Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice.

BACKGROUND: Cardiac-specific JDP2 overexpression provokes ventricular dysfunction and atrial dilatation in mice. We performed in vivo studies on JDP2-overexpressing mice to investigate the impact of JDP2 on the predisposition to spontaneous atrial fibrillation (AF). METHODS: JDP2-overexpression was started by withdrawal of a doxycycline diet in 4-week-old mice. The spontaneous onset of AF was documented by ECG within 4 to 5 weeks of JDP2 overexpression. Gene expression was analyzed by real-time RT-PCR and Western blots. RESULTS: In atrial tissue of JDP2 mice, besides the 3.6-fold increase of JDP2 mRNA, no changes could be detected within one week of JDP2 overexpression. Atrial dilatation and hypertrophy, combined with elongated cardiomyocytes and fibrosis, became evident after 5 weeks of JDP2 overexpression. Electrocardiogram (ECG) recordings revealed prolonged PQ-intervals and broadened P-waves and QRS-complexes, as well as AV-blocks and paroxysmal AF. Furthermore, reductions were found in the atrial mRNA and protein level of the calcium-handling proteins NCX, Cav1.2 and RyR2, as well as of connexin40 mRNA. mRNA of the hypertrophic marker gene ANP, pro-inflammatory MCP1, as well as markers of immune cell infiltration (CD68, CD20) were increased in JDP2 mice. CONCLUSION: JDP2 is an important regulator of atrial calcium and immune homeostasis and is involved in the development of atrial conduction defects and arrhythmogenic substrates preceding paroxysmal AF.

Cheyne-stokes respiration during wakefulness in patients with chronic heart failure.

PURPOSE: Cheyne-Stokes respiration (CSR) during sleep has been studied extensively in patients with chronic heart failure (CHF). Prevalence and prognostic significance of CSR during wakefulness in CHF, however, are largely unknown. METHODS: CSR during wakefulness with an apnea-hypopnea cut-off ≥5/h and moderate to severe CSR with an apnea-hypopnea cutoff ≥15/h were analyzed using polysomnographic recordings in 267 patients with stable CHF with reduced left ventricular (LV) ejection fraction at our institution. Primary endpoint during follow-up was heart transplant-free survival. RESULTS: Fifty of 267 patients (19%) had CSR during wakefulness and 73 of 267 patients (27%) had CSR during sleep. CSR during wakefulness was associated with advanced age, atrial fibrillation, decreased LV ejection fraction, increased LV end-diastolic diameter, brain natriuretic peptide, New York Heart Failure class, and CSR during sleep. During 43 months mean follow-up, 67 patients (25%) died and 4 patients (1%) underwent heart transplantation. Multivariate Cox analysis identified age, male gender, chronic kidney disease, and LV ejection fraction as predictors of reduced transplant-free survival. CSR during wakefulness with an apnea-hypopnea cutoff ≥5/h as well as moderate to severe CSR while awake using an apnea-hypopnea cutoff ≥15/h did not predict reduced transplant-free survival independently from confounding factors. CONCLUSION: CSR during wakefulness appears to be a marker of heart failure severity.

Prognostic impact of central sleep apnea in patients with heart failure.

BACKGROUND: Central sleep apnea (CSA) is common in patients with heart failure (HF). Earlier studies investigating the influence of CSA on mortality in HF patients, however, have yielded contradictory results. METHODS AND RESULTS: In a prospective study involving 267 patients with left ventricular (LV) ejection fractions ≤50%, we performed polysomnography and compared heart transplant-free survival rates between patients with no or mild CSA (apnea-hypopnea index [AHI] ≤15/h) and those with moderate CSA (AHI 15.1-30/h) or severe CSA (AHI >30/h). During 43 ± 18 months' mean follow-up, 67 patients (25%) died and 4 patients (1%) underwent heart transplantation. Multivariate Cox analysis identified age, male sex, chronic kidney disease, and decreased LV ejection fraction, but not moderate CSA or severe CSA, as predictors of transplant-free survival. CONCLUSIONS: In patients with stable HF, moderate CSA as well as severe CSA do not appear to predict transplant-free survival independently from confounding factors.

Severe central sleep apnea is associated with atrial fibrillation in patients with left ventricular systolic dysfunction.

