent in the first coronary atheroma group (P = 0.02). Positive correlations were found between the frequency of apoptotic cells and necrosis (r = 0.41, P = 0.04), and that of matrix vesicles and necrosis (r = 0.63, P = 0.001) only in plaques with unstable angina, but not in those with stable angina. CONCLUSIONS: Our data demonstrate that high cell death due to apoptosis and necrosis is a basic in situ feature found in advanced coronary primary lesions associated with unstable angina, possibly explaining their low density of (viable) SMCs. Thus, antagonization of intimal cell death should be considered in order to stabilize the intimal plaque texture of coronary atheroma with the ultimate goal to prevent plaque rupture.

Incidence of left atrial thrombi in patients in sinus rhythm and with a recent neurologic deficit.

OBJECTIVES: We sought to determine the incidence of left atrial (LA) thrombi in patients in sinus rhythm (SR) and with a recent neurologic deficit and to analyze the relation between LA thrombi and LA chamber and appendage function in patients in SR. METHODS: A prospective study was conducted in 869 consecutive patients. The study group consisted of 583 patients in SR (67%). The remaining 286 patients had atrial fibrillation (AF) and served as controls (33%). RESULTS: The incidence of LA thrombi was significantly higher in patients with AF (n = 39 [14%]) compared with patients in SR (n = 6 [1%]; P <.001). Three of 6 patients with thrombi in SR had mitral stenosis, 1 patient had aortic stenosis, 1 patient had coronary artery disease, and another patient had a cardiomyopathy. Of the patients with detected thrombi, those in SR did not receive anticoagulation, whereas those with AF did in 18 cases. Patients with thrombi in SR and with AF did not significantly differ in LA diameter (5.1 +/- 0.8 cm vs 4.8 +/- 0.7 cm; 95% confidence interval [CI], -0.78 to 0.45), left ventricular ejection fraction (46% +/- 13% vs 42% +/- 15%; 95% CI, -18.7 to 7.4), LA appendage area (5.8 +/- 2.7 cm(2) vs 6.7 +/- 3.2 cm(2); 95% CI, -1.9 to 3.6), peak emptying velocity of the LA appendage (0.19 +/- 0.08 m/s vs 0.17 +/- 0.07 m/s; 95% CI, -0.08 to 0.04), or LA spontaneous echo contrast (3. 5 +/- 0.6 vs 3.9 +/- 0.5; 95% CI, -0.06 to 0.45). CONCLUSIONS: LA appendage thrombi are an infrequent cause of thromboembolism in patients in SR and are associated either with mitral valve disease or LA chamber and appendage dysfunction. Routine transesophageal echocardiography for the exclusion of LA thrombi is not recommended in patients in SR without underlying heart disease and normal LA function as assessed by transthoracic echocardiography.

Pharmacologic treatment of supraventricular tachycardia: the German experience.

Tachyarrhythmias that originate above the bifurcation of the bundle of His or in tissue proximal to it are classified as supraventricular tachyarrhythmias (SVTs). Primary treatment of SVT tries to influence the underlying disease. Symptomatic therapy is subdivided into drug therapy, electrotherapeutic tools (e.g., antitachycardia pacemakers, catheter ablation), and antiarrhythmic surgery. Antiarrhythmic agents that slow conduction and suppress premature beats are efficient for emergency and long-term treatment of SVTs. We evaluated some of the most relevant antiarrhythmic drugs in SVT, including propafenone, diprafenone, cibenzoline, sotalol, and diltiazem; in addition, usage and efficacy of quinidine/verapamil, disopyramide, amiodarone, ajmaline, adenosine, and flecainide are summarized. In 1990, the case load of supraventricular arrhythmias per physician in Germany was more than 30 patients seen per month. About 50% of them were treated with drug therapy; i.e., approximately 17 patients were treated with antiarrhythmic drugs per month per physician for supraventricular arrhythmias. The most important antiarrhythmic agents used in Germany are propafenone (40%), combination of quinidine and verapamil (23%), sotalol (12%), disopyramide (6%), flecainide (6%), and other (13%).

Role of antitachycardia devices in the treatment of ventricular tachyarrhythmias.

