Secondary prevention in diabetic and nondiabetic coronary heart disease patients: Insights from the German subset of the hospital arm of the EUROASPIRE IV and V surveys.

BACKGROUND: Patients with coronary heart disease (CHD) with and without diabetes mellitus have an increased risk of recurrent events requiring multifactorial secondary prevention of cardiovascular risk factors. We compared prevalences of cardiovascular risk factors and its determinants including lifestyle, pharmacotherapy and diabetes mellitus among patients with chronic CHD examined within the fourth and fifth EUROASPIRE surveys (EA-IV, 2012-13; and EA-V, 2016-17) in Germany. METHODS: The EA initiative iteratively conducts European-wide multicenter surveys investigating the quality of secondary prevention in chronic CHD patients aged 18 to 79 years. The data collection in Germany was performed during a comprehensive baseline visit at study centers in Würzburg (EA-IV, EA-V), Halle (EA-V), and Tübingen (EA-V). RESULTS: 384 EA-V participants (median age 69.0 years, 81.3% male) and 536 EA-IV participants (median age 68.7 years, 82.3% male) were examined. Comparing EA-IV and EA-V, no relevant differences in risk factor prevalence and lifestyle changes were observed with the exception of lower LDL cholesterol levels in EA-V. Prevalence of unrecognized diabetes was significantly lower in EA-V as compared to EA-IV (11.8% vs. 19.6%) while the proportion of prediabetes was similarly high in the remaining population (62.1% vs. 61.0%). CONCLUSION: Between 2012 and 2017, a modest decrease in LDL cholesterol levels was observed, while no differences in blood pressure control and body weight were apparent in chronic CHD patients in Germany. Although the prevalence of unrecognized diabetes decreased in the later study period, the proportion of normoglycemic patients was low. As pharmacotherapy appeared fairly well implemented, stronger efforts towards lifestyle interventions, mental health programs and cardiac rehabilitation might help to improve risk factor profiles in chronic CHD patients.

Acute heart failure : An unmet medical need.

Despite recent advances in the management of heart failure with reduced ejection fraction (HFrEF), the burden of acute heart failure (AHF) remains significant with a high morbidity and mortality that has not been improved by any treatment modality. A meta-analysis summarized the study results on the effects of tolvaptan on AHF, which failed to demonstrate an improvement in short-term and long-term mortality, length of hospital stay and reduced frequency of worsening heart failure (WHF). Similar trial results were also reported in other AHF studies, such as the ASCEND-HF and the RELAX-AHF-2 trials. In view of these inconclusive studies it is evident that improving the prognosis of AHF patients remains an unmet medical need. Further efforts should focus on organ damage protection, individualized treatment, patient benefits and standardized management programs, including immediate identification and management of cardiogenic shock and establishment of HF networks for close monitoring of AHF patients.

Sacubitril/valsartan for heart failure with reduced left ventricular ejection fraction : A retrospective cohort study.

BACKGROUND: The combination drug sacubitril/valsartan was reported to be superior to enalapril in reducing all-cause death, cardiovascular mortality, and heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction (HFREF) with NYHA class II-IV. METHODS: Our retrospective cohort study aimed to assess the effects of sacubitril/valsartan in addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients with NYHA class II-III HF vs. conventional therapy (ACE inhibitor or angiotensin II receptor blocker added to a beta-blocker plus an MRA) administered to a control group of HFREF patients with comparable clinical features. In both groups, treatment was supplemented by a loop diuretic, usually furosemide, at variable doses. The primary outcomes were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia, and worsening renal function. RESULTS: Mortality at 6 months was 6.8% in patients taking sacubitril/valsartan vs. 34% in those on conventional therapy (odds ratio [OR] = 0.14; 95% CI: 0.04-0.49). Moreover, there was a 4.5% rate of HF hospitalizations in the sacubitril/valsartan group vs. 59% in the control group (OR = 0.03; 95% CI: 0.01-0.14). Safety outcomes were comparable in the two groups, although hypotension (systolic blood pressure < 100 mm Hg) was found in 15.9% of patients in the sacubitril/valsartan group vs. 5.7% in the control group (OR = 3.14; 95% CI: 0.94-10.55). CONCLUSION: Sacubitril/valsartan offered strong protection against all-cause death and HF hospitalizations at 6 months without any significant side effects. To validate this efficacious molecule, further postmarketing observational studies, focusing mainly on hypotension and angioedema are warranted.

