Stem and progenitor cell-based therapy in ischaemic heart disease: promise, uncertainties, and challenges

In the absence of effective endogenous repair mechanisms after cardiac injury, cell-based therapies have rapidly emerged as a potential novel therapeutic approach in ischaemic heart disease. After the initial characterization of putative endothelial progenitor cells and their potential to promote cardiac neovascularization and to attenuate ischaemic injury, a decade of intense research has examined several novel approaches to promote cardiac repair in adult life. A variety of adult stem and progenitor cells from different sources have been examined for their potential to promote cardiac repair and regeneration. Although early, small-scale clinical studies underscored the potential effects of cell-based therapy largely by using bone marrow (BM)-derived cells, subsequent randomized-controlled trials have revealed mixed results that might relate, at least in part, to differences in study design and techniques, e.g. differences in patient population, cell sources and preparation, and endpoint selection. Recent meta-analyses have supported the notion that administration of BM-derived cells may improve cardiac function on top of standard therapy. At this stage, further optimization of cell-based therapy is urgently needed, and finally, large-scale clinical trials are required to eventually proof its clinical efficacy with respect to outcomes, i.e. morbidity and mortality. Despite all promises, pending uncertainties and practical limitations attenuate the therapeutic use of stem/progenitor cells for ischaemic heart disease. To advance the field forward, several important aspects need to be addressed in carefully designed studies: comparative studies may allow to discriminate superior cell populations, timing, dosing, priming of cells, and delivery mode for different applications. In order to predict benefit, influencing factors need to be identified with the aim to focus resources and efforts. Local retention and fate of cells in the therapeutic target zone must be improved. Further understanding of regenerative mechanisms will enable optimization at all levels. In this context, cell priming, bionanotechnology, and tissue engineering are emerging tools and may merge into a combined biological approach of ischaemic tissue repai

Left ventricular structure and function following renal sympathetic denervation in patients with HFpEF: an echocardiographic 9-year long-term follow-up

BackgroundHigh blood pressure is a major risk factor for cardiac remodeling and left ventricular hypertrophy, increasing cardiovascular risk and leading to heart failure with preserved ejection fraction (HFpEF). Since renal sympathetic denervation (RDN) reduces blood pressure in the long term, we aimed to investigate the long-term effect of RDN in patients with HFpEF in the present analysis.MethodsPatients previously enrolled in a local RDN registry who underwent high-frequency RDN with the use of the Symplicity Flex® renal denervation system between 2011 and 2014 were followed up. The patients were assessed by 24-h ambulatory blood pressure measurement, transthoracic echocardiography, and laboratory tests. We used the echocardiographic and biomarker criteria of the Heart Failure Association (HFA)-PEFF (Pre-test assessment, Echocardiography and Natriuretic Peptide Score, Funkctional testing, and Final aetiology) score to identify patients with HFpEF.ResultsEchocardiographic assessment was available for 70 patients at a 9-year long-term follow-up. Of these patients, 21 had HFpEF according to the HFA-PEFF score. We found a significant reduction of the HFA-PEFF score from 5.48 ± 0.51 points at baseline to 4.33 ± 1.53 points at the 9-year follow-up (P < 0.01). This decrease was due to a greater reduction in morphological and biomarker subcategories [from 1.95 ± 0.22 to 1.43 ± 0.51 points (P < 0.01) and from 1.52 ± 0.52 to 0.90 ± 0.63 points (P < 0.01), respectively] than in the functional one. Morphologically, there was a reduction in left ventricular hypertrophy and left atrial dilation.ConclusionsThe present analysis suggests that RDN may lead to a regression of the extent of HFpEF beyond a reduction in blood pressure and thus possibly contribute to an improvement in prognosis. More detailed information will be provided by ongoing randomized sham-controlled trials

Artificial Intelligence Identifies an Urgent Need for Peripheral Vascular Intervention by Multiplexing Standard Clinical Parameters

