Echocardiographic Biventricular Coupling Index to Predict Precapillary Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a frequent and detrimental condition. Right heart catheterization (RHC) is the gold standard to identify PH subtype (precapillary from postcapillary PH) and is key for treatment allocation. In this study, the novel echocardiographic biventricular coupling index (BCI), based on the ratio between right ventricular stroke work index and left ventricular E/E' ratio, was tested for the discrimination of PH subtype using RHC as the comparator. METHODS: BCI was derived in 334 consecutive patients who underwent transthoracic echocardiography and RHC for all indications. BCI was then tested in a validation cohort of 1,349 patients. RESULTS: The accuracy of BCI to identify precapillary PH was high in the derivation cohort (area under the curve, 0.82; 95% CI, 0.78-0.88; P < .001; optimal cut point, 1.9). BCI identified patients with precapillary PH with high accuracy also in the validation cohort (area under the curve, 0.87 [95% CI, 0.85-0.89; P < .001]; subgroup with PH: area under the curve, 0.91 [95% CI, 0.89-0.93; P < .001]; cut point, 1.9; sensitivity, 82%; specificity, 89%; positive predictive value, 77%; negative predictive value, 92%). BCI outperformed both the D'Alto score (Z = 3.56; difference between areas = 0.05; 95% CI, 0.02-0.07; P < .001) and the echocardiographic pulmonary-to-left atrial ratio index (Z = 2.88; difference between areas = 0.02; 95% CI, 0.01-0.04; P = .004). CONCLUSIONS: BCI is a novel, noninvasive index based on routinely available echocardiographic parameters that identifies with high accuracy patients with precapillary PH. BCI may be of value in the screening workup of patients with PH.

Amyloid Deposits and Fibrosis on Left Ventricular Endomyocardial Biopsy Correlate With Extracellular Volume in Cardiac Amyloidosis.

Background The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. Methods and Results We included all patients diagnosed with amyloid light-chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68-81). Lambda-positive AL was found in 14 of 19 AL cases (38%) and kappa-positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%-30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%-23%; range, 5%-60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (r=0.661, P=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (P=0.035) and N-terminal pro-B-type natriuretic peptide (P=0.002) serum levels. Conclusions Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone.

Safety and efficacy of coronary sinus narrowing in chronic refractory angina: Insights from the RESOURCE study.

INTRODUCTION: Refractory angina (RA) is considered the end-stage of coronary artery disease, and often has no interventional treatment options. Coronary sinus Reducer (CSR) is a recent addition to the therapeutic arsenal, but its efficacy has only been evaluated on small populations. The RESOURCE registry provides further insights into this therapy. METHODS: The RESOURCE is an observational, retrospective registry that includes 658 patients with RA from 20 centers in Europe, United Kingdom and Israel. Prespecified endpoints were the amelioration of anginal symptoms evaluated with the Canadian Cardiovascular Society (CCS) score, the rates of procedural success and complications, and MACEs as composite of all-cause mortality, acute coronary syndromes, and stroke. RESULTS: At a median follow-up of 502 days (IQR 225-1091) after CSR implantation, 39.7% of patients improved by ≥2 CCS classes (primary endpoint), and 76% by ≥1 class. Procedural success was achieved in 96.7% of attempts, with 3% of procedures aborted mostly for unsuitable coronary sinus anatomy. Any complication occurred in 5.7% of procedures, but never required bailout surgery nor resulted in intra- or periprocedural death or myocardial infarction. One patient developed periprocedural stroke after inadvertent carotid artery puncture. At the last available follow-up, overall mortality and MACE were 10.4% and 14.6% respectively. At one, three and five years, mortality rate at Kaplan-Meier analysis was 4%, 13.7%, and 23.4% respectively. CONCLUSIONS: CSR implantation is safe and reduces angina in patients with refractory angina.

A novel echocardiographic method for estimation of pulmonary artery wedge pressure and pulmonary vascular resistance.

