Mircea CINTEZA

Coronary angioplasty (PCI) is probably the most important invasive therapeutic tool developed in cardiology in the last 30-40 years. As we know, it addresses to obtain reperfusion in ischemic heart disease and especially in acute myocardial infarction (AMI). Reperfusion in large coronaries is obtained in almost all cases. But – here comes the drama – reperfusion in the myocardium is less. Some authors believe that no-reflow (NR) is common in about 10% of interventions in AMI, others suggest a proportion of 60% (!) (1), while the solid study published a few years ago by Rezkalla (2) reports that 32% of coronary angioplasties in AMI are followed by the no-reflow phenomenon. These figures may be influenced by the diagnostic method used and we will make further comments on this subject.
No-reflow phenomenon is a serious problem which is caused by many reasons. Firstly, the prognostic impact of no-reflow is great and counterbalances the immense advantage of getting reperfusion in large coronaries. Secondly, we do not know the exact mechanism. Thirdly, current therapies are more or less disappointing (1, 3, 4).
The prognostic implications are important. Firstly, it is clearly demonstrated that the ejection fraction is lower, remodelling of the left ventricle is worth, consecutive heart failure is more severe and cardiac rupture more common after PCI in AMI in patients with NR comparatively to those without NR (1, 3). One simple explanation is that, if there is NR, repairing cells and humoral factors cannot enter in that area to promote healing. What is the most important, the prognostic importance of NR is huge. In patients with NR, the one-year and five-year risk of death is three and two times higher, respectively, than in those without NR (3).
The main diagnostic tools come from coronarography. TIMI Grade less than 3, Myocardial Blush Grade less than 3 or higher TIMI frame count are currently used to diagnose and try to quantify the no-reflow (1, 3). However, all these three methods are not perfect, because the complexity of the NR phenomenon develops after performance of coronarography in the acute phase. For this reason, magnetic nuclear resonance (MRI) is the best method to diagnose NR. It is demonstrated that up to 60% of patients with a TIMI or Blush score of 3 (means normal perfusion) have actally elements of no-reflow at MRI (3). Contrast echocardiography or scintigraphy may also be taken into account, but they do not have the diagnostic value of MRI.
The physiopatholgy of NR is complicated. The main mechanisms involved include myocardial edema developed during acute ischemia prior to reperfusion, which compresses the intramyocardial vessels, and reperfusion injury caused by the free radicals developed during ischemia and which damages the myocardium and microvessels once they are spread when reperfusion is restored or distal embolization of atheroma debris or platelet rich microthrombi are displaced by the baloon during the procedure (1, 3). If so different mechanisms are supposed to act, it is clear that a single therapy cannot be imagined.
Indeed, therapies for every of the imagined mechanisms were applied and unfortunately, not a single one succeeded in being significantly effective. Some benefit is obtained, however.
Non-pharmacological approaches:
• Thrombus aspiration is a logical approach, in order to block supposed microemboli during baloon inflation. Aspiration of thrombi before PCI and stenting as well as using devices distal to the baloon to catch the microemboli showed no reduction of NR and no clinical benefit (1, 3, 4).
• Mechanical ischaemic postconditioning is based on experimental data showing that brief and repeated ischaemia provoked by baloon inflation immediately after reflow may significantly reduce the infarct size. Initial data on few patients suggested such a reduction by 40-50%. However, consecutive studies on large population of reperfused AMI showed no clinical benefit (3).
Pharmacological therapies were addressed to different supposed mechanisms.
• Adenosine is a potent arteriolodilator. It had initially good results in small trials, but later on, serious trials such AMISTAD II showed no clinical benefits. Adenosine was even injected in coronaries, with no effect.
Only some late small trials suggested reduced short term mortality (3).
• Glycoprotein IIb/IIIa inhibitors were supposed to act on microemboli produced by the distruction of the occluding thrombus of the large coronary. Small benefits were noted by using intracoronaru abciximab (2).
• Various calcium channel blockers were tried, including verapamil, diltiazem and nicardipine. The clinical benefit was small, but it was foud repeatedly (1-3).
• Sodium nitroprusside administered by intracoronary repeated small bolus injections showed benefit on major adverse events. Today it is considered the main pharmacologic adjunct, but hypotension should be drastically monitored (2, 3).
• Metoprolol has been also tested, with some promising results (3).
• Other pharmacologic therapies such as epinephrine, nicorandil, imatinib, cyclosporine A or liraglutide were tested on small groups of patients (1-3).
The most promising approach to reduce the no-reflow phenomenon seems to be the combination of mechanical and some pharmacological approaches adjunctive to the large coronary reperfusion procedure (1).
From all these, the only therapy able to fight no-reflow which is mentioned in the 2017 ESC STEMI Guidelines involves the use of abciximab as a bailout procedure in the postinterventional moments. But this is only a IIa C recommendation (5). The ACCF/AHA Guidelines for STEMI date back to 2013 (6). In the text it is mentioned that ”No-reflow is associated with a reduced survival rate”, thrombus aspiration and some pharmacological approachs for NR are mentioned in two phrases, both finishing with the assumptions ”without consistent effect” or ”not all studies have shown positive results” (6). In an American comment on the 2017 ESC Guidelines on STEMI, there are 10 points of observations. From these, the first seven make reference to PCI reperfusion, which may be a main therapeutic tool (7).
No mention of no-reflow in these comments. All the other European or American Guidelines on AMI in the last decade do not comment on the no-reflow phenomenon.
We may say that:
• PCI reperfusion is the main non-pharmacological tool in AMI (and probably the main therapy overall)
• In all cases, no-reflow appears (probably) during the procedure
• No-reflow consistently produces a worth prognosis and increased mortality
• Many possible mechanisms are supposed for NR, but no one is considered to be the main
• From the more than 10 therapies which have been tested, only one – abciximab – is mentioned as a IIaC bailout procedure in only one of the many European and American Guidelines on AMI in the last decade.
Interventional revascularization in AMI is the main therapeutic tool in AMI. The accompanying no-reflow is the main unconquered fortress.

