The effects of cardiac resynchronization therapy on left ventricular function, myocardial energetics, and metabolic reserve in patients with dilated cardiomyopathy and heart failure

OBJECTIVES: The effects of long-term cardiac resynchronization therapy (CRT) on left ventricular (LV) energetics and metabolic reserve were evaluated. BACKGROUND: Cardiac resynchronization therapy is a new therapy for patients with drug-refractory severe heart failure (HF). METHODS: Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of biventricular pacemaker 8 +/- 5 months earlier were studied during two conditions: CRT switched on, and after CRT was switched off for 24 h. Left ventricular function was measured using echocardiography and oxidative metabolism using [(11)C]acetate positron emission tomography. Both measurements were performed at rest and during dobutamine-induced stress (5 microg/kg/min). Basal- and adenosine-stimulated (140 microg/kg/min) myocardial blood flow were quantitated using [(15)O]water. RESULTS: During CRT off, LV stroke volume was significantly reduced at rest (72 +/- 18 ml vs. 63 +/- 15 ml, p < 0.05), but LV oxidative metabolism (K(mono)) remained unchanged (0.046 +/- 0.008 vs. 0.054 +/- 0.016 min(-1)) leading to a significant deterioration of myocardial efficiency of forward work (from 48.2 +/- 16.7 to 36.6 +/- 11.7 mm Hg.l/g, p < 0.05). During dobutamine-induced stress, stroke volume and K(mono) values were not different whether CRT was on or off. However, myocardial efficiency (56.1 +/- 16.1 vs. 49.8 +/- 18.0 mm Hg.ml.g(-1).min(-1), p = 0.099) and metabolic reserve, the response of K(mono) to dobutamine (0.023 +/- 0.014 vs. 0.013 +/- 0.014 min(-1), p = 0.09), tended to reduce when CRT was switched off. Cardiac resynchronization therapy had no effects on myocardial perfusion. Natriuretic peptides increased significantly during CRT-off period. CONCLUSIONS: Long-term CRT has beneficial effects on LV function and myocardial efficiency at rest in patients with HF. These effects are not associated with changes in myocardial perfusion or oxygen consumption. During dobutamine-induced stress, CRT does not affect functional parameters, but myocardial efficiency and metabolic reserve may be increased.     

Acute Kidney Injury Following Aortic Valve Replacement in Patients Without Chronic Kidney Disease

BackgroundThe data on acute kidney injury (AKI) in patients without chronic kidney disease (CKD) after transcatheter aortic valve replacement (TAVR) are limited. The study sought to compare the incidence of AKI and its impact on 5-year mortality after TAVR and surgical aortic valve replacement (SAVR) in patients without CKD.MethodsThis registry included data from 6463 consecutive patients who underwent TAVR or SAVR. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. For sensitivity analysis, propensity-score matching between TAVR and SAVR was performed.ResultsThe study included 4555 consecutive patients (TAVR, n = 1215 and SAVR, n = 3340) without CKD. Propensity-score matching identified 542 pairs. Patients who underwent TAVR had a significantly lower incidence of AKI in comparison to those who underwent SAVR (unmatched 4.7% vs 16.4%, P < 0.001, multivariable analysis: odds ratio, 0.29, 95% confidence interval [CI], 0.20-0.41; matched 5.9% vs 19.0%, P < 0.001). Patients with AKI had significantly increased 5-year mortality compared with those without AKI (unmatched 36.0% vs 19.1%, log-rank P < 0.001; matched 36.3% vs 24.0%, log-rank P < 0.001). The adjusted hazard ratios for 5-year mortality were 1.58 (95% CI, 1.20-2.08) for AKI grade 1, 3.27 (95% CI, 2.09-5.06) for grade 2, and 4.82 (95% CI, 2.93-8.04) for grade 3.ConclusionsTAVR in patients without CKD was associated with a significantly less frequent incidence of AKI compared with SAVR. AKI significantly increased the risk of 5-year mortality after either TAVR or SAVR, and increasing severity of AKI was incrementally associated with 5-year mortality.     