Background: Peripheral artery disease (PAD) is a significant burden, particularly among patients with severe disease requiring invasive treatment. We applied a general Machine Learning (ML) workflow and investigated if a multi-dimensional marker set of standard clinical parameters can identify patients in need of vascular intervention without specialized intra–hospital diagnostics. Methods: This is a retrospective study involving patients with stable PAD (sPAD, Fontaine Class I and II, n = 38) and unstable PAD (unPAD, Fontaine Class III and IV, n = 18) in need of invasive therapeutic measures. ML algorithms such as Random Forest were utilized to evaluate a matrix consisting of multiple routinely clinically available parameters (age, complete blood count, inflammation, lipid, iron metabolism). Results: ML has enabled a generation of an Artificial Intelligence (AI) PAD score (AI-PAD) that successfully divided sPAD from unPAD patients (high AI-PAD in sPAD, low AI-PAD in unPAD, cutoff at 50 AI-PAD units). Furthermore, the probability score positively coincided with gold-standard intra-hospital mean ankle-brachial index (ABI). Conclusion: AI-based tools may be promising to enable the correct identification of patients with unstable PAD by using existing clinical information, thus supplementing clinical decision making. Additional studies in larger prospective cohorts are necessary to determine the usefulness of this approach in comparison to standard diagnostic measures

Cardiac iron concentration in relation to systemic iron status and disease severity in non-ischaemic heart failure with reduced ejection fraction

Aims: Low cardiac iron levels promote heart failure in experimental models. While cardiac iron concentration (CI) is decreased in patients with advanced heart failure with reduced ejection fraction (HFrEF), CI has never been measured in non-advanced HFrEF. We measured CI in left ventricular (LV) endomyocardial biopsies (EMB) from patients with non-advanced HFrEF and explored CI association with systemic iron status and disease severity. Methods and results: We enrolled 80 consecutive patients with non-ischaemic HFrEF with New York Heart Association class II or III symptoms and a median (interquartile range) LV ejection fraction of 25 (18–33)%. CI was 304 (262–373) μg/g dry tissue. CI was not related to immunohistological findings or the presence of cardiotropic viral genomes in EMBs and was not related to biomarkers of systemic iron status or anaemia. Patients with CI in the lowest quartile (CIQ1) had lower body mass indices and more often presented with heart failure histories longer than 6 months than patients in the upper three quartiles (CIQ2–4). CIQ1 patients had higher serum N-terminal pro-B-type natriuretic peptide levels than CIQ2–4 patients [3566 (1513–6412) vs. 1542 (526–2811) ng/L; P = 0.005]. CIQ1 patients also had greater LV end-diastolic (P = 0.001) and end-systolic diameter indices (P = 0.003) and higher LV end-diastolic pressures (P = 0.046) than CIQ2–4 patients. Conclusion: Low CI is associated with greater disease severity in patients with non-advanced non-ischaemic HFrEF. CI is unrelated to systemic iron homeostasis. The prognostic and therapeutic implications of CI measurements in EMBs should be further explored

The No-Win Resuscitation: Ventricular Septal Rupture and Associated Acute Aortic Occlusion

A 66-year-old patient was admitted under continuous resuscitation for pulseless electrical activity. After return of spontaneous circulation ECG showed signs of acute inferior ST-elevation myocardial infarction, and echocardiography showed acute right ventricular failure with a dilated right ventricle. Carotid pulses were present in the absence of femoral pulses. Subsequent computed tomography demonstrated inferior myocardial infarction with ventricular septal rupture and thrombotic occlusion of the thoracic aorta, resulting in a heart-brain-circulation with loss of perfusion downstream of the aortic arch. Teaching Points. The present case prototypically demonstrates the fatal consequence of acute ventricular septal rupture and the eminent value of computed tomography and palpation of carotid in addition to femoral pulses in resuscitated patients. It is, to the best of our knowledge, the first description of an acute aortic occlusion in a patient with acute ventricular septal rupture