Muhammed Z. Khawaja

Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study).

OBJECTIVES This study sought to determine if adenosine administration is required for the pressure-only assessment of coronary stenoses. BACKGROUND The instantaneous wave-free ratio (iFR) is a vasodilator-free pressure-only measure of the hemodynamic severity of a coronary stenosis comparable to fractional flow reserve (FFR) in diagnostic categorization. In this study, we used hyperemic stenosis resistance (HSR), a combined pressure-and-flow index, as an arbiter to determine when iFR and FFR disagree which index is most representative of the hemodynamic significance of the stenosis. We then test whether administering adenosine significantly improves diagnostic performance of iFR. METHODS In 51 vessels, intracoronary pressure and flow velocity was measured distal to the stenosis at rest and during adenosine-mediated hyperemia. The iFR (at rest and during adenosine administration [iFRa]), FFR, HSR, baseline, and hyperemic microvascular resistance were calculated using automated algorithms. RESULTS When iFR and FFR disagreed (4 cases, or 7.7% of the study population), HSR agreed with iFR in 50% of cases and with FFR in 50% of cases. Differences in magnitude of microvascular resistance did not influence diagnostic categorization; iFR, iFRa, and FFR had equally good diagnostic agreement with HSR (receiver-operating characteristic area under the curve 0.93 iFR vs. 0.94 iFRa and 0.96 FFR, p = 0.48). CONCLUSIONS iFR and FFR had equivalent agreement with classification of coronary stenosis severity by HSR. Further reduction in resistance by the administration of adenosine did not improve diagnostic categorization, indicating that iFR can be used as an adenosine-free alternative to FFR.

The effects of VARC-defined acute kidney injury after transcatheter aortic valve implantation (TAVI) using the Edwards bioprosthesis

AIMS The aim of this study was to identify the incidence and risk factors for acute kidney injury (AKI) after TAVI, a potentially serious complication of transcatheter aortic valve implantation (TAVI) that has been redefined by the Valve Academic Research Consortium (VARC). METHODS AND RESULTS We performed a retrospective analysis of 248 patients undergoing TAVI. AKI was defined as a VARC-modified Risk, Injury, Failure, Loss, and End-stage (RIFLE) kidney disease score ≥ 2. Eighty-nine patients suffered AKI (35.9%) and demonstrated increased mortality at 30 days (13.5% vs. 3.8%) and one year (31.5% vs. 15.0%) (p<0.001). Multivariate regression analysis identified diabetes mellitus (p<0.001), peripheral vascular disease (p=0.007), chronic kidney disease stage (p=0.010) as independently associated risk factors for AKI. CONCLUSIONS More than one third of patients sustain AKI after TAVI using the Edwards bioprosthesis, as defined by the VARC-modified RIFLE score. AKI increased the mortality at both 30 days and at one year. A history of diabetes mellitus, peripheral vascular disease and higher chronic kidney disease stage had the strongest independent associations with post-TAVI AKI.

Hemodynamic Response to Intravenous Adenosine and Its Effect on Fractional Flow Reserve Assessment Results of the Adenosine for the Functional Evaluation of Coronary Stenosis Severity (AFFECTS) Study

Background—We studied the hemodynamic response to intravenous adenosine on calculation of fractional flow reserve (FFR). Intravenous adenosine is widely used to achieve conditions of stable hyperemia for measurement of FFR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. Methods and Results—A total of 283 patients (310 coronary stenoses) underwent coronary angiography with FFR using intravenous adenosine 140 mcg/kg per minute via a central femoral vein. Offline analysis was performed to calculate aortic (Pa), distal intracoronary (Pd), and reservoir (Pr) pressure at baseline, peak, and stable hyperemia. Seven different hemodynamic patterns were observed according to Pa and Pd change at peak and stable hyperemia. The average time from baseline to stable hyperemia was 68.2±38.5 seconds, when both &Dgr;Pa and &Dgr;Pd were decreased (&Dgr;Pa, −10.2±10.5 mm Hg; &Dgr;Pd, −18.2±10.8 mm Hg; P<0.001 for both). The fall in Pa closely correlated with the reduction in peripheral Pr (&Dgr;Pr, −12.9±15.7 mm Hg; P<0.001; r=0.9; P<0.001). &Dgr;Pa and &Dgr;Pd were closely related under conditions of peak (r=0.75; P<0.001) and stable hyperemia (r=0.83; P<0.001). On average, 56% (10.2 mm Hg) of the reduction in Pd was because of fall in Pa. FFR lesion classification changed in 9% using an FFR threshold of ⩽0.80 and 5.2% with FFR threshold <0.75 when comparing Pd/Pa at peak and stable hyperemia. Conclusions—Intravenous adenosine results in variable changes in systemic blood pressure, which can lead to alterations in FFR lesion classification. Attention is required to ensure FFR is measured under conditions of stable hyperemia, although the FFR value at this point may be numerically higher.