BACKGROUND: The results of previous studies investigating the association between atrial fibrillation (AF) and central sleep apnea (CSA) in patients with left ventricular (LV) systolic dysfunction are contradictory. METHODS: We prospectively enrolled 267 patients in this cross-sectional study with LV ejection fractions ≤50%, who were screened for sleep disordered breathing using cardiorespiratory polysomnography after patients with predominantly obstructive sleep apnea or insufficient sleep studies had been excluded. RESULTS: AF at study entry was found in 70 of 267 patients (26%). CSA with an apnea/hypopnea index (AHI) ≥15/hour was present in 116 patients (43%) and 67 patients (25%) had severe CSA with an AHI > 30/hour. Univariate analysis revealed a significant association between AF and severe CSA, age, male gender, arterial hypertension, left atrial diameter, brain natriuretic peptide, chronic kidney disease, New York Heart Association class, digitalis, and the lack of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Multivariate analysis revealed a significant association between AF and severe CSA (odds ratio [OR]: 5.21; 95% confidence interval [CI]: 1.67-16.27, P = 0.01), age (OR: 1.22 per 5-year increase; 95% CI: 1.05-1.40, P = 0.01), left atrial diameter (OR 1.61 per 5-mm increase; 95% CI: 1.22-2.01, P < 0.01), and digitalis (OR: 2.7; 95% CI: 1.26-5.79, P = 0.01). CONCLUSIONS: AF is associated with severe CSA but not with moderate CSA in addition to age, use of digitalis, and left atrial size in patients with LV systolic dysfunction. Future studies evaluating the potential benefit of adaptive servo-ventilation therapy to prevent AF or to decrease the AF burden in heart failure patients should therefore focus on patients with severe central sleep apnea.

Cardiac arrhythmias and sleep-disordered breathing in patients with heart failure.

The relationship between heart failure (HF), sleep-disordered breathing and cardiac arrhythmias is complex and poorly understood. Whereas the frequency of predominantly obstructive sleep apnea in HF patients is low and similar or moderately higher to that observed in the general population, central sleep apnea (CSA) has been observed in approximately 50% of HF patients, depending on the methods used to detect CSA and patient selection. Despite this high prevalence, it is still unclear whether CSA is merely a marker or an independent risk factor for an adverse prognosis in HF patients and whether CSA is associated with an increased risk for supraventricular as well as ventricular arrhythmias in HF patients. The current review focuses on the relationship between CSA and atrial fibrillation as the most common atrial arrhythmia in HF patients, and on the relationship between CSA and ventricular tachycardia and ventricular fibrillation as the most frequent cause of sudden cardiac death in HF patients.

Prognosis of pacing-dependent patients with cardiovascular implantable electronic devices.

BACKGROUND: Data on the prognostic significance of pacing dependency in patients with cardiovascular implantable electronic devices (CIEDs) are sparse. METHODS: The prognostic significance of pacing dependency defined as absence of an intrinsic rhythm ≥ 30 bpm was determined in 786 patients with CIEDs at the authors' institution using univariate and multivariate regression analysis to identify predictors of all-cause mortality. RESULTS: During 49 months median follow-up, death occurred in 63 of 130 patients with pacing dependency compared to 241 of 656 patients without pacing dependency (48% versus 37%, hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.02-1.78, P = 0.04). Using multivariate regression analysis, predictors of all-cause mortality included age (HR 1.07; 95% CI: 1.05-1.08, P < 0.01), history of atrial fibrillation (HR 1.32, 95% CI: 1.03-1.69, P < 0.01), chronic kidney disease (HR 1.28; 95% CI: 1.00-1.63, P = 0.048) and New York Heart Association (NYHA) class ≥ III (HR 2.00; 95% CI: 1.52-2.62, P < 0.01), but not pacing dependency (HR 1.15; 95% CI: 0.86-1.54, P = 0.35). CONCLUSIONS: In contrast to age, atrial fibrillation, chronic kidney disease and heart failure severity as indexed by NYHA functional class III or IV, pacing dependency does not appear to be an independent predictor of all-cause mortality in patients with CIEDs.

Left ventricular function improvement after prophylactic implantable cardioverter-defibrillator implantation in patients with non-ischaemic dilated cardiomyopathy.