Nine-month clinical outcomes in patients with diabetes treated with polymer-free sirolimus-eluting stents and 6­month vs. 12­month dual-antiplatelet therapy (DAPT).

BACKGROUND: Diabetes mellitus is known to be associated with worse clinical outcomes in patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions (PCI) with drug-eluting stents (DES). Defining the optimal duration of dual antiplatelet therapy (DAPT) after DES implantation is still under debate. The objective of this subgroup analysis of the all-comers ISAR 2000 registry was to assess the safety and efficacy of a short DAPT (<6 month) versus a longer DAPT (>6 month) in patients with diabetes electively treated with the polymer-free sirolimus-coated ultrathin strut drug-eluting stent (PF-SES). METHODS: Patients who received the PF-SES were investigated in a multicenter all-comers observational study. The primary endpoint was the 9­month target lesion revascularization (TLR) rate, whereas secondary endpoints included the 9­month major adverse cardiac event (MACE) and procedural success rates. RESULTS: In all, 167 patients were treated with DAPT for ≤6 months (S-DAPT group) and 350 patients underwent DAPT treatment for 12 months (L-DAPT group). There was no significant difference in the overall MACE rate (4.6% vs. 3.1%, p = 0.441), the 9­month accumulated stent thrombosis rates (0.8% vs. 0.3%, p = 0.51), or the accumulated rate of bleeding complications (5.3% vs. 3.4%, p = 0.341). CONCLUSION: PF-SES are safe and effective in daily clinical routine with low rates of TLR and MACE in patients with diabetes and stable disease. Our data suggest that extending the duration of DAPT beyond 6 months does not improve MACE or TLR at 9 months in patients with stable CAD (ClinicalTrials.gov Identifier NCT02629575).

[Patients with a wearable cardioverter-defibrillator (WCD) : Prescription, function and rehabilitation support]. / Patienten mit einer tragbaren Defibrillatorweste ("wearable cardioverter-defibrillator", WCD) : Verschreibung, Wirkweise und Nachsorge.

Assessment of a permanent risk of life-threatening ventricular arrhythmia in patients with severely reduced left ventricular ejection fraction (LVEF <35%), e. g. after myocarditis, dilated cardiomyopathy, acute myocardial infarction, in patients with postpartum cardiomyopathy or implantable cardioverter-defibrillator (ICD) and cardiac resynchronization treatment plus defibrillator (CRT-D) infection with temporary explantation of the system is a medical challenge. This is time-consuming and unsafe because life-threatening ventricular arrhythmias may occur during the time of risk assessment. During this phase of risk stratification, a wearable cardioverter-defibrillator (WCD) is indicated. The WCD, which is usually worn by the patient for several months, combines continuous retrievable electrocardiogram (ECG) recordings with a reliable defibrillation capability. The prescription of a WCD guarantees safe rehabilitation procedures for patients following acute inpatient treatment. Rehabilitation measures in patients with a WCD are indicated because of the underlying systolic cardiac insufficiency due to severe myocardial disease. In almost half of the patients, who are potentially threatened by ventricular tachyarrhythmias or sudden cardiac death (SCD), the LVEF and heart failure symptoms improve under controlled medication within a few months. Thus, the risk of SCD is lowered so that in many cases a first line ICD implantation is no longer necessary. The purpose of this article is to provide recommendations for rehabilitation procedures of patients with a WCD. A review of the currently available data on WCD publications was carried out with special emphasis on the current national and international guidelines.

In HFREF patients, sacubitril/valsartan, given at relatively low doses, does not lead to increased mortality or hospitalization : A retrospective cohort study.