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Mircea CINTEZA

Aspirin is known since millennia. The substance called acetylsalicylic acid was given the name Aspirin by Bayer, in 1899. Later on, Bayer lost or saled this trademark and the name aspirin is used today almost like a generic name.
Aspirin was used as an antiinflammatory drug since centuries. It was recognized as an antithrombotic drug since 1950 (1), and from the ’80s of the last century to the present, it has been using for cardiovascular (CV) prevention.
There is absolutely no doubt about its use in secondary prevention, as indicated in all current guidelines (excepting contraindications) – for secondary prevention, the benefit is much larger than the harm.
But what about primary prevention? For decades, the same thing was thought to be true. The benefits, not as large as in secondary prevention, were considered to exceed, however, the harms. The most known argument in this direction was offered by the ATT Collaboration in 2009 (2). Even today, both European and American guidelines on diabetes recommend aspirin for cardiovascular prevention in patients with diabetes without prior major cardiovascular (CV) events (3, 4).
Of course, what represents primary versus secondary prevention remains a matter of discussion. Primary prevention considers the therapy given to a person who did not have any major CV event such as myocardial infarction or stroke. However, someone who has a cluster of cardiovascular risk factors, but not also (yet) a major CV event, is often at a higher risk for a cardiovascular event than an individual who had a – let’s say accidentally – myocardial infarction. In this case, prevention – despite being called ”primary” – may be more important for the first person with a high CV risk than for the second one, when it is called ”secondary”.
And now, the storm comes... After years of accepting that the benefit of Aspirin is greater than the harm in different forms of primary prevention, the most respected New England Journal of Medicine – and not only – has lately published a series of papers demonstrating that, in different forms of primary prevention and various populations, the harm of aspirin exceeds or, in the best case scenario, equals the benefit in what is called ”primary prevention” (5-8).
Trying to find explanations in an analysis on randomized trials of primary prevention on more than 100 000 patients, Rothwell et al (9) considered, among other factors, the necessity of dosing the aspirin according to body weight. No positive result in this direction has been obtained yet (9).
The recent literature regarding the low benefit of aspirin in primary cardiovascular prevention is not limited to the cited titles. The 2018 conclusion to date is not to stop aspirin for primary prevention, but to re-analyze all conditions into which aspirin is prescribed for CV prevention on a lifetime manner.
I think that one of the answers will come when we will abandon the terms primary and secondary cardiovascular prevention. When a person with numerous CV risk factors has been already demonstrated to have atheroscletoric vacular disease, although not yet with a prior major event, we may not say that he/she is in simple primary prevention.
I think we should simply say that we perform cardiovascular prevention rather than secondary or primary prevention – just prevention based on a risk score calculated according to the ”classical” CV risk factors PLUS prior major CV events. The cut-off value where prevention with aspirin is warranted should be clearly defined.

