Impact of coronary calcification assessed by coronary CT angiography on treatment decision in patients with three-vessel CAD: insights from SYNTAX III trial.

OBJECTIVES: The aim of this study was to determine Syntax scores based on coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) and to assess whether heavy coronary calcification significantly limits the CCTA evaluation and the impact of severe calcification on heart team's treatment decision and procedural planning in patients with three-vessel coronary artery disease (CAD) with or without left main disease. METHODS: SYNTAX III was a multicentre, international study that included patients with three-vessel CAD with or without left main disease. The heart teams were randomized to either assess coronary arteries with coronary CCTA or ICA. We stratified the patients based on the presence of at least 1 lesion with heavy calcification defined as arc of calcium >180° within the lesion using CCTA. Agreement on the anatomical SYNTAX score and treatment decision was compared between patients with and without heavy calcifications. RESULTS: Overall, 222 patients with available CCTA and ICA were included in this trial subanalysis (104 with heavy calcification, 118 without heavy calcification). The mean difference in the anatomical SYNTAX score (CCTA derived-ICA derived) was lower in patients without heavy calcifications [mean (-1.96 SD; +1.96 SD) = 1.5 (-19.3; 22.4) vs 5.9 (-17.5; +29.3), P = 0.004]. The agreement on treatment decision did not differ between patients with (Cohen's kappa 0.79) or without coronary calcifications (Cohen's kappa 0.84). The agreement on the treatment planning did not differ between patients with (concordance 80.3%) or without coronary calcifications (concordance 82.8%). CONCLUSIONS: An overall good correlation between CCTA- and ICA-derived Syntax score was found. The presence of heavy coronary calcification moderately influenced the agreement between CCTA and ICA on the anatomical SYNTAX score. However, agreement on the treatment decision and planning was high and irrespective of the presence of calcified lesions.

Impact of Fractional Flow Reserve Derived From Coronary Computed Tomography Angiography on Heart Team Treatment Decision-Making in Patients With Multivessel Coronary Artery Disease: Insights From the SYNTAX III REVOLUTION Trial.

BACKGROUND: Fractional flow reserve (FFR) is a reliable tool for the functional assessment of coronary stenoses. FFR computed tomography (CT) derived (FFRCT) has shown to be accurate, but its clinical usefulness in patients with complex coronary artery disease remains to be investigated. The present study sought to determine the impact of FFRCT on heart team's treatment decision-making and selection of vessels for revascularization in patients with 3-vessel coronary artery disease. METHODS: The trial was an international, multicenter study randomizing 2 heart teams to make a treatment decision between percutaneous coronary interventions and coronary artery bypass grafting using either coronary computed tomography angiography or conventional angiography. The heart teams received the FFRCT and had to make a treatment decision and planning integrating the functional component of the stenoses. Each heart team calculated the anatomic SYNTAX score, the noninvasive functional SYNTAX score and subsequently integrated the clinical information to compute the SYNTAX score III providing a treatment recommendation, that is, coronary artery bypass grafting, percutaneous coronary intervention, or equipoise coronary artery bypass grafting-percutaneous coronary intervention. The primary objective was to determine the proportion of patients in whom FFRCT changed the treatment decision and planning. RESULTS: Overall, 223 patients were included. Coronary computed tomography angiography assessment was feasible in 99% of the patients and FFRCT analysis in 88%. FFRCT was available for 1030 lesions (mean FFRCT value 0.64±13). A treatment recommendation of coronary artery bypass grafting was made in 24% of the patients with coronary computed tomography angiography with FFRCT. The addition of FFRCT changed the treatment decision in 7% of the patients and modified selection of vessels for revascularization in 12%. With conventional angiography as reference, FFRCT assessment resulted in reclassification of 14% of patients from intermediate and high to low SYNTAX score tertile. CONCLUSIONS: In patients with 3-vessel coronary artery disease, a noninvasive physiology assessment using FFRCT changed heart team's treatment decision-making and procedural planning in one-fifth of the patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02813473.

Takotsubo cardiomyopathy after microwave ablation for metastatic liver lesions.

Takotsubo cardiomyopathy (TCMP) is characterized by transient and reversible left ventricular regional wall motion abnormalities triggered by acute and intense emotional or physical stress. We present a case of a 79 year old woman with a hypertensive crisis after microwave ablation (MWA) for metastatic liver lesions. Initial evaluation suggested an acute coronary syndrome with an ST segment elevation and with elevated serum troponin T. No associated chest pain or dyspnea was present. Further evaluation with ECG, echocardiography, coronarography with left ventricle angiogram and MRI was consistent with an apical ballooning syndrome. She was managed medically and the abnormalities resolved in the next 8 weeks during her follow up. The association between MWA and TCMP has been only reported once in the literature. We would like to emphasize one of the risks of MWA in or near the thoracic region potentially leading to TCMP.

