Transcatheter management of valvular regurgitation beyond the aortic valve (mitral - tricuspid valve): Literature overview and future perspectives.

The growth of the available transcatheter treatment approaches for the mitral and tricuspid position was accompanied by important clinical trials and studies through the last years. The selection of appropriate candidates for transcatheter techniques requires significant insight into anatomical limitations of each patient undergoing clinical evaluation. Furthermore, technological characteristics of the available devices, and risks and benefits of each potential therapy, play the most important role in a physician's decision. This knowledge should be valuable to both interventional cardiologists and researchers. This paper aims to offer a concise overview of the technological advances in this field of Interventional Cardiology. Trials and studies announced at the major interventional cardiology congresses during 2018 and 2019 were systematically reviewed. Moreover, a literature search in PubMed for the same period identified an amount of publications eligible for inclusion, based on their relevance to the subject, and their potential impact on current guidelines of good clinical practice.

Left main coronary artery aneurysm.

Left main coronary artery aneurysms (LMCA) are usually asymptomatic and are rarely encountered during coronary angiography. The most serious complications include coronary thrombosis, acute myocardial infarction and sudden death. Atherosclerosis is the most common cause, although several autoimmune diseases and congenital abnormalities have been associated with the presence of coronary aneurysms. The case of a symptom-free 63-year-old man with a giant LMCA and severely ectatic coronary arteries is presented.

Type II diabetes does not prevent the recruitment of collateral vessels and the normal reduction of myocardial ischaemia on repeated balloon inflations during angioplasty.

OBJECTIVE: To test whether type II diabetes prevents the recruitment of collaterals and the normal reduction of myocardial ischaemia on repeated balloon inflations during coronary angioplasty. METHODS: Two groups of patients were studied. A collateral circulation group consisted of 56 patients, 18 diabetic and 38 non-diabetic. All underwent a minimum of three balloon inflations. A pressure guide wire was used for the measurement of coronary wedge pressure (mm Hg). The angioplasty protocol was repeated in another group of 57 patients (myocardial ischaemia group) using both surface and intracoronary ECGs to assess myocardial ischaemia. RESULTS: In diabetic patients, mean (SD) coronary wedge pressure was 35 (12) mm Hg during the first balloon inflation, 39 (15) mm Hg during the second (p < 0.05 v first inflation), and 42 (17) mm Hg during the third (p < 0.05 v first inflation); in non-diabetic patients the respective values were 36 (16), 37 (16), and 37 (16) mm Hg (F = 4.73, p = 0.01). The ratio of coronary wedge pressure to mean arterial pressure in diabetic patients in the three balloon inflations was 0.33 (0.11), 0.36 (0.13), and 0.39 (0.15), respectively (p < 0.05 v the first inflation); and in non-diabetic patients it was 0.33 (0.15), 0.34 (0.15), and 0.35 (0.15) (F = 1.92, p = 0.15). In the diabetic group the response was independent of the type of treatment. No difference between diabetic and non-diabetic patients was observed in the normal reduction of myocardial ischaemia on repeated balloon inflations. CONCLUSIONS: Type II diabetes does not prevent the recruitment of collateral vessels and the normal reduction of myocardial ischaemia on repeated balloon inflations during coronary angioplasty in single vessel disease, regardless of the type of antidiabetic treatment.

Intramuscular administration of estrogen may promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia.

