Hans R. Figulla

Improvement of exercise capacity with treatment of Cheyne-Stokes respiration in patients with congestive heart failure

OBJECTIVES The aim of this study was to determine the impact of nasal nocturnal oxygen therapy on respiration, sleep, exercise capacity, cognitive function and daytime symptoms in patients with congestive heart failure and Cheyne-Stokes respiration. BACKGROUND Cheyne-Stokes respiration is common in patients with congestive heart failure and is associated with significant nocturnal oxygen desaturation and sleep disruption with arousals. Oxygen desaturations and arousals cause an increase in pulmonary artery pressure and sympathoneural activity and therefore may reduce exercise capacity. Oxygen is an effective treatment of Cheyne-Stokes respiration and should improve exercise capacity in these patients. METHODS The study was designed as a randomized crossover, double-blind, placebo-controlled trial: 22 patients were assigned to 1 week each of nocturnal oxygen and room air. After each week, polysomnography, maximal bicycle exercise with expiratory gas analysis and trail-making test were performed, and a health assessment chart was completed. RESULTS Nocturnal oxygen significantly reduced the duration of Cheyne-Stokes respiration (162 +/- 142 vs. 88 +/- 105 min [mean +/- SD]; p < 0.005). Sleep improved as evidenced by less stage 1 sleep and fewer arousals (20 +/- 13 vs. 15 +/- 9/h total sleep time; p < 0.05) as well as more stage 2 and slow-wave sleep; nocturnal oxygen saturation also improved. Peak oxygen consumption during exercise testing increased after oxygen treatment (835 +/- 395 vs. 960 +/- 389 ml/min; p < 0.05). Cognitive function evaluated by the trail-making test improved, but daytime symptoms in the health assessment chart did not improve significantly. CONCLUSIONS Successful treatment of Cheyne-Stokes respiration with nocturnal nasal oxygen improves not only sleep, but also exercise tolerance and cognitive function in patients with congestive heart failure.

Prognostic value of Doppler echocardiographic assessment of left ventricular filling in idiopathic dilated cardiomyopathy.

The relation of left ventricular (LV) diastolic filling with the clinical outcome in patients with idiopathic dilated cardiomyopathy (IDC) was examined. LV diastolic filling was assessed by Doppler echocardiography in 57 patients with IDC at the time that the diagnosis was established by angiocardiography. Patients were followed for 29 +/- 16 months. Fifteen patients died: 12 due to progressive congestive heart failure and 3 suddenly. Four other patients underwent cardiac transplantation because of progressive heart failure (1-year survival 86%). Patients who died of congestive heart failure or underwent cardiac transplantation had a steep increase and decrease in the early filling phase as compared with survivors; the peak early Doppler velocity was higher (0.84 +/- 0.16 vs 0.65 +/- 0.21 m/s; p < 0.005), and the deceleration time of the early velocity peak was shorter (117 +/- 26 vs 188 +/- 62 ms; p < 0.001) than in survivors. Surviving patients and those who died suddenly showed similar patterns of LV filling. Deceleration time and peak early Doppler velocity were the strongest predictors of survival as compared with systolic function and clinical status in a Cox proportional-hazards analysis. Patients with a shortened deceleration time (< or = 140 ms) had a significantly reduced 2-year survival rate of 52% (confidence interval 34 to 71%) as compared with those with a longer deceleration time (94%; confidence interval 89 to 98%) (p < 0.001). Evidence was presented for a relation between LV filling and survival in patients with IDC.