Chronic recurrent ventricular tachycardia (VT) can be terminated reproducibly by programmed endocardial right ventricular stimulation. However, antitachycardia pacing is associated with possible acceleration of VT, while frequent occurrence of VT and discomfort of the patient can limit treatment with an automatic implantable cardioverter/defibrillator (AICD; Cardiac Pacemakers Inc.). The combined use of antitachycardia pacing (Tachylog pacemaker; Siemens-Elema) and AICD was therefore evaluated in 6 of 35 patients (aged 50 to 70 years, mean 60.1 +/- 7.7) in whom AICD had been implanted because of VT, which could be terminated by temporary overdrive pacing. With the interactive mode of the Tachylog, termination of VT by the pacemaker as well as by the AICD was assessed after implantation. In the automatic mode, the Tachylog functioned as a bipolar ventricular inhibited (VVI) device with antitachycardia burst stimulation: 2 to 5 stimuli, interval 260 to 300 ms, 1 to 2 interventions. During follow-up of 32 +/- 17 months, the Tachylog terminated VT reliably 50 to 505 times per patient. When burst stimulation accelerated VT, termination was achieved by AICD discharge. Thus, drug-resistant VT can be terminated by antitachycardia pacing avoiding patient discomfort. In case of acceleration, VT can be controlled by the AICD. A universal pacemaker should combine antibradycardia and antitachycardia pacing with backup cardioversion/defibrillation mode.

Quality of life and driving in recipients of the implantable cardioverter-defibrillator.

UNLABELLED: The efficacy of a treatment is primarily based on objective criteria, such as mortality and morbidity. Besides these criteria, the interest in measuring quality of life (QOL) in relation to health care has increased in recent years. Although the concept of patients' QOL is inherently subjective, and definitions vary, it can be assessed on a basis of 3 major components: physical condition, psychological well-being, and social activities. The basic requirements of QOL assessments are: multidimensional construct, reliability, validity, sensitivity, responsiveness, appropriateness to question or use, and practical utility. The instruments to assess QOL can be disease specific or generic, depending on the context. In 1991 a prospective and systematic evaluation of QOL in implantable cardioverter-defibrillator (ICD) recipients was started at the University of Bonn: psychological profile and patient acceptance were assessed in 57 consecutive patients using a specifically designed questionnaire. The results of this pilot study demonstrated that the acceptance of the ICD was remarkably high. Restrictions on driving a vehicle may have a substantial impact on QOL in patients with ICDs. A specifically designed questionnaire was addressed to 47 European national delegates in order to determine their present practices and criteria utilized when advising driving restrictions to patients after ICD implantation. Of the 39 (83%) respondents, 22 (56%) cardiologists advised all patients to abstain from driving--13 (33%) advising permanent abstinence, while 26 (67%) recommended temporary driving abstinence for periods of 3-18 months (mean 9 +/- 4 months). Despite medical advice not to drive, one third of the patients resume driving; half of the patients resumed driving after 6 months, with the vast majority driving within 12 months after ICD surgery. Two patients experienced ICD discharges while driving, but no motor vehicle accident occurred. Another patient had a motor vehicle collision with a fatal outcome, which was not caused by loss of consciousness or ICD discharge. CONCLUSIONS: (1) Fatal accidents or ICD discharges while driving are a rare finding in ICD patients. (2) About half of the physicians always advise their patients to cease driving for a period of 9 +/- 4 months. Despite this medical advice, the majority of the patients resume driving within 6 months of ICD implantation. (3) Criteria used in advising driving abstinence are not uniform among physicians.

Rate issues in atrial fibrillation: consequences of tachycardia and therapy for rate control.

Atrial fibrillation (AF) is an arrhythmia resulting in loss of atrial contribution to ventricular filling, an irregular ventricular contraction, and an inappropriately rapid ventricular rate. An uncontrolled ventricular response may result in various changes of ventricular function and structure referred to as tachycardia-related cardiomyopathy. However, the effects of tachycardia may be reversible with adequate pharmacologic or nonpharmacologic interventional rate control. The purpose of this review article is to discuss the present knowledge regarding tachycardia-related cardiomyopathy and therapy for rate control.

Usefulness of programmed stimulation in predicting efficacy of propafenone in long-term antiarrhythmic therapy for paroxysmal supraventricular tachycardia.