INTRODUCTION: In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to a gradual increase regimen. Nevertheless, if patients exhibit tolerability problems, a provisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended. MATERIAL AND METHODS: This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan. In addition, a comparison was made to detect possible differences regarding all-cause mortality and heart failure hospitalization in patients treated with the recommended optimum dose compared to those receiving submaximum maintenance doses of sacubitril/valsartan. RESULTS: Patients treated with sacubitril/valsartan in addition to beta-blocker and mineralocorticoid receptor blocker were 68. Among them, 20 patients (29.4%), were identified as having clinical features that were contraindications to the administration of sacubitril/valsartan at full dose. The subsequent decision was to maintain an intermediate dose in 11 patients and to reduce the dose to the minimum level allowed, i.e., 24 mg/26 mg twice daily in nine patients. After a median follow-up of 5.25 months, no differences were found concerning the risk of all-cause death by comparing patients treated with reduced versus those subjected to target doses of sacubitril/valsartan (odds ratio [OR] = 1.666; 95% confidence interval [CI] = 0.256-10.823; p = 0.6266). Patients taking reduced doses had a similar risk of heart failure hospitalizations when compared to patients treated with the target dose (OR = 0.789; 95% CI: 0.077-8.0808; p = 1.00). CONCLUSION: During a median follow-up of 5.25 months, in the group of patients who had proven to be intolerant to the maximum dose of sacubitril/valsartan, use of reduced doses of the drug did not result in increased all-cause mortality or heart failure hospitalization compared to patients treated with sacubitril/valsartan at the target dose.

Cognitive performance of patients with chronic heart failure on sacubitril/valsartan : A retrospective cohort study.

BACKGROUND: Sacubitril, a neprilysin inhibitor in the combination molecule sacubitril/valsartan, slows down degradation of endogenous natriuretic peptides, thereby enhancing their beneficial cardiovascular effects. However, sacubitril might also promote neuronal dysfunction and cognitive impairment in patients with chronic heart failure (CHF) treated with sacubitril/valsartan, due to possible neprilysin inhibition at the level of Central Nervous System. METHODS: A retrospective cohort study was undertaken to detect the effects exerted by sacubitril/valsartan on cognitive function in CHF patients. The patients' clinical data were examined for information provided in the Mini-Mental State Examination (MMSE), which was routinely administered during clinical visits at two centers from 15 March to 31 October 2017. Patients in the sacubitril/valsartan group had a clinical history of at least 3 months of continuous sacubitril/valsartan administration. The control group comprised CHF patients on conventional therapy not taking sacubitril/valsartan. In the between-group comparison, patients were matched for mean age, educational level, sex, NYHA class, and comorbidities. In the present retrospective study only patients in NYHA class II-III were enrolled. RESULTS: The mean MMSE score was 22.72 ± 2.68 (mean ± standard deviation [SD]) in the sacubitril/valsartan group (n = 51 patients) vs. 21.96 ± 2.73 (mean ± SD) in the control group (n = 51; p = 0.1572, independent samples t-test). Thus, a similar mild-to-moderate impairment in cognitive performance was found in the comparison between the two groups. CONCLUSION: In our study, we did not find any evidence of the alleged harmful influence of sacubitril/valsartan on cognitive function. Patients taking sacubitril/valsartan for at least 3 months had similar mean MMSE scores to control subjects.

Minimally invasive direct coronary bypass surgery via distal mini-sternotomy : Promising clinical results with anaortic, multivessel, all-arterial technique.

