Parvovirus B19 in Endomyocardial Biopsy of Patients With Idiopathic Dilated Cardiomyopathy: Foe or Bystander?

BACKGROUND: Parvovirus B19 (PVB19) has emerged as one of the viruses possibly inducing chronic myocarditis and subsequent idiopathic dilated cardiomyopathy (IDCM). The aim of this work was to investigate the presence and long-term consequences of PVB19-DNA within myocardial biopsies from patients with IDCM and to compare the findings with those from donor hearts (control group). METHODS AND RESULTS: Forty hospitalized IDCM patients (age 47 ± 12 y) with mean left ventricular ejection fraction 27 ± 12% were included. The presence of PVB19-DNA in myocardial biopsies and of IgG and IgM antibodies in patient sera was analyzed. The control group consisted of 20 donor hearts. The follow-up time was 112 ± 57 months. PVB19-DNA was found in myocardial biopsies of both patients (73%) and control samples (55%; P = .25).Three deaths and 8 heart transplantations occurred in the IDCM group, and 6 deaths in the control group (ie, the recipients of the control hearts). No difference in transplantation-free survival between the PVB19-DNA positive/negative IDCM patients or transplant recipients was found. CONCLUSIONS: PVB19-DNA is a common finding in both patients with IDCM and in healthy donor hearts, not affecting prognosis. These findings support the view that PVB19 is an innocent bystander, frequently found in myocardium with low DNA copies, and not a plausible cause of IDCM.

Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study.

In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6 ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10 ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4 mL/min (standard deviation [SD] 20.2 mL/min) versus 59.2 mL/min (SD 17.4 mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3 mL/min (95% CI 11.1-25.6 mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade ≥2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage.

Carotid artery remodelling in relation to body fat distribution, inflammation and sustained weight loss in obesity.

BACKGROUND: Obesity is known to be associated with carotid artery remodelling, but less is known about how body fat distribution, inflammation and weight loss may affect this relation. METHODS: Ultrasonography, dual-energy X-ray absorptiometry and computed tomography were performed to evaluate carotid artery intima-media thickness (IMT), body composition and fat distribution, respectively. Participants were divided into three matched study groups (n = 44 per group): obese patients with sustained weight loss 10 years after bariatric surgery [surgery group, body mass index (BMI) 31.5 kg m(-2)]; obese patients who maintained stable weight during the same time period (obese group, BMI 42.5 kg m(-2)); and normal weight subjects (lean group, BMI 24.4 kg m(-2)). RESULTS: Patients in the surgery group, compared with those in the obese group, had slightly lower common carotid artery (CCA) IMT (0.75 ± 0.18 vs. 0.78 ± 0.17 mm) and common carotid bulb (CCB) IMT (0.92 ± 0.32 vs. 0.97 ± 0.32 mm); however, these differences were not statistically significant. Lean individuals, compared with those in the surgery group, had significantly lower CCA and CCB IMT values (P < 0.001). In forward stepwise multiple regression analyses including all subjects (n = 132), CCA IMT was predicted mainly by visceral adipose tissue, but was also related to blood pressure and levels of triglycerides and high-sensitivity C-reactive protein. Carotid lumen diameter was primarily influenced by lean body mass. CONCLUSION: Visceral adiposity was the main determinant of premature carotid artery atherosclerosis, possibly through elevated blood pressure, dyslipidaemia and inflammation. Lean body mass predicted carotid artery lumen diameter. Obese patients with long-term sustained weight loss did not have thinner carotid artery walls compared with their weight-stable obese counterparts.

Self-reported sleep apnoea and mortality in patients from the Swedish Obese Subjects study.

Sleep apnoea is associated with increased mortality in sleep clinic and community population groups. It is unclear whether a clinical report of sleep apnoea results in additional mortality risk in patients with severe obesity. The Swedish Obese Subjects (SOS) study is a nonrandomised controlled trial of bariatric surgery versus conventional treatment for the treatment of severe obesity and its complications (mean ± SD body mass index 41 ± 5 kg · m(-2)). The presence or absence of sleep apnoea (witnessed pauses in breathing) was determined by self-reporting at baseline in 3,953 patients who were observed for 54,236 person-yrs (mean 13.5 maximum 21.0 yrs). Sleep apnoea was reported by 934 (23.6%) patients at baseline and was a significant univariate predictor of mortality (hazard ratio (95% CI) 1.74 (1.40-2.18)). In a range of multivariate models of mortality risk, controlling for ≤ 16 other potential confounders and established mortality risk factors, sleep apnoea remained a significant prognostic factor (fully adjusted model 1.29 (1.01-1.65)). Self-reported sleep apnoea is an independent prognostic marker of all-cause mortality in obese patients.

Relief of cardiorespiratory symptoms and increased physical activity after surgically induced weight loss: results from the Swedish Obese Subjects study.