OBJECTIVE: Promoting angiogenesis may be an effective treatment for patients with diffuse peripheral vascular disease. This study investigated whether estrogen can promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia. METHODS AND RESULTS: Ischemia was induced in one hindlimb of 24 oophorectomized New Zealand White rabbits. Ten days later (day 0), they were randomized into 4 groups for intramuscular treatment in the ischemic limb: controls receiving saline at day 0; Estrogen-1 group receiving estradiol valerate, modified release (EVMR), 1 mg/kg at day 0; Estrogen-2 group receiving EVMR 1 mg/kg at days 0 and 15; and Estrogen-3 group receiving EVMR 2 mg/kg at day 0. Revascularization was evaluated by clinical indexes, such as ischemic/normal limb systolic blood pressure (BPR), and capillary density/muscle fiber in the abductor muscle of the ischemic limb at the time of death (day 30). At day 30 the BPR was increased in all groups (0.39+/-0.08 in the controls, 0.52+/-0.11 in the Estrogen-1 group, 0.65+/-0.13 in the Estrogen-2 group and 0.61+/-0.16 in the Estrogen-3 group, F=2.39, P=0.04). The capillary/muscle fiber at day 30 was 0.87+/-0.09, 1.08+/-0.15, 1.01+/-0.14 and 1.10+/-0.9 (F=5.01, P=0.01), respectively, in the 4 groups. The capillary/muscle fiber was related to BPR (r=0.48, P<0.02) and to 17-beta estradiol plasma levels of day 15 (r=0.58, P=0.003) and of day 30 (r=0.46, P<0.02). CONCLUSION: Administration of estrogen promotes angiogenesis and perfusion in ischemic rabbit hindlimbs. Thus, estrogen may represent a new therapeutic modality in the management of arterial insufficiency.

Cell adhesion molecules in relation to simvastatin and hormone replacement therapy in coronary artery disease.

AIMS: To assess the effect of simvastatin, hormone replacement therapy and their combination on soluble cell adhesion molecules and plasma lipids, in hypercholesterolaemic post-menopausal women with coronary artery disease. METHODS: We studied 16 post-menopausal women with coronary artery disease and hypercholesterolaemia (total cholesterol >200mg x dl(-1) and LDL cholesterol >130 mg x dl(-1)). We compared simvastatin (20 mg daily) with hormone replacement therapy (0.625 mg conjugated oestrogen and 2.5 mg medroxyprogesterone acetate daily) and their combination, in a randomized, crossover, placebo controlled study. Each treatment period was 8 weeks long with a 4 week washout interval between treatments. Circulating cell adhesion molecules and plasma lipids were evaluated at the end of each treatment period. RESULTS: All three active treatments--simvastatin, hormone replacement therapy and the combination therapy--significantly reduced total and LDL cholesterol, compared to placebo (P<0.001). Only hormone replacement therapy, alone and in combination with simvastatin, significantly decreased lipoprotein(a) when compared to placebo (P<0.05), whereas simvastatin had no significant effect. Likewise, hormone replacement therapy and the combination therapy significantly reduced the intercellular adhesion molecule (ICAM-1) plasma levels (P=0.03 and P=0.02, respectively), while simvastatin, which was superior to hormone replacement therapy in lowering total and LDL cholesterol, did not modify ICAM-1 levels; the combination therapy was not more effective than hormone replacement therapy alone in ICAM-1 reduction. Neither the effect, on any treatment when compared to placebo, of VCAM-1 nor E-selectin levels differed significantly. CONCLUSIONS: Hormone replacement therapy may limit the inflammatory response to injury by modulating the expression of cell adhesion molecules from the endothelial cells, possibly in association with lipoprotein (a) reduction.

Intracoronary ketanserin augments coronary collateral blood flow and decreases myocardial ischemia during balloon angioplasty.