[Many possible causes of variant angina]. / Veel mogelijke oorzaken voor vasospastische angina pectoris.

BACKGROUND: Variant angina, or vasospastic angina, is a form of angina caused by vasospasm of the coronary arteries, probably caused by endothelial dysfunction. This form of angina is provoked by non-classical risk factors such as stress, alcohol use, use of sympathomimetics and low environmental temperatures, but also by smoking. Treatment is based on elimination of risk factors and vasodilator therapy with nitrates and long-acting calcium antagonists. CASE DESCRIPTION: We present a 68-year-old woman with recurring thoracalgia at rest and during exercise, suggestive of severe variant angina in more than one coronary artery. Despite elimination of risk factors and administration of vasodilatory therapy the treatment was initially insufficient. It eventually emerged that the probable cause was frequent use of a vasoconstrictive nasal spray, although this was not described in literature, and not originally mentioned by the patient. CONCLUSION: A thorough case history is of vital importance in a patient presenting with a history suggestive of variant angina. Even undescribed and apparently less important risk factors can be responsible for persistence of symptoms, and can lead to an applied treatment not producing the desired result.

Randomised study of a bioabsorbable polymer-coated sirolimus-eluting stent: results of the DESSOLVE II trial.

AIMS: To compare the efficacy and safety of the MiStent absorbable polymer sirolimus-eluting stent (APSES) with a zotarolimus-eluting stent (ZES). METHODS AND RESULTS: The trial was a 2:1 randomisation at 26 sites of 184 patients implanted with an APSES (n=123) versus a ZES (n=61). Following stent implantation, all patients underwent quantitative coronary angiography at baseline and at nine months of follow-up, while a select subgroup also underwent optical coherence tomography (OCT). The primary efficacy hypothesis was superiority of in-stent late lumen loss (LLL) of APSES compared to ZES. At nine months, the primary endpoint was met, with a mean in-stent LLL of 0.27±0.46 mm in 103 APSES patients versus 0.58±0.41 mm in 52 ZES patients (p<0.001). The proportion of uncovered stent struts by OCT at nine months was very low in both groups. The mean neointimal thickness of covered struts (p=0.002) and percent net volume obstruction (p≤0.003) were significantly lower in the APSES than in the ZES group. Major adverse cardiac event and stent thrombosis rates were low and comparable between groups. CONCLUSIONS: The DESSOLVE II trial demonstrated superiority in the primary efficacy endpoint of nine-month mean LLL for APSES compared to ZES. Strut coverage by OCT was high with both stents and the clinical safety endpoints including stent thrombosis were equally low in both groups. ClinicalTrials.gov Identifier: NCT01294748.

Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial.

AIMS: Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). METHODS AND RESULTS: A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed. CONCLUSIONS: Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury.

Creation of an iliac arteriovenous shunt lowers blood pressure in chronic obstructive pulmonary disease patients with hypertension.

OBJECTIVE: Vasodilators are used with caution in patients with chronic obstructive pulmonary disease (COPD). We have developed a device for percutaneous arteriovenous shunt creation in the iliac region to increase cardiac output and oxygen delivery for patients with COPD. Although this device does not cause significant blood pressure changes in normotensive patients with COPD, we hypothesized that arteriovenous shunt creation might cause vasodilator effects in hypertensive patients because of a reduction in vascular resistance. METHODS: Twenty-four patients with COPD and hypertension enrolled in an open label study of arteriovenous shunt creation for COPD. We performed cardiac catheterization at baseline and again 3 to 6 months after the procedure. As a safety measure we also recorded office blood pressure at baseline and again after 3, 6, 9, and 12 months. RESULTS: The procedure increased oxygen delivery (1.1-1.4 L.min(-1)) and cardiac output (6-8.2 L.min(-1)) (P < .001) and lowered both the systemic vascular resistance (P < .001) and the pulmonary vascular resistance (P < .01). After 12 months, however, the average systolic blood pressure was reduced from 145 to 132 mm Hg (P < .0001), and the average diastolic blood pressure was reduced from 86 to 67 mm Hg (P < .0001). CONCLUSIONS: Percutaneous iliac arteriovenous fistula creation for COPD causes a significant and persistent lowering of blood pressure in patients with co-existing hypertension.

