Infarct Combat Project
Originally published in Ars Cvrandi, a Brazilian medical journal, Volume 35 - nº 3 - May 2002.
English translation by ICP, 2013
Cardiotonic: Insuperable in preservation of myocardial stability, as preventive of acute coronary syndromes and responsible for a prolongued survival.
Casuistic of 28 years (1972-2000)
Quintiliano H de Mesquita*, Claudio A. S. Baptista**
* Honorary Professor of the Faculty of Medicine from the Federal University of Paraíba; Founder and Chief of of the Cardiology-Angiology Institute of Matarazzo Hospital, 1945-1979; Founder and Executive Director of the Myocardial Infarction Combat Institute, 1999-2000; Sao Paulo - SP, Brazil
** Cardiologist of the Brazilian Society of Cardiology and of the Brazilian Medical Society; Assistent of the Cardiology-Angiology Institute of Matarazzo Hospital; Duty in Chief of the Coronary Unit of Matarazzo Hospital; Former Chief of the Cardiology Service of Cruz Azul Hospital from Sao Paulo; Cardiologist of the Trainning and Research of Olimpic Center in Sao Paulo; Former President and Actual Member of the Scientific Commission of Sao Paulo for Sport Medicine.
Faithfully about the new pathophysiological concepts of the Myogenic Theory and inspired by the exceptional results of the cessation of unstable angina and of infarcting clinical picture with the use of cardiotonic, we decided to extend its use to the stable symptomatic or asymptomatic coronary-myocardial disease with or without previous myocardial infarction, having as our aim to preserve the myocardial stability and prevention of the acute coronary syndromes – heart failure, unstable angina, acute myocardial infarction and sudden death; representing in this way the specific, essential and insuperable therapeutic, proved through the confrontation of 3 periods and 2 different therapeutic routines and also as responsible for the prolonged survival during the last 28 years.
In coronary-myocardial disease (CMD) the use of the cardiotonic, as specific in the treatment of acute coronary syndromes, was already considered in earlier studies developed by our group (1, 2, 3, 4), with the registry of surprising and immediate restraining of unstable angina in crescendo (UA) – preinfarction angina – without the consequent and usual acute myocardial infarction (AMI).
In cases usually designated as acutely infarcted, the cardiotonic developed important effects over the enzimatic peaks and major clinical and evolutionary transformations. This led us to describe these patients as having infarctioning clinical picture (ICP) with evidences of avoided infarction in 20% of the cases, ICP-halted in 47% and ICP-infarcted, but mitigated, in 33% of the cases treated in this manner, inside an average of 8 hours from crisis-hospital interval. As a direct consequence we have established a revolutionary precocius deambulation determined in the 5º day for the 2 first cases (ICP-avoided and ICP-halted) and 10 days in the last case (ICP-infarcted), discharged from hospital the following day.
This specific therapy has led us to the consideration (1) of the return to myocardial symptomatic stability in these acute syndromes, recognizing such cases without previous myocardial infarction (NPMI), including those with UA restrained that return to compose the list of cases of the 1st stage of CMD, as stable angina pectoris (SAP) or asymptomatic ischemic process, caused by efforts. While in earlier cases affected by ICP, also returning to myocardial symptomatic stability, became designated as cases with previous myocardial infarction (WPMI).
We have already demonstrated the need to separate these two groups of cases because they represent different pathological grades in their clinical course and regarding to prognostic.
We consider UA and AMI as transitory clinical accidents in the natural evolution of CMD by breaking the contractile stability of the myocardial segment coronary-dependent, but easily preventable through cardiotonic therapy.
In reality the two groups of cases considered NPMI and WPMI should represent the permanent objective of the cardiologist: to preserve myocardial and symptomatic stability with lifetime use of the cardiotonic associated with coronary dilator and ACE inhibitor, ensuring the prevention of acute coronary syndromes: UA, AMI, heart failure (HF) and sudden death (SD).
In our book from 1991 (5), in the chapter: "Comparison of two periods and two therapeutic routines", representing a study in periods of 17 years (before and after 1972), it was demonstrated the insuperable and indispensable role of the cardiotonic in the two group of cases, when it became apparent that the incidence of HF was shown always predominant over the AMI in NPMI and WPMI treated with and without cardiotonic. These aspects does not yet received consideration by the orthodox cardiology that is only concerned with surgical and invasive measures of myocardial reperfusion as prevention of AMI in prolonging survival.