BACKGROUND: Minimally invasive direct coronary artery bypass grafting (MIDCAB) was developed to decrease perioperative morbidity, some of which may be related to the use of cardiopulmonary bypass and to cross-clamping of the aorta. We report our initial experience with multivessel MIDCAB via distal mini-sternotomy (DIMS). DIMS is performed to gain access to the left and right internal thoracic arteries and to reach the left anterior descending coronary artery (LAD), diagonal branches, and right coronary artery (RCA). METHODS: Between January 2016 and January 2017, 12 patients with significant coronary artery disease of the LAD and the RCA underwent multivessel, all-arterial MIDCAB through a distal midline skin incision from the fourth intercostal space to the xyphoid process, with L­ or T­shaped division of the sternum. The mean age of the patients was 61.5 ± 5.2 years (range: 52-71 years). RESULTS: We performed all-arterial revascularization using the left internal mammary artery in 12 patients, the radial artery in ten, and the right internal mammary artery in two patients. The mean number of grafts per patient was 2.08 ± 0.4 (range: 2-3). The mean length of the skin incision was 8.5 ± 1.3 cm (range: 7-11 cm). There was no perioperative ischemia, postoperative bleeding, or arrhythmia events. No postoperative cognitive dysfunction occurred. The mean hospital stay was 5.6 days. No major adverse cardiac events (MACE) occurred at the 12-month follow-up. At follow-up, all patients were in New York Heart Association class I and there were no wound complications. CONCLUSION: Although MIDCAB-DIMS is technically more demanding than conventional procedures and our experience is limited, we conclude that this technique can be used safely in selected patients, with promising 12-month follow-up results.

Transcatheter vs. surgical aortic valve replacement and medical treatment : Systematic review and meta-analysis of randomized and non-randomized trials.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as the procedure of choice for patients with severe aortic stenosis (AS) and high perioperative risk. We performed a meta-analysis to compare the mortality related to TAVR with medical therapy (MT) and surgical aortic valve replacement (SAVR). METHODS: A systematic literature search was conducted by two independent investigators from the database inception to 30 December 2014. Relative risk (RR) and odds ratio (OR) were calculated and graphically displayed in forest plots. We used I 2 for heterogeneity (meta-regression) and Egger's regression test of asymmetry (funnel plots). RESULTS: We included 24 studies (n = 19 observational studies; n = 5 randomized controlled trials), with a total of 7356 patients in this meta-analysis. Mean age had a substantial negative impact on the long-term survival of AS patients (OR = 1.544; 95% CI: 1.25-1.90). Compared with MT, TAVR showed a statistically significant benefit for all-cause mortality at 12 months (OR = 0.68; 95% CI: 0.49-0.95). Both TAVR and SAVR were associated with better outcomes compared with MT. TAVR showed lower all-cause mortality over SAVR at 12 months (OR = 0.81; 95% CI: 0.68-0.97). The comparison between SAVR and TAVR at 2 years revealed no significant difference (OR = 1.09; 95% CI: 1.01-1.17). CONCLUSION: In AS, both TAVR and SAVR provide a superior prognosis to MT and, therefore, MT is not the preferred treatment option for AS. Furthermore, our data show that TAVR is associated with lower mortality at 12 months compared with SAVR. Further studies are warranted to compare the long-term outcome of TAVR versus SAVR beyond a 2-year follow-up period.

In-hospital mortality after acute STEMI in patients undergoing primary PCI.

BACKGROUND: Acute myocardial infarction (AMI) is the main cause of global and in-hospital mortality in patients with cardiovascular diseases. We aimed to examine the association between the coronary artery involved and the in-hospital mortality in patients who underwent primary percutaneous coronary intervention (pPCI) after ST segment elevation myocardial infarction (STEMI). METHODS: The in-hospital mortality of STEMI patients who underwent pPCI was assessed at the Department of Cardiology, Harzklinik Goslar, Germany, which has no access to immediate mechanical circulatory support (MCS), between 2013 and 2017. RESULTS: We enrolled 312 STEMI patients, with a mean age of 67.1 ± 13.4 years, of whom 211 (68%) were male. In-hospital mortality was documented in 31 patients (10%). In-hospital mortality was associated with pre-hospital cardiopulmonary resuscitation (CPR; n = 39/12.5%), older age, lower systolic blood pressure, Killip class > 1, triple-vessel disease (each p < 0.0001), female gender (p = 0.0158), and with the localization of the treated culprit lesion in the left main coronary artery (LMCA; p = 0.0083) and in the ramus circumflexus (RCX; p = 0.0141). CONCLUSION: In this monocentric cohort, all-cause in-hospital mortality of STEMI patients after pPCI was significantly higher in those patients with culprit lesions in the LMCA and in the RCX, which may prove to be a substantial novel risk factor for STEMI-related mortality. Increasing age and female gender may be interdependent risk factors for mortality in this patient population. Furthermore, our data highlight the importance of the availability of MCS options in pPCI centers for patients after CPR.

