[Comments on the 2013 ESC/EASD guidelines on diabetes, prediabetes and cardiovascular diseases]. / Kommentar zur ESC/EASD-Leitlinie zu Diabetes, Prädiabetes und kardiovaskulären Erkrankungen 2013.

Patients with type 2 diabetes mellitus have an increased cardiovascular risk compared with non-diabetics. The new guidelines provide physicians with orientation with respect to disorders in glucose metabolism and the risk of occurrence of cardiovascular diseases. An HBA1c level in the range of 6-8% is currently recommended, depending on cardiovascular comorbidities: in young diabetics 6% is recommended to avoid hypoglycemia and in older individuals with cardiovascular complications 8%. The target blood pressure given in the new guidelines is <140/85 mmHg. The guidelines still recommend bypass surgery instead of percutaneous coronary intervention (PCI) for diabetics; however, this recommendation is based on studies that do not reflect current practice and is disputable. Diagnostic measures and therapy of cardiac failure and arrhythmic disorders in the guidelines do not essentially differ between patients with and without diabetes, basically due to a lack of studies.

[Characteristics of therapy of acute myocardial infarction in diabetes]. / Besonderheiten der Infarkttherapie bei Diabetes.

Therapy of acute myocardial infarction (STEMI and NSTEMI) in diabetics does not principally differ from that of non-diabetic patients. Due to the higher mortality in diabetics reperfusion measures, such as direct percutaneous coronary intervention (PCI), should be rapidly performed. An intensive drug treatment with thrombocyte aggregation inhibitors, angiotensin-converting enzyme (ACE) inhibitors and beta-receptor blocking agents must be carried out according to the current guidelines. An important factor is the high risk of renal failure due to the contrast dye administered during PCI in the presence of pre-existing diabetic kidney damage which should be limited to 100 ml if possible. Direct PCI should be limited to the infarcted vessel. After stabilization a comprehensive strategy to cure coronary artery disease, whether with PCI or coronary artery bypass graft (CABG) should be finalized. If severe coronary 3-vessel disease is present, CABG should be favored in diabetic patients. After surviving an acute myocardial infarction differentiated metabolic monitoring is mandatory.

[Cardial target-organ damage in diabetes]. / Kardiale Endorganschäden bei Diabetes.

Coronary heart disease and type 2 diabetes mellitus can be considered as a syntropy. Accordingly, cardiologists and diabetologists should organize an interdisciplinary car of the patient with both cardiac disease and diabetes mellitus. Arterial hypertension is frequently present in the diabetic condition and increases further morbidity and mortality rates due to the involvement of the coronary microcirculation. Coronary artery disease is characterized by a rapid progression and a diffuse distribution particularly in the periphery. Consequently in severe diabetic coronary artery disease coronary bypass surgery should be preferred rather than percutaneous coronary stenting, which should be favored in less severe cases. In the antihyperglycemic treatment a reduction in cardiovascular endpoints has only be documented after metformin. Therapy with thiazolidinediones has been terminated due to an increase in coronary morbidity and mortality under rosiglitazone. In as much glucagon-like peptide-I analogues and dipeptidylpeptidase 4 inhibitors will reduce cardiovascular endpoints has to be waited for. Thus an endpoint orientated antihyperglycemic treatment is limited to insulin, metformin and sulfonylureas.

[Hypertension and heart]. / Hochdruck und Herz.

Arterial hypertension often leads to diseases of kidneys, vessels and brain. Besides these end organ damages the changes of the heart are of important role. Substantial consequences of hypertension are microangiopathy, interstitial fibrosis and left ventricular hypertrophy. Hence, as an early stage diastolic dysfunction results. Due to longer persistent hypertension also systolic dysfunction develops. Clinically, patients suffer from angina pectoris, dyspnoea and cardiac arrhythmias (i.e. atrial arrhythmia, atrial fibrillation). The left ventricular hypertrophy also is associated with an increased risk of malignant ventricular arrhythmias. The risk of sudden cardiac death is raised as well, in particular in patients with dilated heart and reduced left ventricular ejection fraction. Well controlled antihypertensive therapy could lead to a regression of left ventricular hypertrophy. Hence, disorders and prognosis of the patients could be improved.

[Hypertrophy and coronary reserve]. / Hypertrophie und Koronarreserve.