Standalone balloon aortic valvuloplasty: Indications and outcomes from the UK in the transcatheter valve era

We sought to characterize UK‐wide balloon aortic valvuloplasty (BAV) experience in the TAVI era.

The percutaneous coronary intervention prior to transcatheter aortic valve implantation (ACTIVATION) trial: study protocol for a randomized controlled trial

BackgroundCurrent guidelines recommend treatment of significant coronary artery disease by concomitant coronary artery bypass grafting (CABG) in patients undergoing surgical aortic valve replacement. However there is no consensus as to how best to treat coronary disease in high-risk patients requiring transcatheter aortic valve implantation (TAVI).Methods/DesignThe percutaneous coronary intervention prior to transcatheter aortic valve implantation (ACTIVATION) trial is a randomized, controlled open-label trial of 310 patients randomized to treatment of significant coronary artery disease by percutaneous coronary intervention (PCI - test arm) or no PCI (control arm). Significant coronary disease is defined as ≥1 lesion of ≥70% severity in a major epicardial vessel or 50% in a vein graft or protected left main stem lesion. The trial tests the hypothesis that the strategy of performing pre-TAVI PCI is non-inferior to not treating such coronary stenoses with PCI prior to TAVI, with a composite primary outcome of 12-month mortality and rehospitalization. Secondary outcomes include efficacy end-points such as 30-day mortality, safety endpoints including bleeding, burden of symptoms, and quality of life (assessed using the Seattle Angina Questionnaire and the Kansas City Cardiomyopathy Questionnaire).In conclusion, we hope that using a definition of coronary artery disease severity closer to that used in everyday practice by interventional cardiologists - rather than the 50% severity used in surgical guidelines - will provide robust evidence to direct guidelines regarding TAVI therapy and improve its safety and efficacy profile of this developing technique.Trial registrationISRCTN75836930, http://www.controlled-trials.com/ISRCTN75836930 (registered 19 November 2011).

Meta-analysis of the impact of mitral regurgitation on outcomes after transcatheter aortic valve implantation.

Significant mitral regurgitation (MR) constitutes an important co-existing valvular heart disease burden in the setting of aortic valve stenosis. There are conflicting reports on the impact of significant MR on outcomes after transcatheter aortic valve implantation (TAVI). We evaluated the impact of MR on outcomes after TAVI by performing a meta-analysis of 8 studies involving 8,927 patients reporting TAVI outcomes based on the presence or absence of moderate-severe MR. Risk ratios (RRs) were calculated using the inverse variance random-effects model. None-mild MR was present in 77.8% and moderate-severe MR in 22.2% of the patients. The presence of moderate-severe MR at baseline was associated with increased mortality at 30 days (RR 1.35, 95% confidence interval [CI] 1.14 to 1.59, p = 0.003) and 1 year (RR 1.24, 95% CI 1.13 to 1.37, p <0.0001). The increased mortality associated with moderate-severe MR was not influenced by the cause of MR (functional or degenerative MR; RR 0.90, 95% CI 0.62 to 1.30, p = 0.56). The severity of MR improved in 61 ± 6.0% of patients after TAVI. Moderate-severe residual MR, compared with none-mild residual MR after TAVI, was associated with significantly increased 1-year mortality (RR 1.48, 95% CI 1.31 to 1.68, p <0.00001). In conclusion, baseline moderate-severe MR and significant residual MR after TAVI are associated with an increase in mortality after TAVI and represent an important group to target with medical or transcatheter therapies in the future.