Fractal correlation properties of R-R interval dynamics in asymptomatic relatives of patients with dilated cardiomyopathy

BACKGROUND AND AIM: asymptomatic relatives of patients with familial dilated cardiomyopathy who have left ventricular enlargement [LVE] are at risk for progression to dilated cardiomyopathy. A novel index of the fractal correlation properties of heart rate variability (HRV), the short-term scaling component (proportional, variant(1)) in detrended fluctuation analysis, is a promising prognostic tool in left ventricular dysfunction. The aim of this study was to compare values of proportional, variant(1) and conventional HRV indices in LVE relatives with dilated cardiomyopathy patients and normal controls. METHODS: time-domain and spectral HRV measures, and the short-term scaling component ( proportional, variant(1)) were assessed from 24-h Holter recordings from 22 LVE relatives (left ventricular end-diastolic dimension >112% predicted, normal fractional shortening), 24 dilated cardiomyopathy patients and 14 controls. RESULTS: the time domain index SDNN was lower in dilated cardiomyopathy patients [101.8(+/-44.0)] than in LVE relatives [161.7(+/-53.9)] or controls [152.9(+/-51.4)], P=0.01. Similarly, triangular index and spectral measures were reduced in dilated cardiomyopathy patients but not in LVE relatives or controls. In contrast, the short term scaling component ( proportional, variant(1)) in detrended fluctuation analysis was reduced in both dilated cardiomyopathy patients [1.06(+/-0.33)] and in LVE relatives [1.15 (+/-0.20)], compared with controls [1.32(+/-0.16)], P=0.01. Among DCM patients the short-term scaling component ( proportional, variant(1)) was significantly associated with echocardiographic deterioration during follow-up (3.7+/-2.1 year) (P=0.004). CONCLUSION: the short-term scaling component ( proportional, variant(1)) is reduced in asymptomatic relatives of dilated cardiomyopathy patients who have LVE.     

Determinants of bronchial responsiveness at school age in prematurely born children

The bronchial challenge test using isocapnic hyperventilation of cold air (IHCA) was used to evaluate bronchial responsiveness in 63 offspring of multiple pregnancies when they were 8-15 years old. At birth, 27 (43%) children had had intrauterine growth retardation (IUGR, birth weight <-2 SD, or birth weight difference between twin pairs >1.3 SD). The median birth weight was 2,050 g (range, 800-3, 150), and the median gestational age was 35 weeks (range, 28-38). None of the children had asthma or suffered from asthma-like symptoms. In the interpretation of the IHCA test, a fall of 9% or more in the forced expiratory volume in 1 sec (FEV(1)) was considered as abnormal, and these children were classified as "cold air responders." The number of responders was 16 (25%); their baseline FEV(1)/forced vital capacity ratio (FEV(1)/FVC) and forced expiratory flow between 25-75% FVC (FEF(25-75)), but not FEV(1) were significantly lower than the corresponding values in nonresponders. No differences were found in perinatal or neonatal factors between responders or nonresponders. Eight (30%) of the 27 IUGR and 8 (22%) of the 36 appropriate for gestational age (AGA) children were IHCA responders. In particular, IUGR was not correlated with maximal FEV(1) falls following the IHCA test. Respiratory infections after the neonatal period were equally common in IUGR and AGA children; but infections were associated with subsequent IHCA responsiveness. Adenoidectomy, tonsillectomy, and/or myringotomy had been performed significantly more often in the responders than in the nonresponders. At least one of the above invasive procedures had been performed in 20 (32%) of the children; this group was termed the "ENT (ear, nose, throat) surgery group." Fifty-six percent of the responders, but only 26% of the nonresponders, belonged to the ENT surgery group (P = 0.02). We conclude that intrauterine growth retardation or prematurity is not associated with abnormal cold air responsiveness in the IHCA test.     

Concentrations of metronidazole and tinidazole in female reproductive organs after a single intravenous infusion and after repeated oral administration

Summary Concentrations of metronidazole and tinidazole in serum and gynecological organs were analyzed after a single 500 mg intravenous infusion and after three days of treatment with 400 mg t.i.d. of metronidazole or 500 mg b.i.d. of tinidazole. The studies were performed in 67 patients subjected to hysterectomy and/or oophorectomy because of myomatosis uteri, carcinoma uteri or endometriosis. At the time of organ removal (about 30 min after infusion), metronidazole and tinidazole levels in serum were 14.5 ± 0.45 mg/l and 12.3 ± 0.38 mg/l, respectively. Concentrations of both drugs in the uterus and Fallopian tube were about the same as the simultaneous serum levels and concentrations in the ovaries about 55% thereof. At steady-state, the concentrations of tinidazole in serum (23.5 ± 1.0 mg/l) were remarkably higher than those of metronidazole (13.5 ± 0.84 mg/l) about three hours after the last oral dose. Drug concentrations in organs of the female reproductive tract were 70 to 100% those of the simultaneous serum levels.

