Treatment and outcomes of patients with chronic lung disease and acute myocardial infarction: Insights from the nationwide AMIS plus registry.

BACKGROUND: Limited data are available on patients with chronic lung disease (CLD) presenting with acute myocardial infarction (AMI). We aimed to analyse baseline characteristics, treatment and outcome of those patients enrolled in the Swiss nationwide prospective AMIS Plus registry. METHODS: All AMI patients enrolled between January 2002 and December 2021 with data on CLD, as defined in the Charlson Comorbidity Index, were included. The primary endpoints were in-hospital mortality and major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, reinfarction and cerebrovascular events. Baseline characteristics, in-hospital treatments and outcomes were analysed using descriptive statistics and logistic regression. RESULTS: Among 53,680 AMI patients enrolled during this time, 5.8% had CLD. Compared with patients without CLD, CLD patients presented more frequently with non-ST-elevation myocardial infarction (MI) and type 2 MI (12.8% vs. 6.5%, p < 0.001). With respect to treatment, CLD patients were less likely to receive P2Y12 inhibitors (p < 0.001) and less likely to undergo percutaneous coronary interventions (68.7% vs. 82.5%; p < 0.001). In-hospital mortality declined in AMI patients with CLD over time (from 12% in 2002 to 7.3% in 2021). Multivariable regression analysis showed that CLD was an independent predictor for MACCE (adjusted OR was 1.28 [95% CI 1.07-1.52], p = 0.006). CONCLUSION: Patients with CLD and AMI were less likely to receive evidence-based pharmacologic treatments, coronary revascularization and had a higher incidence of MACCE during their hospital stay compared to those without CLD. Over 20 years, in-hospital mortality was significantly reduced in AMI patients, especially in those with CLD.

Improved two-year outcomes after drug-eluting versus bare-metal stent implantation in women and men with large coronary arteries: importance of vessel size.

OBJECTIVES: To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels. METHODS: All 2314 BASKET-PROVE patients randomized to DES versus BMS were followed for 2 years with a primary endpoint of major adverse cardiac events (MACE: cardiac death, non-fatal myocardial infarction, target-vessel revascularization). Cox proportional hazard models were used to evaluate the relative risk for women and men, respectively. All comparisons were adjusted for vessel size. RESULTS: Age, risk factors and complexity of coronary artery disease differed between women and men. DES reduced MACE rates at 2 years compared to BMS--in women: 4% vs. 15%, p<0.0001 with a hazard ratio (HR) of 0.27 (0.15-0.51), and men: 6% vs. 10%, p=0.003 (HR=0.60 (0.43-0.84)), respectively. The association persisted in both women (HR=0.25 (0.13-0.46)) and men (HR=0.60 (0.42-0.84)) following multivariable adjustments. A significant gender-treatment interaction was present (p=0.02). The reduced risk of MACE following DES vs. BMS implantation was present until 6 months in both women (HR=0.15 (0.06-0.36)) and men (HR=0.32 (0.17-0.59)) and remained significant until 2 years in women (HR=0.36 (0.15-0.87)), but not in men (HR=0.87 (0.49-1.55)). CONCLUSIONS: In women and men with similarly sized large coronary arteries, DES reduced 2-year MACE rates compared to BMS, but the significant gender-treatment interaction indicated a greater benefit of DES in women. Thus, factors other than vessel size seem to determine this gender difference.

The impact of statin treatment on presentation mode and early outcomes in acute coronary syndromes.

OBJECTIVES: The role of statin use in the treatment of acute coronary syndromes (ACS) is not clear. The aim of our study was to evaluate the role of statins in ACS. METHODS: Using data from the Acute Myocardial Infarction in Switzerland (AMIS Plus) Project, we compared the effects of chronic statin use, statin therapy after admission and no statin therapy on presentation mode and outcomes in ACS. RESULTS: Available data from the period 2001-2006 including 11,603 patients were analyzed. Major cardiac event rates and in-hospital mortality were more common in statin-naive patients compared to patients who received statins. CONCLUSIONS: Our results support the importance of statin treatment in ACS. Chronic statin therapy seems to alter the initial presentation of ACS but it is questionable whether it provides an additional effect on early outcomes compared to the establishment of statin therapy after admission in statin-naive patients.