Cardiac complications and manifestations of chemotherapy for cancer

The use of potent chemotherapeutic agents and radiotherapy to target cancer cells has certainly improved outcomes for oncology patients. However, there is increasing recognition of the importance of cardiotoxic side effects of such therapy in both specialties, affecting not just patient survival but also quality of life. Consequently, there is an increasing need for cardiologists to work in close collaboration with oncologists to not only develop methods of predicting patient susceptibility to cardiotoxicity, but also to provide long term follow-up for these patients after the cessation of chemotherapy. The impact of cancer therapy upon cardiac status should be part of the knowledge base for all cardiologists and this new interdisciplinary specialty has become known as cardioncology. It has been suggested that the effects should be classified as non-reversible (type I) and reversible (type II), with the former associated with ultrastructural changes on myocardial biopsy.1 This distinction is especially important given the potential for cure or prolonged survival for oncology patients after some treatment regimens, in whom such end-organ disease may affect not only the prognosis but also quality of life. Yet the dysfunction caused by ‘type II’ agents is not always reversible, the distinction not always binary, and the clinical presentation is perhaps just as relevant when identifying causative agents and initiating appropriate therapy. As such we have classified the cardiac complications of the effects of the potentially cardiotoxic agents used in the treatment of oncological disease and their presenting syndrome (heart failure (HF), cardiac ischaemia, arrhythmias, and hypertension). We then consider the current approaches to the diagnosis of cardiotoxicity (especially chemotherapy induced cardiomyopathy) and the contemporary evidence and guidance on patient management. ### Anthracyclines Anthracyclines are among the most commonly used chemotherapeutic agents. Drugs such as doxorubucin and epirubicin are effective in the treatment of both solid tumours such as …

Physiology of Angina and its Alleviation with Nitroglycerine- Insights from Invasive Catheter Laboratory Measurements During Exercise

Background: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. Methods: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. Results: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity–pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. Conclusions: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

Early and late changes in quality of life following transcatheter aortic valve implantation using the transfemoral and transapical approaches.

AIMS To evaluate the effects of access route upon clinical results and quality of life (QoL) in patients undergoing either transfemoral (TF-TAVI) or transapical balloon-expandable transcatheter aortic valve implantation (TA-TAVI) in the real world. METHODS AND RESULTS A prospective analysis was performed upon 264 consecutive patients receiving TF-TAVI or TA-TAVI. QoL was assessed using the EQ-5D questionnaire. At baseline, TA-TAVI patients reported significantly more problems in mobility, self-care, usual activities and lower overall health status domains (p<0.01 for all). At 30 days, the TF-TAVI group reported fewer problems with usual activity (p=0.01) and pain/discomfort (p<0.01), and higher EQ-5D index and visual analogue scale (VAS) (p=0.01 and p<0.01, respectively) than the TA-TAVI group. Nevertheless, the absolute improvements (ΔEQ-5D index and ΔEQ-5D VAS) were larger in the TA-TAVI group, with most dramatically marked QoL absolute improvements (p<0.01 and p=0.02, respectively). By one year, notwithstanding higher all-cause mortality in the sicker TA-TAVI group, there were no differences between groups in any EQ-5D domain. Indeed, surviving TA-TAVI groups greater absolute improvements remained (p<0.01). CONCLUSIONS QoL is greater at the earlier time point of 30 days in the TF-TAVI cohort but equatable by one year. However, the magnitude of improvement in QoL is greater in the TA-TAVI patients at both 30 days and one year.

Redo patent foramen ovale closure for persistent residual right-to-left shunting.

AIMS The success rate in eliminating a right-left-shunting following percutaneous patent foramen ovale closure is estimated to be > 90%. However up to 10% of patients may have residual shunting following initial closure. Little is known as to the optimum treatment strategy for these patients. We report four cases in which to redo patent foramen ovale closure was possible with a second device. METHODS AND RESULTS At our institution during 2008-2009, 101 patients underwent PFO closure: 81 patients (80%) underwent PFO closure for cerebrovascular events, 12 patients (12%) for migraine with aura, eight patients for systemic embolisation (8%), three patients (3%) for decompression illness and one patient underwent PFO closure for platypnea-orthodexia syndrome. Irrespective of the initial device, redo closure was technically feasible in all cases. All patients had at least a moderate residual shunt evident on echocardiographic evaluation at > 6-month follow-up. The patients in the current study were offered a redo procedure based on the presence of persistent disabling symptoms, as well as increased risk of neurological events, despite adequate antiplatelet therapy and anticoagulation. CONCLUSIONS A second percutaneous interatrial septal occluder is feasible in those patients with significant residual shunting following initial closure.