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Mircea CINTEZA

One of them is Eugene Braunwald – the Patriarch of World Modern Cardiology. The other is Leonida Gherasim – the Patriarch of Internal Medicine in Romania. Both are born in 1929. Gherasim in February – the Old. Braunwakd in August – the Youngster.
Let us start with Braunwald. Born in Vienna, his family emigrated to the United States because of the terrible moments that Europe was undergoing. Step by step and in a very short period, young Eugene became master of cardiology at... Harvard, from where he became a guiding light to several generations of cardiologists worldwide.
Since 1980, 11 editions of the Heart Disease Handbook have been published, almost each with more than 2000 pages written in small characters. Also, each edition had Companions of Heart Disease: about 10 different handbooks on Cardiovascular Therapeutics, Heart Failure, Acute Coronary Syndroms, Hypertension, Valvular Heart Disease, Clinical Lipidology, Preventive Cardiology, and others. Professor Braunwald wrote more than 1000 scientific papers in top peer-reviewed journals, more than any other medical author from the 42 000 cited by PubMed.
He had one of the most important qualities of a scientist (and of a human being in general): imagination. His contributions in coronary syndromes, heart failure or valvular heart disease became outstanding.
He was elected to the National Academy of Sciences of the USA, and a permanent endowed chair was established in his name by Harvard Medical School.
Let us move on to Leonida Gherasim. He was born in a very small village in Olt county, Romania. His first years of primary education were spent in neighborhood schools. Then he continued studying diligently and gradually made his way into medicine at the University of Medicine and Pharmacy of Bucharest, Romania, today called ”Carol Davila” University.
He became Professor of Internal Medicine, and furthermore, a honorary member of the National Academy of Romania. He is editor-in-chief of the Romanian Textbook of Internal Medicine – several volumes, several editions, thousands of pages. He is one of the last enciclopedical spirits in medicine, each chapter of all the medicine specialities in this textbook being corrected and revised by himself. Very few doctors of today can navigate in all the fields of medical sciences like professor Gherasim does.
Both Professors, Braunwald and Gherasim, have a distinguishing characteristic of genius: modesty. Making the visit on the ward, they look like very simple and kind doctors at the bedside.
And their activity is briliant even today, when they are nearly 90.
Yesterday, professor Gherasim made the visit on the ward of our department and gave us an unexpected and excellent solution for a complicated case.
At the World Congress of Heart Failure in Vienna, two weeks before, professor Braunwald had five lectures, each linked to the newest domains of medicine. Asked what he would do if he could be 25 years old again and start studying medicine, he answered promptly: ”Genetics! And not only because friends use to call me‚ dear Gene’... but because genetics is the future of medicine”. And one of his brilliant lectures was on Genetics in Cardiomyopathies.
Let us love Braunwald and Gherasim as truly protective parents for us, their young medical suns and daughters who we are!