[Mechanical complications of acute myocardial infarction]. / Mechanische Komplikationen bei akutem Myokardinfarkt.

Rupture of the left ventricular myocardium during the course of an acute myocardial infarction may affect the free wall, the interventricular septum, or the papillary muscles. When a rupture occurs, it is referred to as a mechanical complication of acute myocardial infarction. All mechanical complications may lead to cardiogenic shock. However, the location of the rupture can often be suspected clinically. To confirm the diagnosis, echocardiography must be performed. Since the advent of thrombolytic therapy and percutaneous coronary intervention, the incidence of mechanical complications has declined. Even though mortality remains high, their recognition is important since survivors may have an excellent long-term prognosis. The cases convey two main messages: 1) Mechanical complications must be carefully searched for in any patient with an acute coronary syndrome and signs of cardiogenic shock and/or a systolic murmur. 2) Aggressive and timely medical and surgical treatment should be provided even though in a substantial proportion of these patients prognosis may be dismal.

[Valve disease: what the general practicioner needs to know]. / Klappenvitien in der ärztlichen Praxis.

Patients with mitral or aortic valve disease constitute an important part of patients in cardiology practice. General practitioners and internists have an important role in the long-term care of these patients. We review current knowledge and recommendations for follow-up, medical therapy and indications for surgery in patients with aortic and mitral valve disease. Asymptomatic patients with valve disease need a clinical and echocardiographic follow-up at specific time intervals. Most patients with mild or moderate valve disease do not need medical or surgical therapy. However, once a patient becomes symptomatic, he needs a non-invasive and likely an invasive evaluation for surgical valve repair or replacement. In case the valve disease progresses without the development of clinical symptoms, the indication for surgery must be derived from hemodynamic parameters, the onset of arrhythmias (atrial fibrillation), and pulmonary hypertension. In symptomatic and asymptomatic severe valve disease specific medical therapy can be very beneficial. However, improvement under medical therapy should not delay a prognostically necessary surgical valve repair or replacement.

Coronary artery spasm and non-Q-wave myocardial infarction following intravenous ephedrine in two healthy women under spinal anaesthesia.

Vasovagal episodes occur frequently in young healthy patients undergoing venous cannulation and loco-regional anaesthesia. We report two cases of severe coronary vasospasm and non-Q-wave infarction in healthy young women after administration of ephedrine for vasovagal symptoms at the onset of spinal anaesthesia. In the light of unopposed vagal predominance pre-disposing patients to coronary vasospasm, even in young healthy patients, atrophine and not ephedrine should be the first line treatment for bradycardia with or without hypotension under spinal anaesthesia.

Percutaneous coronary intervention of the left main trunk in congenitally anomalous single coronary artery.

Anomalous origin of the coronary arteries is infrequent and a single coronary artery is seen even less frequently. Accordingly, few reports have described percutaneous coronary interventions in this anomaly. We report successful balloon angioplasty and stenting of a left main trunk originating from the right coronary artery.

Do beta-adrenergic blocking agents increase coronary flow reserve?