AIMS: To assess the incidence and prognostic significance of left ventricular (LV) function improvement in patients with non-ischaemic dilated cardiomyopathy (DCM) and prophylactic implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: A total of 123 patients with DCM and echocardiographic follow-up assessments within 1 year after prophylactic ICD implant were retrospectively studied at our institution. All patients had New York Heart Association class II or III symptoms in the presence of a LV ejection fraction of 23 ± 6% (range: 9-35%) despite optimized medical therapy for at least 3 months prior to ICD implant. Left ventricular function improvement was defined as an increase of LV ejection fraction of more than 5% to more than 35% combined with a decrease LV end-diastolic diameter of at least 5 mm. Left ventricular function improvement after prophylactic ICD implant was found in 30 of 123 patients (24%). Multivariate logistic regression revealed recent onset DCM with symptoms ≤9 months as the only significant predictor of LV function improvement [odds ratio: 6.89; 95% confidence interval (CI): 2.43-21.99, P = 0.0002]. During 74 months mean follow-up, total mortality was higher in patients without vs. with LV function improvement [hazard ratio (HR): 3.75; 95% CI: 1.14-12.31, P = 0.0034], while the incidence of appropriate ICD therapies was similar in both groups in the early phase after prophylactic ICD implant (HR: 1.15; 95% CI: 0.57-2.33, P = 0.70). The incidence of appropriate ICD therapies decreased to ∼1% per year after LV function improvement had occurred. CONCLUSION: Recently diagnosed DCM predicts LV function improvement after prophylactic ICD implant. Overall survival was significantly better in patients with vs. without LV function improvement, while appropriate ICD therapy rates were similar in both groups in the early phase after prophylactic ICD implantation before LV function improvement occurred.

Sleep-disordered breathing in patients with implantable cardioverter-defibrillator.

AIMS: To assess the prognostic significance of screening for sleep-disordered breathing in patients with implantable cardioverter-defibrillator (ICD) with regard to appropriate ICD therapy and total mortality. METHODS AND RESULTS: Overnight sleep studies were performed in 204 ICD recipients not known to have sleep apnoea and with no history of daytime sleepiness. Sleep-disordered breathing was diagnosed in the presence of an apnoea-hypopnea index of five or more events per hour. Seventy patients (34%) had no sleep apnoea, 105 patients (51%) had central sleep apnoea, and 29 patients (14%) had obstructive sleep apnoea. During 38 ± 26 months follow-up, 80 patients (39%) received appropriate ICD therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF), and 54 patients (26%) died. On multivariate Cox regression analysis, age, left ventricular (LV) end-diastolic diameter, secondary prevention ICD indication, use of diuretics, and absence of aldosterone antagonist therapy but not sleep apnoea were associated with appropriate ICD therapy for VT or VF. In addition, multivariate Cox analysis identified age and LV ejection fraction but not sleep apnoea as predictors of total mortality. CONCLUSION: Undiagnosed sleep-disordered breathing is common in ICD recipients. The presence and severity of previously unknown sleep apnoea in ICD recipients, however, does not appear to be an independent predictor of appropriate ICD therapy or morality during follow-up.

Predictors of pacing-dependency in patients with cardiovascular implantable electronic devices.

BACKGROUND: Data on the prevalence and predictors for the development of pacing-dependency in patients with cardiovascular implantable electronic devices (CIEDs) are sparse. METHODS: Pacing-dependency defined as an absence of intrinsic rhythm of ≥ 30 bpm was determined in 802 consecutive patients with CIEDs who visited the documented pacemaker or implantable cardioverter- defibrillator outpatient clinic for routine follow-up. RESULTS: A total of 131 (16%) patients were found to be pacing-dependent 67 ± 70 months after CIED implant. Multivariate analysis revealed a significant association between pacing-dependency and the following clinical variables: second or third-degree atrioventricular (AV) block at implant (OR = 19.9; 95% CI: 10.9-38.5, p < 0.01), atrial fibrillation at implant (OR = 2.15; 95% CI: 1.16-4.05, p = 0.02), left ventricular ejection fraction (LVEF) ≤ 30% (OR = 2.06; 95% CI: 1.03-4.15, p = 0.04), B-type natriuretic peptide (BNP) > 150 pg/mL (OR = 2.12; 95% CI: 1.16-3.97, p = 0.02), chronic kidney disease (OR = 1.86; 95% CI: 1.08-3.26, p = 0.03), and follow-up duration after implantation > 5 years (OR = 3.29; 95% CI: 1.96-5.64, p < 0.01). None of the remaining clinical variables including age, gender, diabetes mellitus, underlying heart disease, prior cardiac surgery or medication during follow-up including betablockers and amiodarone predicted pacing-dependency. CONCLUSIONS: Pacing-dependency is associated with second or third-degree AV-block at implant, atrial fibrillation before implant, low LVEF, elevated BNP, chronic kidney disease and follow-up duration after implant.

