Principles of Intravascular Lithotripsy for Calcific Plaque Modification.

A significant proportion of lesions treated with transcatheter interventions in the coronary and peripheral vascular beds exhibit moderate to severe calcific plaques known to portend lower procedural success rates, increased peri-procedural adverse events, and unfavorable clinical outcomes compared with noncalcific plaques. Adapted from lithotripsy technology used for treatment of ureterorenal calculi, intravascular lithotripsy (IVL) is a novel technique for the treatment of severely calcific plaque lesions that uses acoustic shockwaves in a balloon-based delivery system. Shockwaves induce calcium fractures, which facilitate stent expansion and luminal gain. In this review, the authors summarize the physics, preclinical and clinical data on IVL use in the coronary and peripheral vasculature, and future directions of IVL in transcatheter cardiovascular therapies.

Dose-Dependent Cardioprotection of Moderate (32°C) Versus Mild (35°C) Therapeutic Hypothermia in Porcine Acute Myocardial Infarction.

OBJECTIVES: The study investigated whether a dose response exists between myocardial salvage and the depth of therapeutic hypothermia. BACKGROUND: Cardiac protection from mild hypothermia during acute myocardial infarction (AMI) has yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve myocardial salvage. METHODS: Swine (n = 24) undergoing AMI were assigned to 3 reperfusion groups: normothermia (38°C) and mild (35°C) and moderate (32°C) hypothermia. One-hour anterior myocardial ischemia was followed by rapid endovascular cooling to target reperfusion temperature. Cooling began 30 min before reperfusion. Target temperature was reached before reperfusion and was maintained for 60 min. Infarct size (IS) was assessed on day 6 using cardiac magnetic resonance, triphenyl tetrazolium chloride, and histopathology. RESULTS: Triphenyl tetrazolium chloride area at risk (AAR) was equivalent in all groups (p = 0.2), but 32°C exhibited 77% and 91% reductions in IS size per AAR compared with 35°C and 38°C, respectively (AAR: 38°C, 45 ± 12%; 35°C, 17 ± 10%; 32°C, 4 ± 4%; p < 0.001) and comparable reductions per LV mass (LV mass: 38°C, 14 ± 5%; 35°C, 5 ± 3%; 32°C 1 ± 1%; p < 0.001). Importantly, 32°C showed a lower IS AAR (p = 0.013) and increased immunohistochemical granulation tissue versus 35°C, indicating higher tissue salvage. Delayed-enhancement cardiac magnetic resonance IS LV also showed marked reduction at 32°C (38°C: 10 ± 4%, p < 0.001; 35°C: 8 ± 3%; 32°C: 3 ± 2%, p < 0.001). Cardiac output on day 6 was only preserved at 32°C (reduction in cardiac output: 38°C, -29 ± 19%, p = 0.041; 35°C: -17 ± 33%; 32°C: -1 ± 28%, p = 0.041). Using linear regression, the predicted IS reduction was 6.7% (AAR) and 2.1% (LV) per every 1°C reperfusion temperature decrease. CONCLUSIONS: Moderate (32°C) therapeutic hypothermia demonstrated superior and near-complete cardioprotection compared with 35°C and control, warranting further investigation into clinical applications.

Optical Coherence Tomography Characterization of Coronary Lithoplasty for Treatment of Calcified Lesions: First Description.

OBJECTIVES: This study sought to determine the mechanistic effects of a novel balloon-based lithoplasty system on heavily calcified coronary lesions and subsequent stent placement using optical coherence tomography (OCT). BACKGROUND: The Shockwave Coronary Rx Lithoplasty System (Shockwave Medical, Fremont, California) delivers localized, lithotripsy-enhanced disruption of calcium within the target lesion (i.e., lithoplasty) for vessel preparation before stent implantation. METHODS: We analyzed OCT findings in 31 patients in whom lithoplasty was used to treat severely calcified stenotic coronary lesions. RESULTS: After lithoplasty, intraplaque calcium fracture was identified in 43% of lesions, with circumferential multiple fractures noted in >25%. The frequency of calcium fractures per lesion increased in the most severely calcified plaques (highest tertile vs. lowest tertile; p = 0.009), with a trend toward greater incidence of calcium fracture (77.8% vs. 22.2%; p = 0.057). Post-lithoplasty, mean acute area gain was 2.1 mm2, which further increased with stent implantation, achieving a minimal stent area of 5.94 ± 1.98 mm2 and mean stent expansion of 112.0 ± 37.2%. Deep dissections, as part of the angioplasty effect, occurred in 13% of cases and were successfully treated with stent implantation without incidence of acute closure, slow flow/no reflow, or perforation. CONCLUSIONS: High-resolution imaging by OCT delineated calcium modification with fracture as a major mechanism of action of lithoplasty in vivo and demonstrated efficacy in the achievement of significant acute area gain and favorable stent expansion.

Importance of Both Early Reperfusion and Therapeutic Hypothermia in Limiting Myocardial Infarct Size Post-Cardiac Arrest in a Porcine Model.