BACKGROUND: Beta-adrenergic blocking agents are the cornerstone in the treatment of coronary artery disease (CAD). The exact pathophysiologic mechanism is not clear but depends largely on the oxygen-sparing effect of the drug. Thus, the effect of metoprolol on coronary flow reserve and coronary flow velocity reserve (CFVR) was determined in patients with CAD. METHODS: Coronary blood flow velocity was measured with the Doppler flow wire in 23 patients (age: 56 +/- 10) undergoing percutaneous transluminal coronary angioplasty for therapeutic reasons. Measurements were carried out at rest, after 1-min vessel occlusion (postischemic CFVR) as well as after intracoronary adenosine (pharmacologic CFVR) before and after 5 mg intravenous metoprolol. In a subgroup (n = 15), absolute flow was measured from coronary flow velocity multiplied by coronary cross-sectional area. RESULTS: Rate-pressure product decreased after metoprolol from 9.1 to 8.0 x 10(3) mm Hg/min (p < 0.001). Pharmacologic CFVR was 2.1 at rest and increased after metoprolol to 2.7 (p = 0.002). Likewise, postischemic CFVR increased from 2.6 to 3.3 (p < 0.001). Postischemic CFVR was significantly higher than pharmacologic CFVR before as well as after metoprolol. Coronary vascular resistance decreased after metoprolol from 3.4 +/- 2.0 to 2.3 +/- 0.7 mm Hg x s/cm (p < 0.02). CONCLUSIONS: The following conclusions were drawn from this study. Metoprolol is associated with a significant increase in postischemic and pharmacologic CFVR. However, postischemic CFVR is significantly higher than pharmacologic CFVR. The increase in CFVR by metoprolol can be explained by a reduction in vascular resistance. The increase in CFVR (= increased supply) and the reduction in oxygen consumption (= decreased demand) after metoprolol explain the beneficial effect of this beta-blocker in patients with CAD.

Frequency distribution of collateral flow and factors influencing collateral channel development. Functional collateral channel measurement in 450 patients with coronary artery disease.

OBJECTIVES: We sought to determine the pathogenetic predictors of collateral channels in a large cohort of patients with coronary artery disease (CAD). BACKGROUND: The frequency distribution of collateral flow in patients with CAD is unknown. Only small qualitative studies have investigated which factors influence the development of collateral channels. METHODS: In 450 patients with one- to three-vessel CAD undergoing percutaneous transluminal coronary angioplasty (PTCA), collateral flow was measured. A collateral flow index (CFI; no unit) expressing collateral flow relative to normal anterograde flow was determined using coronary wedge pressure or Doppler measurements through sensor-tipped PTCA guide wires. Frequency distribution analysis of CFI and univariate and multivariate analyses of 32 factors, including gender, age, patient history, cardiovascular risk factors, medication and coronary angiographic data, were performed. RESULTS: Two-thirds of the patients had a CFI < 0.25 and approximately 40% of patients had a CFI < 0.15, but only approximately 10% of the patients had a recruitable CFI > or =0.4. By univariate analysis, the following were predictors of CFI > or =0.25: high levels of high-density lipoprotein cholesterol, the absence of previous non-Q-wave myocardial infarction, angina pectoris during an exercise test, angiographic indicators of severe CAD and the left circumflex or right coronary artery as the collateral-receiving vessel. Percent diameter stenosis of the lesion undergoing PTCA was the only independent predictor of a high CFI. CONCLUSIONS: This large clinical study of patients with CAD in whom collateral flow was quantitatively assessed reveals that two-thirds of the patients do not have enough collateral flow to prevent myocardial ischemia during coronary occlusion, and that coronary lesion severity is the only independent pathogenetic variable related to collateral flow.

Promotion of collateral growth by granulocyte-macrophage colony-stimulating factor in patients with coronary artery disease: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Experimentally, activated macrophages have been documented to induce vascular proliferation. METHODS AND RESULTS: In 21 patients (age 74+/-9 years) with extensive coronary artery disease not eligible for coronary artery bypass surgery, the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF, Molgramostim) on quantitatively assessed collateral flow was tested in a randomized, double-blind, placebo-controlled fashion. The study protocol consisted of an invasive collateral flow index (CFI) measurement immediately before intracoronary injection of 40 microg of GM-CSF (n=10) or placebo (n=11) and after a 2-week period with subcutaneous GM-CSF (10 microg/kg) or placebo, respectively. CFI was determined by simultaneous measurement of mean aortic pressure (P(ao), mm Hg), distal coronary occlusive pressure (P(occl), mm Hg; using intracoronary sensor guidewires), and central venous pressure (CVP, mm Hg): CFI=(P(occl)-CVP)/(P(ao)-CVP). CFI, expressing collateral flow during coronary occlusion relative to normal antegrade flow during vessel patency, changed from 0.21+/-0.14 to 0.31+/-0.23 in the GM-CSF group (P<0.05) and from 0.30+/-0.16 to 0.23+/-0.11 in the placebo group (P=NS). The treatment-induced difference in CFI was +0.11+/-0.12 in the GM-CSF group and -0.07+/-0.12 in the placebo group (P=0.01). ECG signs of myocardial ischemia during coronary balloon occlusion occurred in 9 of 10 patients before and 5 of 10 patients after GM-CSF treatment (P=0.04), whereas they were observed in 5 of 11 patients before and 8 of 11 patients after placebo (P=NS). CONCLUSIONS: This first clinical study investigating the potential of GM-CSF to improve collateral flow in patients with coronary artery disease documents its efficacy in a short-term administration protocol.