AIMS: To test the hypothesis that ketanserin augments coronary collateral blood flow and decreases myocardial ischemia during balloon angioplasty. METHODS AND RESULTS: Forty-four patients with single vessel disease and stable angina were studied. Collateral flow was determined during balloon inflations, based on the distal velocity time integral (13 patients) or on coronary wedge/mean arterial pressure measurements (10 patients). The 2nd and 3rd inflations lasted the same time and between them 1.5 mg intracoronary ketanserin in 10 ml normal saline was administered over 3 min. In 21 control subjects normal saline alone was given. In the flow velocity group the velocity time integral was 78.5+/-53.1 mm during the 2nd inflation and 106.0+/-43.2 mm during the 3rd (p<.05), while the ST deviation was 1.1+/-.7 and .7+/-.7 mm, respectively (p<.05). In the intracoronary pressure group the CWP/MBP was .40+/-.10 during the 2nd inflation and .45+/-.11 during the 3rd (p<.05), while the ST deviation was 1.2+/-.8 and .8+/-.8 mm respectively (p<.05). In the controls no variables changed during the tested inflations. CONCLUSION: Intracoronary administration of ketanserin augments coronary collateral flow and decreases myocardial ischemia during balloon angioplasty. This could be of clinical significance in the management of acute ischemic syndromes.

Absence of effects of short-term estrogen replacement therapy on resting and exertional QT and QTc dispersion in postmenopausal women with coronary artery disease.

Women, on average, have a longer QT interval on the electrocardiogram and are at higher risk of developing torsade de pointes from antiarrhythmic therapy than men. Although endogenous estrogen may play a role in these sex differences, the effect of estrogen replacement therapy has not been examined. Ten women, 65 +/- 7 years of age, with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease (at least one > or = 70%) stenosis were studied. All women had been postmenopausal for at least 1 year, and none had ever received hormone replacement therapy (HRT). The patients received standard dose HRT (0.625 mg/day oral conjugated estrogen) or matching placebo for 4 weeks in random order, with crossover after a 4-week washout period. Exercise testing using the standard Bruce protocol was performed at the end of the first and third months of the study. Antianginal medications remained unchanged throughout the study period. Compared to placebo, HRT caused a significant increase in plasma estradiol levels from 5.55 +/- 1.66 to 31.11 +/- 14.95 pg/mL (P = 0.001). QT and QTc, as well as QT and QTc dispersion, did not differ at rest and at peak exercise between the two exercise tests. Likewise, other test results, including angina score, exercise time, ST-T changes, blood pressure, heart rate, and double product were unchanged. Short-term HRT did not alter cardiac repolarization at rest and during exercise in postmenopausal women with known coronary disease.

The effect of hormone replacement therapy alone and in combination with simvastatin on plasma lipids of hypercholesterolemic postmenopausal women with coronary artery disease.

OBJECTIVES: This study sought to compare hormone replacement therapy (HRT), simvastatin and their combination in the management of hypercholesterolemia in postmenopausal women with coronary artery disease (CAD). BACKGROUND: Lipid-lowering therapy reduces mortality in hypercholesterolemic women with CAD. In postmenopausal women HRT seems to increase survival, particularly those with ischemic heart disease, and this is partly due to changes in lipid levels. METHODS: We studied 16 postmenopausal women with CAD and fasting total cholesterol <200 mg/dl and low-density lipoprotein (LDL) cholesterol <130 mg/dl. We compared HRT (0.625 mg of conjugated estrogen and 2.5 mg of medroxyprogesterone acetate daily) with simvastatin (20 mg daily) and their combination in a randomized, crossover, placebo-controlled study. Each treatment period was 8 weeks long with a 4-week washout interval between treatments. RESULTS: Simvastatin, HRT and their combination significantly reduced total and LDL cholesterol by 35%, 13%, and 33% and 45%, 20%, and 46%, respectively, compared to placebo (p < 0.001). However, simvastatin and the combination was superior to HRT (p < 0.001), and none of our patients had total cholesterol <180 mg/dl and LDL cholesterol <100 mg/dl on HRT alone. High-density lipoprotein cholesterol was not significantly affected by any of the active treatments, and triglycerides were lower during simvastatin therapy compared to placebo (p < 0.01). Apolipoprotein B was significantly reduced by simvastatin, alone and combined with HRT, by 39% and 35%, respectively, compared to placebo (p < 0.001). Alone and in combination with simvastatin, HRT significantly increased apolipoprotein A-I by 11% and 12%, respectively, compared to placebo (p < 0.05) and decreased lipoprotein (a) by 23% and 33%, respectively, compared to placebo (p < 0.05), whereas simvastatin had no significant effect on either of these parameters. CONCLUSIONS: In hypercholesterolemic postmenopausal women with CAD, HRT exerts beneficial effects on plasma lipids but the levels currently recommended for secondary prevention are not achieved. Hormone replacement therapy combined with simvastatin is well tolerated and extremely effective, as the two therapies seem to be additive.