Efficacy of RADPAD protective drape during coronary angiography.

BACKGROUND: Ionizing radiation is an integral part of percutaneous coronary angiographies. Chronic exposure to low-dose radiation confers a risk for skin damage, eye lens opacities or cataracts, and malignant diseases to staff in the catheter laboratory. The RADPAD is a sterile surgical drape that reduces the effect of scatter radiation on the operator. We sought to assess the efficacy of RADPAD shields in reducing radiation dose experienced by operators during routine diagnostic coronary angiography. PATIENTS AND METHODS: Sixty consecutive patients due to undergo elective coronary angiography were randomized in a 1:1 pattern to have their procedures performed with and without the RADPAD drape in situ. Dosimetry was performed on the left arm of the primary operator. RESULTS: There was no significant difference in the two main determents of radiation exposure in both groups: the screening times (102 ± 86 s for the RADPAD group vs. 105 ± 36 s for the control group, p = 0.9) and body mass index (BMI; 27.7 ± 4.2 kg/m2 for the RADPAD group vs. 27.9 ± 5.5 kg/m2 for the control group, p = 0.8). Moreover, there was no difference in the dose-area ratio (1337 ± 582 cGy/cm2 for the RADPAD group vs. 1541 ± 804 cGy/cm2 for the control group, p = 0.3) between the two patient groups. The primary operator radiation dose was significantly lower in the RADPAD group at 8.0 µSv (Q1: 3.2, Q3: 20.1) compared with 19.6 µSv (Q1: 7.1, Q3: 37.7) for the control group (p = 0.02). CONCLUSION: The RADPAD significantly reduces radiation exposure to primary operators during routine diagnostic coronary angiography in patients with a BMI > 25 kg/m2. It reduces total radiation exposure to primary operators by 59%, and the radiation exposure rate by 47%.

Association between TLR2/TLR4 gene polymorphisms and COPD phenotype in a Greek cohort.

BACKGROUND: Considering that the innate immune system plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD), we hypothesized that functional single-nucleotide polymorphisms (SNPs) of innate immune genes affect the disease phenotype and prognosis. AIM: To elucidate the contribution of common functional TLR2 and TLR4 SNPs and genotypic deficiency of the mannose-binding lectin (MBL) protein, both as single parameters and in combination, in Greek COPD patients. RESULTS: In a cohort of 114 Greek COPD patients, we confirmed that the presence of TLR4-D299G or TLR4-T399I SNPs was significantly associated with an earlier COPD stage (p = 0.003 and p = 0.009, respectively). In comparison, the absence of any analyzed polymorphism, including those of TLR2-R753Q and genotypic MBL deficiency, was significantly associated with a more severe disease phenotype, characterized by more frequent exacerbations (p = 0.045). CONCLUSION: Our findings support the notion that the presence of innate immune SNPs, such as functional polymorphisms of TLRs along with MBL deficiency, might exert a protective effect on the COPD phenotype, similar with other immune-mediated disorders.

Cellular immune mechanisms in myocarditis.

The introduction of immunohistological techniques enabled a substantially more reliable diagnosis of inflammatory cardiomyopathy (DCMi) in endomyocardial biopsies (EMB) compared to the histological Dallas criteria. Decisive progress has been made in the understanding of cellular immune mechanisms in DCMi using immunohistological techniques, which apart from the field of diagnosis refinement have had prognostic implications and an influence on the selection criteria of DCMi patients who will likely benefit from immunosuppressive treatment. Digital image analysis systems have been employed to standardize quantification of immunohistological EMB stainings. Quantification of T cell-related genes by a methodologically validated preamplified real-time RT-PCR revealed that the T cells are characterized by differential expression of Th1-, Treg-, and CTL-related markers, while no major role could be confirmed for Th17 cells. The reported virus-associated differential T cell receptor Vbeta dominance suggests an antiviral specificity of virus-induced T cell responses in human DCMi.