Acute heart failure due to fulminant myocardial infiltration by a diffuse large B-cell lymphoma.

Secondary cardiac lymphoma is commonly recognised as one of the most frequent metastatic malignancies involving the heart, after lung and breast carcinomas. Most primary and secondary cardiac lymphoma are non-Hodgkin lymphomas.The pericardium is the most frequently involved cardiac structure. However, the myocardium and the endocardium can also be affected. The patient presented in this case report had a secondary cardiac diffuse large B cell lymphoma. He presented initially with dyspnoea due to cardiac tamponade. He died one month after pericardial fenestration as a result of acute left and right heart failure due to diffuse lymphomatous infiltrations.This cardiac infiltration progressed so quickly that histological diagnosis could not be obtained before death. Autopsy revealed massive infiltration of the heart, the thyroid, abdominal lymph nodes, the left kidney, the pancreas and the right testis.

Evidence that intracoronary-injected CD133+ peripheral blood progenitor cells home to the myocardium in chronic postinfarction heart failure.

OBJECTIVE: To study the biodistribution of purified CD133(+) cells after intracoronary injection in patients with stable chronic postinfarction heart failure. PATIENTS AND METHODS: Patients with longstanding myocardial infarction (>12 months prior to inclusion) and with an accessible left coronary artery were eligible. CD133(+) cells were mobilized with granulocyte colony-stimulating factor and purified with a CliniMACS device. Cells were labeled with (111)Indium and injected through a balloon catheter in a coronary artery feeding the necrotic or viable infarct-related region of the left ventricle during a standard coronary catheterization procedure. The total body biodistribution of (111)Indium was studied with a dual-head gamma camera in combination with (99m)Technetium-sestaMIBI cardiac distribution analysis. RESULTS: The number of CD133(+) cells injected ranged between 5 and 10 x 10(6) cells (low dose, three patients) or between 18.5 and 50 x 10(6) cells (high dose, five patients). In the five patients receiving the higher cell doses, a clear residual radioactivity was observed at the level of the chronic injury at 2, 12, and up to 36 hours after injection. A detailed analysis in two patients showed 6.9% to 8.0% (after 2 hours) and 2.3% to 3.2% (after 12 hours) residual radioactivity at the heart. No adverse events were observed during the procedure and up to 3 months follow-up. CONCLUSIONS: We demonstrate that CD133(+) progenitor cells are capable of homing to the postinfarction remodeling myocardium after intracoronary injections in patients with chronic postinfarction heart failure.

In vivo model of drug-induced valvular heart disease in rats: pergolide-induced valvular heart disease demonstrated with echocardiography and correlation with pathology.

AIMS: Valvular heart disease (VHD), inducing valvular regurgitation, has been described in carcinoid heart disease and recently in Parkinson's patients treated with pergolide. The aim of this study was to develop an in vivo model of drug-induced valvulopathy with pergolide in rats. METHODS AND RESULTS: Thirty male Wistar rats were given daily injections of either pergolide (0.5 mg/kg intraperitoneally) (n = 8), serotonin (20 mg/kg subcutaneously) (n = 8), or the vehicle only (n = 14) for 5 months. At 20 weeks, echocardiography demonstrated the presence of aortic regurgitation (AR) and/or mitral regurgitation (MR) in serotonin (86% AR, P = 0.0001; 57% MR, P = 0.006) and in pergolide animals (67% AR, P = 0.003; 67% MR, P = 0.003) compared with none in placebo. Pulmonary regurgitation (PR) and tricuspid regurgitation (TR) were found in the serotonin (71% PR, P = 0.19; 100% TR, P = 0.06 vs. placebo), pergolide (100% PR, P = 0.014; 83% TR, P = 0.35 vs. placebo), and placebo groups (36% PR; 57% TR). Tricuspid regurgitant area ratio (jet/atrium), however, was more severe in the serotonin [median 26.5 (range 17-42)%; P = 0.02] and pergolide animals [32 (17-39) %; P = 0.03] compared with placebo [12.5 (5-33)%]. We found a good correlation between valvular regurgitation and histologically assessed valvular thickness. Histological examination revealed the presence of diffusely thickened and myxoid aortic, mitral, and tricuspid valves in serotonin and pergolide animals as seen in VHD. CONCLUSION: We demonstrated, for the first time, that long-term pergolide administration led to VHD in rats. This small animal model will permit further in vivo investigation of drug-induced valvulopathies.