Atrial natriuretic peptide augments coronary collateral blood flow: a study during coronary angioplasty.

BACKGROUND AND HYPOTHESIS: In vitro studies have shown that atrial natriuretic peptide (ANP) causes relaxation of preconstricted blood vessel strips and inhibits the contraction of isolated vessels in response to norepinephrine and angiotensin II. The present study examined the effects of exogenous ANP on the coronary collateral blood flow during angioplasty. METHODS: We studied 15 patients undergoing elective balloon angioplasty during the second and third balloon inflations. A Doppler flow guidewire was advanced distal to the lesion and used for the estimation of coronary blood flow velocity. After the second balloon inflation, 25 ng/kg/min of ANP were administered intracoronarily for 8 min. Electrocardiogram, pressure, and flow velocity were recorded immediately before each balloon deflation. Fourteen other patients served as controls and received normal saline infusion. RESULTS: Velocity time integral increased from 65 +/- 40 to 79 +/- 46 mm (p < 0.05) during the third balloon inflation, whereas ST deviation decreased from 1.3 +/- 0.9 to 0.7 +/- 1.0 mV (p < 0.05). These variables did not change in the control group during the two tested balloon inflations. CONCLUSION: Exogenous ANP augments coronary collateral blood flow and ameliorates myocardial ischemia during angioplasty.

Effect of rotational coronary atherectomy on peripheral endothelin-1, atrial natriuretic peptide, and cyclic adenosine monophosphate plasma levels.

We investigated the effects of coronary rotational atherectomy (PTCRA) on plasma levels of endothelin-1 (ET-1), atrial natriuretic peptide (ANP), and cyclic adenosine monophosphate (cAMP). We studied 14 patients undergoing PTCRA and compared them with 14 patients undergoing plain balloon angioplasty. Blood samples were taken from the femoral vein at baseline, after the end of the atherectomy, after the first balloon inflation, after the end of the procedure, and 4 hours later. ET-1 increased in the angioplasty group from 6.3 +/- 3.2 pmol/L at baseline to 8.5 +/- 3.9 pmol/L at the end of the procedure (F = 3.83, P = .02), whereas it did not change in the PTCRA group. ANP increased in the PTCRA group from 78.1 +/- 15.7 pmol/L at baseline to 89.7 +/- 24.0 pmol/L at the end of the procedure (F = 6.75, P = .0001), whereas it did not change in the angioplasty group. cAMP decreased in the PTCRA group, whereas it did not change in the angioplasty group. In conclusion, ET-1 increases less, ANP increases more, and cAMP decreases more during atherectomy than during plain balloon angioplasty.

Short-term atrioventricular sequential pacing does not adversely affect collateral blood flow: a study during angioplasty.