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Mircea CINTEZA

In the era of movement and transport, the name CAR does not mean a moving engine on a road only. It stands for Chimeric Antigen Receptor too, also known as chimeric antigen T cell receptors or briefly, CAR-T. These cells are, and promise to become, one of the most powerfull modalities to cure cancer cells by immunologic therapy (1-3).
CAR-T cells belong to a larger family of immunological therapies of cancer called Adoptive T Cell Therapy (ATC), which includes different models of engineering T cells in order to attack and kill cancer cells (4). Examples of such therapies include TIL (Tumor Inflitrating Lymphocytes), TCR (T-cell receptor Redirected cells), Armoured T-cells and others. However, the most developed technology of ATC is that of CAR-T cells. This was most often used in clinical trials, and in some very difficult conditions it had excelent results in lymphocytic leukemias and different types of Hodgkin disease. The other techniques, as well as CAR-T itself, constitute today a great hope to attack solid tumors (1-4).
The name of CAR-T cells comes from the idea that they are „chimeric”, meaning that they have compounds of different origins. Indeed, the main way to produce a CAR-T cell is to transfer to it a monoclonal antibody directed towards a specific cancer antigen. This is generally obtained by retroviral vectors (1-4). Today, genetic engineers are working with the fourth generation of CAR-T, which constitute a real „living drug” against cancer.
The most remarkable results were obtained in difficult cases of Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphoblastic Leukemia (CLL) in children and adolescents and in Hodgkin Lymphoma in adults. In these cases, the T-cell antibody is directed towards the CD-19 antigen, which is present on the surface of the lymphocyte B-cells and only there. Cancers linked to B-cells, like those mentioned above, present the CD-19 antigen, which is attacked with high efficacy by CAR-T prepared against this antigen.
Eighty percent of children with ALL respond to standard therapies, but those who do not have no other therapeutic alternative and are condemned. In 2014, a team from Philadelphia treated 30 such children with ALL refractory to any other therapy with CAR-T cells, and complete remission at two years was obtained in 27 out of 30 (5). Some other simmilar successes were reported.
Given these achievements, FDA gave two approvals for CAR-T cell therapies in humans in 2017: the first one, in August 2017, was for the so-called tisagenlecleucel (Kymriah™) to treat children and adolescents with ALL, and the second for axicabtagene ciloleucel (Yescarta™) to treat adult solid lymphoma. Both products are based on CAR-T cells directed against the CD-19 lymphocytic B-cell antigen.
The great challenge of ACT therapies, including mainly CAR-T, is to treat solid tumors. The challenge is to find, on the surface of such different solid tumor cells, specific antigens found only there, which can be attacked. Once the antigen is identified, the way of constructing the appropriate antibody seems not to be too complicate.
In the excellent review of D’Alloia et al. regarding this subject, 17 such antigens are described in very different solid tumors against which experimental and clinical trials are already taking place (2). Small clinical trials on mesothelioma (pleural), melanoma, ovarian cancer, brain glioblastoma, hepatic colorectal glioblastoma, peritoneal carcinomatosis, pancreatic cancer and lung cancer are already reported (6). Most of these examples have today no therapeutic alternative. Besides the difficulty to find the appropriate antigen target, there is another common difficulty: around solid tumor cells there is often a liquid micro-ambient which abruptly lowers the power of action of antibodies fixed on the CAR-T (2-4). Using Armored T-cells could be one solution for this obstacle.
Another very important problem is the side effects, sometimes so strong that they kill by themselves. Some examples include: Cytokine release syndrome (CLS), neurological toxicity, On-Target, Off-Tumor Toxicity, Insertional Mutagenesis or anaphylaxis (1, 2).
The professional and financial investment in this domain is huge. Some obstacles and future directions are mentioned below (3):
- in the domain of Recognition, it is to overcome resistance (antigen loss) and tumor heterogeneity, and to identify combination signatures;
- in the domain of Proliferation/Persistence, better control is needed;
- in the domain of microenvironment of solid tumors, it is to identify and block the modalities by which tumors defend themselves against immunologic attack;
- precision medicine, including profound identification and use of genetic information, is another point where Immunologic Therapy of Cancer may interfere with tumor and host genetics to become more and more specific, more and more precise.