The electrophysiologic effects of intravenous (i.v.) and oral propafenone were evaluated in 14 patients with Wolff-Parkinson-White syndrome and in 10 patients with atrioventricular (AV) nodal reentrant tachycardia. The effective refractory periods of the right atrium and the AV node increased after both preparations. In patients with Wolff-Parkinson-White syndrome, i.v. propafenone blocked anterograde accessory pathway conduction in 2 patients and retrograde conduction in 1; during oral therapy, accessory pathway conduction block occurred in 2 additional patients. The mean cycle length of the supraventricular tachycardia (SVT) increased from 338 +/- 60 ms to 387 +/- 56 ms (p less than 0.05) after i.v. application, and from 336 +/- 65 ms to 367 +/- 65 ms (p less than 0.05) during oral propafenone. The shortest pacing interval maintaining a 1:1 AV conduction increased from 325 +/- 65 ms to 368 +/- 81 ms (p less than 0.05) after i.v. infusion, and from 333 +/- 57 ms to 369 +/- 75 ms (p less than 0.05) during oral therapy. There was no difference in the electrophysiologic effects between i.v. and oral propafenone. The induction of SVT was prevented by i.v. propafenone in 10 of 20 patients and in 4 additional patients with oral propafenone. During follow-up, 6 of 7 patients, whose SVT could not be initiated by electrophysiologic drug testing, remained free from recurrences, whereas 5 of 7 patients with inducible tachycardia had recurrences of SVT. Thus, in patients with SVT, propafenone prolonged accessory pathway and AV nodal conduction and had a beneficial effect on circus movement tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonpharmacologic strategies for treating atrial fibrillation.

Nonpharmacologic tools to treat atrial fibrillation (AF) are direct current cardioversion, radiofrequency (RF) current catheter ablation, antiarrhythmic surgery, pacing, and atrial defibrillation. In patients with sustained AF, when no cause can be found for AF or when the associated disease is mild, an attempt should be made to restore sinus rhythm. Electrical cardioversion by synchronized direct current shock can be attempted when drugs have failed and is the first choice in acutely ill patients. Virtually all patients should be anticoagulated. Temporary pacing should be available in patients with evidence of previous bradycardia. Although efficacy may be improved in patients pretreated with antiarrhythmic drugs, there is a considerable risk of adverse events. In AF and sinus node dysfunction, both pacing and antiarrhythmic drugs may be necessary. Pacing should be atrial or dual chamber, since ventricular pacing provokes AF. Failure to control the ventricular rate in AF can be treated by RF: atrioventricular (AV) node ablation, ablation of accessory pathways in preexcitation syndrome with AF, modulation of AV node, or ablation of AF. Antiarrhythmic surgery is a major procedure and may be the therapy of last resort in AF: the so-called corridor procedure isolates the fibrillating atria from a strip of tissue connecting the sinus and AV nodes. The maze procedure attempts to abolish AF by channeling the atrial activation between a series of incisions. In patients with chronic AF, internal cardioversion should be attempted if conventional transthoracic electrical cardioversion is ineffective. Several studies demonstrated the feasibility and efficacy of internal atrial defibrillation in selected patients with recent onset, as well as with chronic, AF. An implantable atrial defibrillator--as a stand-alone device or as part of a whole heart cardioverter--might be an option in the future. Nonpharmacologic tools play only a minor role in the management of paroxysmal and chronic AF. If symptoms persist despite pharmacologic therapy and other causes of persisting symptoms are excluded, consideration should be given to cardiac pacing, RF catheter treatment, or surgery. in some cases nonpharmacologic therapy of the AV node must be followed by implantation of a permanent pacemaker (due to complete AV block) and anticoagulation (due to persistence of underlying AF.

Effects of chronic amiodarone therapy on defibrillation threshold.

In a prospective and parallel, randomized study, the long-term stability of epicardial defibrillation threshold was evaluated in 22 patients, using a patch-patch lead configuration at the time of implantation and generator replacement. The concomitant antiarrhythmic drug treatment consisted of either mexiletine (720 mg/day) or amiodarone (400 mg/day) and was administered to patients in a randomized and parallel manner. During a mean follow-up of 24 +/- 6 months, the defibrillation threshold increased significantly from 14.3 +/- 2.8 to 17.9 +/- 5.3 J (p < 0.05) for the entire patient group. The increase in the chronic defibrillation threshold was due to a marked increase in defibrillation energy needs in the subgroup of patients receiving amiodarone. Whereas no significant change in the defibrillation threshold was documented in the subgroup of patients receiving mexiletine, the mean defibrillation threshold increased from 14.1 +/- 3.0 to 20.9 +/- 5.4 J (p < 0.001) in those receiving amiodarone. In all patients with increased defibrillation thresholds, reevaluation showed a reduction in the defibrillation threshold after discontinuation of antiarrhythmic drug therapy. The only variable associated with an increase in the chronic defibrillation threshold was amiodarone treatment. These findings suggest that the defibrillation threshold should be measured at each generator replacement and in case of a change in antiarrhythmic drug treatment. In particular, if amiodarone treatment is initiated, it is recommended that the defibrillation threshold should be reevaluated to ensure an adequate margin of safety.