Altered sequence of ventricular activation sequence results in marked derangements in mechanical events. In the present study, we investigated the comparative effects of atrial and AV sequential pacing on collateral blood flow during angioplasty. Twenty-eight patients with stable angina and left anterior descending artery disease undergoing balloon angioplasty were studied. Collateral flow was determined during balloon inflation from the distal flow velocity of the ipsilateral artery (17 patients) or from the increase of the maximal diastolic blood flow velocity (Vc) of the contralateral artery (11 patients). Flow measurements were made using the Doppler flow guidewire. The relative resistance in the collateral vascular bed (RR) also was estimated in the latter group of patients. After the first balloon inflation, two similar consecutive balloon inflations were done under atrial and AV sequential pacing, at a rate of 15 beats/min higher than the sinus rate, in the absence of vasoactive medication. One minute after the initiation of pacing, the second and third balloon inflations were begun and the pacing continued until the balloon inflations were completed. In the ipsilateral group, average peak velocity was 84.6 +/- 24.2 mm/2 during atrial pacing and 82.7 +/- 29.7 mm/s during AV sequential pacing (P = NS). In the contralateral group, Vc was 18% +/- 12% during atrial pacing and 17% +/- 14% during AV sequential pacing, and the RR was 4.5 +/- 4.7 and 4.9 +/- 6.4, respectively (both P = NS). The coronary wedge/mean blood pressure was similar during the two tested balloon inflations. Short-term AV sequential pacing at rest does not adversely affect collateral blood flow and resistance in patients with left anterior descending artery disease.

Short-term estrogen reduces myocardial infarct size in oophorectomized female rabbits in a dose-dependent manner.

17 beta-estradiol, administered acutely, protects ischemic myocardium in male rabbits. In the present study we investigated the effect of short-term estrogen on myocardial infarct size in oophorectomized female rabbits. We oophorectomized 24 sexually mature New Zealand white female rabbits. Twelve animals were left untreated and 12 received oral conjugated estrogens, 0.15 mg/day, for 4 weeks. At a second stage, a third group of 12 oophorectomized female rabbits was treated with intramuscular conjugated estrogens, 1 mg/day, also for 4 weeks. All rabbits underwent 30 minutes of coronary artery occlusion and 2 hours of reperfusion while on anesthesia with i.v. pentobarbital. Infarct and risk area were delineated by Zn-Cd fluorescent particles and tetrazolium chloride staining. The infarct size was expressed as a percentage of the risk zone (I/R %). Data are reported on 26 animals that survived the treatment period and the experiment. Heart rate, systolic, and mean blood pressure and double product did not differ between the three groups at baseline, ischemia, and reperfusion. The infarct size of the risk zone was significantly smaller in the intramuscular group compared with both the oral and the placebo group (18.5 +/- 3.5% vs. 41.3 +/- 9.2% and 43 +/- 8.4%, respectively, P = 0.03). Conjugated estrogens, administered intramuscularly at a high dose, protect ischemic myocardium in oophorectomized female rabbits.

Beta-adrenergic blockade decreases coronary collateral blood flow in patients with coronary artery disease.

The effect of beta-adrenergic blockade on coronary collateral blood flow has not been clarified. We examined the acute effects of beta-adrenergic blockade on coronary collateral blood flow. Fifteen patients (Part A) with stable angina were studied while undergoing coronary angioplasty. According to the protocol, all patients underwent a minimum of three balloon inflations. Collateral flow velocity was determined during balloon inflations using the Doppler flow guidewire positioned distally to the lesion. The two tested balloon inflations, the second and third, were maintained for the same length of time. Between the second and third balloon inflations, 1 mg of propranolol was administered IC into the treated artery. Ten controls were studied following saline infusion. In 10 other patients (Part B), the effect of 1 mg IC propranolol on the coronary artery area distal to the lesion was studied, and five patients served as controls. In the treated group, in Part A blood pressure remained stable during the balloon inflations tested. Heart rate decreased from 79 +/- 11 to 73 +/- 12 beats/min (P < .05), velocity time integral from 9.6 +/- 8.2 to 6.6 +/- 4.1 cm (P < .05), and ST elevation from 1.3 +/- .9 to .9 +/- 1.0 mV (P < .05) between the second and third balloon inflations. In the controls the variables examined did not change during the balloon inflations tested. In Part B, neither propranolol nor normal saline had any significant effect on coronary artery lumen area. Thus, IC administration of beta-adrenergic blockade decreases coronary collateral blood flow, and this potentially worsens the ischemic zone. However, beta-adrenergic blockade ameliorates myocardial ischemia during coronary angioplasty.