Sleep-disordered breathing in recipients of implantable defibrillators.

STUDY OBJECTIVES: To examine the prevalence and clinical significance of sleep-disordered breathing in patients with implantable cardioverter defibrillators (ICD). METHODS AND RESULTS: Overnight sleep studies were performed in 129 ICD recipients who had no history of sleep apnea. The mean left ventricular ejection fraction (LVEF) was 29 +/- 11%. Mild, moderate, and severe sleep apnea was diagnosed in the presence of an apnea/hypopnea index (AHI) of 5-15/h, 15.1-30/h, and >30/h, respectively. No sleep apnea was present in 49 patients (38%), 57 (44%) had central sleep apnea (CSA), and 23 patients (18%) had obstructive sleep apnea (OSA). Mild, moderate, and severe sleep apnea were present in 25%, 31%, and 44% of patients with CSA, compared with 52%, 22%, and 26% of patients with OSA (P < 0.05). LVEF was similar in patients with versus without OSA or CSA. Patients with CSA were significantly older and had a higher prevalence of ischemic cardiomyopathy than patients without sleep apnea. CONCLUSIONS: Previously undiagnosed CSA is common in ICD recipients. Severely disordered breathing during sleep was more prevalent among patients with CSA than patients with OSA. This prospective, observational study will examine the long-term clinical significance of sleep-disordered breathing in ICD recipients.

[Cardiac memory following pacemaker implantation]. / Cardiac Memory nach Schrittmacherimplantation.

BACKGROUND: Although T wave inversions due to cardiac memory were described already 50 years ago, little is known about the prevalence and about clinical predictors of this phenomenon. METHODS: After exclusion of 238 patients due to bundle branch block or pacemaker dependency, a total of 325 consecutive patients were enrolled in this study during routine outpatient control of their pacemaker. A 12-lead standard ECG was obtained in all patients during transient inhibition of pacing therapy. RESULTS: Cardiac memory could be documented in 115 of 325 patients (35%) and showed a strong association with the amount of ventricular stimulation. The prevalence of cardiac memory was 9% in patients with ≤25% ventricular stimulation and 86% in patients with ≥75% ventricular stimulation. DISCUSSION: Cardiac memory was observed in one third of patients following pacemaker implantation. The prevalence of cardiac memory in the ECG with intrinsic rhythm is above 80% in patients with frequent ventricular stimulation. Cardiac memory due to ventricular stimulation is benign and should not be confused with similar T wave inversions due to acute coronary syndrome, severe left ventricular hypertrophy, or myocarditis.

B-type natriuretic peptide levels predict event-free survival in patients with implantable cardioverter defibrillators.

INTRODUCTION: We examined whether B-type natriuretic peptide (BNP) levels predict outcome in heart failure patients with implantable cardioverter defibrillators (ICD) using a combined endpoint of malignant tachyarrhythmias, death or heart transplantation. METHODS AND RESULTS: BNP levels were measured in 123 ICD patients with chronic heart failure (age: 63+/-12 years, ejection fraction: 29+/-10%). After a median follow-up of 25 months, the combined endpoint was reached in 28 patients (first tachyarrhythmic event, n=16; death, n=11; heart transplantation, n=1). BNP levels were significantly lower in patients with event-free survival compared to patients reaching the combined endpoint of this study (median: 140 vs. 373 pg/ml; p<0.001). Multivariable Cox regression analysis revealed that BNP levels predict adverse outcome (RR 1.002 per pg/ml increment; 95% CI: 1.001-1.003; p<0.001) and use of beta-blockers was associated with favourable outcome (RR 0.319; 95% CI 0.151-0.670; p=0.004). LV ejection fraction (p=0.66) did not significantly predict event-free survival in multivariable analysis. CONCLUSIONS: BNP plasma levels are useful markers to predict event-free survival in ICD patients with heart failure. Of note, malignant tachyarrhythmias appear responsible for about 50% of fatal outcomes. Our findings suggest that determination of BNP plasma levels is more valuable than determining LV ejection fraction to anticipate event-free survival in this population.