AIMS: This study aimed to evaluate a novel echocardiographic algorithm for quantitative estimation of pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR) in patients with heart failure and pulmonary hypertension (PH) scheduled to right heart catheterization (RHC). METHODS AND RESULTS: In this monocentric study, 795 consecutive patients (427 men; age 68.4 ± 12.1 years) undergoing echocardiography and RHC were evaluated. Multiple regression analysis was performed to identify echocardiographic predictors of PAWP and PVR measured by RHC in the derivation group (the first 200 patients). The diagnostic accuracy of the model was then tested in the validation group (the remaining 595 patients). PH was confirmed by RHC in 507 (63.8%) patients, with 192 (24.2%) cases of precapillary PH, 248 (31.2%) of postcapillary PH, and 67 (8.4%) of combined PH. At regression analysis, tricuspid regurgitation maximal velocity, mitral E/e' ratio, left ventricular ejection fraction, right ventricular fractional area change, inferior vena cava diameter, and left atrial volume index were included in the model (R = 0.8, P < 0.001). The model showed a high diagnostic accuracy in estimating elevated PAWP (area under the receiver operating characteristic curve = 0.97, 92% sensitivity, and 93% specificity, P < 0.001) and PVR (area under the receiver operating characteristic curve = 0.96, 89% sensitivity, and 92% specificity, P < 0.001), outperforming 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations (P < 0.001) and Abbas' equation (P < 0.001). Bland-Altman analysis showed satisfactory limits of agreement between echocardiography and RHC for PAWP (bias 0.7, 95% confidence interval -7.3 to 8.7) and PVR (bias -0.1, 95% confidence interval -2.2 to 1.9 Wood units), without indeterminate cases. CONCLUSIONS: A novel quantitative echocardiographic approach for the estimation of PAWP and PVR has high diagnostic accuracy in patients with heart failure and PH.

Usefulness of Coronary Sinus Reducer Implantation for the Treatment of Chronic Refractory Angina Pectoris.

The coronary sinus (CS) Reducer is a novel device designed for the management of patients with severe angina symptoms refractory to optimal medical therapy and not amenable to further revascularization. Aim of this study was to investigate the efficacy and the safety of the CS Reducer device in a real-world, multicenter, and country-level cohort of patients presenting with refractory angina pectoris. The study included patients affected by refractory angina pectoris who underwent CS Reducer implantation in 16 centers. Clinical follow-up was carried as per each center's protocol. One hundred eighty-seven patients were included. Technical and procedural success were achieved in 98% and 95%, respectively. Minor peri-procedural complications were recorded in 8 patients. During a median follow-up of 18.4 months, 135 (82.8%) patients demonstrated at least 1 CCS class reduction after Reducer implantation, and 80 (49%) patients at least 2 CCS class reduction. Mean CCS class improved from 3.05 ± 0.53 at baseline to 1.63 ± 0.98 at follow-up (p < 0.001). Treatment benefit was also reflected in a significant improvement in quality of life scores and in a reduction of the mean number of anti-ischemic drugs prescribed for patient. In conclusion, in this multicenter, country-level study, the implantation of CS Reducer in patients with refractory angina pectoris resulted to be safe and effective in reducing of angina pectoris and improving quality of life.

Myocardial salvage is increased after sympathetic renal denervation in a pig model of acute infarction.

