Invasive Assessment of the Coronary Microcirculation Using the Index of Microcirculatory Resistance: Description and Validation of an Animal Model

INTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-μm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status.

Multiple Mechanical Complications in ST-Segment Elevation Myocardial Infarction with Angiographically Normal Coronary Arteries

This case report discusses an unusual presentation of ST-segment elevation myocardial infarction (STEMI) with normal coronary arteries and severe mechanical complications successfully treated with surgery. An 82-year-old man presented STEMI with angiographically normal coronary arteries and no major echocardiographic alterations at discharge. At the first month follow-up, he complained of fatigue and dyspnea, and contrast echocardiography complemented by cardiac magnetic resonance imaging revealed a large left ventricular apical aneurysm with a thrombus communicating by two jets of a turbulent flow to an aneurysmatic formation of the right ventricular apex. The patient underwent a Dor procedure, which was successful. Ventricular septal defects and ventricular aneurysms are rare but devastating complications of STEMI, with almost all patients presenting multivessel coronary artery disease. Interestingly in this case, the angiographic pattern was normal.

Percutaneous Treatment of Mitral Valve Regurgitation: Initial Experience with the MitraClip Device

INTRODUCTION: Mitral regurgitation (MR) is the most common valvular disease and has recently become the target of a number of percutaneous approaches. The MitraClip is virtually the only device for which there is considerable experience, with more than 20,000 procedures performed worldwide. OBJECTIVE: To describe our initial experience of the percutaneous treatment of MR with the MitraClip device. METHODS: We describe the first six MitraClip cases performed in this institution (mean age 58.5 ± 13.1 years), with functional MR grade 4+ and New York Heart Association (NYHA) heart failure class III or IV (n=3), with a mean follow-up of 290 ± 145 days. RESULTS: Procedural success (MR ≤ 2+) was 100%. Total procedure time was 115.8 ± 23.7 min, with no in-hospital adverse events and discharge between the fourth and eighth day, and consistent improvement in the six-minute walk test (329.8 ± 98.42 vs. 385.33 ± 106.95 m) and in NYHA class (three patients improved by two NYHA classes). During follow-up there were two deaths, in two of the four patients who had been initially considered for heart transplantation. CONCLUSION: In patients with functional MR the MitraClip procedure is safe, with both a high implantation and immediate in-hospital success rate. A longer follow-up suggests that the clinical benefit decreases or disappears completely in patients with more advanced heart disease, namely those denied transplantation or on the heart transplant waiting list.

Intracoronary Delivery of Human Mesenchymal/Stromal Stem Cells: Insights from Coronary Microcirculation Invasive Assessment in a Swine Model

BACKGROUND: Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status. OBJECTIVES: To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance. METHODS: Healthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups. RESULTS: CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted. CONCLUSION: Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.

Pathogenesis of chronic Chagas cardiomyopathy: the role of coronary microvascular derangements

There is ample experimental and clinical evidence of functional and structural microvascular abnormalities occurring in patients with Chagas cardiomyopathy, possibly due to the inflammatory process and/or autonomic disturbances caused by Trypanosoma cruzi infection. Those microvascular derangements are likely to constitute at least an ancillary factor that potentiates and amplifies the chronic inflammation in myocardial tissue. It is possible to devise appropriate therapeutic interventions aimed at reverting or slowing the progression of the microvascular abnormalities to positively affect the natural history of Chagas cardiomyopathy.

Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy

Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula. PURPOSE: To investigate the role of acute hemodynamic changes in subsequent deposition of cardiac fibrosis in response to aortocaval fistula. METHOD: Aortocaval fistula were created in 4 groups of Wistar rats that were followed over 4 and 8 weeks: aortocaval fistula 4 and aortocaval fistula 8 (10 rats each) and their respective controls (sham-operated controls - Sh), Sh4 and Sh8 (8 rats each). Hemodynamic measurements were performed 1 week after surgery. Hypertrophy and fibrosis were quantified by myocyte diameter and collagen volume fraction at the end of follow up. RESULT: Compared with Sh4 and Sh8, pulse pressure, left ventricular end-diastolic pressure, and +dP/dt were higher in aortocaval fistula 4 and aortocaval fistula 8, but -dP/dt was similar. Coronary driving pressure (mm Hg), used as an estimate of perfusion pressure, was lower in aortocaval fistula 8 (52.6 ± 4.1) than in Sh8 (100.8 ± 1.3), but comparable between aortocaval fistula 4 (50.0 ± 8.9) and Sh4 (84.8 ± 2.3). Myocyte diameter was greater in aortocaval fistula 8, whereas interstitial and subendocardial fibrosis were greater in aortocaval fistula 4 and aortocaval fistula 8. Coronary driving pressure correlated inversely and independently with subendocardial fibrosis (r² = .86, P <.001), whereas left ventricular systolic pressure (r² = 0.73, P = .004) and end-diastolic pressure (r² = 0.55, P = 012) correlated positively and independently with interstitial fibrosis. CONCLUSION: Coronary driving pressure falls and ventricular pressures increase early after aortocaval fistula and are associated with subsequent myocardial fibrosis deposition.