Heart rate variability in patients with cardiac hypertrophy--relation to left ventricular mass and etiology.

BACKGROUND: Decreased heart rate variability (HRV) has been shown to reflect disturbances of the autonomic nervous system that is related to increased cardiovascular mortality. Most studies investigated HRV in patients with systolic left ventricular dysfunction due to remote myocardial infarction or dilated cardiomyopathy. To date, only few data are available on HRV in patients with predominant diastolic dysfunction in the presence of cardiac hypertrophy of different etiologies. METHODS: Time domain analysis of HRV was performed from digital 24-hour Holter electrocardiogram recordings in 86 patients with sinus rhythm and cardiac hypertrophy, which was due to aortic valve stenosis in 33 patients, hypertrophic cardiomyopathy in 29 patients, and hypertensive heart disease in 24 patients. Heart rate variability analysis was compared with 91 healthy controls. RESULTS: The SD of all normal-to-normal R-R intervals (SDNN) was reduced in patients with aortic valve stenosis, hypertrophic cardiomyopathy, and hypertensive heart disease when compared with controls (SDNN 119 +/- 42 vs 154 +/- 36 milliseconds, P < .001). The extent of cardiac hypertrophy indexed by echocardiography based left ventricular mass calculation and increased patient age were independent predictors for depression of SDNN. CONCLUSIONS: Cardiac hypertrophy of various etiologies is related to decreased HRV on 24-hour Holter electrocardiogram. Both the patient age and the extent of left ventricular hypertrophy are independently associated with depression of HRV. These findings are independent of the cause of cardiac hypertrophy. The significance of these findings remains to be determined by future studies.

Effects of synthetic progestagens on autonomic tone, neurohormones and C-reactive protein levels in young healthy females in reproductive age.

BACKGROUND: Heart rate variability and baroreceptor sensitivity are measures of autonomic control. While progestagen-containing replacement therapy in postmenopausal women adversely affects autonomic balance, the impact of hormonal contraceptives with synthetic progestagens on autonomic activity, neurohormones and C-reactive protein levels is not well characterized. METHODS AND RESULTS: We analyzed parameters of heart rate variability and baroreceptor sensitivity in young healthy females without (n = 27) or on oral contraceptives with synthetic progestagens (n = 31). Demographic characteristics were not different among the examined groups. Total power (controls: 5682+/-3618 vs. hormones: 4800+/-2957 ms2; NS), standard deviation of beat-to-beat intervals (SDNN; 66+/-24 vs. 63+/-20 ms; p = 0.74), other time- and frequency-dependent parameters of heart rate variability and baroreceptor sensitivity (6.0+/-3.2 vs. 6.5+/-2.7 ms/mm Hg; NS) were not significantly different among the groups. Total cholesterol and triglyceride as well as C-reactive protein (CRP) levels were significantly higher in users of hormonal contraceptives than in non-users (cholesterol: 187+/-37 vs. 166+/-28 mg/dL; p = 0.05; triglycerides: 110+/-35 vs. 68+/-30 mg/dL; p = 0.01; CRP: 2.7+/-2.1 vs. 1.0+/-1.4 mg/L; p < 0.001). Heart rate variability, baroreceptor sensitivity, lipid parameters and CRP levels were not affected during the ovarian cycle in non-users of hormonal contraception. CONCLUSIONS: The use of oral contraceptives containing synthetic progestagens was not associated with a modulation of autonomic tone, while lipid parameters and CRP levels were adversely affected. These data suggest that synthetic progestagens in modern oral contraceptives do not modulate the autonomic balance, but probably affect the atherogenic risk profile of young females in reproductive age.

[Multiple inappropriate defibrillator shocks due to insulation failure of a Biotronik Linox defibrillator lead with externalized conductor]. / Multiple inadäquate Defibrillatorschocks bei Isolationsdefekt einer Biotronik-Linox®-Defibrillatorelektrode mit externalisiertem Leiter.