RATIONALE: Despite advances in treatment of acute myocardial infarction (AMI), many patients suffer significant myocardial damage with cardiac dysfunction. Sympathetic renal denervation (RD) may reduce adrenergic activation following AMI. OBJECTIVE: To investigate the potential role of RD limiting myocardial damage and remodeling when performed immediately after AMI. METHODS AND RESULTS: Sixteen farm pigs underwent 90 min left anterior descending artery balloon occlusion. Eight pigs underwent RD immediately after reperfusion. LV function, extent of myocardium at risk, and myocardial necrosis were quantified by cardiac magnetic resonance 5 and 30 days after AMI. 123I-MIBG scintigraphy was performed 31 days after AMI to image myocardial sympathetic innervation. Heart norepinephrine was quantified (from necrotic, border and remote zone). RD and control did not differ in myocardium at risk extent (59 ± 9 vs 55 ± 11% of LV mass) at 5 days. At 30 days CMR, RD pigs had smaller necrotic areas than control as assessed by gadolinium delay enhancement (18 ± 7 vs 30 ± 12% of LV mass, p = 0.021) resulting in improved myocardial salvage index (60 ± 11 vs 44 ± 27%, p < 0.001). RD pigs had higher cardiac output (3.7 ± 0.8 vs 2.66 ± 0.7 L/min, p < 0.001) and lower LV end diastolic volume (98 ± 16 vs 113 ± 31 ml, p = 0.041). 123I-MIBG defect extension was smaller in RD than control (60 ± 28 vs 78 ± 17%, p < 0.05) with significant reduction in the difference between innervation and perfusion defects (25 ± 12 vs 36 ± 30%, p = 0.013). NE content from necrotic area (238; IQR 464 vs 2546; IQR 1727 ng/g in RD and control, respectively, p < 0.001) and from border zone (295; IQR 264 vs 837; IQR 207 in RD and control, respectively, p = 0.031) was significantly lower in RD than control. CONCLUSIONS: RD results in increased myocardial salvage and better cardiac function, when performed immediately after AMI. Reduction of sympathetic activation with preservation of cardiac sympathetic functionality warranted by RD may sustain these effects.

Quantitative analysis of epicardial fat volume: effects of scanning protocol and reproducibility of measurements in non-contrast cardiac CT vs. coronary CT angiography.

BACKGROUND: Several studies have focused on the role of epicardial fat in the pathogenesis of cardiovascular disease (CVD). The main purpose of the study was to evaluate a computerized method for the quantitative analysis of epicardial fat volume (EFV) by non-contrast cardiac CT (NCT) for coronary calcium scan and coronary CT angiography (coronary CTA). METHODS: Thirty patients (61±12.5 years, 73% male, body mass index (BMI) =25.9±6.3 kg/m2) referred to our Institution for suspected coronary artery disease (CAD) underwent NCT and coronary CTA. Epicardial boundaries were traced by 2 experienced operators (operator 1, operators 2) on 3 and 6 short-axis (SA) slices. EFV was computed with a semi-automatic method using an in-house developed software based on spherical harmonic representation of the epicardial surface. In order to analyze the inter-observer variability both the Coefficient of Repeatability (CR) and Intra Class Correlation (ICC) were computed. RESULTS: The total EFV was 103.62±50.97 and 94.96±67.91 cc in NCT and coronary CTA with non-significant difference (P=0.292). CR error was 10.22 cc for operator 1 and 11.31 cc for operator 2 in NCT and 7.99 cc for operator 1 and 7.75 cc for operator 2 in coronary CTA. To analyze the inter-observer variability CR and ICC were computed. CR was 8.17 and 8.39 cc with NCT and 7.07 and 7.21 cc with CTA for 6 and 3 SA slices respectively. ICC values >0.99 were obtained in all cases. The right ventricular EFV was 67.23±31.4 and 57.41±34.3 cc for NCT and coronary CTA respectively; the corresponding values for left ventricular EFV were 38.01±19.1 and 35.27±25.9 cc. CONCLUSIONS: Both NCT and coronary CTA can be used with low intra- and inter-observer variability for computer-assisted measurements of EFV. Cardiac CT may allow a fast and reliable computation of EFV in clinical setting.

Self-expanding stent for complex percutaneous coronary interventions: A real life experience.

AIM: Self-expanding stents represent a re-emerging option for percutaneous coronary interventions. Their application covers a wide spectrum of angiographic situations, i.e., coronary bifurcations, acute coronary syndromes with large thrombotic burden and stenosis of ectatic coronaries. We review our experience with self-expanding stents for different clinical and angiographic indications, with long clinical follow-up. METHODS: From 2011 to 2013 we used self-expanding STENTYS® stents in 40 consecutive patients followed-up for death from any cause and from cardiovascular cause, myocardial infarction, target lesion revascularization (TLR), stent thrombosis (mean 21±13months). We also revised rate of procedural outcomes, acute stent thrombosis and TLR in patients treated with conventional stents for similar clinical/angiographic situations, in the same period at our institution. RESULTS: We identified three anatomical settings of STENTYS® use: coronary bifurcations with proximal/distal main branch diameter discrepancy (55% of cases), massive thrombotic burden in the setting of acute coronary syndrome (35% of cases) and stenosis of ectatic coronaries (15%). We observed one death related to acute heart failure and 1 case (2.5%) of acute stent thrombosis (2.5% in the control group). During follow-up 2 cases of stent restenosis leading to TLR (5%) occurred (6.25% in the control group). CONCLUSIONS: According to our real life experience, self-expanding STENTYS® stents appear to be an effective tool for different angiographic situations in which they may be preferable to balloon-expandable stents, showing a low rate of complications and good results at long term follow-up.