Methods and Results of the Therapeutic
In the present paper is showed the casuistry of the last 28 years (1972-2000) with both groups NPMI and WPMI, as proof of the new therapeutic concepts advocated by the Myogenic Theory.
From the appreciation of Tables 1-6 we reach important data, by comparing the records and the distribution of 994 NPMI cases and 156 WPMI cases by the different age groups on the admission (Table 1) and at the end of the observations (Table 2). Was well characterized the long term survival, with particular record of 29 cases that reached more than 90 years and with low mortality in 10 cases.
Since our 1st study on the comparison of cases treated with and without the cardiotonic, it became apparent that the cases WPMI have advanced pathology and prognostic more severe through the morbidity and mortality rates, even though they have been shown to benefit from the use of the cardiotonic.
It was clear that even cases NPMI and WPMI treated with cardiotonics should be distinctly displayed in order to obtain true statistical indices, especially because when aggregated the 2 groups, the indices are reduced by the presence of NPMI cases.
Note that the cases with restrained UA well as cases of stable angina or asymptomatic coronary-myocardial disease, the NPMI and WPMI patients treated with cardiotonics show preserved myocardial and symptomatic stability with low morbidity and mortality rates.
It should be considered that at the time of admission of patients the global average age for NPMI was 60 years and for WPMI, 57 years (Table 1); while at the closure of the observations (Table 2) are shown respectively with 69 and 66 years. Characterized in both groups the numerical prevalence and percentage of cases in the age groups of 40-79 years in the 1st phase; however recording in the final phase the displacement of the highest rates of the age groups of relatively younger to the older, flagrantly of 70 to over 90 years. Thus correspond to important prolongation of survival in cases of CMD patients treated with cardiotonics within the last 28 years.
We should point out (Table 5) that the rates of mortality proved rather encouraging when compared with the records of cases treated without cardiotonic. Especially in WPMI cases whose pathology is more advanced and in which our indexes show significantly reduced in both periods 17 and 28 years when faced with that observed in the 17 year period without the cardiotonic use (Table 6: Groups 1a and 2a – 1b e 2b – 1c and 2c).
Results and Confrontation of 3 Periods and 2 Therapeutic Routines
Since our first work on the confrontation of periods and therapeutic routines, the registry of elevated ages at death has been confirmed also in the overall period of 28 years with an average of 76 years in cases NPMI and 72 years in WPMI, treated with cardiotonics, while without the use of cardiotonics the average age in both groups was recorded in 64 years.
According to the precepts of the Myogenic Theory the therapeutic of CMD from the period 1972-00 has been exclusively clinic, with the goal of preservation of myocardial and symptomatic stability in NPMI cases and WPMI cases, actually preventing the UA, AMI, HF and SD which started to be seen with low morbidity and mortality rates and prolonged survival.
The confrontation between the periods of treatment with and without cardiotonics (Table 6) shows that the morbidity and mortality of patients treated only with the use of coronary vasodilators (Papaverine, prenylamine, Verapamil, and nitrates) presented exaggerated indices in marked contrast to those treated with the use of cardiotonics. At the same time it also became evident that the WPMI cases were characterized by advanced pathology and poor prognosis compared to NPMI cases.
When we consider the 3rd period as globalization of the study of cases treated with cardiotonic during the 28 years, we verified at its end that the morbidity and mortality rates are perfectly acceptable and serve as a demonstration of the therapeutic advance and that the cardiotonic has demonstrated to be specific, indispensable and insuperable.
We have registered in CMD the heart failure as the condition of higher incidence and predominant over the acute myocardial infarction. So it has caused us great concern that the cardiologic orthodoxy has dispensed the latter, making every effort and resources of medical therapy, invasive and surgical, for the restoration of myocardial reperfusion. Our therapeutic approach is complemented by the myocardial revascularization providentially developed by coronary collateral circulation which has shown dynamic, permanent and continuous, especially in cases of complete obstruction of the major epicardial arteries without registration of MI or HF. On the other hand the invasive and surgical procedures, intending to myocardial reperfusion have been temporary and repetitive.