OBJECTIVES: The aim of this study was to test the hypothesis that hypothermia and early reperfusion are synergistic for limiting infarct size when an acutely occluded coronary is associated with cardiac arrest. BACKGROUND: Cohort studies have shown that 1 in 4 post-cardiac arrest patients without ST-segment elevation has an acutely occluded coronary artery. However, many interventional cardiologists remain unconvinced that immediate coronary angiography is needed in these patients. METHODS: Thirty-two swine (mean weight 35 ± 5 kg) were randomly assigned to 1 of the following 4 treatment groups: group A, hypothermia and reperfusion; group B, hypothermia and no reperfusion; group C, no hypothermia and reperfusion; and group D, no hypothermia and no reperfusion. The left anterior descending coronary artery was occluded with an intracoronary balloon, and ventricular fibrillation was electrically induced. Cardiopulmonary resuscitation was begun after 4 min of cardiac arrest. Defibrillation was attempted after 2 min of cardiopulmonary resuscitation. Resuscitated animals randomized to hypothermia were rapidly cooled to 34°C, whereas those randomized to reperfusion had such after 45 min of left anterior descending coronary artery occlusion. RESULTS: At 4 h, myocardial infarct size was calculated. Group A had the smallest infarct size at 16.1 ± 19.6% (p < 0.05). Group C had an intermediate infarct size at 29.5 ± 20.2%, whereas groups B and D had the largest infarct sizes at 41.5 ± 15.5% and 41.1 ± 15.0%, respectively. CONCLUSIONS: Acute coronary occlusion is often associated with cardiac arrest, so treatment of resuscitated patients should include early coronary angiography for potential emergent reperfusion, while providing hypothermia for both brain and myocardial protection. Providing only early hypothermia, while delaying coronary angiography, is not optimal.

Volume infusion cooling increases end-tidal carbon dioxide and results in faster and deeper cooling during intra-cardiopulmonary resuscitation hypothermia induction.

BACKGROUND: Intra-arrest hypothermia induction may provide more benefit than inducing hypothermia after return of spontaneous circulation. However, little is understood about the interaction between patient physiology and hypothermia induction technology choice during ongoing chest compressions. METHODS: After 10 min of untreated ventricular fibrillation, mechanical chest compressions were provided for 60 min (100 CPM, 1.25" deep) in 26 domestic swine (30.5 ± 1.7 kg) with concurrent hypothermia induction using one of eight cooling methods. Four cooling methods included volume infusion with cold saline or an ice particulate slurry through the femoral vein or carotid artery (volume infusion cooling group, VC); three included cooling via an intra-vascular heat exchange catheter, nasal cooling, or surface ice bags (no volume cooling group, NVC); and the other was a control group with no cooling (no cooling group, NC). Physiological monitoring included end-tidal carbon dioxide, aortic pressure, right atrial pressure, brain temperature, esophageal temperature, and rectal temperature. RESULTS: During cardiopulmonary resuscitation (CPR), the volume infusion cooling group cooled faster and to lower temperatures than the other groups (VC vs. NVC or NC; ∆T = -5.6 vs. -2.1 °C or -0.6 °C; p < 0.01). The aortic pressure and right atrial pressure were higher in the volume cooling group than the other groups (VC vs. NVC or NC; AOP = 23.6 vs. 16.7 mmHg or 14.7 mmHg; p < 0.02). End-tidal carbon dioxide measurements during CPR were also higher in the volume cooling group (VC vs. NVC; EtCO2 = 23.4 vs. 13.1 mmHg; p < 0.05). Intra-corporeal temperature gradients larger than 3 °C were created by volume cooling during ongoing chest compressions. CONCLUSIONS: Volume infusion cooling significantly altered physiology relative to other cooling methods during ongoing chest compressions. Volume cooling led to faster cooling rates, lower temperatures, higher end-tidal carbon dioxide levels, and higher central vascular pressures. IACUC protocol numbers: UPenn (803178), CHOP (997).

Outcomes from low versus high-flow cardiopulmonary resuscitation in a swine model of cardiac arrest.

BACKGROUND: Return of spontaneous circulation (ROSC) is improved by greater vital organ blood flow during cardiopulmonary resuscitation (CPR). We tested the hypothesis that myocardial flow above the threshold needed for ROSC may be associated with greater vital organ injury and worse outcome. METHODS: Aortic and right atrial pressures were measured with micromanometers in 27 swine. After 10 minutes of untreated ventricular fibrillation, chest compression was performed with an automatic, load-distributing band. Animals were randomly assigned to receive flows just sufficient for ROSC (low flow: target coronary perfusion pressure = 12 mm Hg) or well above the minimally effective level (high flow: coronary perfusion pressure = 30 mm Hg). Myocardial flow was measured with microspheres, defibrillation was performed after 3.5 minutes of CPR, and ejection fraction was measured with echocardiography. RESULTS: Return of spontaneous circulation was achieved by 9 of 9 animals in the high-flow group and 15 of 18 in the low-flow group. All animals in the high-flow group defibrillated initially into a perfusing rhythm, whereas 12 of 15 animals achieving ROSC in the low-flow group defibrillated initially into pulseless electrical activity (P < .05, Fisher exact test). Compared with animals in the low-flow group, animals in the high-flow group had shorter resuscitation times, higher mean aortic pressures at ROSC, and higher ejection fractions at 2 hours post-ROSC (all P < .05). CONCLUSION: High-flow CPR significantly improved arrest hemodynamics, rates of ROSC, and post-ROSC indicators of myocardial status, all indicating less injury with higher flows. No evidence of organ injury from vital organ blood flow substantially above the threshold for ROSC was found.