Drug eluting balloon: a multipurpose tool for coronary revascularization with optimal long-term follow-up results.

AIMS: This study aimed to evaluate safety and efficacy of drug-coated balloon (DCB) at long-term follow-up; a large series of real-life patients underwent revascularization with DCB for a wide spectrum of clinical and angiographic situations. METHODS AND RESULTS: One hundred ten patients underwent percutaneous revascularization using paclitaxel eluting balloon (Sequent Please, Braun, Germany). End-points were major adverse cardiac events (MACE; all-cause death, myocardial infarction [MI], target vessel revascularisation [TVR], and vessel thrombosis). DCB were used for stable angina (58%), unstable angina/nonST elevation MI (31%) and ST elevation MI (11%). DCB were used for in-stent restenosis (61%), small vessel disease (25%), with bare metal stent (BMS) to avoid long dual antiplatelet therapy (10%) or for impossibility to place a stent (4%). Cumulative MACE at follow-up (median 23 months, IQR 13-32) was 12.7%, with 8.2% all-cause death (1 fatal MI), 4.5% TVR, 3.6% TLR, and no vessel thrombosis. Three of four TLRs occurred in patients who received DEB for DES restenosis. CONCLUSIONS: DCB are a very effective tool for a variety of clinical and angiographic situations. DCB use seems to be affected by a low rate of complications and adequate results at long-term follow-up.

Surgical correction of left coronary artery origin from the right coronary artery.

We describe the case of a patient with limiting angina pectoris and anomalous origin of the left coronary artery from the right coronary artery, with a retroaortic course. Myocardial ischemia in the left anterior descending territory was documented by positron emission tomography, confirmed by fractional flow reserve, and relieved by surgical coronary reimplantation. This patient did not have coronary atherosclerosis or any other significant anatomic abnormality, such as myocardial bridging or compression between the aorta and the pulmonary artery. We attempt to describe the mechanisms of myocardial ischemia that contributed to the clinical manifestations in our patient.

How should I treat a perimembranous interventricular defect following aortic valve replacement surgery?

BACKGROUND: A 73-year-old man was admitted to our Institute for repeated episodes of congestive heart failure. The patient was affected by arterial hypertension, dyslipidaemia, severe chronic obstructive pulmonary disease, and recurrent atrial fibrillation. Two months earlier he had undergone aortic valve replacement with a biological prosthesis for severe stenosis. Echocardiography showed a left-to-right shunt localised in the left ventricular outflow tract, normal morphology and function of the aortic valve prosthesis, and a hyperkinetic left ventricle. INVESTIGATION: Physical examination, electrocardiography, transthoracic and transoesophageal echocardiography, right heart catheterisation, left ventricular angiography. DIAGNOSIS: Post-surgical perimembranous interventricular defect with a clinically significant left-to-right shunt. MANAGEMENT: Percutaneous closure with a ventricular septal defect occluder.

Contrast medium nephrotoxicity after renal artery and coronary angioplasty.