Direct coronary stenting without predilatation: A new therapeutic approach with a special balloon catheter design

Coronary stenting is the primary therapeutic option for many coronary lesions, after the risk of subacute stent thrombosis and bleeding complications has been reduced by antithrombotic regimens and improved stent expansion. It would be desirable to shorten the procedure and the duration of ischemia, and to reduce the risk of ischemic complications during balloon inflation by implanting the stent without previous dilatation of the lesion. This is not possible with the presently available stent delivery systems. This new therapeutic concept was tested with a specially designed balloon catheter, on which slotted-tube stents can be fixed between two conical radiopaque markers. Sixty-one patients eligible for angioplasty underwent direct stent implantation without predilatation. Four procedures were performed for acute myocardial infarction, and two as high-risk PTCA. Single slotted-tube stents (Palmaz-Schatz, NIR, or JOStent) of 14-16-mm length were mounted between the conical radiopaque markers of a special balloon which provided a fixation for the crimped stent. The direct implantation was successful in 80% of all patients, while in 10% the stent could be deployed after predilatation of the lesion. In 10% of lesions a stent could not be implanted with this and any other delivery system. When patients with successful direct stenting were compared with those with indirect (after predilatation) or unsuccessful stent deployment, the presence of angiographically visible calcification was higher in the unsuccessful cases (75% vs. 19%; P < 0.01), and the patients were older (72+/-8 vs. 61+/-12 years; P < 0.01). Radiation exposure time was only 8.7+/-5.1 min as compared with 12.6+/-7.6 min in conventional stent procedures with predilatation (P < 0.05). The number of balloons used per lesion was also lower than with conventional stenting. Stent dislocation was observed in 5%, and no embolization occurred. The new therapeutic approach of direct stenting without predilatation proved to be a safe and successful procedure in this initial series of coronary angioplasties. When calcified coronary lesions are avoided, it provides a way to rationalize stent implantation with shorter radiation exposure times, fewer balloons, and the potential advantage of fewer ischemic complications as no balloon predilatation is required.

Myocardial enterovirus infection with left ventricular dysfunction: A benign disease compared with idiopathic dilated cardiomyopathy

OBJECTIVES Endomyocardial biopsy samples from patients with idiopathic dilated cardiomyopathy were screened for the presence of enterovirus genome. Patients with enterovirus-positive samples were further studied with regard to disease course, histologic variables and response to interferon-alpha treatment. BACKGROUND Studies of patients with idiopathic dilated cardiomyopathy have reported widely divergent clinical outcomes, suggesting that there is no unique underlying pathogenetic mechanism. METHODS Five left ventricular endomyocardial biopsy samples were screened for the presence of the enterovirus genome by an established in situ hybridization technique in combination with a histologic, histomorphometric and immunohistologic workup. The course of the disease was then prospectively followed for up to 50 months. Virus-positive patients whose condition deteriorated were treated with interferon-alpha. RESULTS Of 77 patients, 20 (26%) had enterovirus-positive and 57 (74%) enterovirus-negative biopsy samples. During a mean follow-up period of 25.8 +/- 13.7 months, 1 patient in the enterovirus-positive group and 11 in the enterovirus-negative group died. Four patients in the enterovirus-negative group underwent heart transplantation (p < 0.05). The surviving 19 enterovirus-positive patients had a decrease in mean left ventricular end-diastolic diameter from 66 to 61 mm (p < 0.05) and a mean increase in left ventricular ejection fraction from 0.35 to 0.43 (p < 0.05). In contrast, enterovirus-negative patients had no significant change in end-diastolic diameter or left ventricular ejection fraction. Four patients in the enterovirus-positive group whose condition deteriorated were treated with a 6-month course of subcutaneous interferon-alpha (3 x 10(6) U every second day). This treatment induced hemodynamic improvement in all four patients and eliminated the persistent enteroviral infection in two. CONCLUSIONS Enterovirus-positive patients have a better heart transplantation-free survival rate and hemodynamic course, with fewer histologic changes, than do enterovirus-negative patients. In addition, enterovirus-positive patients respond favorably to interferon-alpha treatment. These observations indicate that myocardial enteroviral infection with associated left ventricular dysfunction is a distinct disease entity with a benign course.

Inhomogenous capillary flow and its prevention by verapamil and hydralazine in the cardiomyopathic Syrian hamster.