Left ventricular hypertrophy represents the structural mechanism of adaptation of the left ventricle as the answer of a chronic pressure overload in arterial hypertension. Initially an increment in left ventricular wall thickness occurs. In this stadium of "concentric hypertrophy" LV systolic wall stress, LV ejection fraction and myocardial oxygen consumption per weight unit myocardium remain unchanged. In the further time course of disease LV dilatation will be present. In this phase of "excentric hypertrophy" LV systolic wall stress and myocardial oxygen consumption per weight unit myocardium rise and LV ejection fraction decreases. Patients with arterial hypertension frequently complain of angina pectoris. Angina pectoris and the positive exercise tolerance test or the positive myocardial scintigraphy are the consequence of the impaired coronary flow reserve. The coronary flow reserve is diminished due to structural and functional changes of the coronary circulation. ACE-inhibitors and AT1-receptor blockers cause a significant improvement of coronary flow reserve and regression of both left ventricular hypertrophy and myocardial fibrosis.

[Stent therapy with diabetic patients who have coronary artery disease]. / Stenttherapie bei diabeteskranken Koronarpatienten.

When bare-metal stents are used, diabetic patients with coronary artery disease have a poorer prognosis than non-diabetic patients after coronary interventions. In clinical studies, it could be demonstrated that the disadvantage for diabetic patients is not present when drug-eluting stents are used. Today, two types of drug-eluting stents are clinically used: the sirolimus-eluting stent (Cypher) and the paclitaxel-eluting stent (Taxus). Even the high risk group of patients with in-stent stenosis can be efficiently treated with drug-eluting stents.

[Arterial hypertension, left ventricular hypertrophy, and ventricular arrhythmias]. / Arterielle Hypertonie, linksventrikuläre Hypertrophie und ventrikuläre Herzrhythmusstörungen.

Patients with hypertensive heart disease have frequently ventricular arrhythmias in the 24-h-holter-EKG. Those patients with severe forms of arterial hypertension have more high grade ventricular tachycardia than those with less severe hypertension. Sudden cardiac death in arterial hypertensive seems to be linked with the prevalence of coronary artery disease, whereas LV hypertrophy is only a co-factor.

[Right ventricle in arterial hypertension]. / Rechter Ventrikel bei arterieller Hypertonie.

Left ventricular hypertrophy is the best known and most evident cardiac organ manifestation of arterial hypertension. However, only limited findings are available on function and structure of the right ventricle. The published studies show that the right ventricle is also affected in the course of hypertensive heart disease. Particularly hypertrophy of the right ventricular free wall, impaired right ventricular diastolic filling, elevated right ventricular filling pressure as well as impairment of right ventricular ejection fraction in the late phase of arterial hypertension were reported. Possible causes of these structural and functional changes of the right ventricle are (1) translation of the increased left ventricular filling pressure in the pulmonary circulation, (2) interaction of the right and left ventricle, and (3) systemic circulation of cytokines and growth hormones such as angiotensin II, aldosterone, and others.

Minimal metabolic data set for patients at high vascular risk.

Vascular events still represent the leading cause of death in the western world. The pathogenesis of atherothrombotic events is multifactorial. Epidemiological studies indicate that the presence of several concomitant risk factors, especially in the metabolic syndrome, markedly exacerbates the vascular risk. In the prevention and management of cardiovascular disease, a multi-dimensional risk factor approach is therefore required to reduce the "vascular burden". Consequently it is absolutely necessary to identify and to subsequently monitor these factors during intervention/therapy. The present MMDS represents a tool for the daily clinical routine to assess and document important cardiovascular risk factors. This data set is the result of a consensus of the two German working groups of the German Cardiology Society and the German Diabetes Society. The identification and detection of all relevant vascular risk factors should result in improved patient care and a more comprehensive documentation of cardiovascular risk factors in clinical studies.

Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study.