A perda precoce do diâmetro luminal após angioplastia coronária e sua influência no fenômeno da reestenose

OBJETIVO: Analisar a perda do diâmetro luminal mínimo (DLM) nos primeiros 15min após angioplastia coronária por balão (AC), quantificando sua influência na reestenose coronária. MÉTODOS: Foram estudadas, prospectivamente, 86 AC em 86 pacientes. Os pacientes foram divididos em dois subgrupos de acordo com a presença ou ausência de reestenose; o 1º grupo compreendendo as 31 lesões com reestenose e o 2º, as 55 lesões sem reestenose. RESULTADOS: A análise univariada mostrou que a relação balão/artéria foi menor no grupo com reestenose (0,92±0,01 vs 1,00±0,11, P= .003). O grupo com reestenose apresentou maior recolhimento elástico absoluto e relativo no 1°min (0,79±0,54 vs 0,68±0,59mm; P= 0,007 e 32,04±14,27 vs 22,15±16,65%; P= 0,006.) e no controle angiográfico do 15°min (1,25±0,59 vs 0,90±0,65mm, P= 0,017 e 46,75±15,69 vs 29,18±17,84%, P<0,00001) do que o grupo sem reestenose. O DLM no 1°min foi menor no grupo com reestenose (2,15±0,42 vs 2,43±0,58mm; P=0,022). O grupo com reestenose apresentou uma maior perda precoce no DLM (0,46±0,34 vs 0,22±0,35mm, P= 0,004). Este decréscimo na luz do vaso determinou que o DLM do 15°min fosse ainda menor no grupo com reestenose (1,69±0,48 vs 2,20±0,61; P= 0,0001). Da análise multivariada, entretanto, identificou-se apenas a relação balão/artéria e o DLM do 15°min como os dois fatores independentes mais relacionados à reestenose. CONCLUSÃO: O recolhimento elástico e a perda do DLM ao longo dos 15min são fatores diretamente relacionados à reestenose. Entretanto, a análise multivariada mostrou que a relação balão/artéria e o DLM de 15min são os dois fatores independentes mais fortemente preditores de reestenose.

Percutaneous closure of atrial septal defects. The role of transesophageal echocardiography

PURPOSE: Evaluation of the role of transesophageal echocardiography in percutaneous closure of atrial septal defects (ASD) with the Amplatzer septal occluder. METHODS: Patients were selected for percutaneous closure of ASD by transesophageal echocardiography (TEE), which was also used to monitor the procedure, helping to select the appropriate size of the Amplatzer device, to verify its position, and to access the immediate results of the procedure. During the follow-up, TEE was used to evaluate the presence and magnitude of residual shunt (RS), device position, and right cardiac chamber diameters. RESULTS: Twenty-two (40%) of a total of 55 studied patients were selected. Thirteen underwent Amplatzer device implantation, eight are still waiting for it, and one preferred the conventional surgical treatment. All procedures were successful, which was mainly due to proper patient selection. Six (23%) patients acutely developed RS, which spontaneously disapeared at the three-month follow-up examination in three patients. There was a significant reduction in the right ventricle diastolic diameter, from 27mm (average) to 24mm and 20mm, one and three months after the procedure, respectively (p<0.0076). CONCLUSION: With the aid of TEE, percutaneous closure of ASD can be successfully, safely, and effectively performed.

Protective effect of left ventricular hypertrophy in right coronary artery occlusions

OBJECTIVE: To test the hypothesis that left ventricular hypertrophy (LVH) reduces the electrocardiographic and functional effects of right coronary artery occlusion. METHODS: We analysed 215 patients (166 males and 49 women,age of 58.9±10.6 years), with occlusion of the right coronary artery without other associated lesions. There was no significant difference (p>0.05) in age and gender distribution between the 78 patients with LVH (left ventricular mass >100g/m²) (Group A) when compared with the 137 patients without LVH (left ventricular mass <100g/m²) (Group B). RESULTS: The electrocardiographic finding of transmural necrosis was more often found in group B patients than in group A patients (56.9% and 30.8%, respectively; p<0.05). The left ventricular function parameters of group A were better than those of group B: the ratio end-diastolic pressure/systolic pressure (EDP/SP) (A: 0.108±0.036; B: 0.121±0.050; p<0.05); the end-diastolic volume index (A: 75.9±31.3ml/m²; B: 88.0±31.0ml/m²; p<0.01); the end-systolic volume index (A: 16.0±10.0ml/m²; B: 27.0 ±20.0ml/m²; p<0.001); the ejection fraction (A 78.6±10.8%; B 67.7±17.9%; p<0.001); the anteroinferior shortening (A: 43.9±10.3%; B: 35.1±12.8%; p<0.001). A higher degree of coronary tortuosity was observed in group A than in group B (78.2% and 24.1%; p<0.001) and also a more frequent absent or minimal diaphragmatic hypokinetic area (A: 80.8%; B: 54.0%; p<0.05). CONCLUSION: LVH reduces the effects of myocardial sequela and protects LV function when right coronary occlusion develops.