BACKGROUND: Obese people frequently suffer from shortness of breath and chest discomfort on exertion, and they often have a sedentary lifestyle. In the present study of patients with severe obesity, we investigated the effects of surgically induced weight loss on cardiorespiratory symptoms and leisure-time physical activity. METHODS: The Swedish Obese Subjects study is an ongoing intervention trial of obesity consisting of 1 surgically treated group and 1 matched control group. Information on smoking habits, hypertension, diabetes, and sleep apnea was obtained from 1210 surgical cases and 1099 controls who were observed for 2 years. Patients were also asked about symptoms of breathlessness and chest pain and their levels of leisure-time physical activity. RESULTS: The surgically treated group displayed a mean weight loss of 28 kg (23%) compared with the control group in which the average weight remained unchanged (P<.001). The rates of hypertension, diabetes, and apneas during sleep decreased in surgical cases compared with controls (P<.001), while smoking habits remained largely the same. The surgical group also displayed highly significant improvements in dyspnea and chest pain and increases in physical activity compared with the control group (P<.001). The odds ratio for self-reported breathlessness, chest discomfort, or sedentary behavior after 2 years decreased progressively with the degree of weight loss. Furthermore, patients who recovered from apneas during sleep reduced their odds of having dyspnea and chest discomfort at follow-up, independent of changes in weight. CONCLUSIONS: Surgically induced weight loss in patients with severe obesity is associated with a marked relief in symptoms of dyspnea and chest pain and promotes increased leisure-time physical activity. Sleep-disordered breathing may be involved in the pathophysiology of breathlessness and chest discomfort in obese subjects.

Weight loss and progression of early atherosclerosis in the carotid artery: a four-year controlled study of obese subjects.

OBJECTIVE: To investigate the extent of carotid artery atherosclerosis in obese subjects and to examine the possible effects of weight loss on atherosclerotic development. DESIGN: Controlled 4 y intervention study. SUBJECTS: 20 obese patients treated with weight-reducing gastroplasty, 19 obese patients treated with dietary recommendations and 35 lean subjects. MEASUREMENTS: Body weight, blood pressure, blood lipids, glucose and insulin were measured. A B-mode ultrasound was recorded to determine the intima-media thickness (IMT) and lumen diameter (LD) of the carotid artery. Study groups were investigated at baseline and re-examined after 3 to 4 y of follow-up. RESULTS: At baseline, obese patients had higher blood pressure, serum total cholesterol, triglycerides, glucose and insulin compared with lean subjects; they also had a larger IMT in the carotid artery bulb (P<0.05) and a larger LD in the common carotid artery (P<0.01). After 4 y of follow-up, obese patients treated with surgery displayed a mean weight loss of 22 kg (19%), while the average weight in the obese control group remained unchanged (P<0.001). The weight loss group showed improvements in blood pressure, HDL-cholesterol, triglycerides and insulin compared with the obese control group (P<0.05). The progression rate of carotid bulb IMT in the weight loss group was similar to that observed in the lean control group (0.024 vs 0.025 mm/y, n.s.), whereas the IMT progression rate was almost three times higher in the obese control group (0.068 mm/y, P<0.05 compared with lean controls). CONCLUSION: Obese people have an unfavourable risk factor profile and signs of premature carotid artery atherosclerosis. Weight loss is followed by an improvement in several risk factors and may reduce the progression rate of atherosclerotic changes in the carotid artery bulb.

Heart rate variability in obesity and the effect of weight loss.

To investigate the effects of obesity and weight loss on cardiovascular autonomic function, we examined 28 obese patients referred for weight-reducing gastroplasty, 24 obese patients who received dietary recommendations, and 28 lean subjects. Body weight, blood pressure, and 24-hour urinary norepinephrine excretion were measured, and time and frequency domain indexes of heart rate variability (HRV) were obtained from 24-hour Holter recordings. A measure of long-term HRV, the SD of all normal RR intervals (SDANN), was used as an index of sympathetic activity and the high-frequency (HF) component of the frequency domain, reflecting short-term HRV, as an estimate of vagal activity. All 3 study groups were investigated at baseline, and the 2 obese groups were reexamined at 1-year follow-up. Obese patients had higher blood pressure, higher urinary norepinephrine excretion, and attenuated SDANN and HF values than lean subjects (p <0.01). Obese patients treated with surgery had a mean weight loss of 32 kg (28%), whereas the obese group treated with dietary recommendations remained weight stable (p <0.001). At follow-up the weight-loss group displayed decreases in blood pressure and norepinephrine excretion and showed increments in SDANN and HF values. These changes were significantly greater than those observed in the obese control group (p <0.05). Our findings suggest that obese patients have increased sympathetic activity and a withdrawal of vagal activity and that these autonomic disturbances improve after weight loss.

Effects of obesity and weight loss on left ventricular mass and relative wall thickness: survey and intervention study.

OBJECTIVES: To investigate the consequences of longstanding obesity on left ventricular mass and structure and to examine the effects of weight loss on these variables. DESIGN: Cross sectional survey and controlled intervention study. SETTING: City of Gothenburg and surrounding areas. Sweden. SUBJECTS: 41 obese patients treated with weight reducing gastric surgery, 31 obese patients treated conventionally, and 43 non-obese subjects. MAIN OUTCOME MEASURES: Changes in left ventricular mass and relative wall thickness. RESULTS: Obese patients had higher blood pressure, greater left ventricular mass, and increased relative wall thickness than did matched non-obese control subjects. Obese subjects treated with gastric surgery had a substantial weight loss and a significant reduction in all variables when compared with conventionally treated obese subjects. Univariate and multivariate analysis of pooled data from the two groups of obese subjects showed that changes in relative wall thickness and left ventricular mass were more closely related to the change in weight than to the concomitant change in blood pressure. CONCLUSIONS: Structural heart abnormalities occurring in conjunction with obesity diminish after weight loss. The regression in these structural aberrations is better predicted by the weight loss than by the accompanying reduction in blood pressure. To prevent or improve abnormalities of heart structure in obese people, weight control should be the primary goal; it should be regarded as at least as important as regulating blood pressure.