There is clinical evidence that human dilated cardiomyopathy is related to microcirculatory disorders. We used an experimental preparation of the disease that consisted of a study of the microcirculation of 45 cardiomyopathic Syrian and 18 control hamsters with timed plasma staining. To investigate dynamic vascular disorders a double injection technique was used that permitted demonstration of all permanently and temporarily perfused capillaries in the same animal. The results showed a total capillary density of 3423 +/- 470 capillaries/mm2 in the cardiomyopathic hamster during the premyocytolic phase (30 days of age) and that of 3289 +/- 506 capillaries/mm2 during the myocytolytic phase (44 days). These values were not significantly different from those in the control group (3349 +/- 473 capillaries/mm2 at 30 days and 3383 +/- 556 capillaries/mm2 at 44 days). However, tissue areas with extended coronary transit times were detected only in the cardiomyopathic hamsters. These areas were of the same individual and cumulative size at 30 days (diameter approximately 200 micron, 4% of the tissue) as the myocytolytic zones at 44 days. In cardiomyopathic hamsters verapamil and hydralazine prevented both hypoperfusion and myocytolysis. The results favor the view that microcirculatory disorders generate tissue damage in the cardiomyopathic hamster and that these disorders can be prevented through treatment with the calcium antagonist verapamil or with the vasodilator hydralazine.

Coxsackievirus Genome in Myocardium of Patients with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Enteroviruses are known as major infectious agents for inflammatory heart diseases such as myocarditis and dilated cardiomyopathy (DCM). Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by replacement of right ventricular myocardium by fatty and fibrous tissue. In about 65% of patients inflammatory infiltrates suggest an inflammatory or infectious etiopathogenesis. To test this hypothesis, we investigated endomyocardial biopsies of patients with ARVC, with myocarditis or DCM, and from patients with non-inflammatory cardiac disorders for the presence of enteroviral genome. Enteroviral RNA with homology to coxsackieviruses type B was detected in 3 of 8 patients with ARVC (37.5%), in 7 of 23 patients with myocarditis or DCM (30.4%), but in none of 5 patient with non-infectious myocardial diseases (p < 0.05 compared to ARVC patients). These results support earlier suggestions that coxsackievirus infection of the myocardium is possibly related to the pathogenesis of ARVC.

Doppler echocardiographic assessment of left ventricular filling in idiopathic dilated cardiomyopathy during a one-year follow-up: Relation to the clinical course of disease

In idiopathic dilated cardiomyopathy (IDC), an impaired left ventricular filling as assessed by the Doppler echocardiographic mitral flow pattern is closely related to the severity of congestive heart failure. This study examined the relation of left ventricular filling and the clinical course of the disease in patients with a recent diagnostic procedure and initiation of medical therapy (group 1, n = 15) as compared with patients in a chronic stage of the disease (group 2, n = 24) with the diagnosis established > 1 year before. All patients had to be in sinus rhythm to facilitate the Doppler echocardiographic evaluation of left ventricular filling. The clinical status was assessed by the New York Heart Association classification and a heart failure score at baseline and after a period of 12 +/- 7 months. At baseline the ratio of the peak early/atrial Doppler velocities (VE/VA) was shifted toward the early diastole in group 1 as compared to group 2 (1.84 +/- 1.02 vs 1.12 +/- 0.55; p < 0.05). Symptoms of heart failure were more severe in group 1. During follow-up, VE/VA tended to decrease in group 1 from 1.84 +/- 1.02 to 1.35 +/- 1.03 (p = 0.07) and remained unchanged in group 2 (1.12 +/- 0.55 and 1.34 +/- 1.23; not significant). In a subgroup of 10 patients who underwent repeat right heart catheterization, the decrease of VE/VA coincided with a decrease of the pulmonary capillary wedge pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of the Jak-Stat pathway in cells that exhibit selective sensitivity to the antiviral effects of IFN-beta compared with IFN-alpha.