In this article the case of a patient who received a total of 35 inappropriate defibrillator shocks due to insulation failure with externalized conductor of a Biotronik Linox® lead is described. The implanted defibrillator was immediately inactivated and the failed lead was extracted using a laser sheath system.

Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study.

BACKGROUND: Arrhythmia risk stratification with regard to prophylactic implantable cardioverter-defibrillator therapy is a completely unsolved issue in idiopathic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Arrhythmia risk stratification was performed prospectively in 343 patients with IDC, including analysis of left ventricular (LV) ejection fraction and size by echocardiography, signal-averaged ECG, arrhythmias on Holter ECG, QTc dispersion, heart rate variability, baroreflex sensitivity, and microvolt T-wave alternans. During 52+/-21 months of follow-up, major arrhythmic events, defined as sustained ventricular tachycardia, ventricular fibrillation, or sudden death, occurred in 46 patients (13%). On multivariate analysis, LV ejection fraction was the only significant arrhythmia risk predictor in patients with sinus rhythm, with a relative risk of 2.3 per 10% decrease of ejection fraction (95% CI, 1.5 to 3.3; P=0.0001). Nonsustained ventricular tachycardia on Holter was associated with a trend toward higher arrhythmia risk (RR, 1.7; 95% CI, 0.9 to 3.3; P=0.11), whereas beta-blocker therapy was associated with a trend toward lower arrhythmia risk (RR, 0.6; 95% CI, 0.3 to 1.2; P=0.13). In patients with atrial fibrillation, multivariate Cox analysis also identified LV ejection fraction and absence of beta-blocker therapy as the only significant arrhythmia risk predictors. CONCLUSIONS: Reduced LV ejection fraction and lack of beta-blocker use are important arrhythmia risk predictors in IDC, whereas signal-averaged ECG, baroreflex sensitivity, heart rate variability, and T-wave alternans do not seem to be helpful for arrhythmia risk stratification. These findings have important implications for the design of future studies evaluating prophylactic implantable cardioverter-defibrillator therapy in IDC.

Implantable defibrillator event rates in patients with idiopathic dilated cardiomyopathy, nonsustained ventricular tachycardia on Holter and a left ventricular ejection fraction below 30%.

OBJECTIVES: This study investigated the incidence of appropriate implantable cardioverter defibrillator (ICD) interventions for ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with idiopathic dilated cardiomyopathy (IDC) and nonsustained VT in the presence of a left ventricular ejection fraction below 30%, versus in patients with syncope and patients with a history of VT or VF. BACKGROUND: To date, only limited information is available about the prophylactic use of ICDs in patients with IDC. METHODS: From January 1993 to July 2000, 101 patients with IDC underwent implantation of ICDs with electrogram storage capability at our institution. Patients were placed into one of three groups according to their clinical presentation: asymptomatic or mildly symptomatic nonsustained VT in the presence of a left ventricular ejection fraction < or = 30% (49 patients, prophylactic group), unexplained syncope or near syncope (26 patients, syncope group) and a history of sustained VT or VF (26 patients, VT/VF group). RESULTS: During 36 +/- 22 months follow-up, 18 of 49 patients (37%) in the prophylactic group received appropriate shocks for VT or VF, compared with 8 of 26 patients (31%) in the syncope group and with 9 of 26 patients (35%) of the VT/VF group. Multivariate Cox analysis of baseline clinical variables identified left ventricular ejection fraction, atrial fibrillation and a history of sustained VT or VF as predictors for appropriate ICD interventions during follow-up. CONCLUSIONS: Patients with IDC and prophylactic ICD implantation for nonsustained VT in the presence of a left ventricular ejection fraction < or = 30% had an incidence of appropriate ICD interventions similar to that of patients with a history of syncope or sustained VT or VF. These findings indicate that ICDs may have a role in not only secondary but also primary prevention of sudden death in IDC.