Left ventricular diastolic dysfunction during demand ischemia: rigor underlies increased stiffness without calcium-mediated tension. Amelioration by glycolytic substrate.

OBJECTIVES: The goal of this study was to determine the subcellular mechanism(s) underlying increased left ventricular (LV) diastolic chamber stiffness (DCS) during angina (demand ischemia). BACKGROUND: Increased DCS may result from increased diastolic myocyte calcium concentration and/or rigor. Therefore, we assessed the effects of direct alterations of both calcium-activated tension and high-energy phosphates on increased DCS. METHODS: Demand ischemia was reproduced in isolated, isovolumic, red-cell perfused rabbit hearts by imposing low-flow ischemia and pacing tachycardia. This resulted in increased DCS. Interventions were performed after LV end-diastolic pressure had increased approximately 7 mm Hg. Initially, to determine the effects of altered calcium concentration or myofilament calcium responsiveness, hearts received either: 1) 5 or 14 mmol/L calcium chloride; 2) 8 mmol/L egtazic acid; 3) 5 mmol/L butane-dione-monoxime (BDM); or 4) 50 mmol/L ammonium chloride (NH4Cl). Then, to assess the contribution of decreased high-energy phosphate supply, hearts received 5) glucose (25 mmol/L) and insulin (400 microU/ml). RESULTS: 1) Calcium chloride, 5 and 14 mmol/L, increased LV systolic pressure by 42% and 70%, respectively (p < 0.001), indicating increased calcium-activated tension, but did not further increase DCS, implying intact diastolic calcium resequestration. 2) Egtazic acid reduced LV systolic pressure by 30% (p < 0.001), indicating reduced intracellular calcium, but failed to reduce increased DCS. 3) Butane-dione-monoxime and NH4Cl chloride affected contractile function (i.e., a calcium-driven force) but did not alter increased DCS. 4) Glucose and insulin, which increase high-energy phosphates during ischemia, reduced increased DCS by 50% (p < 0.001). CONCLUSIONS: Increased DCS during demand ischemia was insensitive to maneuvers altering intracellular calcium concentration or myofilament calcium-responsiveness, that is, evidence against an etiology of calcium-activated tension. In contrast, increased glycolytic substrate ameliorated increased DCS, supporting a primary mechanism of rigor-bond formation.

ET(A)-receptor blockade prevents matrix metalloproteinase activation late postmyocardial infarction in the rat.

Endothelin (ET) A (ET(A)) receptors activate matrix metalloproteinases (MMP). Since endothelin-1 (ET) is increased in myocardium late postmyocardial infarction (MI), we hypothesized that stimulation of ET(A) receptors contributes to activation of myocardial MMPs late post-MI. Three days post-MI, rats were randomized to treatment with the ET(A)-selective receptor antagonist sitaxsentan (n = 12) or a control group (n = 12). Six weeks later, there were rightward shifts of the left ventricular (LV) end-diastolic and end-systolic pressure-volume relationships, as measured ex vivo by the isovolumic Langendorff technique. Both shifts were markedly attenuated by sitaxsentan. In LV myocardium remote from the infarct, the activities of MMP-1, MMP-2, and MMP-9 were increased in the post-MI group, and the increases were prevented by sitaxsentan treatment. Expression of tissue inhibitor of MMP-1 was decreased post-MI, and the decrease was prevented by sitaxsentan treatment. Chronic post-MI remodeling is associated with activation of MMPs in myocardium remote from the infarct. Inhibition of ET(A) receptors prevents MMP activation and LV dilation, suggesting that ET, acting via the ET(A) receptor, contributes to chronic post-MI remodeling by its effects on MMP activity.

