[Kidney insufficiency and cardiovascular disease]. / Niereninsuffizienz und kardiovaskuläre Erkrankungen.

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with chronic renal disease. Severe cardiac and arterial disorders such as left ventricular hypertrophy, coronary artery disease, and arteriosclerosis of the large vessels are already evident in early renal disease, even in young patients. Despite major advances in dialysis therapy and treatment options for acute coronary syndromes, mortality remains high--up to 10-30 times higher than in the general population. The increased risk for cardiovascular disorders results from the additive effect of traditional risk factors, volume overload, and endocrine and metabolic abnormalities in uremia. During the course of the renal disease, the progression of CVD disease manifestations significantly influences outcome. Thus, preventive measures and optimal treatment are mandatory and should be among the main targets of early management of patients with chronic renal disease.

The Na+/H+ exchange inhibitor cariporide is washed out of the myocardium by crystalloid cardioplegia.

BACKGROUND: Inhibition of the Na (+)/H (+) exchanger (NHE) is cardioprotective, but dosage and timing of NHE-inhibitors are critical for their efficacy. We studied the effect of a new dosing regime of the NHE-inhibitor cariporide on myocardial function and damage after cardioplegic arrest (CPA) and determined its myocardial and serum concentrations. METHODS: 3 pigs received a bolus of 180 mg cariporide intravenously (i. v.) and were sacrificed shortly thereafter to allow measurement of the myocardial concentrations of cariporide. Subsequently, 10 pigs were randomized to receive either i. v. cariporide (bolus followed by an infusion of 40 mg/h) or placebo. Cardiopulmonary bypass was initiated, and the heart was arrested for 60 minutes by infusion of St. Thomas Hospital solution. Left ventricular (LV) function was studied using microsonometry. Myocardial damage was assessed by troponin T. Serum concentrations of cariporide were measured throughout the study, and myocardial concentrations were measured before the end of CPA and 180 minutes thereafter. RESULTS: Cariporide was present in all myocardial specimens (median: 1.4 ng/mg) studied previously. In the main study, LV function or myocardial damage did not differ significantly between the groups at any time point. Stable serum cariporide concentrations were achieved (3.4 +/- 0.5 microg/ml). Cariporide was detectable in only one of the myocardial biopsies obtained before the end of CPA, but 180 minutes thereafter, the myocardial cariporide concentration was 2.5 +/- 0.3 ng/mg. CONCLUSION: We observed no effect of i. v. cariporide on LV function or myocardial damage after cardioplegic arrest. Our data suggest that cariporide is washed out of the myocardium by repeated application of crystalloid cardioplegia. Thus, the mode of delivery also appears to be critical for cardioprotection with NHE-inhibitors.

Admission troponin T level predicts clinical outcomes, TIMI flow, and myocardial tissue perfusion after primary percutaneous intervention for acute ST-segment elevation myocardial infarction.

BACKGROUND: In ST-segment elevation myocardial infarction, a troponin T >/=0.1 microg/L on admission indicates poorer prognosis despite early reperfusion. To evaluate the underlying reason, we studied the value of cardiac troponin T (cTnT) for prediction of outcomes, epicardial blood flow, and myocardial reperfusion after primary percutaneous intervention. METHODS AND RESULTS: Patients (n=140) admitted within 12 hours after onset of symptoms were stratified by admission cTnT. Epicardial and myocardial reperfusion were graded by the TIMI score and by measurement of relative increases of myoglobin, cTnT, and creatine kinase (CK)-MB 60 minutes after recanalization, respectively. cTnT was positive in 64 patients (45.7%) and was associated with longer median time intervals to admission (5.5 versus 3.5 hours, P<0.001) and higher mortality rates after 30 days (12.5% versus 3.9%, P=0.06) and 9 months (14% versus 3.9%, P=0.005). cTnT independently predicted a 3.2-fold risk for incomplete epicardial reperfusion (P=0.03). In addition, cTnT >/=0.1 microg/L was associated with more severely impaired myocardial perfusion despite normal epicardial flow, as indicated by lower 60-minute ratios of myoglobin (2.6 versus 7.6, P=0.007), cTnT (6.6 versus 29.2, P<0.001), and CK-MB (3.5 versus 21.4, P=0.002) and a tendency for less resolution of ST-segment elevations (54% versus 60%, P=0.08). CONCLUSIONS: cTnT predicts poorer clinical outcomes, lower rates of postprocedural TIMI 3 flow, and more severely compromised myocardial perfusion despite normal epicardial flow. Thus, a cTnT-positive patient may require more aggressive adjunctive therapy when treated by percutaneous coronary intervention. The impact of preexisting or evolving microvascular dysfunction and the effect of therapies that target myocardial perfusion require further prospective evaluation.