OBJECTIVE: To compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH). DESIGN: The LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril) was a 1 year, prospective, randomized, double-blind study. For the first time, a committee validated LVH before inclusion, provided on-going quality control during the study, and performed an end-study reading of all echocardiograms blinded to sequence. SETTING: European hospitals, general practitioners and cardiologists. PATIENTS: Hypertensive patients aged > or = 20 years with LVH (LVMI in men > 120 g/m2; LVMI in women > 100 g/m2). Data were obtained from 411 of 505 randomized patients. INTERVENTIONS: Indapamide SR 1.5 mg, or enalapril 20 mg, daily for 48 weeks. MAIN OUTCOME MEASURES: LVMI variation in the perprotocol population. RESULTS: Indapamide SR 1.5 mg significantly reduced LVMI (-8.4 +/- 30.5 g/m2 from baseline; P< 0.001), but enalapril 20 mg did not (-1.9 +/- 28.3 g/m2). Indapamide SR 1.5 mg reduced LVMI significantly more than enalapril 20 mg: -6.5 g/m2, P = 0.013 (-4.3 g/m2 when adjusted for baseline values; P = 0.049). Both drugs equally and significantly reduced blood pressures (P< 0.001), without correlation with LVMI changes. Indapamide SR progressively reduced wall thicknesses throughout the 1-year treatment period. In contrast, the effect of enalapril observed at 6 months was not maintained at 12 months. CONCLUSIONS: Indapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH.

The angiotensinogen gene 235T variant is associated with an increased risk of restenosis after percutaneous transluminal coronary angioplasty.

The therapeutic benefit of percutaneous transluminal coronary angioplasty (PTCA) is limited by restenosis in 30-40% of patients. The underlying mechanisms are currently not well understood. Besides clinical and angiographic variables, genetic factors may be involved. In the present study, we investigated the associations between the angiotensinogen T174M and M235T, the angiotensin I-converting enzyme (ACE) I/D and the angiotensin II type 1 receptor A1166C gene polymorphisms and restenosis in 511 patients who had undergone successful PTCA (without stenting) and follow-up angiography. Clinical and angiographic variables were also considered as possible predictors of restenosis. Stenosis severity was estimated by visual inspection of the angiograms. Altogether, 160 patients had restenosis, as defined by a greater than 50% reduction in the diameter of the dilated segment at follow-up angiography compared with the findings immediately following angioplasty. There were significantly more carriers of the angiotensinogen 235T allele and more patients with the ACE DD genotype in the restenosis group than in the no restenosis group, but only the angiotensinogen 235T allele (and not the ACE DD genotype) remained significantly associated with restenosis following multifactorial analyses. No differences between the two groups were found with respect to the other gene polymorphisms. Patients who subsequently developed restenosis had a higher degree of stenosis and more severe lesions before PTCA, as well as less residual stenosis immediately after PTCA. We conclude that the angiotensinogen M235T gene polymorphism may be an independent predictor of restenosis after PTCA.

Atypical heparin-induced thrombocytopenia complicated by intracardiac thrombus, effectively treated with ultra-low-dose rt-PA lysis and recombinant hirudin (Lepirudin).

A serious retroperitoneal bleeding occurred in a 56-year-old male patient receiving unfractionated heparin due to multiple pulmonary embolism. After reducing the heparin dose, the patient developed a new pulmonary embolism and a large thrombus in the right atrium. Concomitantly, the platelet count dropped to a value of 29 g/l. Heparin-induced thrombocytopenia (HIT) was confirmed by a functional assay, the heparin-induced platelet activation (HIPA) assay, whereas the results of a platelet factor 4/heparin complex ELISA were repeatedly negative. This indicated that the patient's HIT antibodies were directed towards an antigen other than platelet factor 4/heparin complexes. For treatment of the atrial thrombus, an ultra-low-dose lysis with rt-PA (2 mg/h, intravenously) was administered for a period of 52 h, overlapping with systemic treatment with recombinant hirudin (Lepirudin, Refludan, 0.06-0.14 mg/kg/h intravenously). The aim was to enhance lysis of the thrombus without increasing the haematoma, and at the same time keep the risk of fulminant pulmonary embolism due to thrombus fragmentation as low as possible. The cardiac thrombus disappeared within 48 h, without new signs of pulmonary embolism. Platelet counts normalized within nine days.

Impaired coronary flow reserve in NIDDM: a possible role for diabetic cardiopathy in humans.