We determined whether selective activation of components of the Jak-Stat pathway by different type I interferons (IFN) occurs in human myocardial fibroblasts that exhibit much higher sensitivity to the antiviral effects of IFN-beta than of IFN-alpha. Similar levels of activation of the Tyk2 kinase and the Stat3 transcription factor were induced in response to either IFN-beta or IFN-alpha treatment. However, activation of the Jak1 tyrosine kinase was detectable only in IFN-beta-treated but not IFN-alpha-treated cells. Consistent with this, tyrosine phosphorylation of Stat1 and Stat2 and formation of the IFN-stimulated gene factor 3 (ISGF3) complex occurred to a much higher degree in response to IFN-beta stimulation. These findings demonstrate that differential activation of distinct components of the Jak-Stat pathway by different type I IFN can occur. Furthermore, they strongly suggest that such selective activation accounts for the occurrence of differences in the antiviral properties of distinct type I IFN in certain cell types.

Beneficial effects of long-term diltiazem treatment in dilated cardiomyopathy☆☆☆

There is increasing evidence that chronic enhanced exogenous or endogenous catecholamine stimulation in patients with dilated cardiomyopathy may worsen hemodynamic status and prognosis. The cause of this deterioration may lie in myocellular calcium accumulation and microcirculatory disorders. In a prospective study, the calcium channel antagonist diltiazem was given to 22 patients with dilated cardiomyopathy (60 to 90 mg three times daily) in addition to conventional therapy of digitalis, diuretics and vasodilators. Twenty-five patients received the conventional therapy and served as historical controls. Eight additional patients who were not originally included in this control group received adjunctive diltiazem treatment after initially receiving conventional therapy alone. The three patient groups were similar in all hemodynamic and anamnestic features. Only patients with reduced myofibrillar volume fraction on myocardial biopsy were included in the trial, because they could be expected to show hemodynamic deterioration. The mean survival time was 29 months in the control group, whereas no patient in the diltiazem group died over a mean follow-up period of 15.4 months (p less than 0.001). Mean left ventricular ejection fraction increased from 0.34 to 0.44 (p less than 0.001) and New York Heart Association functional class improved significantly in the diltiazem group and during the diltiazem period in the crossover patients, but deteriorated in the control group. The results suggest that adjunctive diltiazem treatment in dilated cardiomyopathy has beneficial effects on mortality, hemodynamics and symptoms.

Need for Active Left-Ventricular Decompression during Percutaneous Cardiopulmonary Support in Cardiac Arrest

During ventricular fibrillation, myocardial hemodynamic and metabolic effects of percutaneous cardiopulmonary support (PCPS) were analyzed in 11 adult sheep (body weight 77-112 kg). During supported fibrillation, an abrupt increase in left-ventricular pressures with alignment to aortic pressures was observed in 2 animals, which was probably due to spontaneous aortic regurgitation, and resulted in deterioration of coronary perfusion. In 9 animals, left-ventricular pressures rose from 22.9 +/- 4.9 to 31.2 +/- 7.9 mm Hg elevating left ventricular wall stress from 16,750 +/- 8,745 to 28,835 +/- 8,892 dyn/cm2 after 10 min of PCPS-supported fibrillation (mean flow rate 4.5 +/- 0.7 liters/min). Simultaneously, myocardial perfusion pressures decreased from an average of 32.4 +/- 11.7 to 22.3 +/- 9.4 mm Hg and myocardial lactate release was observed. Additional transapical LV venting using a 9-Fr catheter led to a decrease in both LV pressure (to 25.7 +/- 5.3 mm Hg) and wall stress (to 20,612 +/- 7,499 dyn/cm2). Left-ventricular decompression decreased myocardial oxygen consumption (from 5.3 +/- 1.4 to 4.8 +/- 0.9 ml/min.100 g), and reduced myocardial lactate release, which indicates myocardial protection. Protective effects were most pronounced using 12-Fr-, and 21-Fr-venting cannulas (with 21 Fr: decrease in myocardial oxygen consumption to 2.7 +/- 0.6 ml/min.100 g, and reversal of myocardial lactate release to lactate uptake during fibrillation). Conclusions. Hemodynamic and metabolic data clearly demonstrate the deleterious effects of PCPS to the unvented left ventricle during cardiac arrest. The results emphasize the need for active left-ventricular decompression during PCPS in ventricular fibrillation.