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Mircea CINTEZA

Reccomendations of the major guidelines in Hypertension (HT, with the meaning of systemic arterial hypertension) until November 2017 indicate almost uniform blood pressure (BP) therapeutic targets for the majority of pathologic conditions. Figure 1 makes a comparison between guidelines as in the year 2014 (1). The compared guidelines are the 2013 European Guideline (2), two North American Guidelines from 2014 (3, 4), one old American Guideline from 2003 (5) and the Canadian Guideline from 2013 (6). As we see, most of the blood pressure (BP) therapeutic targets were 140/90 mm Hg, with few timid exceptions: 140/85 mm Hg (only!) for diabetics in ESC/ESH Guideline (2), 130/80 mm Hg for diabetics in CHEP (6) and 130/90 mm Hg in patients with renal involvement in ESC Guideline (2). For the rest of the guidelines, till that date the targets are 140/90 for everybody, except for older people, for whom the accepted target could be 150/90 mm Hg.
It is curious that former guidelines, the cited JNC 7 guideline (5) and the ESC/ESH Guideline from 2007 (7) indicated other BP targets, such as 130/80 mm Hg, for some special conditions, like diabetes (5, 7). The argument for higher BP targets in the subsequent guidelines was that there were not sufficient data from large clinical trials to support lower BP targets. But we think that not every medical item which rises some questions finds a financial support for a new trial quickly enough to give a definitive answer. In our thought, the analysis from 2003 (5) or 2007 (7) to indicate a BP target of less than 130/80 for diabetics had enough scientific substance not to be necessarily replicated with new large clinical trials.
In 2015, the SPRINT clinical trial (8) changed the rationale of hypertension therapy as perceived until then. This was an important trial on more than 9000 hypertensive patients followed for 3.26 years. Patients in the intensively treated group (systolic BP target under 120 mm Hg) had a clearly better outcome than those in the standard therapy group (BP target under 140 mm Hg). The hypertensive patients included were at high risk for cardiovascular disease, but the trial did not include diabetics. Cardiovascular mortality at 3.26 years was reduced by 27% (from 0.43% per year to 0.25% per year, p=0.003) in the intensively treated group and the primary composite endpoint (myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes) was reduced from 2.19% per year to 1.65% per year (p<0.001). There were more adverse effects in the intensively treated group, but no important difference in serious adverse effects (SAEs). Overall, benefit exceeded harm.

Effect of SPRINT trial on Guidelines
Since the publication of SPRINT trial, hundreds of pages in serious journals appeared with Pro or Con comments to this study. However, as to date (October 2017), no official point of view regarding possible lower BP targets was communicated at the great European and North American Congresses on Hypertension or Cardiology. Key opinion leaders who participated in Task Forces responsible for the development of European and American Guidelines on Hypertension (2-4) published their opinions which seemed to show agreement with the higher therapeutic targets of those guidelines (9-11).
However, some official guidelines which appeared since 2015 began to promote another opinion.
The Canadian Hypertension Guideline from 2016 (12) indicates a target for BP treatment of under 120 mm Hg for systolic BP (without a specified target for diastolic BP) for the population considered at high risk, under 130/80 mm Hg for diabetics, and under 140/90 mm Hg for the rest of the patients, including those with chronic kidney disease, respectively. High risk patients include clinical or subclinical cardiovascular disease, estimated 10 years global cardiovascular risk of more than 15%, kidney disease patients with some characteristics, but also people over 75 years of age. Elderly often do not tolerate low BP levels.
The Australian Guideline for the diagnosis and management of hypertension in adults (13) recommends that all patients receiving treatment should reach a target of less than 140/90 mm Hg. However, in those who were judged on clinical grounds to be at high risk and in whom more intense treatment was considered to be clinically safe and therapy was well tolerated, a target of less than 120 mm Hg systolic BP was considered to be reasonable. The guideline makes comments on this. Firstly, the diastolic target is not suggested by the new trials taken into consideration, e.g., the SPRINT trial. The diastolic target remains less than 90 mm Hg. Secondly, reaching a target of 120 mm Hg could be difficult in patients with a very high initial BP or with a long history of HT, and could involve some risk in patients with several comorbidities. Thirdly, the calculation of the Australian algorithm of the total cardiovascular risk differs from that applied in the SPRINT trial. The Australian guideline concludes that the current recommendation to take a less than 120 mm Hg BP target in the selected population mentioned is subject to review in accordance with new information. To date it was not reviewed.
The American Guideline on Heart Failure revised in 2017 (14) is most decided in recommending low for BP targets for patients with heart failure (HF). For patients with increased risk among those with Stage A HF (high risk for HF), the target BP would be less than 130/80 mm Hg. High risk is defined as a population with established cardiovascular disease, those over 75 years of age, those with a Framingham risk score over 15% or those with chronic renal disease. Again, the taken age limit is 75 (like in CHEP – 12), and lowering BP at 130/80 in such a fragile population is an interesting new point of view. To note that the Class of recommendation is the best (Class I) and the strength is good enough (Level of Evidence B-R). This guideline recommends a target for systolic BP under 130 mm Hg for all patients with reduced systolic function or even preserved systolic function in stage C of HF (structural heart disease with symptoms of HF). In this case there is no diastolic threshold. Again, the Class is I, but with level of evidence C.