Diabetic cardiopathy represents a cardiac disorder with involvement of myocardial, interstitial, coronary, and neural structures. One of the main manifestations refers to coronary microangiopathy, which has not yet been clearly identified. Coronary hemodynamics, including the determination of coronary flow reserve, were therefore analyzed in normal subjects and in nine patients with NIDDM and clinically suspected coronary heart disease but normal coronary arteriogram. Coronary flow reserve was determined as the quotient of baseline and minimal coronary resistance after dipyridamole (0.5 mg/kg i.v.). Coronary blood flow was measured quantitatively by the argon method. Systolic left ventricular function was analyzed by ventriculography and diastolic function by M-mode and Doppler echocardiography. Twelve healthy normotensive subjects served as the control group (CON). In the diabetic patients, maximal coronary flow was significantly reduced (172 +/- 50 vs. 395 +/- 103 ml/min x 100 g; P < 0.001), and minimal coronary resistance was increased (0.60 +/- 0.19 vs. 0.24 +/- 0.06 mmHg x min x 100 g/ml; P < 0.001). Coronary reserve in the diabetic subjects was markedly reduced (1.84 +/- 0.39 vs. 4.23 +/- 0.52; P < 0.001). No difference existed with respect to myocardial oxygen consumption (12.4 +/- 2.3 vs. 11.8 +/- 2.8 ml O2/100 g x min; NS). Global systolic function was normal in all patients (ejection fraction: NIDDM 72 +/- 13 vs. CON 77 +/- 12%, NS; CI: NIDDM 3.2 +/- 0.8 vs. CON 3.3 +/- 1.2 l/min x m2, NS). Diastolic function was impaired in diabetic patients with an increase in relaxation time index (97 +/- 23 vs. 45 +/- 18 ms; P < 0.01) and an impaired diastolic inflow pattern, indicated by the ratio between early and late transmitral flow (0.75 +/- 0.14 vs. 1.66 +/- 0.13; P < 0.05). We conclude that the markedly reduced coronary flow reserve in diabetic patients may play a key role in the induction and perpetuation of coronary insufficiency in myocardial ischemia, in diastolic and systolic dysfunction, and in the initiation of diabetic cardiopathy.

Evidence for reduced coronary flow reserve in patients with insulin-dependent diabetes. A possible cause for diabetic heart disease in man.

UNLABELLED: In diabetic heart disease myocardial, interstitial, coronary and neural structures are often involved. Coronary microangiopathy is supposed to contribute an essential part, which has not yet been clearly analysed. METHODS: In 9 normotensive patients with insulin-treated diabetes (DP) with clinically suspected coronary heart disease but normal epicardial coronary arteries, coronary microcirculation was studied. Coronary flow was determined as the quotient of base line and minimal coronary resistance after dipyridamole (0.5 mg/kg i.v.), using the argon-gas-chromatography method. Systolic left ventricular function was analysed by ventriculography, diastolic function by M-Mode-echocardiography and Doppler-echocardiograhy. Twelve normotensive subjects served as control group (CON). RESULTS: In diabetic patients maximal coronary flow was significantly reduced (172 +/- 5 versus 395 +/- 103 ml/min x 100 g, p < or = 0.001) and minimal coronary resistance increased (0.6 +/- 0.19 versus 0.24 +/- 0.06 mmHg x min x 100 g/ml, p < 0.001). Coronary reserve in diabetics was markedly reduced (1.84 +/- 0.39 versus 4.23 +/- 0.52, p < or = 0.001). Global systolic function was normal in all patients (EF: DP: 72 +/- 13 versus CON: 77 +/- 12%, n.s.; cardiac index: DP: 3.2 +/- 0.8 versus CON: 3.3 +/- 1.2 1/ min x m2, n.s.). Diastolic function was impaired in diabetics with an increased relaxation time index (97 +/- 23 versus 45 +/- 18 msec, p < or = 0.01) and an impaired diastolic inflow pattern, indicated by the E/A-ratio (0.75 +/- 0.14 versus 1.66 +/- 0.13, p < or = 0.05). CONCLUSIONS: The reduced coronary flow reserve in patients with insulin-treated diabetes mellitus may play a crucial role in the pathophysiology of diabetic cardiopathy, causing myocardial ischaemia due to a disturbance of coronary microcirculation leading to diastolic dysfunction and progressing assumably to systolic failure.

Left ventricular mass is linked to cardiac noradrenaline in normotensive and hypertensive patients.