Collateral and collateral-adjacent hyperemic vascular resistance changes and the ipsilateral coronary flow reserve. Documentation of a mechanism causing coronary steal in patients with coronary artery disease.

OBJECTIVES: The goal of this clinical study was to assess the influence of hyperemic ipsilateral, collateral and contralateral vascular resistance changes on the coronary flow velocity reserve (CFVR) of the collateral-receiving (i.e. ipsilateral) artery, and to test the validity of a model describing the development of collateral steal. METHODS: In 20 patients with one- to two-vessel coronary artery disease (CAD) undergoing angioplasty of one stenotic lesion, adenosine induced intracoronary (i.c.) CFVR during vessel patency was measured using a Doppler guidewire. During stenosis occlusion, simultaneous i.c. distal ipsilateral flow velocity and pressure (P(occl), using a pressure guidewire) as well as contralateral flow velocity measurements via a third i.c. wire were performed before and during intravenous adenosine. From those measurements and simultaneous mean aortic pressure (P(ao)), a collateral flow index (CFI), and the ipsilateral, collateral, and contralateral vascular resistance index (R(ipsi), R(coll), R(contra)) were calculated. The study population was subdivided into groups with CFI<0.15 and with CFI> or =0.15. RESULTS: The percentage-diameter coronary artery stenosis (%-S) to be dilated was similar in the two groups: 78+/-10% versus 82+/-12% (NS). CFVR was not associated with %-S. In the group with CFI> or =0.15 but not with CFI<0.15, CFVR was directly and inversely associated with R(coll) and R(contra), respectively. CONCLUSIONS: A hemodynamic interaction between adjacent vascular territories can be documented in patients with CAD and well developed collaterals among those regions. The CFVR of a collateralized region may, thus, be more dependent on hyperemic vascular resistance changes of the collateral and collateral-supplying area than on the ipsilateral stenosis severity, and may even fall below 1.

Metabolic support as an adjunct to inotropic support in the hypoperfused heart.

In situations such as severe low-flow ischemia, where myocardial work output is low and dependence on anaerobic glycolysis is high, increasing the myocardial supply of glucose and insulin is cardioprotective. Our goal was to determine whether this strategy of "metabolic support" would also be cardioprotective in the moderately hypoperfused heart receiving inotropic stimulation, i.e. when myocardial work was near normal, and reliance on anaerobic glycolysis was minimal. Isovolumic left ventricular performance and cardiac energetics (31P-NMR spectroscopy) were measured in 20 isolated rat hearts perfused with red blood cell containing perfusate (hematocrit 40%) with either normal (5 m M, 15 microU/ml) or increased (19.5 m M, 250 microU/ml) glucose and insulin in addition to normal levels of lactate and free fatty acids. Lowering global coronary flow to 30% of normal decreased left ventricle developed pressure by 50%. Administering dobutamine for 40 min restored developed pressure to 95+/-13% of baseline but caused diastolic pressure to increase by 23+/-6 mmHg and [ATP] to decrease by 44+/-6%. Glucose and insulin prevented the increase in end-diastolic pressure, and [ATP] fell by only 14+/-3%. Despite these improvements in cardiac energetics and diastolic function, left ventricle developed pressure was not improved by increased glucose and insulin during, or after the hypoperfusion. We conclude that inotropic support of the hypoperfused heart can cause new diastolic dysfunction, but that this diastolic dysfunction can be eliminated by preserving myocardial high-energy phosphates with increased glucose and insulin.