Two Types of Hypertension?
It is unusual that the results of clinical studies are so different from study to study and guidelines constructed on their basis have to change dramatically in short time intervals. And this happens today in a very clear clinical condition, which is hypertension.
Or maybe things are not yet completely understood or analysed. Let us make a short judgement regarding the distribution of hypertension with age. According to most of the epidemiological studies, HT becomes evident in a population at the age of 40 and increases continuously until the age of 80. The overall prevalence in all the adult population, including young people, is about 40-45% (2, 3). We may say, according to a AHA Statistics, that HT is present in 35% of adults at the age of 45, 55% at the age of 55, 65% at the age of 65 and 75% at the age of 75 (15, page e114). At the age of 65, the number of hypertensive patients is twice that of people with HT at the age of 45.
We may consider that HT developed over the age of 65 is mainly due to stiffness of the great arteries, is mainly systolic and accounts for half of the hypertension at the advanced age (about 40% of the total population). This category is added to the other half of the hypertensive patients at that age who had high BP starting with the adult age and whose HT is systolo-diastolic.
We may approximate that at the age of 75, 20% of the population is normotensive, 40% has systolo-diastolic HT and 40% has mainly systolic HT (Figure 2).
As it is known from epidemiologic studies and guidelines, systolic HT has different mechanisms, appears in a more fragile population and has to be treated in a different way than the systolo-diastolic HT of the middle age. The last one appears at a more robust population who has a much longer natural duration of life than old people.
We may conclude that there are two main types of hypertension: the middle age people HT, systolo-diastolic and present in a most robust population with a long expectancy of life, and the old people HT, half systolic due to stiffness and half coming from the middle age, systolodiastolic with a new systolic component. The old people are more fragile and have a shorter expectancy of life.
Together, these two types of hypertension appear in more than three quarters of the population who have attained the age of 75.

The bomb
On the 13th of November 2017, AHA, ACC and other 11 North American Medical organizations published their new “High Blood Pressure Clinical Practice Guideline” (16). It is a monograph of more than 150 pages analysing the evidence in hypertension available until mid-2017. After an analysis of more than 100 pages, the final table indicates a target BP for different categories of patients with a single value: 130/80 mm Hg.
Here are the categories of patients (16):
• clinical CVD or 10-year ASCVD risk ≥10%
• no clinical CVD and 10-year ASCVD risk <10%
• older persons (≥65; noninstitutionalized, ambulatory, community-living adults)
• diabetes mellitus
• chronic kidney disease
• chronic kidney disease after renal transplantation
• heart failure
• stable ischemic heart disease
• secondary stroke prevention
• secondary stroke prevention (lacunar)
• peripheral arterial disease.
For each of these categories, the target therapeutic BP is 130/80 mm Hg, except for the “older persons” one, for whom only the systolic BP target of less than 130 mm Hg is indicated.
I want to say from the beginning that I consider this radical change in the philosophy of treatment of hypertension as very positive. However, some curious things still exist.
Firstly, in 2014, over 40 North American medical societies claimed in JNC 8 that the almost uniform BP therapeutic target shoud be 140/90 mm Hg (3). Since then, no major evidence appeared, except the SPRINT trial, in which the „good” systolic BP target is... under 120 mm Hg. However, the re-appraisal of analyses of all the other available proofs leads today to a completely different conclusion.
Secondly, there is not enough differential analyses of the systolo-diastolic HT of the middle age and the systolic HT of the advanced age. As discussed before, the mechanism is different and the therapeutic consequences could be different. And different BP therapeutic targets should be probably defined for these two huge categories of hypertensive patients.

Conclusion
To date, we see that the same school of medicine, the North American one (it is right – with different groups of scientists), changed the phylosophy of hypertension therapy from an almost uniform target of 140/90 in 2014 towards an almost uniform target of 130/80 mm Hg in 2017. This happened taken into account mainly a clinical study in which the „best” BP target was... under 120 mm Hg for systolic BP. 2018 is the year in which the European guidelines are announced to be re-appraised. I think some confusion remains in this field of pathology, which includes hundreds of millions of patients worldwide.
Till then, I want to conclude with my own analyses of the main points of view. I think there enough arguments for the following:
• for middle age (40-65) hypertensive patients with little comorbidity and a long life expectancy, the BP therapeutic target should be under 120 mm for systolic BP;
• for middle age (40-65) hypertensive patients with diabetes, ischemic heart disease, mild to moderate heart failure or chronic kidney disease, the target BP should be 130/80 mm Hg;
• in old (over 65) hypertensive people with little comorbidity, the target BP should be 140/90 mm Hg;
• in frail old (over 65) hypertensive people with important comorbidities, the target BP should be under 150/90 mm Hg.
Not neglecting the guidelines, let us always look at the patient in face of us, and act according to his/her particular status, arguing our decision in written!