Risk stratification in patients with inferior acute myocardial infarction treated by percutaneous coronary interventions: the role of admission troponin T.

BACKGROUND: Cardiac troponin T (cTnT) elevations on admission indicate a high-risk subgroup of patients with ST-segment elevation acute myocardial infarction (AMI). This finding has been attributed to less effective reperfusion after thrombolytic therapy. The aim of this study was to determine the role of admission cTnT on the efficacy of percutaneous coronary interventions (PCIs) in inferior AMI. METHODS AND RESULTS: One hundred fifty-nine consecutive patients with inferior ST-segment AMI were enrolled and followed up for a mean of 448 days. Patients were stratified by cTnT on admission. A cTnT >/=0.1 microg/L was found in 58% of patients. These patients had longer time intervals from onset of symptoms to therapy (P:<0. 001) and higher 30-day (10.8% versus 1.5%, P:=0.027) and long-term (17.2% versus 4.5%, P:=0.023) cardiac mortalities. Rates of the combined end point of death, nonfatal reinfarction, and need for repeated target vessel revascularization procedures were not different in cTnT groups (log rank, 0.69; P:=0.41). PCI was attempted in 93.3% of cTnT-positive and 98.5% cTnT-negative patients (P:=0.24) but was less frequently successful in patients with cTnT >/=0.1 microg/L (77.9% versus 96.9%, P:<0.001). Coronary stenting reduced 30-day and long-term cardiac mortality, particularly among cTnT-positive patients. In a multivariate analysis, cTnT indicated an approximately 5-fold-higher risk (adjusted OR, 4.6; 95% CI, 0.79 to 27.11; P:=0.089) and was a strong albeit not independent risk predictor. CONCLUSIONS: In inferior AMI, a positive admission cTnT is associated with lower success rates of direct PCI and higher rates of cardiac events over the short and long term. These patients benefit from coronary stenting.

Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism.

BACKGROUND: Cardiac troponin T (cTnT) is a sensitive and specific marker, allowing the detection of even minor myocardial cell injury. In patients with severe pulmonary embolism (PE), myocardial ischemia may lead to progressive right ventricular dysfunction. It was therefore the purpose of this study to test the presence of cTnT and its prognostic implications in patients with confirmed PE. METHODS AND RESULTS: Fifty-six consecutive patients with confirmed PE were enrolled in this prospective study. PE was confirmed by pulmonary angiography, lung scan, or echocardiography and subsidiary analyses. Severity of PE was assessed by a clinical scoring system, and cTnT was measured within 12 hours after admission. cTnT was elevated (>/=0.1 microg/L) in 18 (32%) patients with massive and moderate PE but not in patients with small PE. In-hospital death (odds ratio 29. 6, 95% CI 3.3 to 265.3), prolonged hypotension and cardiogenic shock (odds ratio 11.4, 95% CI 2.1 to 63.4), and need for resuscitation (odds ratio 18.0, 95% CI 2.6 to 124.3) were more prevalent in patients with elevated cTnT. cTnT-positive patients more often needed inotropic support (odds ratio 37.6, 95% CI 5.8 to 245.6) and mechanical ventilation (odds ratio 78.8, 95% CI 9.5 to 653.2). After adjustment, cTnT remained an independent predictor of 30-day mortality (odds ratio 15.2, 95% CI 1.22 to 190.4). CONCLUSIONS: cTnT may improve risk stratification in patients with PE and may aid in the identification of patients in whom a more aggressive therapy may be warranted.