Percutaneous closure of patent foramen ovale in symptomatic patients.

BACKGROUND: Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) have been associated with stroke in young adults. Patients with PFO suffering from paradoxical embolism are at increased risk for recurrent events. Percutaneous PFO closure is a new treatment modality aimed at secondary prevention. METHODS AND RESULTS: Since April 1994, 132 consecutive patients, aged 51 +/- 12 years with PFO and with at least one paradoxical embolic event, underwent percutaneous PFO closure using six different device types. The embolic index event was an ischemic stroke in 62% of patients, a transient ischemic attack (TIA) in 33% of patients, and a peripheral embolism in 5% of patients. Thirty-six (27%) patients had PFO associated with ASA, whereas 96 (73%) patients had PFO only. The implantation procedure was successful in 130 (98%) patients. During and up to 6 years of follow-up (mean 1.8 +/- 1.6 years, 231 patient years), a total of eight recurrent embolic events were observed, with six TIAs, two peripheral emboli, and no ischemic stroke. The actuarial freedom from recurrence of the combined end point of TIA, ischemic stroke, and peripheral embolism was 95.3% (95% confidence interval [CI], 91.0%-96.4%) at 1 year and 90.5% (95% CI, 83.6%-97.2%) at 6 years. CONCLUSIONS: Percutaneous PFO closure can be performed with a high success rate. The procedure appears a promising therapeutic modality for secondary prevention of recurrent embolism in patients with PFO. Randomized trials must define its therapeutic value.

Decreased rate of coronary restenosis after lowering of plasma homocysteine levels.

BACKGROUND: We have previously demonstrated an association between elevated total plasma homocysteine levels and restenosis after percutaneous coronary angioplasty. We designed this study to evaluate the effect of lowering plasma homocysteine levels on restenosis after coronary angioplasty. METHODS: A combination of folic acid (1 mg), vitamin B12 (400 microg), and pyridoxine (10 mg)--referred to as folate treatment--or placebo was administered to 205 patients (mean [+/-SD] age, 61+/-11 years) for six months after successful coronary angioplasty in a prospective, double-blind, randomized trial. The primary end point was restenosis within six months as assessed by quantitative coronary angiography. The secondary end point was a composite of major adverse cardiac events. RESULTS: Base-tine characteristics and initial angiographic results after coronary angioplasty were similar in the two study groups. Folate treatment significantly lowered plasma homocysteine levels from 11.1+/-4.3 to 7.2+/-2.4 micromol per liter (P<0.001). At follow-up, the minimal luminal diameter was significantly larger in the group assigned to folate treatment (1.72+/-0.76 vs. 1.45+/-0.88 mm, P=0.02), and the degree of stenosis was less severe (39.9+/-20.3 vs. 48.2+/-28.3 percent, P=0.01). The rate of restenosis was significantly lower in patients assigned to folate treatment (19.6 vs. 37.6 percent, P=0.01), as was the need for revascularization of the target lesion (10.8 vs. 22.3 percent, P=0.047). CONCLUSIONS: Treatment with a combination of folic acid, vitamin B12, and pyridoxine significantly reduces homocysteine levels and decreases the rate of restenosis and the need for revascularization of the target lesion after coronary angioplasty. This inexpensive treatment, which has minimal side effects, should be considered as adjunctive therapy for patients undergoing coronary angioplasty.

Mechanical compression of coronary artery stents: potential hazard for patients undergoing cardiopulmonary resuscitation.

Mechanical compression of coronary artery stents may be associated with a fatal outcome as the result of refractory myocardial ischemia. We present the history of an 83-yr-old patient, who died owing to hemorrhagic shock 3 days after stent implantation, despite immediate cardiopulmonary resuscitation (CPR). Postmortem examination showed stent compression, probably due to mechanical deformation during CPR. This complication has been reported in two other cases in the literature, suggesting that CPR may be hazardous to patients with coronary artery stents.