Registry in Admission of Patients with
Stable Coronary-Myocardial Disease NPMI and WPMI
|Cases NPMI||Cases WPMI|
|20-29 y||1-0,1%||1||28 y|
|30-39 y||7-0,7%||7||36 y||3-1,9%||3||35 y|
|40-49 y||49-4,9%||30||19||44 y||13-8,3%||11||2||45 y|
|50-59 y||164-16,4%||81||83||55 y||23-14,7%||21||2||55 y|
|60-69 y||258-25,9%||127||131||64 y||49-31,4%||38||11||64 y|
|70-79 y||304-30,5%||156||148||74 y||51-32,6%||43||8||74 y|
|80-89 y||182-18,3%||93||89||83 y||15-9,6%||13||2||83 y|
|> 90 y||29-2,9%||9||20||91 y||2-1,2%||2||92 y|
|Global mean age: 69 years||Global mean age: 66 years|
|Male: Min: 28 y - Max.: 94 y||Male: Min: 32 y - Max: 95 y|
|Female: Min: 43 y - Max: 98 y||Female: Min: 47 y - Max: 84 y|
Duration of Observations and Treatment: 994 NPMI Cases
Deaths in the period (1972-00)
|Cases||Age groups with number of cases subtracted the deaths|
|1 -- 28 years||20-29 y||30-39 y||40-49 y||50-59 y||60-69 y||70-79 y||80-89 y||> 90 y|
|1º - 994||3||11 - 2||15 - 3||15 - 3||3||47 (-8)|
|2º - 947||2||13||33 - 3||37 - 3||36 - 4||7 - 2||1||129 (-12)|
|3º - 818||9||20||26 - 1||15 - 5||11 - 3||81 (-9)|
|4º - 737||2||4||23 - 2||11||28 - 4||8 - 3||1||77 (-9)|
|5º - 660||3||7||20||36 - 1||19 - 2||15 - 2||1||101 (-5)|
|6º - 559||5||6||18 - 1||19 - 2||17 - 4||65 (-7)|
|7º - 494||12 - 1||15 - 3||20 - 3||8 - 4||55 (-11)|
|8º - 439||1||5||8 - 1||13 - 2||20||6 - 4||4 - 3||57 (-10)|
|9º - 382||2||6 - 1||12||18 - 4||13 - 5||3 - 1||54 (-11)|
|10º - 328||1||5 - 2||11 - 2||22 - 3||14 - 4||2||55 (-11)|
|11º - 273||5||12 - 2||9 - 1||4 - 2||3||33 (-5)|
|12º - 240||3||10 - 2||14 - 4||10 - 4||2 - 1||39 (-11)|
|13º - 201||2||8||7 - 2||10 - 1||2 - 1||29 (-4)|
|14º - 172||4 - 1||4 - 1||8 - 1||10 - 2||2 - 1||28 (-6)|
|15º - 144||1||4||7 - 1||9 - 4||1||22 (-5)|
|16º - 122||2||3||9 - 2||6||20 (-2)|
|17º - 102||5 - 1||6 - 2||5 - 3||16 (-6)|
|18º - 086||1||3||7 - 1||1||12 (-1)|
|19º - 074||2 - 1||5 - 1||2 - 1||1||10 (-3)|
|20º - 064||1||1||2||7||2 - 2||13 (-2)|
|21º - 051||3||3||4 - 1||10 (-1)|
|22º - 041||1||5||2 - 1||2 - 1||10 (-2)|
|23º - 031||2||3||2 - 1||2||9 (-1)|
|24º - 022||2||1||3|
|25º - 019||1||1||1||3|
|26º - 016||4||4|
|27º - 012||3||3||1||7|
|28º - 005||1||3||1||5|
Duration of Observations and Treatment: 156 WPMI Cases
Deaths in the Period (1972-00)
|Cases||Age groups with number of cases subtracted the deaths|
|1 -- 28 years||30-39 y||40-49 y||50-59 y||60-69 y||70-79 y||80-89 y||> 90 y|
1º - 156
|1||4||3||9.||2||1 - 1||20 (-1)|
2º - 136
|2||3||4 - 1||1 - 1||3 - 1|
3º - 122
|1||3||3 - 1||5||2 - 1||1||1 - 1||16 (-3)|
4º - 107
|2||2||1 - 1||2||7 (-1)|
5º - 100
|1||1||4 - 2||2 - 1||5 - 2||1||14 (-5)|
6º - 086
|1 - 1||2 - 2||4 - 1||7 (-4)|
7º - 079
|3 - 1||1 - 1||1||5 (-2)|
8º - 074
|1||2 - 2||1 - 1||4 (-3)|
9º - 070
|3 - 1||3 - 3||2 - 2||2 - 2||10 (-8)|
10º - 060
|6 - 3||2 - 1||1 - 1||9 (-5)|
11º - 051
|3 - 2||6 - 2||9 (-4)|
12º - 042
|1||2 - 2||1||2 - 2||6 (-4)|
13º - 036
|2 - 2||3 - 3||1 - 1||6 (-6)|
14º - 030
|2||3 - 1||1 - 1||6 (-2)|
15º - 024