N-acetylcysteine attenuates nitroglycerin tolerance in patients with angina pectoris and normal left ventricular function.

The aim of this study was to assess whether N-acetylcysteine (NAC) is able to prevent tolerance to a 48-hour infusion of nitroglycerin (NTG) in the setting of normal left ventricular function. In 16 patients, the hemodynamic response to 0.8 mg sublingual (s.l.) NTG was assessed by measuring mean arterial, pulmonary artery, pulmonary capillary wedge and right atrial pressures, cardiac output, and calculation of the systemic and pulmonary vascular resistances. The parameters were obtained at baseline and 1 to 10 minutes after the s.l. NTG application (day 1). NTG was started at 1.5 microg/kg/min; concomitantly, a bolus of 2,000 mg of NAC was administered, followed by an infusion of 5 mg/kg/hour. Both infusions were continued for 48 hours, and the hemodynamic study was repeated (day 3). The same measurements were obtained in a matched control group of 15 patients with NTG infusion alone. Plasma renin activity, aldosterone, and norepinephrine were measured before and after the infusion period. The first s.l. NTG infusion (day 1) caused a significant decrease in mean arterial (p <0.01), pulmonary artery (p <0.001), and right atrial pressures (p <0.001), and in systemic (p <0.01) and pulmonary vascular resistances (p <0.001) in both groups. After the 48-hour infusion (day 3), there was a total loss of nitrate-mediated vasodilation (pressure values and vascular resistances day 3 > day 1) in 5 of 16 patients (NAC nonresponders), whereas in the other 11 of 16 patients (NAC responders), there was significant vasodilation throughout the infusion period. Tolerance had developed in 14 of 15 patients with NTG infusion alone. The same difference (responder vs nonresponder vs NTG alone) held true regarding the response to the second s.l. NTG infusion after 48 hours. The neurohormonal counter-regulation and intravascular volume expansion (increase in plasma renin activity, p <0.001, and norepinephrine, p <0.05; decrease in aldosterone, p <0.01) did not differ between responders and nonresponders. We conclude that NAC attenuates tolerance development to a continuous NTG infusion in a specific patient subgroup and that this occurs despite the same amount of neurohormonal counter-regulation and intravascular volume expansion compared with patients with tolerance development.

Multiplane transesophageal echocardiographic assessment of mitral regurgitation by Doppler color flow mapping of the vena contracta.

Assessment of the severity of mitral regurgitation (MR) by Doppler color flow mapping is limited by dependence of jet area on hemodynamic and technical variables. The width of the MR jet at its origin may be less dependent on hemodynamic variables, and thus should more accurately reflect the severity of MR. Doppler color flow mapping was performed in 80 subjects by transesophageal echocardiography (TEE) within 48 hours of catheterization. Width of the MR jet at its vena contracta was measured by both single plane and multiplane TEE and compared with the angiographic grade of MR and regurgitant volume. The width of the MR jet correlated closely with angiographic grade by both methods. A jet width > or = 6 mm identified angiographically severe MR with a sensitivity and specificity of 100% and 83% by single-plane TEE, and 95% and 98% by multiplane TEE. The sensitivity and specificity for detecting a regurgitant volume > or = 80 ml was 93% and 76% for single-plane TEE, and 86% and 95% for multiplane TEE. Thus, the width of the MR jet at its vena contracta by Doppler color flow mapping is an accurate marker of the severity of MR. By virtue of its ability to obtain orthogonal views specifically oriented to mitral leaflet coaptation, multiplane TEE is superior to single-plane TEE in assessing MR jet width.

Color-coded Doppler imaging of the vena contracta as a basis for quantification of pure mitral regurgitation.