Prognostic significance of morphometric endomyocardial biopsy analysis in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: To date, considerable controversy exists on the prognostic significance of morphometric endomyocardial biopsy findings in patients with idiopathic dilated cardiomyopathy (IDC). METHODS: Quantitative analyses of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters of left ventricular endomyocardial biopsy specimens were performed in 124 patients with IDC. RESULTS: During 51 +/- 22 months follow-up after left ventricular endomyocardial biopsy, major arrhythmic events, defined as sustained ventricular tachycardia (VT), ventricular fibrillation (VF), or sudden cardiac death, were observed in 24 patients (19%). Death from any cause or heart transplant was observed in 39 patients (31%). The amount of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters determined from left ventricular endomyocardial biopsy specimens did not differ significantly between patients with and patients without major arrhythmic events or between patients with and patients without transplant-free survival during follow-up. CONCLUSIONS: Quantitative analysis of the amount of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters in left ventricular endomyocardial biopsy specimens does not appear to be useful for predicting arrhythmic events and transplant-free survival in IDC.

Effects of a weight reduction program with and without aerobic exercise in the metabolic syndrome.

BACKGROUND: In the setting of a rural, primary care practice, evidence for the efficacy of intentional weight loss with or without aerobic exercise training (AET) in hypertensive patients with the metabolic syndrome remains controversial. DESIGN OF STUDY, METHODS: We analysed data of 52 hypertensives with the metabolic syndrome, who attended a weight management program with or without AET (diet/exercise group, n = 18; diet group, n = 20) for 36 months. Patients with a similar risk profile, who declined antihypertensive therapy beyond ACE inhibition, served as controls (n = 14). RESULTS: Body mass index (BMI) was significantly reduced over time in the diet and diet/exercise group (DeltaBMI: -7.2 +/- 1.1 and -6.6 +/- 1.5 kg/m2) vs. the control group (DeltaBMI: +0.4 +/- 1.3 kg/m2; p < 0.001 at 36 m). While systolic and diastolic blood pressures (BPs) did not change over time in controls (175 +/- 5/89 +/- 7 mm Hg), BPs were significantly reduced in the diet group (151 +/- 8/75 +/- 10 mm Hg) and in the diet/exercise group (139 +/- 12/71 +/- 8 mm Hg; p < 0.001 vs. diet group). Metabolic abnormalities were significantly improved over time in the diet group vs. controls, while AET did not add further benefits. However, heart rate recovery after acute exercise was improved and body cell mass (BCM) was increased in the diet/exercise group vs. patients without AET (p < 0.001 vs. others). CONCLUSIONS: Weight management significantly improves the lipid and nonlipid abnormalities of the metabolic syndrome, which is associated with reduced blood pressure. Addition of AET does not add further benefits on metabolic parameters, but improves blood pressure regulation. Effective lifestyle modifications are feasible even in the setting of a rural practice.

Daytime sleepiness in patients with obstructive sleep apnea and severe obesity: prevalence, predictors, and therapy.

BACKGROUND: We sought to determine prevalence and predictors of excessive daytime sleepiness in patients with severe obesity with a body mass index (BMI) > 35 kg/m(2) and obstructive sleep apnea (OSA) with an apnea-hypopnea index > 15/h. METHODS: The study population consisted of 245 obese OSA patients with a BMI > 35 kg/m(2), who were retrospectively recruited from 3256 consecutive patients who underwent polysomnography at our sleep laboratory between 2006 and 2009. Baseline clinical characteristics and polysomnography results of these 245 patients were compared between patients with and without excessive daytime sleepiness, which was diagnosed in the presence of an Epworth Sleepiness Scale score (ESS) ≥ 11. RESULTS: A total of 123 of 245 study patients (50.2 %) had an ESS ≥ 11. Patients with an ESS ≥ 11 were younger and less often unemployed or retired compared with patients with an ESS < 11. Polysomnography revealed a longer total sleep time (TST), higher sleep efficiency, and shorter sleep latency in patients with ESS ≥ 11. In addition, obstructive apneas during TST as well as oxygen saturations < 80 % occurred significantly more often in patients with versus without an ESS ≥ 11. Improvement of daytime sleepiness after initiation of continuous positive airway pressure (CPAP) therapy occurred more often in patients with versus without ESS ≥ 11 (93 versus 73 %, p < 0.01). CONCLUSION: Obese patients with OSA and excessive daytime sleepiness are characterized by younger age, longer TSTs, more frequent obstructive apneas, and oxygen desaturations < 80 % compared with patients without excessive daytime sleepiness. Excessive daytime sleepiness can be improved in more than 90 % of patients using CPAP therapy.