BACKGROUND: Left ventricular hypertrophy constitutes a powerful independent risk factor for heart failure, sudden death and ventricular dysrhythmia. Experimental data suggest that, apart from increased cardiac work load, noradrenaline may be one of the factors triggering myocardial hypertrophy. OBJECTIVE: To test the hypothesis that the extent of left ventricular hypertrophy is coupled to cardiac noradrenaline independently from the magnitude of arterial blood pressure. PATIENTS AND METHODS: Following exclusion of coronary artery disease by cardiac catheterization, cardiac noradrenaline release was measured in relation to left ventricular mass in 25 patients with arterial hypertension (HT), of whom five had left ventricular hypertrophy (HT + LVH) and 20 had normal left ventricular mass (HT - LVH), seven normotensive patients with hypertrophic cardiomyopathy (HCM) and a normotensive control group (n = 7). Noradrenaline was measured in arterial and coronary venous plasma using high-performance liquid chromatography. Coronary blood flow was quantified using the gas chromatographic argon method. Indices of left ventricular mass were calculated from the end-diastolic thicknesses of the interventricular septum and the posterior wall determined by echocardiography. RESULTS: The coronary venous plasma concentration of noradrenaline was significantly higher in HT - LVH, HT + LVH and HCM than it was in normotensives. Whereas in normotensives there was a net uptake of noradrenaline (17 +/- 10 pmol/min) across the coronary circulation, a net release of noradrenaline was observed in HT - LVH (69 +/- 26 pmol/min), in HT + LVH (121 +/- 55 pmol/min) and in HCM (341 +/- 96 pmol/min). In a multivariate linear regression analysis model, left ventricular mass correlated significantly with the net noradrenaline release rate (r = 0.64, P < 0.001), whereas arterial blood pressure as an additional independent variable did not correlate with left ventricular mass. CONCLUSION: The present data demonstrate that an increased left ventricular mass in normotensive and in hypertensive patients is closely coupled to an increased cardiac sympathetic activity, supporting the need for additional studies to determine whether adjunctive sympatholytic therapy is beneficial in patients with left ventricular hypertrophy and increased cardiac noradrenaline release.

Improvement of coronary flow reserve after long-term therapy with enalapril.

To date, no clinical study shows an improvement in coronary flow reserve due to long-term antihypertensive therapy. in view of the contribution of the renin-angiotensin system to the process of hypertensive remodeling of the heart and coronary circulation, angiotensin-converting enzyme (ACE) inhibitors might act as cardioreparative drugs in arterial hypertension. Accordingly, our objective in this investigation was to examine under clinical conditions to what extent long-term antihypertensive treatment with an angiotensin-converting enzyme inhibitor improved the diminished coronary flow reserve in hypertensive patients with microvascular angina pectoris. For the purpose of comparison, we also treated a normotensive control group of 6 patients with hypertrophic nonobstructive cardiomyopathy. Fifteen hypertensive individuals (10 men, 5 women; age, 58 +/- 6 years) were treated with enalapril (10 to 20 mg/d; mean, 16.7 +/- 4.9 mg/d) for 11 to 13 months. At the end of the treatment period, systolic pressure decreased from 178 +/- 14 to 137 +/- 12 mm Hg and diastolic pressure from 102 +/- 11 to 86 +/- 4 mm Hg under ambulatory conditions. Left ventricular muscle mass index decreased by 8%, from 149 +/- 32 to 137 +/- 28 g/m2 (P < .05). Maximal coronary blood flow after dipyridamole was increased by 43%, from 181 +/- 69 to 258 +/- 116 mL/min per 100 g (P < .001), and minimal coronary vascular resistance was diminished by 29%, from 0.66 +/- 0.23 to 0.47 +/- 0.24 mm Hg x min x 100g x mL-1 (P < .001) after enalapril treatment. Consequently, the calculated coronary reserve increased from 2.2 +/- 0.6 to 3.3 +/- 1.2 (P < .001). After enalapril therapy, the functional class of angina pectoris according to the Canadian classification system had changed from 2.5 +/- 0.6 to 1.5 +/- 0.6 (P < .01). The maximal working capacity had increased from 23.775 +/- 3.970 to 26.255 +/- 4.598 J (mean +/- SE, P < .05). The maximal ST-segment depression at maximal work-load was reduced from 0.18 +/- 0.02 to 0.06 +/- 0.02 (mean +/- SE, (P < .01). In summary, long-term therapy with the angiotensin-converting enzyme inhibitor enalapril must be considered a cardioreparative treatment with respect to the coronary microcirculation in hypertensive heart disease.