The narrowest central flow region of a jet is defined as the vena contracta. This term is applied also to the contracted zone of the Doppler color flow image of a jet at its passage through an incompetent mitral valve. The clinical applicability of measuring the size of the vena contracta by transthoracic color-coded Doppler echocardiography for estimating the severity of mitral regurgitation (MR) was evaluated. In 78 of 82 patients with angiographically proved MR, a coherent flow image across the valve was visualized. The maximal diameter in the apical long-axis view was considered as a representative value for the size of the vena contracta. In comparison with the maximal left atrial velocity pixel area, this parameter revealed higher correlations to the angiographic degree of MR and to the regurgitant volume (r = 0.94 vs 0.72, and 0.83 vs 0.71, respectively). The highest positive and negative predictive accuracies for differentiating mild-to-moderate from severe MR were determined for a diameter of 6.5 mm (88 and 96%, respectively). Because the vena contracta is directly related to the severity of MR, it is concluded that it is helpful to use this parameter instead of the maximal velocity pixel area for semiquantitative grading.

Heart rate to work rate relation throughout peak exercise in normal subjects as a guideline for rate-adaptive pacemaker programming.

We investigated the physiologic heart rate (HR) to work rate (WR) relation throughout peak exercise in normal subjects as a guideline for rate-adaptive pacemaker slope programming. The study group consisted of 41 middle-aged subjects (22 men and 19 women) without evidence of cardiopulmonary disease. Peak-exercise stress tests were performed on a calibrated treadmill by using the symptom-limited "ramping incremental treadmill exercise" (RITE) protocol. The HR response, oxygen uptake, and treadmill workload increments were assessed simultaneously. The HR/WR slope, as determined using linear regression analysis, was 0.37 +/- 0.13 beats/min/W for the entire study group, which indicates an upper range increase of 5 beats/10 W increase of external treadmill work performed, using the mean value +/- 1 SD. Men generated an HR/WR slope of 0.32 +/- 0.09 beats/min/W, and women, 0.43 +/- 0.15 beats/min/W, indicating a significant sex-related difference in the HR/WR relation (p < 0.01). Thus, to achieve an appropriate matching of HR with patient effort, rate-adaptive pacemakers should generate an average increase of approximately 5 beats per increase in 10 W of external treadmill work. The HR/WR relation can easily be determined to provide the clinician with a minimal check system to avoid a hyper- or hypochronotropic paced response to exercise.

Radiofrequency ablation of atrial flutter due to administration of class IC antiarrhythmic drugs for atrial fibrillation.

In selected patients, atrial fibrillation (AF) converts to atrial flutter (AFI) due to treatment with class IC antiarrhythmic drugs. In this study, we prospectively investigated the effects of AFI ablation and continuation of drug therapy in patients with AF who developed AFI due to long-term administration of class IC antiarrhythmic drugs. The study population consisted of 187 patients from an AF registry with paroxysmal AF who were orally treated with flecainide (n = 96) or propafenone (n = 91). Twenty-four patients (12.8%) developed AFI during the course of treatment. In 20 of these patients (10.7%), electrophysiologic study revealed typical AFI. These patients underwent radiofrequency ablation of AFI. Ablation failed in 1 patient. All patients continued preexisting drug treatment. Recurrence of AF was assessed by ambulatory Holter monitoring and serial questionnaires. During a mean follow-up of 11 +/- 4 months, the incidence of AF episodes was significantly lower in patients with a combined therapy (2.7 +/- 3.6 per year) than in control subjects with a sole drug treatment (7.8 +/- 9.2 per year, p <0.05) and than before therapy (10.2 +/- 5.4 per year, p <0.001). Subgroup analysis revealed that 7 patients (36.8%) remained symptom free with no evidence of atrial tachyarrhythmia. Eight additional patients (42.1%) had ongoing paroxysmal AF, however, with a significantly lower incidence of AF episodes than before therapy (2.3 +/- 1.6 per year vs 11.5 +/- 5.0 per year, p <0.001). In the remaining 4 patients (14.7%), no beneficial effect of AFI ablation was found. It is concluded that in patients with AF who develop typical AFI due to administration of class IC antiarrhythmic agents, a combined therapy with catheter ablation of AFI and continuation of drug treatment is highly effective in reducing occurrence and duration of atrial tachyarrhythmias.