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Mircea CINTEZA

The last fifteen years... maybe twenty. If you drive and you approach the crossing corner, at least one passes in front of you looking attentively in his/her smartphone. You travel by train. Nobody is looking to the landscape. Everybody is playing on his/her tablet. Life through device. Farewell, real life!
Then it is normal that life preserved by medicine is more and more preserved by devices. The problem is to figure out what is the proportion in which therapy is delivered by devices instead of surgey or tablets. And another important problem – how much training it needs and how device therapy becomes a science per se.
I will try to check two specialities for device-based treatments – cardiology and neurology. Let us remember that there are at least 30 medical specialities and each of them is using some devices for therapeutic and diagnostic purposes.
What links cardiology most tightly to neurology is vascular involvement – which also produces pathology in any other teritories – upper limbs, legs, mesenteric territory, renal vessels and the whole aorta pathology. Everywhere in these territories, stents are used – starting with bare metal, continuing with drug eluting stents, covered stents and now with resorbable scaffolds. Sometimes, someone has several stents on one single vessel – means he or she lives, for instance, simply with a metal coronary artery. We have also managed to implant portions of plastic aorta – but unfortunately, to date, we did not succeed in replacing smaller diameter vessels with plastic – these still develop trombi, which cannot be managed.
We also use coils to close unwanted aneurysms or fistullae in vascular pathology, and umbrellas or other devices in the very complex and various pathology of congenital heart and vessel disease.
We largely use devices in electrophysiology, starting with pacemakers and continuing with implanted defibrillators. We also use energy to ablate anything unwanted – ectopies or pathological electric circuits – as well as resynchronisation of ventricular contraction to restore their pumping force.
Speaking of heart failure, here the progress is outstanding. We currently use implanted left ventricular assist devices, right ventricular assist devices or both. Their energy consumption is minimal, becasue they rotate in a magnetic field with no friction, except that with the blood. The batteries are kept at the belt and may be recharged in a room with transmit resonators which charge the batteries wireless through the receiving resonators of the patient.
These ventricular assist devices may be used as bridge to transplant, but already they are used as destination therapy, with several years of succesfull functioning.
The left or right assist devices are so small, that soon they will be implanted not surgically, but by interventional cardiology, as they are today only experimentally. The whole artificial heart to be implanted is also constructed – not yet for daily use in humans.
Valvular pathology is also treated by devices. TAVR or TAVI (Trans Aortic Valvular Replacement or Intervention) is currently used on hundreds – probably even thousands – of fragile patients with severe aortic stenosis. Severe mitral regurgitation may also be treated interventionally by the mitral clip.
In neurologic pathology, different pumps are used to deliver drugs on a very long term in disabling pathologies that until now have been considered not curable. For instance, such a pump may deliver intrajejunal Levodopa in advanced Parkinson disease and also Baclofen intratecal for severe spasticity.
Deep Brain Stimulation (DBS) is used for advanced Parkinson disease, neuromuscular distonies or essential tremor. Stimulation in the hipocampus is used in epilepsy but also for this illness vagal nerve stimulation. Spinal stimulation is also used for neuropathic pain.
Only the issues presented here for two medical specialities filled almost two pages. And we have only mentioned devices used for therapy, not those used for diagnosis as well. Knowledge about how to implant each device fills entire mono graphs and takes years of training. But without such devices, all the pathology we mentioned cannot be better cured or cannot be cured at all.
Let us imagine the years and years of imagination, passion and work it took the engineeres who have designed and constructed such devices! Hats off and a deep bow of respect for their hard effort!
Aknowledgements: Many thanks to Professor Ovidiu Bajenaru for his advice in the field of neurology.

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