|1||1 - 1||2 (-1)|
16º - 022
|3 - 1||3 - 3||6 (-4)|
17º - 016
|3 - 2||1 - 1||4 (-3)|
18º - 012
|1||1 - 1||2 (-1)|
19º - 010
|1 - 1||1 - 1||2 (-2)|
22º - 008
|1 - 1.||1 (-1)|
23º - 007
|1||2 - 1.||3 (-1)|
24º - 004
25º - 003
27º - 002
28º - 001
Recording on Morbidity and Mortality in Stable Coronary-Myocardial Disease
|Cases NPMI||Cases WPMI|
|994 Cases||156 Cases|
|Myocardial Infarction: 14 cases (1,4%)||MI: 8 cases (5,1%)|
|Heart Failure: 35 cases (3,5%)||HF: 17 cases (10,8%)|
|Mortality: 142 cases (14,2)||Mortality: 64 cases (41%)|
|Male: 81 cases (57%)||Male: 55 cases (85,9%)|
|Female: 61 cases (43%)||Female 9 cases (14,0%)|
|Cause of Death||Cases %||M||F||Cases %||M||F|
|Sudden Death||72 (7,2%)||39||33||32 (20,5%)||26||6|
|Heart Failure||32 (3,2%)||18||14||17 (10,8%||15||2|
|Stroke||13 (1,3%)||8||5||7 (4,4%)||6||1|
|Cancer||14 (1,4%)||8||6||3 (1,9%)||3|
|Other causes and|
|Surgical||6 (0,6%)||4||2||2 (1,2%)||2|
|Rupture of abdominal|
|aortic aneurysm||1 (0,1%)||1||2 (1,2%)||2|
|Accident||4 (0,4%)||3||1||1 (0,6%)||1|
|Median age at death: 76 years||Median age at death: 72 years|
|Male: 81 cases; mean age: 78 years||Male: 55 cases, mean age: 71 years|
|Mín: 52 y and Max: 91 y||Mín 55 y and max 95 y|
|Female: 61 cases; mean age: 74 years||Female: 9 cases, mean age: 72 years|
|Mín: 50 years and Max: 93 years||Mín: 58 y and Max: 86 y|
Confrontation of Three Periods and Two Therapeutic Routines
Over almost three decades we have followed other treatment options for CMD and unfortunately many aspects still remain undefined.
Often in the daily clinical practice we have observed different conducts in presentations of similar angiographic or clinical pictures.
The techniques of reperfusion with the use of thrombolytic agents or catheter are based on the paper from Wood et al., having as substrate the presence of primary coronary thrombosis (6). Regarding thrombolytics, important observations and comments also deserve attention based on studies (7-8):Absolute contraindications for use in 20% of patients; no benefits for patients with previous CABG, poor myocardial function and cardiogenic shock, which are excluded in most trials; side effects, especially bleeding (3.9% per 1000 patients) and above the 75 years, 20% remain at risk of developing recurrent ischemia and reinfarction, even with the combination of aspirin and heparin (8).
Controversies persist comparing the use of trombolytics and primary angioplasty with some very well-conducted studies concluding that the experience of the assistance medical service and its availability are critical to the results, which may bring difficulties to realize if the data information is really correct (9).
Restenosis in angioplasty cases still remains a challenge. Stents, although interfering significantly in reducing restenosis, and new interventions, do not reduce mortality, a fact that would not be expected (10).
In the same period we remained faithful to the cardiotonic therapy.