BACKGROUND: Renal dysfunction induced by iodinated contrast medium (CM) administration can minimize the benefit of the interventional procedure in patients undergoing renal angioplasty (PTRA). PURPOSE: To compare the susceptibility to nephrotoxic effect of CM in patients undergoing PTRA with that of patients submitted to percutaneous coronary intervention (PCI). MATERIAL AND METHODS: A total of 33 patients successfully treated with PTRA (PTRA group, mean age 70+/-12 years, 23 female, basal creatinine 1.46+/-0.79, range 0.7-4.9 mg/dl) were compared with 33 patients undergoing successful PCI (PCI group), matched for basal creatinine (1.44+/-0.6, range 0.7-3.4 mg/dl), gender, and age. In both groups postprocedural (48 h) serum creatinine was measured. RESULTS: Postprocedural creatinine level decreased nonsignificantly in the PTRA group (1.46+/-0.8 vs. 1.34+/-0.5 mg/dl, P=NS) and increased significantly in the PCI group (1.44+/-0.6 vs. 1.57+/-0.7 mg/dl, P<0.02). Changes in serum creatinine after intervention (after-before) were significantly different between the PTRA and PCI groups (-0.12+/-0.5 vs. 0.13+/-0.3, P=0.014). This difference was not related to either a different clinical risk profile or to the volume of CM administered. CONCLUSION: In this preliminary study patients submitted to PTRA showed a lower susceptibility to renal damage induced by CM administration than PCI patients. The effectiveness of PTRA on renal function seems to be barely influenced by CM toxicity.

Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy.

Under resting conditions, the failing heart shifts fuel use toward greater glucose and lower free fatty acid (FFA) oxidation. We hypothesized that chronic metabolic abnormalities in patients with dilated cardiomyopathy (DCM) are associated with the absence of the normal increase in myocardial glucose uptake and maintenance of cardiac mechanical efficiency in response to pacing stress. In 10 DCM patients and 6 control subjects, we measured coronary flow by intravascular ultrasonometry and sampled arterial and coronary sinus blood. Myocardial metabolism was determined at baseline, during atrial pacing at 130 beats/min, and at 15 min of recovery by infusion of [(3)H]oleate and [(13)C]lactate and measurement of transmyocardial arteriovenous differences of oxygen and metabolites. At baseline, DCM patients showed depressed coronary flow, reduced uptake and oxidation of FFA, and preferential utilization of carbohydrates. During pacing, glucose uptake increased by 106% in control subjects but did not change from baseline in DCM patients. Lactate release increased by 122% in DCM patients but not in control subjects. Cardiac mechanical efficiency in DCM patients was not different compared with control subjects at baseline but was 34% lower during stress. Fatty acid uptake and oxidation did not change with pacing in either group. Our results show that in DCM there is preferential utilization of carbohydrates, which is associated with reduced flow and oxygen consumption at rest and an impaired ability to increase glucose uptake during stress. These metabolic abnormalities might contribute to progressive cardiac deterioration and represent a target for therapeutic strategies aimed at modulating cardiac substrate utilization.

Contrasting effects of acute and chronic cigarette smoking on skin microcirculation in young healthy subjects.

OBJECTIVE: The aim of our study was to assess the effects of acute and chronic smoking on skin microvascular properties of young healthy subjects. DESIGN: An observational study, using a totally non-invasive approach, employing continuous palmar microvascular flow (laser Doppler) and arterial pressure measurements, to compute estimates of microvascular resistive (Z0) and oscillatory (impedance, i.e. ZC) properties. Measures were obtained at baseline and after iontophoretic administration of acetylcholine (ACh), an endothelium-dependent vasodilator and of sodium nitroprusside (NP), an endothelium-independent vasodilator. PARTICIPANTS: A total of 20 healthy male subjects (nine habitual smokers and 11 non-smokers; aged 27 +/- 1 and 29 +/- 2 years, respectively) in resting conditions and during administration of ACh and of NP (in two different days), before and after smoking one cigarette were evaluated. RESULTS: Smokers showed significant lower baseline Z0 and ZC than non-smokers. In non-smokers, ACh and NP iontophoresis induced a significant decrease of both Z0 and ZC, before and after smoking one cigarette (P < 0.02). Conversely, in smokers, both Z0 and ZC were not affected by ACh iontophoresis before acute smoking, while, after smoking, a significant decrease of both Z0 and ZC (P < 0.02) was detected after ACh challenge. In smokers, both Z0 and ZC were not affected by NP iontophoresis, either before or after smoking a cigarette. CONCLUSIONS: Smokers appeared characterized by a complex disruption of peripheral microcirculatory regulation, including inappropriate resting vasodilation, impaired endothelium-dependent and independent vasodilation, paradoxical recovery of endothelium-dependent vasodilation in response to acute smoking.