Anomalous origin of the left coronary artery from the pulmonary trunk. Clinical features and midterm results after surgical treatment

OBJECTIVE: To report the authors' experience with the anomalous origin of the left coronary artery (AOLCA) from the pulmonary trunk, emphasizing preoperative data, surgical aspects and midterm results of the follow-up. METHODS: Retrospective analysis of 11 patients operated upon at the Royal Brompton Hospital from October, 84 to April, 97. RESULTS: Nine infants had heart failure (HF) and two other children presented with dyspnea and chest pain. All had ECG changes. The echocardiogram identified the anomalous origin of the coronary artery in 7 (64%) patients and hemodynamic studies were performed in 7 patients. All infants were operated upon between the 2nd and 10th month of life. Six patients were treated with aortic reimplantation of the left coronary artery, whereas five were operated upon according to the Takeuchi technique. All patients are alive, with clear improvement of the ECG changes and ventricular function, as evaluated by echocardiography. Two patients operated upon according to the Takeuchi technique required additional surgery due to severe supravalvular pulmonary stenosis. CONCLUSION: AOLCA is a rare disease. Most patients show early signs of severe HF associated with ECG findings. Surgical therapy must be instituted early in the disease, preferentially through aortic implantation of the anomalous coronary artery, with a high possibility of success. Shortly after surgery, clinical and ECG improvement, as well as normalization of left ventricular function, should be expected.

Transmyocardial laser revascularization. Early clinical experience

OBJECTIVE: To analyze the initial clinical experience of transmyocardial laser revascularization (TMLR) in patients with severe diffuse coronary artery disease. METHODS: Between February, 1998 and February, 1999, 20 patients were submitted to TMLR at the Heart Institute (InCor), University of São Paulo Medical School, Brazil, isolated or in association with conventional coronary artery bypass graft (CABG). All patients had severe diffuse coronary artery disease, with angina functional class III/IV (Canadian Cardiovascular Society score) unresponsive to medical therapy. Fourteen patients were submitted to TMLR as the sole therapy, whereas 6 underwent concomitant CABG. Fifty per cent of the patients had either been previously submitted to a CABG or to a percutaneous transluminal coronary angioplasty (PTCA). Mean age was 60 years, ranging from 45 to 74 years. RESULTS: All patients had three-vessel disease, with normal or mildly impaired left ventricular global function. Follow-up ranged from 1 to 13 months (mean 6.6 months), with no postoperative short or long term mortality. There was significant symptom improvement after the procedure, with 85% of the patients free of angina, and the remaining 15 % of the patients showing improvement in functional class, as well as in exercise tolerance. CONCLUSION: This novel technique can be considered a low risk alternative for a highly selected group of patients not suitable for conventional revascularization procedures.

Detection of the viable myocardium. A perfusion scintigraphic study, before and after coronary bypass surgery in myocardial infarction patients

OBJECTIVE: To compare single-photon-emission computed tomography (SPECT) imaging scans using 201Tl and 99mTc-MIBI in detection of viable myocardium, in regions compromised by infarction. METHODS: Thirty-two (59.3±9.8 years old and 87% male) myocardial infarction patients were studied. All had Q waves on the ECG and left ventricle ejection fraction of <50%. They underwent coronary and left ventricle angiographies and SPECT before (including 201Tl reinjection) and after coronary artery bypass surgery (CABG). Improvement in perfusion observed after surgery was considered the gold standard for myocardial viability. RESULTS: Among 102 studied regions of the heart, there were 40 (39.2%) areas of transient perfusion defects in the conventional protocol with 201Tl and 52 (51.0%) after reinjection. Therefore, 12/62 (19.4%) more viable regions were identified by reinjection. Using 99mTc-MIBI, only 14 (13.7%) regions with transient defects were identified, all of which were seen also in 201Tl protocols. After surgery, 49 of a total of 93 regions analyzed (52.7%) were viable. Sensitivity, specificity, accuracy, positive and negative prediction values were, respectively, 201Tl SPECT scans - 65.3%, 90.9%, 77.4%, 88.9% and 70.2%, reinjection protocol with 201Tl scans - 81.6%, 81.8%, 81.7%, 83.3% and 80.0%; 99mTc-MIBI SPECT scans - 20.4%, 90.9%, 53.8%, 71.4% and 50.6%. Logistic regression demonstrated that the reinjection protocol with 201Tl was the best predictor of viability (P<0.001). CONCLUSION: Our data suggest the election of 201Tl for viability studies, especially when using the reinjection protocol.