The confrontation between the NPMI cases with and without cardiotonic the morbidity and mortality rates show up really acceptable, but the treated with cardiotonic are exceptionally better defined, however, WPMI cases without the cardiotonic use are marked by alarming rates and compared with those treated by cardiotonic there is the consecration of our therapeutic concepts advocated by the Myogenic Theory. Furthermore, it is evident that the incidence of heart failure is actually prevailing over the myocardial infarction. Also the life expectation rose from 64 years (1954-71), in cases NPMI and WPMI, to 70 and 72 years (1972-89) and to 72-76 years in the global period (1972-00) using the cardiotonic, representing exceptional mortality of 1.4% per year in cases with previous myocardial infarction and of 0.5% per year in cases without previous myocardial infarction.
In the natural evolution of coronary-myocardial disease becomes evident that the period of myocardial stability is long both in symptomatic and asymptomatic or silent, marked with tolerable rates of morbidity and mortality even without the use of cardiotonic, with the heart failure showing with levels prevailing on the incidence of myocardial infarction.
However, with the declared myocardial and symptomatic instability the evolution to the acute myocardial infarction is readily noticed by the usual sequence of unstable angina and acute myocardial infarction with or without Q-wave.
From this point what has been observed is that all indexes are excessively aggravated, while the use of cardiotonic appears very effective in cases NPMI as well in WPMI, the indices of morbidity and mortality are repressed and show low levels that characterize very well our concepts of the cardiotonic as specific, essential and insuperable, with the addition of coronary dilators and angiotensin-converting enzyme.
Related papers translated to English in 2013, published at ICP
1) Quintiliano H. de Mesquita, Claudio A. S. Baptista, Sostenes V. Kerbrie, Sonia Maria Mari, Maria Consuelo B. M. Grossi, Jose Monteiro. Effects of the Cardiotonic + Coronary Dilator in Chronic Stable Coronary-Myocardial Disease, with and without Prior Myocardial Infarction, in the Long Run. Ars Cvrandi 2002 (september);35:7
2) Quintiliano H. de Mesquita, Cláudio A. S. Baptista, Sóstenes V. Kerbrie, Sônia Maria Mari, Maria Consuelo B. M. Grossi, José Monteiro. Effects of the Cardiotonic + Coronary Dilator in Unstable Angina.
3) Quintiliano H. de Mesquita, Cláudio A. S. Baptista, Sóstenes V. Kerbrie, Sônia Maria Mari, Maria Consuelo B. M. Grossi, José Monteiro. Effects of the Cardiotonic + Coronary Dilator in the Infarcting Clinical Picture.
Mesquita, QHde: Livro, Teoria Miogênica do Enfarte Miocárdico – Novos conceitos de Fisiopatologia e Terapêutica, Edição do autor; julho, 1979. (Myogenic Theory of Myocardial Infarction – Book, Download free of Charge - Summary in English at http://www.infarctcombat.org/MyogenicTheory.html )
Mesquita, QHde: Cardiotônico e enfarte agudo do miocárdio no homem, RBCTA; 1981:10646-63 .
Mesquita, QHde, Baptista CAS: Porque Teoria Miogênica e não Teoria Trombogênica; Arq Bras Cardiol: Vol 62 (nº 4), 1994
Mesquita, QHde, Baptista, CAS, Mari, SM: Angina Instável: Etiologia Aterosclerótica, Fisiopatologia Miogênica e Terapêutica Cardiotônica , Ars Curandi, 1999; 32:12-19.
Mesquita, QHde: Como escapar da ponte de safena e do enfarte do miocárdio só com remédio, Editora Ícone, 1991.
De Wood, MA, Spires J, Notske R, et al, Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction N Engl J Med, 1980;303:897-902
Fibrinolytic Therapy Trialists (FTT) Collaborative Goup. Indications for fibrinolytic therapy in suspected acute myocardial infarction. Collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet 1994;334:311-22
The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO Trial. N Engl J Med 1993;329:673-80
Gibbons RJ, Holmes DR, Reeder GS et al, Immediate angioplasty compared with the administration of a thrombolytic therapy agent followed by conservative treatment for myocardial infarction. The Mayo Coronary care Unit and Catheterization Laboratory Groups. N Engl J Med 1993;328:685-91
Antoniucci DA, Santoro GM, Bologuese L et al, A clinical trial comparing primary stenting of the infarct-related artery with optimal primary angioplasty for acute myocardial infarction. J Am Coll Cardiol 1998;31:1234-9