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Konzentrationen von Metronidazol und Tinidazol in weiblichen Genitalorganen nach intravenöser Einzelinfusion und wiederholter oraler Gabe

Zusammenfassung Die Konzentrationen von Metronidazol und Tinidazol in Serum und Genitalorganen wurden nach einer intravenösen Einzelinfusion von 500 mg sowie nach dreitägiger oraler Behandlung mit 400 mg Metronidazol dreimal täglich oder 500 mg Tinidazol, zweimal täglich, bestimmt. Die Untersuchungen wurden bei 67 Patientinnen durchgeführt, bei denen eine Hysterektomie und/oder Oophorektomie wegen Myomatosis uteri, Uteruskarzinom oder Endometriose vorgenommen wurde. Zum Zeitpunkt der Organentnahme (etwa 30 min nach Infusion) betrugen die Metronidazol-und Tinidazolspiegel im Serum 14,5 ± 0,45 mg/l bzw. 12,3 ± 0,38 mg/l. Die Konzentrationen der beiden Medikamente im Uterus und in der Tube entsprachen den gleichzeitig bestimmten Serumspiegeln; die Konzentrationen in den Ovarien lagen bei etwa 55% der Serumspiegel. Im Steady state, etwa drei Stunden nach der letzten oralen Dosis, waren die Serumkonzentrationen von Tinidazol mit 23,5 ± 1,0 mg/l erheblich höher als die Metronidazolserumspiegel (13,5 ± 0,84 mg/l). Die Konzentrationen der Medikamente in den weiblichen Genitalorganen lagen bei 70 bis 100% der simultanen Serumspiegel.

     

Use of hospitals at age 90. A population-based study

People live longer than ever before, and the rapidly growing population of the oldest-old are increasingly frequent users of health care services. To determine the extent and causes of hospital care in the population aged 90, we examined the hospital discharge registers for the annual cohorts of Tampere residents born in 1907-1910 at age 90. The basic population consisted of 1077 people, 20.6% of who were men and 79.4% women. Close on one-fifth or 18.7% of this group died during the year under review. During this year, 43.2% of men and 50.3% of women had been admitted to hospital. Men spent significantly fewer days in hospital than women: the mean length of stay for men was 19 days, for women 46 days. Of the 90-year olds, 6.7% were permanently staying in hospitals. The most common diagnoses at discharge were cardiovascular diseases, infections, psychiatric diseases including dementia, and trauma. Of those who had been admitted to hospital once or more within the year, 31.7% died during the follow-up time, while the figure for those not admitted was only 6.2%. People aged 90 are an important group of hospital users. In the future, hospitals need to be prepared to provide adequate care for the most common diseases affecting the growing population of the oldest-old.     

Frequency of hereditary nonpolyposis colorectal cancer

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome characterized by early onset of colorectal carcinomas (CRC). Recently, two HNPCC genes have been mapped and cloned, one in the short arm of chromosome 2 and another in the short arm of chromosome 3. There has been a major controversy about the frequency of HNPCC. The few estimates available have been based on series selected by age or series representing local area. The purpose of the present study was to design a nonselected, prospective, multicenter study, taking into account the family background and other risk factors of CRC. METHODS: The proportion of HNPCC of all (N=406) CRC cases was evaluated in a prospective multicenter study. Family history and other risk factors were investigated over a 12-month period for all new CRC patients in ten hospitals. These cases constituted 23 percent of all CRCs diagnosed in Finland during the study period. RESULTS: Three (0.7 percent) cases of verified and seven (1.7 percent) cases of suspected HNPCC were identified, following the evaluation of all families with features indicative of susceptibility to cancer. The proportion of identifiable risk factors of CRC was 5.8–7.5 percent (HNPCC, 0.7-2.4 percent; previous CRC, 3.4 percent; ulcerative colitis, 1.0 percent; familial adenomatous polyposis coli, 0.7 percent). CONCLUSION. This prospective multicenter study revealed that the frequency of hereditary colorectal cancer is lower than in some previous studies, when diagnosis is based on extensive pedigree analysis. This result with recent findings of common ancestral founding mutation in Finnish HNPCC families indicates that there may be geographic differences in the occurrence of HNPCC. However, this does not change the fact that identification of HNPCC—perhaps one of the most common inherited diseases identified in humans—has become a question of vital importance now when diagnosis of the syndrome and largescale screening of gene carriers using specific tests are on the horizon.Supported by grants from the Finnish Cancer Society, the Finnish Foundation for Gastroenterological Research, the Sigrid Juselius Foundation, and the Academy of Finland, Helsinki, Finland.